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Hypotrichosis-lymphedema-telangiectasia syndrome (HLTS) is a rare condition that, as the name suggests, is associated with sparse hair (hypotrichosis), lymphedema, and telangiectasia, particularly on the palms of the hands. Symptoms usually begin at birth or in early childhood and become worse over time. HLTS is thought to be caused by changes (mutations) in the SOX18 gene. It can follow both an autosomal dominant or an autosomal recessive pattern of inheritance, depending on the affected family. There is currently no cure for the condition. Treatment is based on the signs and symptoms present in each person.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Hypotrichosis-lymphedema-telangiectasia syndrome | c1843004 | 4,000 | gard | https://rarediseases.info.nih.gov/diseases/12827/hypotrichosis-lymphedema-telangiectasia-syndrome | 2021-01-18T17:59:51 | {"mesh": ["C564327"], "omim": ["607823"], "orphanet": ["69735"], "synonyms": ["HLTS", "Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome", "Hypotrichosis-lymphedema-telangiectasia-membranoproliferative glomerulonephritis syndrome", "Hypotrichosis lymphedema telangiectasia syndrome"]} |
## Clinical Features
Kayes-Wandover et al. (2001) studied 5 patients in 4 unrelated kindreds with hyperreninemic hypoaldosteronism in whom they were unable to find mutations in the aldosterone synthase gene (CYP11B2; 124080). All presented in infancy with failure to thrive, hyponatremia, hyperkalemia, markedly elevated plasma renin activity, and low or inappropriately normal aldosterone levels. All had normal cortisol levels and no signs or symptoms of congenital adrenal hyperplasia.
Molecular Genetics
In 5 patients from 4 unrelated kindreds with hyperreninemic hypoaldosteronism, Kayes-Wandover et al. (2001) found no mutations in exons or splice junctions of CYP11B2. Linkage of the disorder to CYP11B2 was studied in 2 unrelated consanguineous patients and in an affected sib pair. The consanguineous patients were each heterozygous for at least 1 of 3 polymorphic microsatellite markers near CYP11B2, excluding linkage to CYP11B2. However, linkage of the disease to CYP11B2 could not be excluded in the affected sib pair. The authors concluded that their results demonstrated the existence of an inherited form of hyperreninemic hypoaldosteronism, which they termed 'familial hyperreninemic hypoaldosteronism 2' (FHHA2), distinct from aldosterone synthase deficiency (FHHA1; 203400), caused by mutations in CYP11B2.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| HYPERRENINEMIC HYPOALDOSTERONISM, FAMILIAL, 2 | c1846990 | 4,001 | omim | https://www.omim.org/entry/606984 | 2019-09-22T16:09:48 | {"mesh": ["C564638"], "omim": ["606984"], "orphanet": ["427"], "synonyms": ["Alternative titles", "FHHA2"]} |
"Emphysema" and "Chronic bronchitis" redirect here. For the abnormal occurrence of gas within tissue, see pneumatosis. For the long-term productive cough, see Bronchitis § Chronic bronchitis.
Lung disease involving long-term poor airflow
Chronic obstructive pulmonary disease
Other namesChronic obstructive lung disease (COLD), chronic obstructive airway disease (COAD), chronic bronchitis, emphysema, pulmonary emphysema, others
Gross pathology of a lung showing centrilobular emphysema characteristic of smoking. This close-up of the fixed, cut lung surface shows multiple cavities filled with heavy black carbon deposits.
SpecialtyPulmonology
SymptomsShortness of breath, cough with sputum production.[1]
ComplicationsAcute exacerbation of chronic obstructive pulmonary disease[2]
Usual onsetOver 40 years old[3]
DurationLong term[3]
CausesTobacco smoking, air pollution, genetics[2]
Diagnostic methodLung function tests[4]
Differential diagnosisAsthma,[3] Asbestosis, Bronchiectasis, Tracheobronchomalacia
PreventionImproving indoor and outdoor air quality, tobacco control measures[3]
TreatmentStopping smoking, respiratory rehabilitation, lung transplantation[2]
MedicationVaccinations, inhaled bronchodilators and steroids, long-term oxygen therapy[2][5]
Frequency174.5 million (2015)[6]
Deaths3.2 million (2015)[7]
Chronic obstructive pulmonary disease (COPD) is a type of obstructive lung disease characterized by long-term breathing problems and poor airflow.[1][8] The main symptoms include shortness of breath and cough with sputum production.[1] COPD is a progressive disease, meaning it typically worsens over time.[9] Eventually, everyday activities such as walking or getting dressed become difficult.[3] Chronic bronchitis and emphysema are older terms used for different types of COPD.[10][11][12] The term "chronic bronchitis" is still used to define a productive cough that is present for at least three months each year for two years.[1] Those with such a cough are at a greater risk of developing COPD.[13] The term "emphysema" is also used for the abnormal presence of air or other gas within tissues.[14]
The most common cause of COPD is tobacco smoking, with a smaller number of cases due to factors such as air pollution and genetics.[2] In the developing world, common sources of air pollution are wood combustion[15] and cooking fires.[3] Long-term exposure to these irritants causes an inflammatory response in the lungs, resulting in narrowing of the small airways and breakdown of lung tissue.[5] The diagnosis is based on poor airflow as measured by lung function tests.[4] In contrast to asthma, the airflow reduction generally does not improve much with the use of a bronchodilator.[3][16]
Most cases of COPD can be prevented by reducing exposure to risk factors.[17] This includes decreasing rates of smoking and improving indoor and outdoor air quality.[3] While treatment can slow worsening, no cure is known.[3] COPD treatments include smoking cessation, vaccinations, respiratory rehabilitation, and often inhaled bronchodilators and steroids.[2] Some people may benefit from long-term oxygen therapy or lung transplantation.[5] In those who have periods of acute worsening, increased use of medications, antibiotics, steroids, and hospitalization may be needed.[2][18]
As of 2015, COPD affected about 174.5 million people (2.4% of the global population).[6] It typically occurs in people over the age of 40.[3] Males and females are affected equally commonly.[3] In 2015, it caused 3.2 million deaths, more than 90% in the developing world,[3] up from 2.4 million deaths in 1990.[7][19] The number of deaths is projected to increase further because of higher smoking rates in the developing world, and an ageing population in many countries.[20] It resulted in an estimated economic cost of US$2.1 trillion in 2010.[21]
## Contents
* 1 Signs and symptoms
* 1.1 Cough
* 1.2 Shortness of breath
* 1.3 Physical activity limitation
* 1.4 Other symptoms
* 1.5 Exacerbation
* 2 Cause
* 2.1 Smoking
* 2.2 Air pollution
* 2.3 Occupational exposure
* 2.4 Genetics
* 2.5 Other
* 2.6 Exacerbations
* 3 Pathophysiology
* 4 Diagnosis
* 4.1 Spirometry
* 4.2 Severity
* 4.3 Other tests
* 4.4 Differential diagnosis
* 5 Prevention
* 5.1 Smoking cessation
* 5.2 Occupational health
* 5.3 Air pollution
* 6 Management
* 6.1 Exercise
* 6.2 Bronchodilators
* 6.3 Corticosteroids
* 6.4 Other medications
* 6.5 Oxygen
* 6.6 Surgery
* 6.7 Exacerbations
* 7 Prognosis
* 8 Epidemiology
* 9 History
* 10 Society and culture
* 10.1 Economics
* 11 Research
* 12 Other animals
* 13 References
* 14 Further reading
* 15 External links
## Signs and symptoms[edit]
Wheezing
The sound of wheezing as heard with a stethoscope.
* * *
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The most common symptoms of COPD are shortness of breath, and a cough that produces sputum.[22] These symptoms are present for a prolonged period of time[23] and typically worsen over time.[5] It is unclear whether different types of COPD exist.[2][24] While previously divided into emphysema and chronic bronchitis, emphysema is only a description of lung changes rather than a disease itself, and chronic bronchitis is simply a descriptor of symptoms that may or may not occur with COPD.[3][25]
### Cough[edit]
A chronic cough is often the first symptom to develop.[22] Early on it may just occur occasionally or may not result in sputum.[22] When a cough persists for more than three months each year for at least two years, in combination with sputum production and without another explanation, it is by definition chronic bronchitis.[22] Chronic bronchitis can occur before the restricted airflow and thus COPD fully develops.[22] The amount of sputum produced can change over hours to days.[22] In some cases, the cough may not be present or may only occur occasionally and may not be productive.[22] Some people with COPD attribute the symptoms to a "smoker's cough".[22] Sputum may be swallowed or spat out, depending often on social and cultural factors.[22] In severe COPD, vigorous coughing may lead to rib fractures or to a brief loss of consciousness.[26] Those with COPD often have a history of "common colds" that last a long time.[22]
### Shortness of breath[edit]
Shortness of breath is a common symptom and is often the most distressing.[27] It is commonly described as: "my breathing requires effort," "I feel out of breath," or "I can't get enough air in."[28] Different terms, however, may be used in different cultures.[22] Typically, the shortness of breath is worse on exertion of a prolonged duration and worsens over time.[22] In the advanced stages, or end stage pulmonary disease, it occurs during rest and may be always present.[29][30] Shortness of breath is a source of both anxiety and a poor quality of life in those with COPD.[22] Many people with more advanced COPD breathe through pursed lips and this action can improve shortness of breath in some.[31][32]
### Physical activity limitation[edit]
COPD often leads to reduction in physical activity, in part due to shortness of breath.[33] In later stages of COPD muscle wasting (cachexia) may occur.[34] Low levels of physical activity are associated with worse outcomes.[35]
### Other symptoms[edit]
In COPD, breathing out may take longer than breathing in.[36] Chest tightness may occur,[22] but is not common and may be caused by another problem.[27] Those with obstructed airflow may have wheezing or decreased sounds with air entry on examination of the chest with a stethoscope.[36] A barrel chest is a characteristic sign of COPD, but is relatively uncommon.[36] Tripod positioning may occur as the disease worsens.[23]
Advanced COPD leads to high pressure on the lung arteries, which strains the right ventricle of the heart.[5][37][38] This situation is referred to as cor pulmonale, and leads to symptoms of leg swelling[22] and bulging neck veins.[5] COPD is more common than any other lung disease as a cause of cor pulmonale.[37] Cor pulmonale has become less common since the use of supplemental oxygen.[23]
COPD often occurs along with a number of other conditions, due in part to shared risk factors.[2] These conditions include ischemic heart disease, high blood pressure, diabetes mellitus, muscle wasting, osteoporosis, lung cancer, anxiety disorder, sexual dysfunction, and depression.[2][39] In those with severe disease, a feeling of always being tired is common.[22] Fingernail clubbing is not specific to COPD and should prompt investigations for an underlying lung cancer.[40]
### Exacerbation[edit]
An acute exacerbation of COPD is defined as increased shortness of breath, increased sputum production, a change in the color of the sputum from clear to green or yellow, or an increase in cough in someone with COPD.[36] They may present with signs of increased work of breathing such as fast breathing, a fast heart rate, sweating, active use of muscles in the neck, a bluish tinge to the skin, and confusion or combative behavior in very severe exacerbations.[36][41] Crackles may also be heard over the lungs on examination with a stethoscope.[42]
## Cause[edit]
The primary cause of COPD is tobacco smoke, with occupational exposure and pollution from indoor fires being significant causes in some countries.[9] Typically, these must occur over several decades before symptoms develop.[9] A person's genetic makeup also affects the risk.[9]
### Smoking[edit]
Percentage of females smoking tobacco as of the late 1990s early 2000s
Percentage of males smoking tobacco as of the late 1990s and early 2000s. Note the scales used for females and males differ.[43]
The primary risk factor for COPD globally is tobacco smoking.[9] Of those who smoke, about 20% will get COPD,[44] and of those who are lifelong smokers, about half will get COPD.[45] In the United States and United Kingdom, of those with COPD, 80–95% are either current or previous smokers.[44][46][47] The likelihood of developing COPD increases with the total smoke exposure.[48] Additionally, women are more susceptible to the harmful effects of smoke than men.[47] In non-smokers, exposure to second-hand smoke is the cause in up to 20% of cases.[46] Other types of smoke, such as, marijuana, cigar, and water-pipe smoke, also confer a risk.[9] Water-pipe smoke appears to be as harmful as smoking cigarettes.[49] Problems from marijuana smoke may only be with heavy use.[50] Women who smoke during pregnancy may increase the risk of COPD in their child.[9] For the same amount of cigarette smoking, women have a higher risk of COPD than men.[51]
### Air pollution[edit]
Access to clean fuels and technologies for cooking as of 2016[52]
Poorly ventilated cooking fires, often fueled by coal or biomass fuels such as wood and dung, lead to indoor air pollution and are one of the most common causes of COPD in developing countries.[53] These fires are a method of cooking and heating for nearly 3 billion people, with their health effects being greater among women due to greater exposure.[9][53] They are used as the main source of energy in 80% of homes in India, China and sub-Saharan Africa.[17]
People who live in large cities have a higher rate of COPD compared to people who live in rural areas.[54] While urban air pollution is a contributing factor in exacerbations, its overall role as a cause of COPD is unclear.[9] Areas with poor outdoor air quality, including that from exhaust gas, generally have higher rates of COPD.[17] The overall effect in relation to smoking, however, is believed to be small.[9]
### Occupational exposure[edit]
Intense and prolonged exposure to workplace dusts, chemicals, and fumes increases the risk of COPD in both smokers and nonsmokers.[55] Workplace exposure is believed to be the cause in 10–20% of cases.[56] In the United States, it is believed that it is related to more than 30% of cases among those who have never smoked and probably represents a greater risk in countries without sufficient regulations.[9]
A number of industries and sources have been implicated, including[17] high levels of dust in coal mining, gold mining, and the cotton textile industry, occupations involving cadmium and isocyanates, and fumes from welding.[55] Working in agriculture is also a risk.[17] In some professions, the risks have been estimated as equivalent to that of one-half to two packs of cigarettes a day.[57] Silica dust and fiberglass dust exposure can also lead to COPD, with the risk unrelated to that for silicosis.[58][59] The negative effects of dust exposure and cigarette smoke exposure appear to be additive or possibly more than additive.[57]
### Genetics[edit]
Genetics play a role in the development of COPD.[9] It is more common among relatives of those with COPD who smoke than unrelated smokers.[9] Currently, the only clearly inherited risk factor is alpha 1-antitrypsin deficiency (AAT).[60] This risk is particularly high if someone deficient in alpha 1-antitrypsin also smokes.[60] It is responsible for about 1–5% of cases[60][61] and the condition is present in about three to four in 10,000 people.[23] Other genetic factors are being investigated,[60] of which many are likely.[17]
### Other[edit]
A number of other factors are less closely linked to COPD. The risk is greater in those who are poor, although whether this is due to poverty itself or other risk factors associated with poverty, such as air pollution and malnutrition, is not clear.[9] Tentative evidence indicates that those with asthma and airway hyperreactivity are at increased risk of COPD.[9] Birth factors such as low birth weight may also play a role, as do a number of infectious diseases, including HIV/AIDS and tuberculosis.[9] Respiratory infections such as pneumonia do not appear to increase the risk of COPD, at least in adults.[23]
### Exacerbations[edit]
An acute exacerbation (a sudden worsening of symptoms)[62] is commonly triggered by infection or environmental pollutants, or sometimes by other factors such as improper use of medications.[63] Infections appear to be the cause of 50 to 75% of cases,[63][64] with bacteria in 30%, viruses in 23%, and both in 25%.[65] Environmental pollutants include both poor indoor and outdoor air quality.[63] Exposure to personal smoke and second-hand smoke increases the risk.[17] Cold temperatures may also play a role, with exacerbations occurring more commonly in winter.[66] Those with more severe underlying disease have more frequent exacerbations: in mild disease 1.8 per year, moderate 2 to 3 per year, and severe 3.4 per year.[67] Those with many exacerbations have a faster rate of deterioration of their lung function.[68] A pulmonary embolism (PE) (blood clot in the lung) can worsen symptoms in those with pre-existing COPD.[2] Signs of a PE in COPD include pleuritic chest pain and heart failure without signs of infection.[69]
## Pathophysiology[edit]
On the left is a diagram of the lungs and airways with an inset showing a detailed cross-section of normal bronchioles and alveoli. On the right are lungs damaged by COPD with an inset showing a cross-section of damaged bronchioles and alveoli.
COPD is a type of obstructive lung disease in which chronic, incompletely reversible poor airflow (airflow limitation) and inability to breathe out fully (air trapping) exist.[2] The poor airflow is the result of breakdown of lung tissue (known as emphysema), and small airways disease known as obstructive bronchiolitis.[9] The relative contributions of these two factors vary between people.[9] Severe destruction of small airways can lead to the formation of large focal lung pneumatoses, known as bullae, that replace lung tissue. This form of disease is called bullous emphysema.[70]
COPD develops as a significant and chronic inflammatory response to inhaled irritants.[9] Chronic bacterial infections may also add to this inflammatory state.[68] The inflammatory cells involved include neutrophil granulocytes and macrophages, two types of white blood cells. Those who smoke additionally have Tc1 lymphocyte involvement and some people with COPD have eosinophil involvement similar to that in asthma. Part of this cell response is brought on by inflammatory mediators such as chemotactic factors. Other processes involved with lung damage include oxidative stress produced by high concentrations of free radicals in tobacco smoke and released by inflammatory cells, and breakdown of the connective tissue of the lungs by proteases that are insufficiently inhibited by protease inhibitors. The destruction of the connective tissue of the lungs leads to emphysema, which then contributes to the poor airflow, and finally, poor absorption and release of respiratory gases.[9] General muscle wasting that often occurs in COPD may be partly due to inflammatory mediators released by the lungs into the blood.[9]
Micrograph showing emphysema (left – large empty spaces) and lung tissue with relative preservation of the alveoli (right)
Narrowing of the airways occurs due to inflammation and scarring within them. This contributes to the inability to breathe out fully. The greatest reduction in air flow occurs when breathing out, as the pressure in the chest is compressing the airways at this time.[71] This can result in more air from the previous breath remaining within the lungs when the next breath is started, resulting in an increase in the total volume of air in the lungs at any given time, a process called hyperinflation or air trapping.[71][72] Hyperinflation from exercise is linked to shortness of breath in COPD, as breathing in is less comfortable when the lungs are already partly filled.[73] Hyperinflation may also worsen during an exacerbation.[74]
Some also have a degree of airway hyperresponsiveness to irritants similar to those found in asthma.[23]
Low oxygen levels, and eventually, high carbon dioxide levels in the blood, can occur from poor gas exchange due to decreased ventilation from airway obstruction, hyperinflation, and a reduced desire to breathe.[9] During exacerbations, airway inflammation is also increased, resulting in increased hyperinflation, reduced expiratory airflow, and worsening of gas transfer. This can also lead to insufficient ventilation, and eventually low blood oxygen levels.[5] Low oxygen levels, if present for a prolonged period, can result in narrowing of the arteries in the lungs, while emphysema leads to breakdown of capillaries in the lungs. Both of these changes result in increased blood pressure in the pulmonary arteries, which may cause right-sided heart failure secondary to lung disease, also known as cor pulmonale.[9]
## Diagnosis[edit]
A person blowing into a spirometer. Smaller handheld devices are available for office use.
The diagnosis of COPD should be considered in anyone over the age of 35 to 40 who has shortness of breath, a chronic cough, sputum production, or frequent winter colds and a history of exposure to risk factors for the disease.[22][27] Spirometry is then used to confirm the diagnosis.[22][75] Screening those without symptoms is not recommended.[76]
### Spirometry[edit]
Spirometry measures the amount of airflow obstruction present and is generally carried out after the use of a bronchodilator, a medication to open up the airways.[75] Two main components are measured to make the diagnosis, the forced expiratory volume in one second (FEV1), which is the greatest volume of air that can be breathed out in the first second of a breath, and the forced vital capacity (FVC), which is the greatest volume of air that can be breathed out in a single large breath.[77] Normally, 75–80% of the FVC comes out in the first second[77] and a FEV1/FVC ratio less than 70% in someone with symptoms of COPD defines a person as having the disease.[75] Based on these measurements, spirometry would lead to over-diagnosis of COPD in the elderly.[75] The National Institute for Health and Care Excellence criteria additionally require a FEV1 less than 80% of predicted.[27] People with COPD also exhibit a decrease in diffusing capacity of the lung for carbon monoxide (DLCO) due to decreased surface area in the alveoli, as well as damage to the capillary bed.[78]
Evidence for using spirometry among those without symptoms in an effort to diagnose the condition earlier is of uncertain effect, so currently is not recommended.[22][75] A peak expiratory flow (the maximum speed of expiration), commonly used in asthma, is not sufficient for the diagnosis of COPD.[27]
### Severity[edit]
MRC shortness of breath scale[27] Grade Activity affected
1 Only strenuous activity
2 Vigorous walking
3 With normal walking
4 After a few minutes of walking
5 With changing clothing
GOLD grade[22] Severity FEV1 % predicted
Mild (GOLD 1) ≥80
Moderate (GOLD 2) 50–79
Severe (GOLD 3) 30–49
Very severe (GOLD 4) <30
A number of methods can determine how much COPD is affecting a given individual.[22] The modified British Medical Research Council questionnaire or the COPD assessment test (CAT) are simple questionnaires that may be used to determine the severity of symptoms.[22] Scores on CAT range from 0–40 with the higher the score, the more severe the disease.[79] Spirometry may help to determine the severity of airflow limitation.[22] This is typically based on the FEV1 expressed as a percentage of the predicted "normal" for the person's age, gender, height, and weight.[22] Both the American and European guidelines recommend partly basing treatment recommendations on the FEV1.[75] The GOLD guidelines suggest dividing people into four categories based on symptoms assessment and airflow limitation.[22] Weight loss and muscle weakness, as well as the presence of other diseases, should also be taken into account.[22]
### Other tests[edit]
A chest X-ray and complete blood count may be useful to exclude other conditions at the time of diagnosis.[80] Characteristic signs on X-ray are hyperinflated lungs, a flattened diaphragm, increased retrosternal airspace, and bullae, while it can help exclude other lung diseases, such as pneumonia, pulmonary edema, or a pneumothorax.[81] A high-resolution CT scan of the chest may show the distribution of emphysema throughout the lungs and can also be useful to exclude other lung diseases.[23] Unless surgery is planned, however, this rarely affects management.[23] A saber-sheath trachea deformity may also be present.[82] An analysis of arterial blood is used to determine the need for oxygen; this is recommended in those with an FEV1 less than 35% predicted, those with a peripheral oxygen saturation less than 92%, and those with symptoms of congestive heart failure.[22] In areas of the world where alpha-1 antitrypsin deficiency is common, people with COPD (particularly those below the age of 45 and with emphysema affecting the lower parts of the lungs) should be considered for testing.[22]
* Chest X-ray demonstrating severe COPD: Note the small heart size in comparison to the lungs.
* A lateral chest X-ray of a person with emphysema: Note the barrel chest and flat diaphragm.
* Lung bulla as seen on chest X-ray in a person with severe COPD
* A severe case of bullous emphysema
* Axial CT image of the lung of a person with end-stage bullous emphysema
* Very severe emphysema with lung cancer on the left (CT scan)
### Differential diagnosis[edit]
COPD may need to be differentiated from other causes of shortness of breath such as congestive heart failure, pulmonary embolism, pneumonia, or pneumothorax. Many people with COPD mistakenly think they have asthma.[36] The distinction between asthma and COPD is made on the basis of the symptoms, smoking history, and whether airflow limitation is reversible with bronchodilators at spirometry.[83] Tuberculosis may also present with a chronic cough and should be considered in locations where it is common.[22] Less common conditions that may present similarly include bronchopulmonary dysplasia and obliterative bronchiolitis.[80] Chronic bronchitis may occur with normal airflow and in this situation it is not classified as COPD.[23]
## Prevention[edit]
Most cases of COPD are potentially preventable through decreasing exposure to smoke and improving air quality.[17] Annual influenza vaccinations in those with COPD reduce exacerbations, hospitalizations and death.[84][85] Pneumococcal vaccination may also be beneficial.[84] Eating a diet high in beta-carotene may help but taking supplements does not seem to.[86] A review of an oral Haemophilus influenzae vaccine found 1.6 exacerbations per year as opposed to a baseline of 2.1 in those with COPD.[87] This small reduction was not deemed significant.[87]
### Smoking cessation[edit]
Keeping people from starting smoking is a key aspect of preventing COPD.[88] The policies of governments, public health agencies, and antismoking organizations can reduce smoking rates by discouraging people from starting and encouraging people to stop smoking.[89] Smoking bans in public areas and places of work are important measures to decrease exposure to secondhand smoke, and while many places have instituted bans, more are recommended.[17]
In those who smoke, stopping smoking is the only measure shown to slow down the worsening of COPD.[90][91] Even at a late stage of the disease, it can reduce the rate of worsening lung function and delay the onset of disability and death.[92] Often, several attempts are required before long-term abstinence is achieved.[89] Attempts over 5 years lead to success in nearly 40% of people.[93]
Some smokers can achieve long-term smoking cessation through willpower alone. Smoking, however, is highly addictive,[94] and many smokers need further support. The chance of quitting is improved with social support, engagement in a smoking cessation program, and the use of medications such as nicotine replacement therapy, bupropion, or varenicline.[89][91][93] Combining smoking-cessation medication with behavioral therapy is more than twice as likely to be effective in helping people with COPD stop smoking, compared with behavioral therapy alone.[95]
### Occupational health[edit]
A number of measures have been taken to reduce the likelihood that workers in at-risk industries—such as coal mining, construction, and stonemasonry—will develop COPD.[17] Examples of these measures include the creation of public policy,[17] education of workers and management about the risks, promoting smoking cessation, checking workers for early signs of COPD, use of respirators, and dust control.[96][97] Effective dust control can be achieved by improving ventilation, using water sprays and by using mining techniques that minimize dust generation.[98] If a worker develops COPD, further lung damage can be reduced by avoiding ongoing dust exposure, for example by changing their work role.[99]
### Air pollution[edit]
Both indoor and outdoor air quality can be improved, which may prevent COPD or slow the worsening of existing disease.[17] This may be achieved by public policy efforts, cultural changes, and personal involvement.[62]
A number of developed countries have successfully improved outdoor air quality through regulations. This has resulted in improvements in the lung function of their populations.[17] Those with COPD may experience fewer symptoms if they stay indoors on days when outdoor air quality is poor.[5]
One key effort is to reduce exposure to smoke from cooking and heating fuels through improved ventilation of homes and better stoves and chimneys.[62] Proper stoves may improve indoor air quality by 85%. Using alternative energy sources such as solar cooking and electrical heating is also effective. Using fuels such as kerosene or coal might be less bad than traditional biomass such as wood or dung.[17]
## Management[edit]
No cure for COPD is known, but the symptoms are treatable and its progression can be delayed.[88] People with COPD can experience flare-ups that are often triggered by a viral or bacterial respiratory infection.[100] The major goals of management are to reduce risk factors, manage stable COPD, prevent and treat acute exacerbations, and manage associated illnesses.[5] The only measures that have been shown to reduce mortality are smoking cessation and supplemental oxygen.[101] Stopping smoking decreases the risk of death by 18%.[2] Other recommendations include influenza vaccination once a year, pneumococcal vaccination once every five years, and reduction in exposure to environmental air pollution.[2] In those with advanced disease, palliative care may reduce symptoms, with morphine improving the feelings of shortness of breath.[102] Noninvasive ventilation may be used to support breathing.[102][103] Providing people with a personalized action plan, an educational session, and support for use of their action plan in the event of an exacerbation, reduces the number of hospital visits and encourages early treatment of exacerbations.[104] When self-management interventions, such as taking corticosteroids and using supplemental oxygen, is combined with action plans, health-related quality of life is improved compared to usual care.[105] Self-management is also associated with improved health-related quality of life, reduced respiratory-related and all-cause hospital admissions and improvement in shortness of breath.[106] The 2019 NICE guidelines also recommends treatment of associated conditions.[107]
### Exercise[edit]
Pulmonary rehabilitation is a program of exercise, disease management, and counseling, coordinated to benefit the individual.[108] In those who have had a recent exacerbation, pulmonary rehabilitation appears to improve the overall quality of life and the ability to exercise.[109][110] If pulmonary rehabilitation improves mortality rates or hospital readmission rates is unclear.[109] Pulmonary rehabilitation has been shown to improve the sense of control a person has over their disease, as well as their emotions.[111] These programs appear to improve exercise capacity, improve health‐related quality of life, and may lower the risk of being readmitted to hospital in people recovering from an exacerbation.[112]
The optimal exercise routine, use of noninvasive ventilation during exercise, and intensity of exercise suggested for people with COPD, is unknown.[110][113][114] Performing endurance arm exercises improves arm movement for people with COPD, and may result in a small improvement in breathlessness.[115] Performing arm exercises alone does not appear to improve quality of life.[115] Breathing exercises in and of themselves appear to have a limited role.[32] Pursed lip breathing exercises may be useful.[31][32] Tai chi exercises appear to be safe to practice for people with COPD, and may be beneficial for pulmonary function and pulmonary capacity when compared to a regular treatment program.[116] Tai Chi was not found to be more effective than other exercise intervention programs.[116] Inspiratory and expiratory muscle training (IMT, EMT) is an effective method for improving activities of daily living (ADL). A combination of IMT and walking exercises at home may help limit breathlessness in cases of severe COPD.[117] Additionally, the use of low amplitude high velocity joint mobilization together with exercise improves lung function and exercise capacity.[118] The goal of spinal manipulation therapy (SMT) is to improve thoracic mobility in an effort to reduce the work on the lungs during respiration, to in turn increase exercise capacity as indicated by the results of a systemic medical review.[118] Airway clearance techniques (ACTs), such as postural drainage, percussion/vibration, autogenic drainage, hand-held positive expiratory pressure (PEP) devices and other mechanical devices, may reduce the need for increased ventilatory assistance, the duration of ventilatory assistance, and the length of hospital stay in people with acute COPD.[119] In people with stable COPD, ACTs may lead to short-term improvements in health-related quality of life and a reduced long-term need for hospitalisations related to respiratory issues.[119]
Being either underweight or overweight can affect the symptoms, degree of disability, and prognosis of COPD. People with COPD who are underweight can improve their breathing muscle strength by increasing their calorie intake.[5] When combined with regular exercise or a pulmonary rehabilitation program, this can lead to improvements in COPD symptoms. Supplemental nutrition may be useful in those who are malnourished.[120]
### Bronchodilators[edit]
Inhaled bronchodilators are the primary medications used,[2] and result in a small overall benefit.[121] The two major types are β2 agonists and anticholinergics; both exist in long-acting and short-acting forms.[122] They reduce shortness of breath, wheeze, and exercise limitation, resulting in an improved quality of life.[123] It is unclear if they change the progression of the underlying disease.[2]
In those with mild disease, short-acting agents are recommended on an as needed basis.[2] In those with more severe disease, long-acting agents are recommended.[2] Long-acting agents partly work by reducing hyperinflation.[74] If long-acting bronchodilators are insufficient, then inhaled corticosteroids are typically added.[2] Which type of long-acting agent, long-acting muscarinic antagonist (LAMA) such as tiotropium or a long-acting beta agonist (LABA) is better is unclear, and trying each and continuing with the one that works best may be advisable.[124] Both types of agent appear to reduce the risk of acute exacerbations by 15–25%.[2] A 2018 review found the combination of LABA/LAMA may reduce COPD exacerbations and improve quality-of-life compared to long-acting bronchodilators alone.[125] The 2018 NICE guideline recommends use of dual long-acting bronchodilators with economic modelling suggesting that this approach is preferable to starting one long acting bronchodilator and adding another later.[107]
Several short-acting β2 agonists are available, including salbutamol (albuterol) and terbutaline.[62] They provide some relief of symptoms for four to six hours.[62] LABAs such as salmeterol, formoterol, and indacaterol are often used as maintenance therapy. Some feel the evidence of benefits is limited,[126] while others view the evidence of benefit as established.[127][128][129] Long-term use appears safe in COPD[130] with adverse effects include shakiness and heart palpitations.[2] When used with inhaled steroids they increase the risk of pneumonia.[2] While steroids and LABAs may work better together,[126] it is unclear if this slight benefit outweighs the increased risks.[131] There is some evidence that combined treatment of LABAs with long-acting muscarinic antagonists (LAMA), an anticholinergic, may result in less exacerbations, less pneumonia, an improvement in forced expiratory volume (FEV1%), and potential improvements in quality of life when compared to treatment with LABA and an inhaled corticosteriod (ICS).[132] All three together, LABA, LAMA, and ICS, have some evidence of benefits.[133] Indacaterol requires an inhaled dose once a day, and is as effective as the other long-acting β2 agonist drugs that require twice-daily dosing for people with stable COPD.[129]
Two main anticholinergics are used in COPD, ipratropium and tiotropium. Ipratropium is a short-acting agent, while tiotropium is long-acting. Tiotropium is associated with a decrease in exacerbations and improved quality of life,[134] and tiotropium provides those benefits better than ipratropium.[135] It does not appear to affect mortality or the overall hospitalization rate.[134] Anticholinergics can cause dry mouth and urinary tract symptoms.[2] They are also associated with increased risk of heart disease and stroke.[136][137] Aclidinium, another long-acting agent, reduces hospitalizations associated with COPD and improves quality of life.[138][139][140] The LAMA umeclidinium bromide is another anticholinergic alternative.[141] When compared to tiotropium, the LAMAs aclidinium, glycopyrronium, and umeclidinium appear to have a similar level of efficacy; with all four being more effective than placebo.[142] Further research is needed comparing aclidinium to tiotropium.[140]
### Corticosteroids[edit]
Corticosteroids are usually used in inhaled form, but may also be used as tablets to treat acute exacerbations. While inhaled corticosteroids (ICSs) have not shown benefit for people with mild COPD, they decrease acute exacerbations in those with either moderate or severe disease.[143] By themselves, they have no effect on overall one-year mortality.[101][144] Whether they affect the progression of the disease is unknown.[2] When used in combination with a LABA, they may decrease mortality compared to either ICSs or LABA alone.[145][146] Inhaled steroids are associated with increased rates of pneumonia.[147] Long-term treatment with steroid tablets is associated with significant side effects.[62]
The 2018 NICE guidelines recommend use of ICS in people with asthmatic features or features suggesting steroid responsiveness. These include any previous diagnosis of asthma or atopy, a higher blood eosinophil count, substantial variation in FEV1 over time (at least 400 mL) and at least 20% diurnal variation in peak expiratory flow. “Higher” eosinophil count was chosen, rather than specifying a particular value as it is not clear what the precise threshold should be or on how many occasions or over what time period it should be elevated.[148]
### Other medications[edit]
Long-term antibiotics, specifically those from the macrolide class such as erythromycin, reduce the frequency of exacerbations in those who have two or more a year.[149][150] This practice may be cost effective in some areas of the world.[151] Concerns include the potential for antibiotic resistance and side effects including hearing loss, tinnitus, and changes to the heart rhythm (long QT syndrome).[150] Methylxanthines such as theophylline generally cause more harm than benefit and thus are usually not recommended,[152] but may be used as a second-line agent in those not controlled by other measures.[5] Mucolytics may help to reduce exacerbations in some people with chronic bronchitis; noticed by less hospitalization and less days of disability in one month.[153] Cough medicines are not recommended.[62]
For people with COPD, the use of cardioselective (heart-specific) beta-blocker therapy does not appear to impair respiratory function.[154] Cardioselective beta-blocker therapy should not be contraindicated for people with COPD.[154][155] In those with low levels of vitamin D, supplementation reduces the risk of exacerbations.[156]
### Oxygen[edit]
Supplemental oxygen is recommended in those with low oxygen levels at rest (a partial pressure of oxygen less than 50–55 mmHg or oxygen saturations of less than 88%).[62][157] In this group of people, it decreases the risk of heart failure and death if used 15 hours per day[62][157] and may improve people's ability to exercise.[158] In those with normal or mildly low oxygen levels, oxygen supplementation may improve shortness of breath when given during exercise, but may not improve breathlessness during normal daily activities or affect the quality of life.[159] A risk of fires and little benefit exist when those on oxygen continue to smoke.[160] In this situation, some (including NICE) recommend against its use.[161][162] During acute exacerbations, many require oxygen therapy; the use of high concentrations of oxygen without taking into account a person's oxygen saturations may lead to increased levels of carbon dioxide and worsened outcomes.[163][164] In those at high risk of high carbon dioxide levels, oxygen saturations of 88–92% are recommended, while for those without this risk, recommended levels are 94–98%.[164]
### Surgery[edit]
For those with very severe disease, surgery is sometimes helpful and may include lung transplantation or lung volume-reduction surgery,[2] which involves removing the parts of the lung most damaged by emphysema, allowing the remaining, relatively good lung to expand and work better.[62][165] It seems to be particularly effective if emphysema predominantly involves the upper lobe, but the procedure increases the risks of adverse events and early death for people who have diffuse emphysema.[166] The procedure also increases the risk of adverse effects for people with moderate to severe COPD.[165] Lung transplantation is sometimes performed for very severe COPD, particularly in younger individuals.[62]
### Exacerbations[edit]
Acute exacerbations are typically treated by increasing the use of short-acting bronchodilators.[2] This commonly includes a combination of a short-acting inhaled beta agonist and anticholinergic.[62] These medications can be given either via a metered-dose inhaler with a spacer or via a nebulizer, with both appearing to be equally effective.[62][167] Nebulization may be easier for those who are more unwell.[62] Oxygen supplementation can be useful. Excessive oxygen; however, can result in increased CO
2 levels and a decreased level of consciousness.[168]
Corticosteroids by mouth improve the chance of recovery and decrease the overall duration of symptoms.[2][62] They work equally well as intravenous steroids but appear to have fewer side effects.[169] Five days of steroids work as well as ten or fourteen.[170] In those with a severe exacerbation, antibiotics improve outcomes.[171] A number of different antibiotics may be used including amoxicillin, doxycycline and azithromycin; whether one is better than the others is unclear.[84] The FDA recommends against the use of fluoroquinolones when other options are available due to higher risks of serious side effects.[172] There is no clear evidence for those with less severe cases.[171] For people with type 2 respiratory failure (acutely raised CO
2 levels) non-invasive positive pressure ventilation decreases the probability of death or the need of intensive care admission.[2] Additionally, theophylline may have a role in those who do not respond to other measures.[2] Fewer than 20% of exacerbations require hospital admission.[62] In those without acidosis from respiratory failure, home care ("hospital at home") may be able to help avoid some admissions.[62]
## Prognosis[edit]
Chronic obstructive pulmonary disease deaths per million persons in 2012
9–63
64–80
81–95
96–116
117–152
153–189
190–235
236–290
291–375
376–1089
Disability-adjusted life years lost to chronic obstructive pulmonary disease per 100,000 inhabitants in 2004.[173]
no data
≤110
110–220
220–330
330–440
440–550
550–660
660–770
770–880
880–990
990–1100
1100–1350
≥1350
COPD usually gets gradually worse over time and can ultimately result in death. It is estimated that 3% of all disability is related to COPD.[174] The proportion of disability from COPD globally has decreased from 1990 to 2010 due to improved indoor air quality primarily in Asia.[174] The overall number of years lived with disability from COPD, however, has increased.[175]
The rate at which COPD worsens varies with the presence of factors that predict a poor outcome, including severe airflow obstruction, little ability to exercise, shortness of breath, significant underweight or overweight, congestive heart failure, continued smoking, and frequent exacerbations.[5] Long-term outcomes in COPD can be estimated using the BODE index which gives a score of zero to ten depending on FEV1, body-mass index, the distance walked in six minutes, and the modified MRC dyspnea scale.[176] Significant weight loss is a bad sign.[23] Results of spirometry are also a good predictor of the future progress of the disease but are not as good as the BODE index.[23][27]
## Epidemiology[edit]
Globally, as of 2010, COPD affected approximately 329 million people (4.8% of the population).[175] The disease affects men and women almost equally, as there has been increased tobacco use among women in the developed world.[177] The increase in the developing world between 1970 and the 2000s is believed to be related to increasing rates of smoking in this region, an increasing population and an aging population due to fewer deaths from other causes such as infectious diseases.[2] Some developed countries have seen increased rates, some have remained stable and some have seen a decrease in COPD prevalence.[2] The global numbers are expected to continue increasing as risk factors remain common and the population continues to get older.[88]
Between 1990 and 2010 the number of deaths from COPD decreased slightly from 3.1 million to 2.9 million[178] and became the fourth leading cause of death.[2] In 2012 it became the third leading cause as the number of deaths rose again to 3.1 million.[179] In some countries, mortality has decreased in men but increased in women.[180] This is most likely due to rates of smoking in women and men becoming more similar.[23] COPD is more common in older people;[9] it affects 34–200 out of 1000 people older than 65 years, depending on the population under review.[9][81]
In England, an estimated 0.84 million people (of 50 million) have a diagnosis of COPD; this translates into approximately one person in 59 receiving a diagnosis of COPD at some point in their lives. In the most socioeconomically deprived parts of the country, one in 32 people were diagnosed with COPD, compared with one in 98 in the most affluent areas.[181] In the United States approximately 6.3% of the adult population, totaling approximately 15 million people, have been diagnosed with COPD.[182] 25 million people may have COPD if currently undiagnosed cases are included.[183] In 2011, there were approximately 730,000 hospitalizations in the United States for COPD.[184] In the United States, COPD is estimated to be the third leading cause of death in 2011.[185]
## History[edit]
Giovanni Battista Morgagni, who made one of the earliest recorded descriptions of emphysema in 1769
The word "emphysema" is derived from the Greek ἐμφυσᾶν emphysan meaning "inflate" -itself composed of ἐν en, meaning "in", and φυσᾶν physan, meaning "breath, blast".[186] The term "chronic bronchitis" came into use in 1808[187] while the term "COPD" is believed to have first been used in 1965.[188] Previously it has been known by a number of different names, including chronic obstructive bronchopulmonary disease, chronic obstructive respiratory disease, chronic airflow obstruction, chronic airflow limitation, chronic obstructive lung disease, nonspecific chronic pulmonary disease, and diffuse obstructive pulmonary syndrome. The terms chronic bronchitis and emphysema were formally defined in 1959 at the CIBA guest symposium and in 1962 at the American Thoracic Society Committee meeting on Diagnostic Standards.[188]
Early descriptions of probable emphysema include: in 1679 by T. Bonet of a condition of "voluminous lungs" and in 1769 by Giovanni Morgagni of lungs which were "turgid particularly from air".[188][189] In 1721 the first drawings of emphysema were made by Ruysh.[189] These were followed with pictures by Matthew Baillie in 1789 and descriptions of the destructive nature of the condition. In 1814 Charles Badham used "catarrh" to describe the cough and excess mucus in chronic bronchitis. René Laennec, the physician who invented the stethoscope, used the term "emphysema" in his book A Treatise on the Diseases of the Chest and of Mediate Auscultation (1837) to describe lungs that did not collapse when he opened the chest during an autopsy. He noted that they did not collapse as usual because they were full of air and the airways were filled with mucus. In 1842, John Hutchinson invented the spirometer, which allowed the measurement of vital capacity of the lungs. However, his spirometer could measure only volume, not airflow. Tiffeneau and Pinelli in 1947 described the principles of measuring airflow.[188]
In 1953, Dr. George L. Waldbott, an American allergist, first described a new disease he named "smoker's respiratory syndrome" in the 1953 Journal of the American Medical Association. This was the first association between tobacco smoking and chronic respiratory disease.[190]
Early treatments included garlic, cinnamon and ipecac, among others.[187] Modern treatments were developed during the second half of the 20th century. Evidence supporting the use of steroids in COPD was published in the late 1950s. Bronchodilators came into use in the 1960s following a promising trial of isoprenaline. Further bronchodilators, such as salbutamol, were developed in the 1970s, and the use of LABAs began in the mid-1990s.[191]
## Society and culture[edit]
See also: COPD Awareness Month
COPD is known colloquially as "smoker's lung", but it may also occur in people who have never smoked.[192] People with emphysema have been known as "pink puffers" or "type A" due to their frequent pink complexion, fast respiratory rate and pursed lips,[193][194] and people with chronic bronchitis have been referred to as "blue bloaters" or "type B" due to the often bluish color of the skin and lips from low oxygen levels and their swollen ankles.[194][195] This terminology is no longer accepted as useful as most people with COPD have a combination of both emphysema and chronic bronchitis.[23][194]
Many health systems have difficulty ensuring appropriate identification, diagnosis and care of people with COPD; Britain's Department of Health has identified this as a major issue for the National Health Service and has introduced a specific strategy to tackle these problems.[196]
### Economics[edit]
Globally, as of 2010, COPD is estimated to result in economic costs of $2.1 trillion, half of which occurring in the developing world.[21] Of this total an estimated $1.9 trillion are direct costs such as medical care, while $0.2 trillion are indirect costs such as missed work.[197] This is expected to more than double by the year 2030.[21] In Europe, COPD represents 3% of healthcare spending.[9] In the United States, costs of the disease are estimated at $50 billion, most of which is due to exacerbation.[9] COPD was among the most expensive conditions seen in U.S. hospitals in 2011, with a total cost of about $5.7 billion.[184]
## Research[edit]
See also: COPD: Journal of Chronic Obstructive Pulmonary Disease
Mass spectrometry is being studied as a diagnostic tool in COPD.[198]
Infliximab, an immune-suppressing antibody, has been tested in COPD; there was a possibility of harm with no evidence of benefit.[199] Roflumilast, and cilomilast, are phosphodiesterase-4 inhibitors (PDE4) and act as anti-inflammatories. They show promise in decreasing the rate of exacerbations, but do not appear to change a person's quality of life.[2][200] Roflumilast and cilomilast may be associated with side effects such as gastrointestinal issues and weight loss. Sleep disturbances and mood disturbances related to roflumilast have also been reported.[200] A PDE4 is recommended to be used as an add-on therapy in case of failure of the standard COPD treatment during exacerbations.[200]
Several new long-acting agents are under development.[2] Treatment with stem cells is under study.[201] While there is tentative data that it is safe, and the animal data is promising, there is little human data as of 2017.[202][203][204][205] The small amount of human data there is has shown poor results.[202][206]
A procedure known as targeted lung denervation, which involves decreasing the parasympathetic nervous system supply of the lungs, is being studied but does not have sufficient data to determine its use.[207] The effectiveness of alpha-1 antitrypsin augmentation treatment for people who have alpha-1 antitrypsin deficiency is unclear.[208]
Research continues into the use of telehealthcare to treat people with COPD when they experience episodes of shortness of breath; treating people remotely may reduce the number of emergency-room visits and improve the person's quality of life.[209]
## Other animals[edit]
Chronic obstructive pulmonary disease may occur in a number of other animals and may be caused by exposure to tobacco smoke.[210][211] Most cases of the disease, however, are relatively mild.[212] In horses it is known as recurrent airway obstruction, can be quite severe, and most often is linked to an allergic reaction to a fungus contained in contaminated hay or straw.[213] COPD is also commonly found in old dogs.[214]
## References[edit]
1. ^ a b c d Vogelmeier CF, Criner GJ, Martinez FJ, Anzueto A, Barnes PJ, Bourbeau J, et al. (April 2017). "Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Lung Disease 2017 Report: GOLD Executive Summary". Respirology. 22 (3): 575–601. doi:10.1111/resp.13012. PMID 28150362. S2CID 42027653.
2. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah Decramer M, Janssens W, Miravitlles M (April 2012). "Chronic obstructive pulmonary disease". Lancet. 379 (9823): 1341–51. CiteSeerX 10.1.1.1000.1967. doi:10.1016/S0140-6736(11)60968-9. PMC 7172377. PMID 22314182.
3. ^ a b c d e f g h i j k l m "Chronic obstructive pulmonary disease (COPD) Fact sheet N°315". WHO. January 2015. Archived from the original on 4 March 2016. Retrieved 4 March 2016.
4. ^ a b Nathell L, Nathell M, Malmberg P, Larsson K (December 2007). "COPD diagnosis related to different guidelines and spirometry techniques". Respiratory Research. 8 (1): 89. doi:10.1186/1465-9921-8-89. PMC 2217523. PMID 18053200.
5. ^ a b c d e f g h i j k l Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, Fukuchi Y, Jenkins C, Rodriguez-Roisin R, van Weel C, Zielinski J (September 2007). "Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary". American Journal of Respiratory and Critical Care Medicine. 176 (6): 532–55. doi:10.1164/rccm.200703-456SO. hdl:2066/51740. PMID 17507545. S2CID 20863981.
6. ^ a b GBD 2015 Disease and Injury Incidence and Prevalence Collaborators (October 2016). "Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1545–1602. doi:10.1016/S0140-6736(16)31678-6. PMC 5055577. PMID 27733282.
7. ^ a b GBD 2015 Mortality and Causes of Death Collaborators (October 2016). "Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1459–1544. doi:10.1016/S0140-6736(16)31012-1. PMC 5388903. PMID 27733281.
8. ^ Roversi S, Corbetta L, Clini E (5 May 2017). "GOLD 2017 recommendations for COPD patients: toward a more personalized approach". COPD Research and Practice. 3. doi:10.1186/s40749-017-0024-y.
9. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa Vestbo J (2013). "Definition and Overview". Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. American Journal of Respiratory and Critical Care Medicine. 187. Global Initiative for Chronic Obstructive Lung Disease. pp. 1–7. doi:10.1164/rccm.201204-0596PP. PMID 22878278.
10. ^ "Chronic obstructive pulmonary disease (COPD)". WHO. Retrieved 6 June 2019. "The more familiar terms of "chronic bronchitis" and "emphysema" have often been used as labels for this condition."
11. ^ Craig JA (2012). Ferri's netter patient advisor (2nd ed.). Saunders. p. 913. ISBN 9781455728268. "Traditionally, two types of COPD were known as chronic bronchitis and emphysema. Most cases of COPD are a mixture of both diseases."
12. ^ "Chronic obstructive pulmonary disease (COPD)". WHO. Retrieved 5 June 2019. "Chronic Obstructive Pulmonary Disease (COPD) is not one single disease but an umbrella term used to describe chronic lung diseases that cause limitations in lung airflow. The more familiar terms 'chronic bronchitis' and 'emphysema' are no longer used, but are now included within the COPD diagnosis."
13. ^ Global Initiative for Chronic Obstructive Lung Disease (PDF). 2019. p. 13. Retrieved 1 May 2019.
14. ^ Taylor, Jayne (2019). Bailliere's Dictionary E-Book: for Nurses and Health Care Workers. Elsevier Health Sciences. p. 128. ISBN 9780702075643.
15. ^ Torres-Duque CA, García-Rodriguez MC, González-García M (August 2016). "Is Chronic Obstructive Pulmonary Disease Caused by Wood Smoke a Different Phenotype or a Different Entity?". Archivos De Bronconeumologia. 52 (8): 425–31. doi:10.1016/j.arbres.2016.04.004. PMID 27207325.
16. ^ "Asthma vs. COPD: What's the Difference?". WebMD. 2019-01-30. Retrieved 2019-12-26.
17. ^ a b c d e f g h i j k l m n Pirozzi C, Scholand MB (July 2012). "Smoking cessation and environmental hygiene". The Medical Clinics of North America. 96 (4): 849–67. doi:10.1016/j.mcna.2012.04.014. PMID 22793948.
18. ^ Dobler CC, Morrow AS, Beuschel B, Farah MH, Majzoub AM, Wilson ME, et al. (March 2020). "Pharmacologic Therapies in Patients With Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review With Meta-analysis". Annals of Internal Medicine. 172 (6): 413–422. doi:10.7326/M19-3007. PMID 32092762. S2CID 211476101.
19. ^ GBD 2013 Mortality and Causes of Death Collaborators (January 2015). "Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013". Lancet. 385 (9963): 117–71. doi:10.1016/S0140-6736(14)61682-2. PMC 4340604. PMID 25530442.
20. ^ Mathers CD, Loncar D (November 2006). "Projections of global mortality and burden of disease from 2002 to 2030". PLOS Medicine. 3 (11): e442. doi:10.1371/journal.pmed.0030442. PMC 1664601. PMID 17132052.
21. ^ a b c Lomborg B (2013). Global problems, local solutions : costs and benefits. Cambridge University Press. p. 143. ISBN 978-1-107-03959-9.
22. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac Vestbo J (2013). "Diagnosis and Assessment" (PDF). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Global Initiative for Chronic Obstructive Lung Disease. pp. 9–17. Archived from the original (PDF) on 28 March 2016.
23. ^ a b c d e f g h i j k l m Reilly JJ, Silverman EK, Shapiro SD (2011). "Chronic Obstructive Pulmonary Disease". In Longo D, Fauci A, Kasper D, Hauser S, Jameson J, Loscalzo J (eds.). Harrison's Principles of Internal Medicine (18th ed.). McGraw Hill. pp. 2151–9. ISBN 978-0-07-174889-6.
24. ^ Miravitlles M, Calle M, Soler-Cataluña JJ (March 2012). "Clinical phenotypes of COPD: identification, definition and implications for guidelines". Archivos de Bronconeumologia (English ed.). 48 (3): 86–98. doi:10.1016/j.arbr.2012.01.003. PMID 22196477.
25. ^ Global Initiative for Chronic Obstructive Lung Disease (PDF). 2019. p. 4. Retrieved 1 May 2019.
26. ^ "Additional features in severe disease" (PDF). p. 26. Retrieved 22 September 2019.
27. ^ a b c d e f g National Institute for Health and Clinical Excellence. Clinical guideline 101: Chronic Obstructive Pulmonary Disease. London, June 2010.
28. ^ Mahler DA (May 2006). "Mechanisms and measurement of dyspnea in chronic obstructive pulmonary disease". Proceedings of the American Thoracic Society. 3 (3): 234–8. doi:10.1513/pats.200509-103SF. PMID 16636091.
29. ^ "What Are the Signs and Symptoms of COPD?". National Heart, Lung, and Blood Institute. July 31, 2013. Archived from the original on November 18, 2013. Retrieved November 29, 2013.
30. ^ MedlinePlus Encyclopedia: Chronic obstructive pulmonary disease
31. ^ a b Goldstein NE, Morrison RS (2013). Evidence-based practice of palliative medicine. Elsevier/Saunders. p. 124. ISBN 978-1-4377-3796-7.
32. ^ a b c Holland AE, Hill CJ, Jones AY, McDonald CF (October 2012). Holland AE (ed.). "Breathing exercises for chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews. 10: CD008250. doi:10.1002/14651858.CD008250.pub2. PMID 23076942.
33. ^ O'Donnell DE, Milne KM, James MD, de Torres JP, Neder JA (January 2020). "Dyspnea in COPD: New Mechanistic Insights and Management Implications". Advances in Therapy. 37 (1): 41–60. doi:10.1007/s12325-019-01128-9. PMC 6979461. PMID 31673990.
34. ^ Ebner N, Springer J, Kalantar-Zadeh K, Lainscak M, Doehner W, Anker SD, von Haehling S (July 2013). "Mechanism and novel therapeutic approaches to wasting in chronic disease". Maturitas. 75 (3): 199–206. doi:10.1016/j.maturitas.2013.03.014. PMID 23664695.
35. ^ Gimeno-Santos E, Frei A, Steurer-Stey C, de Batlle J, Rabinovich RA, Raste Y, et al. (August 2014). "Determinants and outcomes of physical activity in patients with COPD: a systematic review". Thorax. 69 (8): 731–9. doi:10.1136/thoraxjnl-2013-204763. PMC 4112490. PMID 24558112.
36. ^ a b c d e f Gruber P (November 2008). "The Acute Presentation of Chronic Obstructive Pulmonary Disease in the Emergency Department: A Challenging Oxymoron". Emergency Medicine Practice. 10 (11). Archived from the original on 2013-10-05.
37. ^ a b Weitzenblum E, Chaouat A (2009). "Cor pulmonale". Chronic Respiratory Disease. 6 (3): 177–85. doi:10.1177/1479972309104664. PMID 19643833. S2CID 25808105.
38. ^ "Cor pulmonale". Professional guide to diseases (9th ed.). Wolters Kluwer Health/Lippincott Williams & Wilkins. 2009. pp. 120–2. ISBN 978-0-7817-7899-2.
39. ^ Levack WM, Poot B, Weatherall M, Travers J (2015). "Interventions for sexual dysfunction in people with chronic obstructive pulmonary disease (COPD)". Cochrane Database of Systematic Reviews. doi:10.1002/14651858.CD011442.pub2.
40. ^ Aboussouan L (2009). "Chapter 35: Obstructive Lung Diseae: Asthma and Chronic Obstructive Pulmonary Disease". In Stoller JK, Michota FA, Mandell BF (eds.). The Cleveland Clinic Foundation intensive review of internal medicine (5th ed.). Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 419. ISBN 978-0-7817-9079-6.
41. ^ Brulotte CA, Lang ES (May 2012). "Acute exacerbations of chronic obstructive pulmonary disease in the emergency department". Emergency Medicine Clinics of North America. 30 (2): 223–47, vii. doi:10.1016/j.emc.2011.10.005. PMID 22487106.
42. ^ Spiro S (2012). "Chapter 43: Management of Exacerbations in Chronic Obstructive Pulmonary Disease". Clinical respiratory medicine expert consult (4th ed.). Saunders. ISBN 978-1-4557-2329-4.
43. ^ World Health Organization (2008). WHO Report on the Global Tobacco Epidemic 2008: The MPOWER Package (PDF). World Health Organization. pp. 268–309. ISBN 978-92-4-159628-2. Archived (PDF) from the original on 2013-11-12.
44. ^ a b Ward H (2012). Oxford Handbook of Epidemiology for Clinicians. Oxford University Press. pp. 289–290. ISBN 978-0-19-165478-7.
45. ^ Laniado-Laborín R (January 2009). "Smoking and chronic obstructive pulmonary disease (COPD). Parallel epidemics of the 21 century". International Journal of Environmental Research and Public Health. 6 (1): 209–24. doi:10.3390/ijerph6010209. PMC 2672326. PMID 19440278.
46. ^ a b Rennard S (2013). Clinical management of chronic obstructive pulmonary disease (2nd ed.). Informa Healthcare. p. 23. ISBN 978-0-8493-7588-0.
47. ^ a b Sharma A, Barclay J (2010). COPD in primary care. Radcliffe Pub. p. 9. ISBN 978-1-84619-316-3.
48. ^ Goldman L (2012). Goldman's Cecil medicine (24th ed.). Elsevier/Saunders. p. 537. ISBN 978-1-4377-1604-7.
49. ^ Raad D, Gaddam S, Schunemann HJ, Irani J, Abou Jaoude P, Honeine R, Akl EA (April 2011). "Effects of water-pipe smoking on lung function: a systematic review and meta-analysis". Chest. 139 (4): 764–774. doi:10.1378/chest.10-0991. PMID 20671057.
50. ^ Joshi M, Joshi A, Bartter T (March 2014). "Marijuana and lung diseases". Current Opinion in Pulmonary Medicine. 20 (2): 173–9. doi:10.1097/MCP.0000000000000026. PMID 24384575. S2CID 8010781.
51. ^ Amaral AF, Strachan DP, Burney PG, Jarvis DL (May 2017). "Female Smokers Are at Greater Risk of Airflow Obstruction Than Male Smokers. UK Biobank" (PDF). American Journal of Respiratory and Critical Care Medicine. 195 (9): 1226–1235. doi:10.1164/rccm.201608-1545OC. hdl:10044/1/45106. PMID 28075609. S2CID 9360093.
52. ^ "Access to clean fuels and technologies for cooking". Our World in Data. Retrieved 15 February 2020.
53. ^ a b Kennedy SM, Chambers R, Du W, Dimich-Ward H (December 2007). "Environmental and occupational exposures: do they affect chronic obstructive pulmonary disease differently in women and men?". Proceedings of the American Thoracic Society. 4 (8): 692–4. doi:10.1513/pats.200707-094SD. PMID 18073405.
54. ^ Halbert RJ, Natoli JL, Gano A, Badamgarav E, Buist AS, Mannino DM (September 2006). "Global burden of COPD: systematic review and meta-analysis". The European Respiratory Journal. 28 (3): 523–32. doi:10.1183/09031936.06.00124605. PMID 16611654.
55. ^ a b Devereux G (May 2006). "ABC of chronic obstructive pulmonary disease. Definition, epidemiology, and risk factors". BMJ. 332 (7550): 1142–4. doi:10.1136/bmj.332.7550.1142. PMC 1459603. PMID 16690673.
56. ^ Laine C (2009). In the Clinic: Practical Information about Common Health Problems. ACP Press. p. 226. ISBN 978-1-934465-64-6.
57. ^ a b Barnes PJ, Drazen JM, Rennard SI, Thomson NC, eds. (2009). "Relationship between cigarette smoking and occupational exposures". Asthma and COPD: Basic Mechanisms and Clinical Management. Academic. p. 464. ISBN 978-0-12-374001-4.
58. ^ Rushton L (2007). "Chronic obstructive pulmonary disease and occupational exposure to silica". Reviews on Environmental Health. 22 (4): 255–72. doi:10.1515/REVEH.2007.22.4.255. PMID 18351226. S2CID 13486935.
59. ^ Hopper T (2014). Mosby's Pharmacy Technician – E-Book: Principles and Practice. Elsevier Health Sciences. p. 610. ISBN 9780323292450.
60. ^ a b c d Foreman MG, Campos M, Celedón JC (July 2012). "Genes and chronic obstructive pulmonary disease". The Medical Clinics of North America. 96 (4): 699–711. doi:10.1016/j.mcna.2012.02.006. PMC 3399759. PMID 22793939.
61. ^ Brode SK, Ling SC, Chapman KR (September 2012). "Alpha-1 antitrypsin deficiency: a commonly overlooked cause of lung disease". CMAJ. 184 (12): 1365–71. doi:10.1503/cmaj.111749. PMC 3447047. PMID 22761482.
62. ^ a b c d e f g h i j k l m n o p q Vestbo J, Hurd SS, Agustí AG, Jones PW, Vogelmeier C, Anzueto A, et al. (February 2013). "Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary". American Journal of Respiratory and Critical Care Medicine. 187 (4): 347–65. doi:10.1164/rccm.201204-0596PP. PMID 22878278.
63. ^ a b c Dhar R (2011). Textbook of pulmonary and critical care medicine. New Delhi: Jaypee Brothers Medical Publishers. p. 1056. ISBN 978-93-5025-073-0.
64. ^ Palange P (2013). ERS Handbook of Respiratory Medicine. European Respiratory Society. p. 194. ISBN 978-1-84984-041-5.
65. ^ Lötvall J (2011). "Anti-infective treatments in asthma and COPD (10)". Advances in combination therapy for asthma and COPD. Wiley. p. 251. ISBN 978-1-119-97846-6.
66. ^ Barnes P (2009). Asthma and COPD : basic mechanisms and clinical management (2nd ed.). Academic. p. 837. ISBN 978-0-12-374001-4.
67. ^ Hanania N (2010-12-09). COPD a Guide to Diagnosis and Clinical Management (1st ed.). Springer Science+Business Media, LLC. p. 197. ISBN 978-1-59745-357-8.
68. ^ a b Beasley V, Joshi PV, Singanayagam A, Molyneaux PL, Johnston SL, Mallia P (2012). "Lung microbiology and exacerbations in COPD". International Journal of Chronic Obstructive Pulmonary Disease. 7: 555–69. doi:10.2147/COPD.S28286. PMC 3437812. PMID 22969296.
69. ^ Aleva FE, Voets LW, Simons SO, de Mast Q, van der Ven AJ, Heijdra YF (March 2017). "Prevalence and Localization of Pulmonary Embolism in Unexplained Acute Exacerbations of COPD: A Systematic Review and Meta-analysis". Chest. 151 (3): 544–554. doi:10.1016/j.chest.2016.07.034. PMID 27522956. S2CID 7181799.
70. ^ Murphy DM, Fishman AP (2008). "Chapter 53". Fishman's Pulmonary Diseases and Disorders (4th ed.). McGraw-Hill. p. 913. ISBN 978-0-07-145739-2.
71. ^ a b Calverley PM, Koulouris NG (January 2005). "Flow limitation and dynamic hyperinflation: key concepts in modern respiratory physiology". The European Respiratory Journal. 25 (1): 186–99. doi:10.1183/09031936.04.00113204. PMID 15640341.
72. ^ Currie GP (2010). ABC of COPD (2nd ed.). Wiley-Blackwell, BMJ Books. p. 32. ISBN 978-1-4443-2948-3.
73. ^ O'Donnell DE (April 2006). "Hyperinflation, dyspnea, and exercise intolerance in chronic obstructive pulmonary disease". Proceedings of the American Thoracic Society. 3 (2): 180–4. doi:10.1513/pats.200508-093DO. PMID 16565429. S2CID 20644418.
74. ^ a b Cooper CB (October 2006). "The connection between chronic obstructive pulmonary disease symptoms and hyperinflation and its impact on exercise and function". The American Journal of Medicine. 119 (10 Suppl 1): 21–31. doi:10.1016/j.amjmed.2006.08.004. PMID 16996896.
75. ^ a b c d e f Qaseem A, Wilt TJ, Weinberger SE, Hanania NA, Criner G, van der Molen T, Marciniuk DD, Denberg T, Schünemann H, Wedzicha W, MacDonald R, Shekelle P (August 2011). "Diagnosis and management of stable chronic obstructive pulmonary disease: a clinical practice guideline update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory Society". Annals of Internal Medicine. 155 (3): 179–91. doi:10.7326/0003-4819-155-3-201108020-00008. PMID 21810710. S2CID 18830625.
76. ^ Siu AL, Bibbins-Domingo K, Grossman DC, Davidson KW, Epling JW, García FA, Gillman M, Kemper AR, Krist AH, Kurth AE, Landefeld CS, Mangione CM, Harper DM, Phillips WR, Phipps MG, Pignone MP (April 2016). "Screening for Chronic Obstructive Pulmonary Disease: US Preventive Services Task Force Recommendation Statement". JAMA. 315 (13): 1372–7. doi:10.1001/jama.2016.2638. PMID 27046365.
77. ^ a b Young VB (2010). Blueprints medicine (5th ed.). Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 69. ISBN 978-0-7817-8870-0.
78. ^ Bailey KL (July 2012). "The importance of the assessment of pulmonary function in COPD". The Medical Clinics of North America. 96 (4): 745–52. doi:10.1016/j.mcna.2012.04.011. PMC 3998207. PMID 22793942.
79. ^ "COPD Assessment Test (CAT)". American Thoracic Society. Archived from the original on December 3, 2013. Retrieved November 29, 2013.
80. ^ a b National Institute for Health and Clinical Excellence. Clinical guideline 101: Chronic Obstructive Pulmonary Disease. London, June 2010.
81. ^ a b Torres M, Moayedi S (May 2007). "Evaluation of the acutely dyspneic elderly patient". Clinics in Geriatric Medicine. 23 (2): 307–25, vi. doi:10.1016/j.cger.2007.01.007. PMID 17462519.
82. ^ Brant WE, Helms CA (2007). Fundamentals of Diagnostic Radiology. Lippincott Williams & Wilkins. p. 513. ISBN 9780781761352.
83. ^ BTS COPD Consortium (2005). "Spirometry in practice – a practical guide to using spirometry in primary care". pp. 8–9. Archived from the original on 26 August 2014. Retrieved 25 August 2014.
84. ^ a b c Mackay AJ, Hurst JR (July 2012). "COPD exacerbations: causes, prevention, and treatment". The Medical Clinics of North America. 96 (4): 789–809. doi:10.1016/j.mcna.2012.02.008. PMID 22793945.
85. ^ Kopsaftis Z, Wood-Baker R, Poole P (June 2018). "Influenza vaccine for chronic obstructive pulmonary disease (COPD)". The Cochrane Database of Systematic Reviews. 6: CD002733. doi:10.1002/14651858.CD002733.pub3. PMC 6513384. PMID 29943802.
86. ^ "Beta-carotene: MedlinePlus Supplements". medlineplus.gov. Archived from the original on 26 December 2016. Retrieved 26 December 2016.
87. ^ a b Teo E, Lockhart K, Purchuri SN, Pushparajah J, Cripps AW, van Driel ML (June 2017). "Haemophilus influenzae oral vaccination for preventing acute exacerbations of chronic bronchitis and chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews. 6: CD010010. doi:10.1002/14651858.CD010010.pub3. PMC 6481520. PMID 28626902.
88. ^ a b c Vestbo J (2013). "Introduction" (PDF). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Global Initiative for Chronic Obstructive Lung Disease. xiii–xv. Archived from the original (PDF) on 2013-10-04.
89. ^ a b c Policy Recommendations for Smoking Cessation and Treatment of Tobacco Dependence. World Health Organization. 2003. pp. 15–40. ISBN 978-92-4-156240-9. Archived from the original on 2008-09-15.
90. ^ Jiménez-Ruiz CA, Fagerström KO (March 2013). "Smoking cessation treatment for COPD smokers: the role of counselling". Monaldi Archives for Chest Disease. 79 (1): 33–7. doi:10.4081/monaldi.2013.107. PMID 23741944.
91. ^ a b "Chronic obstructive pulmonary disease in over 16s: diagnosis and management | Guidance and guidelines | NICE". www.nice.org.uk. Retrieved 2018-06-05.
92. ^ Kumar P, Clark M (2005). Clinical Medicine (6th ed.). Elsevier Saunders. pp. 900–1. ISBN 978-0-7020-2763-5.
93. ^ a b Tønnesen P (March 2013). "Smoking cessation and COPD". European Respiratory Review. 22 (127): 37–43. doi:10.1183/09059180.00007212. PMID 23457163.
94. ^ "Why is smoking addictive?". NHS Choices. December 29, 2011. Archived from the original on October 13, 2013. Retrieved November 29, 2013.
95. ^ van Eerd EA, van der Meer RM, van Schayck OC, Kotz D (August 2016). "Smoking cessation for people with chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews (8): CD010744. doi:10.1002/14651858.CD010744.pub2. PMC 6400424. PMID 27545342.
96. ^ Smith BK, Timby NE (2005). Essentials of nursing : care of adults and children. Lippincott Williams & Wilkins. p. 338. ISBN 978-0-7817-5098-1.
97. ^ Rom WN, Markowitz SB, eds. (2007). Environmental and occupational medicine (4th ed.). Wolters Kluwer/Lippincott Williams & Wilkins. pp. 521–2. ISBN 978-0-7817-6299-1.
98. ^ "Wet cutting". Health and Safety Executive. Archived from the original on December 3, 2013. Retrieved November 29, 2013.
99. ^ George RB (2005). Chest medicine : essentials of pulmonary and critical care medicine (5th ed.). Lippincott Williams & Wilkins. p. 172. ISBN 978-0-7817-5273-2.
100. ^ Ranard, MD, MSHP, Benjamin (September 30, 2020). "COPD: Chronic Obstructive Pulmonary Disease Causes & Symptoms". Buoy Health. buoyhealth.com.CS1 maint: multiple names: authors list (link)
101. ^ a b Drummond MB, Dasenbrook EC, Pitz MW, Murphy DJ, Fan E (November 2008). "Inhaled corticosteroids in patients with stable chronic obstructive pulmonary disease: a systematic review and meta-analysis". Jama. 300 (20): 2407–16. doi:10.1001/jama.2008.717. PMC 4804462. PMID 19033591.
102. ^ a b Carlucci A, Guerrieri A, Nava S (December 2012). "Palliative care in COPD patients: is it only an end-of-life issue?". European Respiratory Review. 21 (126): 347–54. doi:10.1183/09059180.00001512. PMID 23204123.
103. ^ Wilson ME, Dobler CC, Morrow AS, Beuschel B, Alsawas M, Benkhadra R, et al. (February 2020). "Association of Home Noninvasive Positive Pressure Ventilation With Clinical Outcomes in Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis". Jama. 323 (5): 455–465. doi:10.1001/jama.2019.22343. PMC 7042860. PMID 32016309.
104. ^ Howcroft M, Walters EH, Wood-Baker R, Walters JA (December 2016). "Action plans with brief patient education for exacerbations in chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews. 12: CD005074. doi:10.1002/14651858.CD005074.pub4. PMC 6463844. PMID 27990628.
105. ^ Lenferink A, Brusse-Keizer M, van der Valk PD, Frith PA, Zwerink M, Monninkhof EM, et al. (August 2017). "Self-management interventions including action plans for exacerbations versus usual care in patients with chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews. 8: CD011682. doi:10.1002/14651858.CD011682.pub2. PMC 6483374. PMID 28777450.
106. ^ Zwerink M, Brusse-Keizer M, van der Valk PD, Zielhuis GA, Monninkhof EM, van der Palen J, et al. (Cochrane Airways Group) (March 2014). "Self management for patients with chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews (3): CD002990. doi:10.1002/14651858.CD002990.pub3. PMC 7004246. PMID 24665053.
107. ^ a b Hopkinson NS, Molyneux A, Pink J, Harrisingh MC (July 2019). "Chronic obstructive pulmonary disease: diagnosis and management: summary of updated NICE guidance". BMJ. 366: l4486. doi:10.1136/bmj.l4486. hdl:10044/1/72505. PMID 31358491. S2CID 198984181.
108. ^ "COPD – Treatment". U.S. National Heart Lung and Blood Institute. Archived from the original on 2012-04-27. Retrieved 2013-07-23.
109. ^ a b Puhan MA, Gimeno-Santos E, Cates CJ, Troosters T (December 2016). "Pulmonary rehabilitation following exacerbations of chronic obstructive pulmonary disease" (PDF). The Cochrane Database of Systematic Reviews. 12: CD005305. doi:10.1002/14651858.CD005305.pub4. PMC 6463852. PMID 27930803.
110. ^ a b Zainuldin R, Mackey MG, Alison JA (November 2011). "Optimal intensity and type of leg exercise training for people with chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews (11): CD008008. doi:10.1002/14651858.CD008008.pub2. PMID 22071841.
111. ^ McCarthy B, Casey D, Devane D, Murphy K, Murphy E, Lacasse Y (February 2015). "Pulmonary rehabilitation for chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews. 2 (2): CD003793. doi:10.1002/14651858.CD003793.pub3. PMID 25705944.
112. ^ Puhan MA, Gimeno-Santos E, Cates CJ, Troosters T (December 2016). "Pulmonary rehabilitation following exacerbations of chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews. 12: CD005305. doi:10.1002/14651858.CD005305.pub4. PMC 6463852. PMID 27930803.
113. ^ McNamara RJ, McKeough ZJ, McKenzie DK, Alison JA (December 2013). "Water-based exercise training for chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews (12): CD008290. doi:10.1002/14651858.CD008290.pub2. PMID 24353107.
114. ^ Menadue C, Piper AJ, van 't Hul AJ, Wong KK (May 2014). "Non-invasive ventilation during exercise training for people with chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews (5): CD007714. doi:10.1002/14651858.CD007714.pub2. PMID 24823712.
115. ^ a b McKeough ZJ, Velloso M, Lima VP, Alison JA (November 2016). "Upper limb exercise training for COPD". The Cochrane Database of Systematic Reviews. 11: CD011434. doi:10.1002/14651858.CD011434.pub2. PMC 6464968. PMID 27846347.
116. ^ a b Ngai SP, Jones AY, Tam WW (June 2016). "Tai Chi for chronic obstructive pulmonary disease (COPD)". The Cochrane Database of Systematic Reviews (6): CD009953. doi:10.1002/14651858.CD009953.pub2. PMID 27272131.
117. ^ Thomas MJ, Simpson J, Riley R, Grant E (June 2010). "The impact of home-based physiotherapy interventions on breathlessness during activities of daily living in severe COPD: a systematic review". Physiotherapy. 96 (2): 108–19. doi:10.1016/j.physio.2009.09.006. PMID 20420957.
118. ^ a b Wearing J, Beaumont S, Forbes D, Brown B, Engel R (February 2016). "The Use of Spinal Manipulative Therapy in the Management of Chronic Obstructive Pulmonary Disease: A Systematic Review". Journal of Alternative and Complementary Medicine. 22 (2): 108–14. doi:10.1089/acm.2015.0199. PMC 4761829. PMID 26700633.
119. ^ a b Osadnik CR, McDonald CF, Jones AP, Holland AE (March 2012). "Airway clearance techniques for chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews. 3 (3): CD008328. doi:10.1002/14651858.CD008328.pub2. PMID 22419331.
120. ^ Ferreira IM, Brooks D, White J, Goldstein R (December 2012). Ferreira IM (ed.). "Nutritional supplementation for stable chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews. 12: CD000998. doi:10.1002/14651858.CD000998.pub3. PMID 23235577.
121. ^ van Dijk WD, van den Bemt L, van Weel C (2013). "Megatrials for bronchodilators in chronic obstructive pulmonary disease (COPD) treatment: time to reflect". Journal of the American Board of Family Medicine. 26 (2): 221–4. doi:10.3122/jabfm.2013.02.110342. PMID 23471939.
122. ^ Kew KM, Dias S, Cates CJ (March 2014). "Long-acting inhaled therapy (beta-agonists, anticholinergics and steroids) for COPD: a network meta-analysis" (PDF). The Cochrane Database of Systematic Reviews (3): CD010844. doi:10.1002/14651858.CD010844.pub2. PMID 24671923.
123. ^ Liesker JJ, Wijkstra PJ, Ten Hacken NH, Koëter GH, Postma DS, Kerstjens HA (February 2002). "A systematic review of the effects of bronchodilators on exercise capacity in patients with COPD". Chest. 121 (2): 597–608. doi:10.1378/chest.121.2.597. PMID 11834677. S2CID 12284963.
124. ^ Farne HA, Cates CJ (October 2015). "Long-acting beta2-agonist in addition to tiotropium versus either tiotropium or long-acting beta2-agonist alone for chronic obstructive pulmonary disease" (PDF). The Cochrane Database of Systematic Reviews (10): CD008989. doi:10.1002/14651858.CD008989.pub3. PMC 4164463. PMID 26490945.
125. ^ Oba Y, Keeney E, Ghatehorde N, Dias S, et al. (Cochrane Airways Group) (December 2018). "Dual combination therapy versus long-acting bronchodilators alone for chronic obstructive pulmonary disease (COPD): a systematic review and network meta-analysis". The Cochrane Database of Systematic Reviews. 12: CD012620. doi:10.1002/14651858.CD012620.pub2. PMC 6517098. PMID 30521694.
126. ^ a b Cave AC, Hurst MM (May 2011). "The use of long acting β₂-agonists, alone or in combination with inhaled corticosteroids, in chronic obstructive pulmonary disease (COPD): a risk-benefit analysis". Pharmacology & Therapeutics. 130 (2): 114–43. doi:10.1016/j.pharmthera.2010.12.008. PMID 21276815.
127. ^ Spencer S, Karner C, Cates CJ, Evans DJ (December 2011). Spencer S (ed.). "Inhaled corticosteroids versus long-acting beta(2)-agonists for chronic obstructive pulmonary disease" (PDF). The Cochrane Database of Systematic Reviews (12): CD007033. doi:10.1002/14651858.CD007033.pub3. PMC 6494276. PMID 22161409.
128. ^ Wang J, Nie B, Xiong W, Xu Y (April 2012). "Effect of long-acting beta-agonists on the frequency of COPD exacerbations: a meta-analysis". Journal of Clinical Pharmacy and Therapeutics. 37 (2): 204–11. doi:10.1111/j.1365-2710.2011.01285.x. PMID 21740451. S2CID 45383688.
129. ^ a b Geake JB, Dabscheck EJ, Wood-Baker R, Cates CJ (January 2015). "Indacaterol, a once-daily beta2-agonist, versus twice-daily beta₂-agonists or placebo for chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews. 1: CD010139. doi:10.1002/14651858.CD010139.pub2. PMC 6464646. PMID 25575340.
130. ^ Decramer ML, Hanania NA, Lötvall JO, Yawn BP (2013). "The safety of long-acting β2-agonists in the treatment of stable chronic obstructive pulmonary disease". International Journal of Chronic Obstructive Pulmonary Disease. 8: 53–64. doi:10.2147/COPD.S39018. PMC 3558319. PMID 23378756.
131. ^ Nannini LJ, Lasserson TJ, Poole P (September 2012). Nannini LJ (ed.). "Combined corticosteroid and long-acting beta(2)-agonist in one inhaler versus long-acting beta(2)-agonists for chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews. 9 (9): CD006829. doi:10.1002/14651858.CD006829.pub2. PMC 4170910. PMID 22972099.
132. ^ Horita N, Goto A, Shibata Y, Ota E, Nakashima K, Nagai K, Kaneko T (February 2017). "Long-acting muscarinic antagonist (LAMA) plus long-acting beta-agonist (LABA) versus LABA plus inhaled corticosteroid (ICS) for stable chronic obstructive pulmonary disease (COPD)". The Cochrane Database of Systematic Reviews. 2: CD012066. doi:10.1002/14651858.CD012066.pub2. PMC 6464543. PMID 28185242.
133. ^ Zheng Y, Zhu J, Liu Y, Lai W, Lin C, Qiu K, et al. (November 2018). "Triple therapy in the management of chronic obstructive pulmonary disease: systematic review and meta-analysis". BMJ. 363: k4388. doi:10.1136/bmj.k4388. PMC 6218838. PMID 30401700.
134. ^ a b Karner C, Chong J, Poole P (July 2014). "Tiotropium versus placebo for chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews (7): CD009285. doi:10.1002/14651858.CD009285.pub3. PMID 25046211.
135. ^ Cheyne L, Irvin-Sellers MJ, White J (September 2015). "Tiotropium versus ipratropium bromide for chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews (9): CD009552. doi:10.1002/14651858.CD009552.pub3. PMID 26391969.
136. ^ Singh S, Loke YK, Furberg CD (September 2008). "Inhaled anticholinergics and risk of major adverse cardiovascular events in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis". JAMA. 300 (12): 1439–50. doi:10.1001/jama.300.12.1439. PMID 18812535. S2CID 205102861.
137. ^ Singh S, Loke YK, Enright P, Furberg CD (January 2013). "Pro-arrhythmic and pro-ischaemic effects of inhaled anticholinergic medications". Thorax. 68 (1): 114–6. doi:10.1136/thoraxjnl-2011-201275. PMID 22764216.
138. ^ Jones P (April 2013). "Aclidinium bromide twice daily for the treatment of chronic obstructive pulmonary disease: a review". Advances in Therapy. 30 (4): 354–68. doi:10.1007/s12325-013-0019-2. PMID 23553509. S2CID 3530290.
139. ^ Cazzola M, Page CP, Matera MG (June 2013). "Aclidinium bromide for the treatment of chronic obstructive pulmonary disease". Expert Opinion on Pharmacotherapy. 14 (9): 1205–14. doi:10.1517/14656566.2013.789021. PMID 23566013. S2CID 24973904.
140. ^ a b Ni H, Soe Z, Moe S (September 2014). "Aclidinium bromide for stable chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews. 9 (9): CD010509. doi:10.1002/14651858.CD010509.pub2. PMID 25234126.
141. ^ Ni H, Htet A, Moe S (June 2017). "Umeclidinium bromide versus placebo for people with chronic obstructive pulmonary disease (COPD)". The Cochrane Database of Systematic Reviews. 6: CD011897. doi:10.1002/14651858.CD011897.pub2. PMC 6481854. PMID 28631387.
142. ^ Ismaila AS, Huisman EL, Punekar YS, Karabis A (2015). "Comparative efficacy of long-acting muscarinic antagonist monotherapies in COPD: a systematic review and network meta-analysis". International Journal of Chronic Obstructive Pulmonary Disease. 10: 2495–517. doi:10.2147/COPD.S92412. PMC 4655912. PMID 26604738.
143. ^ Gartlehner G, Hansen RA, Carson SS, Lohr KN (2006). "Efficacy and safety of inhaled corticosteroids in patients with COPD: a systematic review and meta-analysis of health outcomes". Annals of Family Medicine. 4 (3): 253–62. doi:10.1370/afm.517. PMC 1479432. PMID 16735528.
144. ^ Chinet T, Dumoulin J, Honore I, Braun JM, Couderc LJ, Febvre M, Mangiapan G, Maurer C, Serrier P, Soyez F, Terrioux P, Jebrak G (December 2016). "[The place of inhaled corticosteroids in COPD]". Revue des Maladies Respiratoires. 33 (10): 877–891. doi:10.1016/j.rmr.2015.11.009. PMID 26831345.
145. ^ Dong YH, Lin HH, Shau WY, Wu YC, Chang CH, Lai MS (January 2013). "Comparative safety of inhaled medications in patients with chronic obstructive pulmonary disease: systematic review and mixed treatment comparison meta-analysis of randomised controlled trials". Thorax. 68 (1): 48–56. doi:10.1136/thoraxjnl-2012-201926. PMID 23042705.
146. ^ Nannini LJ, Poole P, Milan SJ, Kesterton A (August 2013). "Combined corticosteroid and long-acting beta(2)-agonist in one inhaler versus inhaled corticosteroids alone for chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews. 8 (8): CD006826. doi:10.1002/14651858.CD006826.pub2. PMC 6486274. PMID 23990350.
147. ^ Kew KM, Seniukovich A (March 2014). "Inhaled steroids and risk of pneumonia for chronic obstructive pulmonary disease" (PDF). The Cochrane Database of Systematic Reviews. 3 (3): CD010115. doi:10.1002/14651858.CD010115.pub2. PMID 24615270.
148. ^ "Recommendations | Chronic obstructive pulmonary disease in over 16s: diagnosis and management | Guidance | NICE". www.nice.org.uk. Retrieved 2019-10-30.
149. ^ Mammen MJ, Sethi S (2012). "Macrolide therapy for the prevention of acute exacerbations in chronic obstructive pulmonary disease". Polskie Archiwum Medycyny Wewnetrznej. 122 (1–2): 54–9. doi:10.20452/pamw.1134. PMID 22353707. S2CID 35183033.
150. ^ a b Herath SC, Normansell R, Maisey S, Poole P (October 2018). "Prophylactic antibiotic therapy for chronic obstructive pulmonary disease (COPD)". The Cochrane Database of Systematic Reviews. 10: CD009764. doi:10.1002/14651858.CD009764.pub3. PMC 6517028. PMID 30376188.
151. ^ Simoens S, Laekeman G, Decramer M (May 2013). "Preventing COPD exacerbations with macrolides: a review and budget impact analysis". Respiratory Medicine. 107 (5): 637–48. doi:10.1016/j.rmed.2012.12.019. PMID 23352223.
152. ^ Barr RG, Rowe BH, Camargo CA (2003). Barr RG (ed.). "Methylxanthines for exacerbations of chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews (2): CD002168. doi:10.1002/14651858.CD002168. PMID 12804425.
153. ^ Poole P, Sathananthan K, Fortescue R (May 2019). "Mucolytic agents versus placebo for chronic bronchitis or chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews. 5: CD001287. doi:10.1002/14651858.CD001287.pub6. PMC 6527426. PMID 31107966.
154. ^ a b Salpeter S, Ormiston T, Salpeter E (October 2005). "Cardioselective beta-blockers for chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews (4): CD003566. doi:10.1002/14651858.CD003566.pub2. PMID 16235327.
155. ^ Ni Y, Shi G, Wan H (2012). "Use of cardioselective β-blockers in patients with chronic obstructive pulmonary disease: a meta-analysis of randomized, placebo-controlled, blinded trials". The Journal of International Medical Research. 40 (6): 2051–65. doi:10.1177/030006051204000602. PMID 23321161.
156. ^ Jolliffe DA, Greenberg L, Hooper RL, Mathyssen C, Rafiq R, de Jongh RT, et al. (April 2019). "Vitamin D to prevent exacerbations of COPD: systematic review and meta-analysis of individual participant data from randomised controlled trials". Thorax. 74 (4): 337–345. doi:10.1136/thoraxjnl-2018-212092. PMID 30630893.
157. ^ a b COPD Working Group (2012). "Long-term oxygen therapy for patients with chronic obstructive pulmonary disease (COPD): an evidence-based analysis". Ontario Health Technology Assessment Series. 12 (7): 1–64. PMC 3384376. PMID 23074435.
158. ^ Bradley JM, O'Neill B (October 2005). Bradley JM (ed.). "Short-term ambulatory oxygen for chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews. 4 (4): CD004356. doi:10.1002/14651858.CD004356.pub3. PMID 16235359.
159. ^ Ekström M, Ahmadi Z, Bornefalk-Hermansson A, Abernethy A, Currow D (November 2016). "Oxygen for breathlessness in patients with chronic obstructive pulmonary disease who do not qualify for home oxygen therapy". The Cochrane Database of Systematic Reviews. 11: CD006429. doi:10.1002/14651858.CD006429.pub3. PMC 6464154. PMID 27886372.
160. ^ Chapman S (2009). Oxford handbook of respiratory medicine (2nd ed.). Oxford University Press. p. 707. ISBN 978-0-19-954516-2.
161. ^ Blackler L (2007). Managing chronic obstructive pulmonary disease. Wiley. p. 49. ISBN 978-0-470-51798-7.
162. ^ Hopkinson NS, Molyneux A, Pink J, Harrisingh MC (July 2019). "Chronic obstructive pulmonary disease: diagnosis and management: summary of updated NICE guidance". BMJ. 366: l4486. doi:10.1136/bmj.l4486. hdl:10044/1/72505. PMID 31358491. S2CID 198984181.
163. ^ Jindal SK (2013). Chronic Obstructive Pulmonary Disease. Jaypee Brothers Medical. p. 139. ISBN 978-93-5090-353-7.
164. ^ a b O'Driscoll BR, Howard LS, Davison AG (October 2008). "BTS guideline for emergency oxygen use in adult patients". Thorax. 63 Suppl 6 (6): vi1-68. doi:10.1136/thx.2008.102947. PMID 18838559.
165. ^ a b van Agteren JE, Hnin K, Grosser D, Carson KV, Smith BJ (February 2017). "Bronchoscopic lung volume reduction procedures for chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews. 2: CD012158. doi:10.1002/14651858.CD012158.pub2. PMC 6464526. PMID 28230230.
166. ^ van Agteren JE, Carson KV, Tiong LU, Smith BJ (October 2016). "Lung volume reduction surgery for diffuse emphysema". The Cochrane Database of Systematic Reviews. 10: CD001001. doi:10.1002/14651858.CD001001.pub3. PMC 6461146. PMID 27739074.
167. ^ Van Geffen WH, Douma WR, Slebos DJ, Kerstjens HA (29 August 2016). "Bronchodilators delivered by nebuliser versus inhalers for lung attacks of chronic obstructive pulmonary disease". Cochrane Database of Systematic Reviews. doi:10.1002/14651858.cd011826. hdl:11370/95fc3e6e-ebd0-440f-9721-489729f80add. Archived from the original on 13 September 2016.
168. ^ Wise R. "Chronic Obstructive Pulmonary Disease (COPD) – Pulmonary Disorders – Merck Manuals Professional Edition". Merck Manuals Professional Edition. Archived from the original on 28 December 2016. Retrieved 16 December 2016.
169. ^ Walters JA, Tan DJ, White CJ, Gibson PG, Wood-Baker R, Walters EH (September 2014). "Systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews. 9 (9): CD001288. doi:10.1002/14651858.CD001288.pub4. PMID 25178099.
170. ^ Walters JA, Tan DJ, White CJ, Wood-Baker R (March 2018). "Different durations of corticosteroid therapy for exacerbations of chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews. 3: CD006897. doi:10.1002/14651858.CD006897.pub4. PMC 6494402. PMID 29553157.
171. ^ a b Vollenweider DJ, Frei A, Steurer-Stey CA, Garcia-Aymerich J, Puhan MA (October 2018). "Antibiotics for exacerbations of chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews. 10: CD010257. doi:10.1002/14651858.CD010257.pub2. PMC 6517133. PMID 30371937.
172. ^ "Fluoroquinolone Antibacterial Drugs: Drug Safety Communication – FDA Advises Restricting Use for Certain Uncomplicated Infections". FDA. 12 May 2016. Archived from the original on 16 May 2016. Retrieved 16 May 2016.
173. ^ "WHO Disease and injury country estimates". World Health Organization. 2009. Archived from the original on 2009-11-11. Retrieved Nov 11, 2009.
174. ^ a b Murray CJ, Vos T, Lozano R, Naghavi M, Flaxman AD, Michaud C, et al. (December 2012). "Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010" (PDF). Lancet. 380 (9859): 2197–223. doi:10.1016/S0140-6736(12)61689-4. PMID 23245608. S2CID 205967479.
175. ^ a b Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, et al. (December 2012). "Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010". Lancet. 380 (9859): 2163–96. doi:10.1016/S0140-6736(12)61729-2. PMC 6350784. PMID 23245607.
176. ^ prepared by the Department of Medicine, Washington University School of Medicine (2009). The Washington manual general internal medicine subspecialty consult (2nd ed.). Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 96. ISBN 978-0-7817-9155-7.
177. ^ "Chronic obstructive pulmonary disease (COPD) Fact sheet N°315". WHO. January 2015. Archived from the original on 2016-03-04.
178. ^ Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. (December 2012). "Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010". Lancet. 380 (9859): 2095–128. doi:10.1016/S0140-6736(12)61728-0. hdl:10536/DRO/DU:30050819. PMID 23245604. S2CID 1541253.
179. ^ "The 10 leading causes of death in the world, 2000 and 2011". World Health Organization. July 2013. Archived from the original on December 2, 2013. Retrieved November 29, 2013.
180. ^ Rycroft CE, Heyes A, Lanza L, Becker K (2012). "Epidemiology of chronic obstructive pulmonary disease: a literature review". International Journal of Chronic Obstructive Pulmonary Disease. 7: 457–94. doi:10.2147/COPD.S32330. PMC 3422122. PMID 22927753.
181. ^ Simpson CR, Hippisley-Cox J, Sheikh A (July 2010). "Trends in the epidemiology of chronic obstructive pulmonary disease in England: a national study of 51 804 patients". The British Journal of General Practice. 60 (576): 277–84. doi:10.3399/bjgp10X514729. PMC 2894402. PMID 20594429.
182. ^ Centers for Disease Control and Prevention (November 2012). "Chronic obstructive pulmonary disease among adults—United States, 2011". MMWR. Morbidity and Mortality Weekly Report. 61 (46): 938–43. PMID 23169314. Archived from the original on 3 December 2013.
183. ^ "Morbidity & Mortality: 2009 Chart Book on Cardiovascular, Lung, and Blood Diseases" (PDF). National Heart, Lung, and Blood Institute. Archived from the original (PDF) on 2013-10-19.
184. ^ a b Torio CM, Andrews RM (2006). "National Inpatient Hospital Costs: The Most Expensive Conditions by Payer, 2011: Statistical Brief #160". Healthcare Cost and Utilization Project (HCUP) Statistical Briefs. PMID 24199255. Archived from the original on 2017-03-14.
185. ^ Hoyert DL, Xu J (October 2012). "Deaths: preliminary data for 2011". National Vital Statistics Reports. 61 (6): 1–51. PMID 24984457.
186. ^ "Emphysema". Dictionary.com. Archived from the original on 24 November 2013. Retrieved 21 November 2013.
187. ^ a b Ziment I (1991). "History of the treatment of chronic bronchitis". Respiration; International Review of Thoracic Diseases. 58 (Suppl 1): 37–42. doi:10.1159/000195969. PMID 1925077.
188. ^ a b c d Petty TL (2006). "The history of COPD". International Journal of Chronic Obstructive Pulmonary Disease. 1 (1): 3–14. doi:10.2147/copd.2006.1.1.3. PMC 2706597. PMID 18046898.
189. ^ a b Wright JL, Churg A (2008). "Pathologic Features of Chronic Obstructive Pulmonary Disease: Diagnostic Criteria and Differential Diagnosis" (PDF). In Fishman A, Elias J, Fishman J, Grippi M, Senior R, Pack A (eds.). Fishman's Pulmonary Diseases and Disorders (4th ed.). McGraw-Hill. pp. 693–705. ISBN 978-0-07-164109-8.
190. ^ Waldbott GL (1965). A struggle with Titans. Carlton Press. p. 6.
191. ^ Fishman AP (May 2005). "One hundred years of chronic obstructive pulmonary disease". American Journal of Respiratory and Critical Care Medicine. 171 (9): 941–8. doi:10.1164/rccm.200412-1685OE. PMID 15849329.
192. ^ Yuh-Chin TH (2012). A clinical guide to occupational and environmental lung diseases. Humana Press. p. 266. ISBN 978-1-62703-149-3.
193. ^ "Pink Puffer – definition of Pink Puffer in the Medical dictionary – by the Free Online Medical Dictionary, Thesaurus and Encyclopedia". Medical-dictionary.thefreedictionary.com. Retrieved 2013-07-23.
194. ^ a b c Weinberger SE (2013). Principles of pulmonary medicine (6th ed.). Elsevier/Saunders. p. 165. ISBN 978-1-62703-149-3.
195. ^ Des Jardins T (2013). Clinical Manifestations & Assessment of Respiratory Disease (6th ed.). Elsevier Health Sciences. p. 176. ISBN 978-0-323-27749-5.
196. ^ An outcomes strategy for people with chronic obstructive pulmonary disease (COPD) and asthma in England (PDF). Department of Health. 18 July 2011. p. 5. Archived (PDF) from the original on 5 December 2013. Retrieved 27 November 2013.
197. ^ Bloom D (2011). The Global Economic Burden of Noncommunicable Diseases (PDF). World Economic Forum. p. 24. Archived (PDF) from the original on 2015-02-04.
198. ^ Nambiar S, Bong How S, Gummer J, Trengove R, Moodley Y (February 2020). "Metabolomics in chronic lung diseases". Respirology. 25 (2): 139–148. doi:10.1111/resp.13530. PMID 30907495.
199. ^ Nici L (2011). Chronic Obstructive Pulmonary Disease: Co-Morbidities and Systemic Consequences. Springer. p. 78. ISBN 978-1-60761-673-3.
200. ^ a b c Janjua S, Fortescue R, Poole P (May 2020). "Phosphodiesterase-4 inhibitors for chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews. 5: CD002309. doi:10.1002/14651858.CD002309.pub6. PMC 7193764. PMID 32356609.
201. ^ Inamdar AC, Inamdar AA (October 2013). "Mesenchymal stem cell therapy in lung disorders: pathogenesis of lung diseases and mechanism of action of mesenchymal stem cell". Experimental Lung Research. 39 (8): 315–27. doi:10.3109/01902148.2013.816803. PMID 23992090. S2CID 46052894.
202. ^ a b Oh DK, Kim YS, Oh YM (January 2017). "Lung Regeneration Therapy for Chronic Obstructive Pulmonary Disease". Tuberculosis and Respiratory Diseases. 80 (1): 1–10. doi:10.4046/trd.2017.80.1.1. PMC 5256352. PMID 28119741.
203. ^ Conese M, Piro D, Carbone A, Castellani S, Di Gioia S (2014). "Hematopoietic and mesenchymal stem cells for the treatment of chronic respiratory diseases: role of plasticity and heterogeneity". TheScientificWorldJournal. 2014: 859817. doi:10.1155/2014/859817. PMC 3916026. PMID 24563632.
204. ^ McQualter JL, Anthony D, Bozinovski S, Prêle CM, Laurent GJ (November 2014). "Harnessing the potential of lung stem cells for regenerative medicine". The International Journal of Biochemistry & Cell Biology. 56: 82–91. doi:10.1016/j.biocel.2014.10.012. PMID 25450456.
205. ^ Tzouvelekis A, Ntolios P, Bouros D (2013). "Stem cell treatment for chronic lung diseases". Respiration; International Review of Thoracic Diseases. 85 (3): 179–92. doi:10.1159/000346525. PMID 23364286.
206. ^ Tzouvelekis A, Laurent G, Bouros D (February 2013). "Stem cell therapy in chronic obstructive pulmonary disease. Seeking the Prometheus effect". Current Drug Targets. 14 (2): 246–52. doi:10.2174/1389450111314020009. PMID 23256721.
207. ^ Gompelmann D, Eberhardt R, Herth FJ (August 2015). "Novel Endoscopic Approaches to Treating Chronic Obstructive Pulmonary Disease and Emphysema". Seminars in Respiratory and Critical Care Medicine. 36 (4): 609–15. doi:10.1055/s-0035-1555614. PMID 26238645.
208. ^ Gøtzsche PC, Johansen HK (September 2016). "Intravenous alpha-1 antitrypsin augmentation therapy for treating patients with alpha-1 antitrypsin deficiency and lung disease". The Cochrane Database of Systematic Reviews. 9: CD007851. doi:10.1002/14651858.CD007851.pub3. PMC 6457738. PMID 27644166.
209. ^ McLean S, Nurmatov U, Liu JL, Pagliari C, Car J, Sheikh A (July 2011). "Telehealthcare for chronic obstructive pulmonary disease" (PDF). The Cochrane Database of Systematic Reviews (7): CD007718. doi:10.1002/14651858.CD007718.pub2. PMID 21735417.
210. ^ Akers RM, Denbow DM (2008). Anatomy and Physiology of Domestic Animals. Wiley. p. 852. ISBN 978-1-118-70115-7.
211. ^ Wright JL, Churg A (December 2002). "Animal models of cigarette smoke-induced COPD". Chest. 122 (6 Suppl): 301S–306S. doi:10.1378/chest.122.6_suppl.301S. PMID 12475805. S2CID 30461445.
212. ^ Churg A, Wright JL (2007). "Animal models of cigarette smoke-induced chronic obstructive lung disease". Models of Exacerbations in Asthma and COPD. Contributions to Microbiology. 14. pp. 113–25. doi:10.1159/000107058. ISBN 978-3-8055-8332-9. PMID 17684336.
213. ^ Marinkovic D, Aleksic-Kovacevic S, Plamenac P (2007). Cellular basis of chronic obstructive pulmonary disease in horses. International Review of Cytology. 257. pp. 213–47. doi:10.1016/S0074-7696(07)57006-3. ISBN 978-0-12-373701-4. PMID 17280899.
214. ^ Miller MS, Tilley LP, Smith FW (January 1989). "Cardiopulmonary disease in the geriatric dog and cat". The Veterinary Clinics of North America. Small Animal Practice. 19 (1): 87–102. doi:10.1016/S0195-5616(89)50007-X. PMID 2646821.
## Further reading[edit]
* National Institute for Health and Clinical Excellence. Clinical guideline 101: Chronic Obstructive Pulmonary Disease. London, June 2010.
## External links[edit]
Wikimedia Commons has media related to Chronic obstructive pulmonary disease.
* Chronic obstructive pulmonary disease at Curlie
* "COPD". MedlinePlus. U.S. National Library of Medicine.
Classification
D
* ICD-10: J40–J44, J47
* ICD-9-CM: 490–492, 494–496
* OMIM: 606963
* MeSH: D029424
* DiseasesDB: 2672
* SNOMED CT: 13645005
External resources
* MedlinePlus: 000091
* eMedicine: med/373 emerg/99
* Patient UK: Chronic obstructive pulmonary disease
* v
* t
* e
Diseases of the respiratory system
Upper RT
(including URTIs,
common cold)
Head
sinuses
Sinusitis
nose
Rhinitis
Vasomotor rhinitis
Atrophic rhinitis
Hay fever
Nasal polyp
Rhinorrhea
nasal septum
Nasal septum deviation
Nasal septum perforation
Nasal septal hematoma
tonsil
Tonsillitis
Adenoid hypertrophy
Peritonsillar abscess
Neck
pharynx
Pharyngitis
Strep throat
Laryngopharyngeal reflux (LPR)
Retropharyngeal abscess
larynx
Croup
Laryngomalacia
Laryngeal cyst
Laryngitis
Laryngopharyngeal reflux (LPR)
Laryngospasm
vocal cords
Laryngopharyngeal reflux (LPR)
Vocal fold nodule
Vocal fold paresis
Vocal cord dysfunction
epiglottis
Epiglottitis
trachea
Tracheitis
Laryngotracheal stenosis
Lower RT/lung disease
(including LRTIs)
Bronchial/
obstructive
acute
Acute bronchitis
chronic
COPD
Chronic bronchitis
Acute exacerbation of COPD)
Asthma (Status asthmaticus
Aspirin-induced
Exercise-induced
Bronchiectasis
Cystic fibrosis
unspecified
Bronchitis
Bronchiolitis
Bronchiolitis obliterans
Diffuse panbronchiolitis
Interstitial/
restrictive
(fibrosis)
External agents/
occupational
lung disease
Pneumoconiosis
Aluminosis
Asbestosis
Baritosis
Bauxite fibrosis
Berylliosis
Caplan's syndrome
Chalicosis
Coalworker's pneumoconiosis
Siderosis
Silicosis
Talcosis
Byssinosis
Hypersensitivity pneumonitis
Bagassosis
Bird fancier's lung
Farmer's lung
Lycoperdonosis
Other
* ARDS
* Combined pulmonary fibrosis and emphysema
* Pulmonary edema
* Löffler's syndrome/Eosinophilic pneumonia
* Respiratory hypersensitivity
* Allergic bronchopulmonary aspergillosis
* Hamman-Rich syndrome
* Idiopathic pulmonary fibrosis
* Sarcoidosis
* Vaping-associated pulmonary injury
Obstructive / Restrictive
Pneumonia/
pneumonitis
By pathogen
* Viral
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* Klebsiella
* Atypical bacterial
* Mycoplasma
* Legionnaires' disease
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* noninfectious
* Chemical/Mendelson's syndrome
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By vector/route
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* Hospital-acquired
By distribution
* Broncho-
* Lobar
IIP
* UIP
* DIP
* BOOP-COP
* NSIP
* RB
Other
* Atelectasis
* circulatory
* Pulmonary hypertension
* Pulmonary embolism
* Lung abscess
Pleural cavity/
mediastinum
Pleural disease
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* Pneumothorax/Hemopneumothorax
Pleural effusion
Hemothorax
Hydrothorax
Chylothorax
Empyema/pyothorax
Malignant
Fibrothorax
Mediastinal disease
* Mediastinitis
* Mediastinal emphysema
Other/general
* Respiratory failure
* Influenza
* Common cold
* SARS
* Coronavirus disease 2019
* Idiopathic pulmonary haemosiderosis
* Pulmonary alveolar proteinosis
Authority control
* NDL: 00942909
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Chronic obstructive pulmonary disease | c0024117 | 4,002 | wikipedia | https://en.wikipedia.org/wiki/Chronic_obstructive_pulmonary_disease | 2021-01-18T19:01:02 | {"mesh": ["D029424"], "umls": ["C0024117"], "icd-9": ["496", "490", "492", "494"], "wikidata": ["Q199804"]} |
Askin's tumor is a rare, primitive neuroectodermal tumor which arises from the soft tissues of the chest wall, particularly of the paravertebral region.[1][2] It was first described by Askin et al in 1979.[3] Askin's tumor is now recognized as part of the Ewing's sarcoma family of tumors.[4] This neoplasm tended to recur locally, but did not seem to disseminate as widely as some of the other small cell tumors of childhood such as rhabdomyosarcoma or neuroblastoma.
## References[edit]
1. ^ Askin FB, Rosai J, Sibley RK, Dehner LP, McAlister WH (June 1979). "Malignant small cell tumor of the thoracopulmonary region in childhood: a distinctive clinicopathologic entity of uncertain histogenesis". Cancer. 43 (6): 2438–51. doi:10.1002/1097-0142(197906)43:6<2438::AID-CNCR2820430640>3.0.CO;2-9. PMID 222426.
2. ^ Coindre JM (1993). "[Askin's tumor: a clinicopathologic entity?]". Annales de Pathologie. 13 (2): 139–40. PMID 8363677.
3. ^ Benbrahim Z, Arifi S, Daoudi K, Serraj M, Amara B, Benjelloun MC, et al. (January 2013). "Askin's tumor: a case report and literature review". World Journal of Surgical Oncology. 11: 10. doi:10.1186/1477-7819-11-10. PMC 3556149. PMID 23339634.
4. ^ Grünewald TG, Cidre-Aranaz F, Surdez D, Tomazou EM, de Álava E, Kovar H, et al. (July 2018). "Ewing sarcoma". Nature Reviews. Disease Primers. 4 (1): 5. doi:10.1038/s41572-018-0003-x. PMID 29977059. S2CID 49571421.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Askin's tumor | c0877849 | 4,003 | wikipedia | https://en.wikipedia.org/wiki/Askin%27s_tumor | 2021-01-18T18:39:13 | {"mesh": ["C563168", "Askin Tumor"], "umls": ["C0877849"], "wikidata": ["Q18553335"]} |
Trichorrhexis invaginata
Other namesBamboo hair[1]
SpecialtyDermatology
Trichorrhexis invaginata is a distinctive hair shaft abnormality that may occur sporadically, either in normal hair or with other hair shaft abnormalities, or regularly as a marker for Netherton's syndrome.[1]:638[2]:766–7 The primary defect appears to be abnormal keratinization of the hair shaft in the keratogenous zone, allowing for intussusception of the fully keratinized and hard distal shaft into the incompletely keratinized and soft proximal portion of the shaft.[1]:638[3]
## Contents
* 1 Genetics
* 2 Epidemiology
* 3 History
* 4 See also
* 5 References
* 6 External links
## Genetics[edit]
"Bamboo hair" is a rare autosomal recessive genodermatosis characterized by congenital ichthyosiform erythroderma, trichorrhexis invaginata, and atopic diathesis with failure to thrive. Chronic skin inflammation results in scaling and exfoliation, predisposing these patients to life-threatening infections, sepsis, and dehydration. The Netherton syndrome Mendelian Inheritance in Man is inherited as an autosomal recessive disorder due to mutations of both copies of the SPINK5 gene (localized to band 5q31-32), which encodes the serine protease inhibitor LEKTI (lymphoepithelial Kazal-type-related inhibitor). LEKTI is expressed in epithelial and mucosal surfaces and in the thymus. Each SPINK5 mutation leads to a different length of LEKTI protein, resulting in genotype/phenotype correlations in cutaneous severity, susceptibility to atopic dermatitis, growth retardation, skin infection, increased stratum corneum protease activities, and elevated kallikrein levels in the stratum corneum.[4][5]
Trichorrhexis invaginata, or bamboo hair, is a hair shaft abnormality that occurs as a result of an intermittent keratinizing defect of the hair cortex. Incomplete conversion of the sulfhydryl –SH group onto S-S disulfide bonds in the protein of the cortical fibers leads to cortical softness and subsequent invagination of the fully keratinized distal hair shaft into the softer, abnormally keratinized proximal hair shaft. Intussusception of the distal hair shaft into the proximal hair shaft results in a distinctive ball-and-socket hair shaft deformity. The affected hairs are brittle and breakage is common, resulting in short hairs.[6]
Migratory lesions of ichthyosis linearis circumflexa may be caused by a dermal influx of inflammatory cells that undergo phagocytosis and digestion by keratinocytes, resulting in disruption of keratinization.[7]
Increased transepidermal water loss resulting from the disturbance of corneocyte barrier function in erythroderma may cause profound metabolic abnormalities and hypernatremia, particularly in neonates.[8][9]
## Epidemiology[edit]
Approximately 200 cases of trichorrhexis invaginata (bamboo hair) have been reported in the literature, but the true incidence is not known. The incidence of trichorrhexis invaginata (bamboo hair) may be as high as 1 case in 50,000 population. Girls are affected more often by trichorrhexis invaginata (bamboo hair) than boys, but is present in all races.[10]
## History[edit]
In 1937, Touraine and Solente first noted the association between hair-shaft defects (bamboo node) and ichthyosiform erythroderma. Còme first coined the term ichthyosis linearis circumflexa in 1949, although Rille had previously recorded the distinctive features of ichthyosis linearis circumflexa by 1922.[11] In 1958, Netherton described a young girl with generalized scaly dermatitis and fragile nodular hair-shaft deformities, which he termed trichorrhexis nodosa. Later, this was more appropriately renamed as trichorrhexis invaginata (bamboo hair) for a ball-and-socket–type hair-shaft deformity at the suggestion of Wilkinson et al.[12][13] In 1974, Mevorah et al. established the clinical relationship between ichthyosis linearis circumflexa and Netherton syndrome, and an atopic diathesis was found to occur in approximately 75% of patients with Netherton syndrome.[14]
## See also[edit]
* Trichomegaly
* List of cutaneous conditions
## References[edit]
1. ^ a b c Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0.
2. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
3. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.
4. ^ Bonnart C, Deraison C, Lacroix M, Uchida Y, Besson C, Robin A, Briot A, Gonthier M, Lamant L, Dubus P, Monsarrat B, Hovnanian A (2010). "Elastase 2 is expressed in human and mouse epidermis and impairs skin barrier function in Netherton syndrome through filaggrin and lipid misprocessing". J. Clin. Invest. 120 (3): 871–82. doi:10.1172/JCI41440. PMC 2827963. PMID 20179351.
5. ^ Sales KU, Masedunskas A, Bey AL, et al. (August 2010). "Matriptase initiates activation of epidermal pro-kallikrein and disease onset in a mouse model of Netherton syndrome". Nat. Genet. 42 (8): 676–83. doi:10.1038/ng.629. PMC 3081165. PMID 20657595.
6. ^ http://reference.medscape.com/medline/abstract/10712206
7. ^ http://reference.medscape.com/medline/abstract/3718867
8. ^ http://reference.medscape.com/medline/abstract/11693786
9. ^ http://reference.medscape.com/medline/abstract/8806118
10. ^ Traupe H. The Ichthyoses. A Guide to Clinical Diagnosis, Genetic Counseling, and Therapy. Berlin: Springer Verlag, 1989.
11. ^ Ali M, Marks R, Young E, et al. Netherton's syndrome. A familial occurrence. Br J Dermatol. 1998.
12. ^ http://reference.medscape.com/medline/abstract/13582191
13. ^ Fruhwald R. Zur frage der comelschen krankheit. Dermatol Wochenschr. 1949;150:289.
14. ^ Mevorah B, Frenk E, Brooke EM. Ichthyosis linearis circumflexa comel. A clinico-statistical approach to its relationship with Netherton's syndrome. Dermatologica. 1974.
## External links[edit]
Classification
D
* ICD-10: L67.8 (ILDS L67.830)
* v
* t
* e
Disorders of skin appendages
Nail
* thickness: Onychogryphosis
* Onychauxis
* color: Beau's lines
* Yellow nail syndrome
* Leukonychia
* Azure lunula
* shape: Koilonychia
* Nail clubbing
* behavior: Onychotillomania
* Onychophagia
* other: Ingrown nail
* Anonychia
* ungrouped: Paronychia
* Acute
* Chronic
* Chevron nail
* Congenital onychodysplasia of the index fingers
* Green nails
* Half and half nails
* Hangnail
* Hapalonychia
* Hook nail
* Ingrown nail
* Lichen planus of the nails
* Longitudinal erythronychia
* Malalignment of the nail plate
* Median nail dystrophy
* Mees' lines
* Melanonychia
* Muehrcke's lines
* Nail–patella syndrome
* Onychoatrophy
* Onycholysis
* Onychomadesis
* Onychomatricoma
* Onychomycosis
* Onychophosis
* Onychoptosis defluvium
* Onychorrhexis
* Onychoschizia
* Platonychia
* Pincer nails
* Plummer's nail
* Psoriatic nails
* Pterygium inversum unguis
* Pterygium unguis
* Purpura of the nail bed
* Racquet nail
* Red lunulae
* Shell nail syndrome
* Splinter hemorrhage
* Spotted lunulae
* Staining of the nail plate
* Stippled nails
* Subungual hematoma
* Terry's nails
* Twenty-nail dystrophy
Hair
Hair loss/
Baldness
* noncicatricial alopecia: Alopecia
* areata
* totalis
* universalis
* Ophiasis
* Androgenic alopecia (male-pattern baldness)
* Hypotrichosis
* Telogen effluvium
* Traction alopecia
* Lichen planopilaris
* Trichorrhexis nodosa
* Alopecia neoplastica
* Anagen effluvium
* Alopecia mucinosa
* cicatricial alopecia: Pseudopelade of Brocq
* Central centrifugal cicatricial alopecia
* Pressure alopecia
* Traumatic alopecia
* Tumor alopecia
* Hot comb alopecia
* Perifolliculitis capitis abscedens et suffodiens
* Graham-Little syndrome
* Folliculitis decalvans
* ungrouped: Triangular alopecia
* Frontal fibrosing alopecia
* Marie Unna hereditary hypotrichosis
Hypertrichosis
* Hirsutism
* Acquired
* localised
* generalised
* patterned
* Congenital
* generalised
* localised
* X-linked
* Prepubertal
Acneiform
eruption
Acne
* Acne vulgaris
* Acne conglobata
* Acne miliaris necrotica
* Tropical acne
* Infantile acne/Neonatal acne
* Excoriated acne
* Acne fulminans
* Acne medicamentosa (e.g., steroid acne)
* Halogen acne
* Iododerma
* Bromoderma
* Chloracne
* Oil acne
* Tar acne
* Acne cosmetica
* Occupational acne
* Acne aestivalis
* Acne keloidalis nuchae
* Acne mechanica
* Acne with facial edema
* Pomade acne
* Acne necrotica
* Blackhead
* Lupus miliaris disseminatus faciei
Rosacea
* Perioral dermatitis
* Granulomatous perioral dermatitis
* Phymatous rosacea
* Rhinophyma
* Blepharophyma
* Gnathophyma
* Metophyma
* Otophyma
* Papulopustular rosacea
* Lupoid rosacea
* Erythrotelangiectatic rosacea
* Glandular rosacea
* Gram-negative rosacea
* Steroid rosacea
* Ocular rosacea
* Persistent edema of rosacea
* Rosacea conglobata
* variants
* Periorificial dermatitis
* Pyoderma faciale
Ungrouped
* Granulomatous facial dermatitis
* Idiopathic facial aseptic granuloma
* Periorbital dermatitis
* SAPHO syndrome
Follicular cysts
* "Sebaceous cyst"
* Epidermoid cyst
* Trichilemmal cyst
* Steatocystoma
* simplex
* multiplex
* Milia
Inflammation
* Folliculitis
* Folliculitis nares perforans
* Tufted folliculitis
* Pseudofolliculitis barbae
* Hidradenitis
* Hidradenitis suppurativa
* Recurrent palmoplantar hidradenitis
* Neutrophilic eccrine hidradenitis
Ungrouped
* Acrokeratosis paraneoplastica of Bazex
* Acroosteolysis
* Bubble hair deformity
* Disseminate and recurrent infundibulofolliculitis
* Erosive pustular dermatitis of the scalp
* Erythromelanosis follicularis faciei et colli
* Hair casts
* Hair follicle nevus
* Intermittent hair–follicle dystrophy
* Keratosis pilaris atropicans
* Kinking hair
* Koenen's tumor
* Lichen planopilaris
* Lichen spinulosus
* Loose anagen syndrome
* Menkes kinky hair syndrome
* Monilethrix
* Parakeratosis pustulosa
* Pili (Pili annulati
* Pili bifurcati
* Pili multigemini
* Pili pseudoannulati
* Pili torti)
* Pityriasis amiantacea
* Plica neuropathica
* Poliosis
* Rubinstein–Taybi syndrome
* Setleis syndrome
* Traumatic anserine folliculosis
* Trichomegaly
* Trichomycosis axillaris
* Trichorrhexis (Trichorrhexis invaginata
* Trichorrhexis nodosa)
* Trichostasis spinulosa
* Uncombable hair syndrome
* Wooly hair nevus
Sweat
glands
Eccrine
* Miliaria
* Colloid milium
* Miliaria crystalline
* Miliaria profunda
* Miliaria pustulosa
* Miliaria rubra
* Occlusion miliaria
* Postmiliarial hypohidrosis
* Granulosis rubra nasi
* Ross’ syndrome
* Anhidrosis
* Hyperhidrosis
* Generalized
* Gustatory
* Palmoplantar
Apocrine
* Body odor
* Chromhidrosis
* Fox–Fordyce disease
Sebaceous
* Sebaceous hyperplasia
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Trichorrhexis invaginata | c0702164 | 4,004 | wikipedia | https://en.wikipedia.org/wiki/Trichorrhexis_invaginata | 2021-01-18T18:50:20 | {"icd-10": ["L67.8"], "wikidata": ["Q7840964"]} |
Meigs syndrome is a rare neoplastic disease characterized by the clinical triad of benign ovarian tumor (typically, ovarian fibroma or fibroma-like tumor), hydrothorax and ascites, which resolve after tumor resection. Patients usually present with dyspnea, pelvic mass with or without a tender, distended abdomen and/or weight loss.
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Meigs syndrome | c0025184 | 4,005 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=314451 | 2021-01-23T18:48:02 | {"mesh": ["D008539"], "umls": ["C0025184"], "icd-10": ["D27"], "synonyms": ["Demons-Meigs syndrome"]} |
McLeod neuroacanthocytosis syndrome (MLS) is a form of neuroacanthocytosis (see this term) and is characterized clinically by a Huntington's disease-like phenotype with an involuntary hyperkinetic movement disorder, psychiatric manifestations and cognitive alterations, and biochemically by absence of the Kx antigen and by weak expression of the Kell antigens.
## Epidemiology
Prevalence and incidence are not known, but the disorder is very rare and a few hundred cases are suspected worldwide. MLS has been described in Europe, North and South America, and Japan without obvious clustering. The disease primarily affects males; female carriers rarely develop a neurological syndrome.
## Clinical description
Onset of neurological symptoms is at 25-60 years of age and disease duration may be more than 30 years. About 1/3 of patients present with chorea indistinguishable from that observed in Huntington disease (see this term), and most patients will develop chorea during the course of the disease. Additional involuntary movements include facial dyskinesias, vocalizations and rarely feeding dystonia. Psychiatric manifestations including depression, schizophrenia-like psychosis and obsessive compulsive disorder (OCD) are frequent and may appear many years prior to the movement disorders. A subset of patients develops cognitive deficits, particularly in later disease stages. Generalized seizures and muscle weakness (rarely severe) and atrophy occur in about 1/2 of patients. MLS myopathy may predispose some to rhabdomyolysis, particular with neuroleptic medication use. Neuromuscular signs include sensorimotor axonal neuropathy, neurogenic muscle atrophy and variable additional myopathy. About 60% of patients develop cardiomyopathy manifesting with atrial fibrillation, malignant arrhythmias or dilated cardiomyopathy. Cardiac complications are a frequent cause of death. Some female heterozygote carriers show CNS manifestations related to MLS as well as corresponding neuropathological changes. MLS may be part of a ''contiguous gene syndrome'' on the X chromosome including chronic granulomatous disease, Duchenne muscular dystrophy or X-linked retinitis pigmentosa (see these terms).
## Etiology
MLS is caused by mutations of the XK gene (Xp21.1) encoding the XK protein, which includes the Kx erythrocyte antigen. Most pathogenic mutations are nonsense mutations or deletions predicting an absent or shortened XK protein lacking the Kell protein binding site.
## Diagnostic methods
Diagnosis may be challenging. CK levels are almost always elevated. The procedure of choice is determination of absent Kx antigen and reduced Kell antigens on erythrocytes in males, and fluorescence absorbent cell sorting with Kell antigens in female heterozygotes. Analysis of the XK gene revealing a mutation confirms the diagnosis.
## Differential diagnosis
The differential diagnoses depend on the presenting symptoms and include chorea-acanthocytosis, Huntington disease, Huntington disease-like disorders, and Tourette's syndrome (see these terms).
## Antenatal diagnosis
Routine methods for prenatal testing can be applied.
## Genetic counseling
MLS is an X-linked disorder and genetic counseling is recommended. Affected males will pass on the mutant X chromosome to their daughters, whose sons will have a 1:2 risk of developing MLS and whose daughters will have a 1:2 risk of being carriers.
## Management and treatment
So far, no curative or disease-modifying treatments are available and management is symptomatic. MLS patients and asymptomatic carriers of the McLeod blood group phenotype should undergo cardiologic evaluation due to serious cardiac complications.
## Prognosis
MLS is relentlessly progressive and the prognosis is poor. Sudden death may be due to seizures, possibly autonomic dysfunction, and sudden cardiac death. There may be gradual generalized weakness with fatal aspiration pneumonia or systemic infections.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| McLeod neuroacanthocytosis syndrome | c0398568 | 4,006 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=59306 | 2021-01-23T17:56:58 | {"gard": ["10731"], "mesh": ["C564038"], "omim": ["300842"], "umls": ["C0398568"], "icd-10": ["G10"], "synonyms": ["MLS", "X-linked McLeod syndrome"]} |
Mosaic trisomy 15 is a rare chromosomal anomaly syndrome principally characterized by intrauterine growth restriction, congenital cardiac anomalies (incl. ventricular and atrial septal defects, patent ductus arteriosus) and craniofacial dysmorphism (incl. hypertelorism, downslanting palpebral fissures, wide nasal bridge). Patients also present brain (e.g. hypoplastic cerebellum, ventricular asymmetry), renal (e.g. small dysplastic kidneys), and/or genital (undescended testis, small penis, hypoplastic labia majora) anomalies. Digital and skin pigmentation abnormalities have also been reported.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Mosaic trisomy 15 | c2931707 | 4,007 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1706 | 2021-01-23T17:19:40 | {"gard": ["5313"], "mesh": ["C538037"], "umls": ["C2931707"], "icd-10": ["Q92.1"], "synonyms": ["Mosaic trisomy chromosome 15", "Trisomy 15 mosaicism"]} |
A rare, genetic neurological disorder characterized by early-onset progressive ataxia associated with myoclonic seizures, generalized tonic-clonic seizures (which are often sleep-related), and normal to mild intellectual disability. Dysarthria, upward gaze palsy, sensory neuropathy, developmental delay and autistic disorder have also been associated.
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Progressive myoclonic epilepsy type 5 | c1843852 | 4,008 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=402082 | 2021-01-23T18:40:57 | {"mesh": ["C564395"], "omim": ["607459"], "icd-10": ["G40.3"], "synonyms": ["EPM5", "PME type 5", "Progressive myoclonus epilepsy type 5"]} |
Ocular pemphigoid is a rare inflammatory eye disease characterized by sub-epithelial blistering manifesting with bilateral, asymmetrical, chronic or recurrent conjunctivitis and aberrant tissue regeneration leading to progressive conjunctival fibrosis, secondary corneal vascularization and, in some cases, blindness. Patients typically present with conjunctival redness, increased lacrimation, burning and/or foreign body sensation, edema, limbitis and/or varying degrees of ocular pain. Ankyloblepharon may be observed in end stages of the disease.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Ocular cicatricial pemphigoid | c0157721 | 4,009 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99922 | 2021-01-23T18:27:41 | {"umls": ["C0157721"], "icd-10": ["H13.3*", "L12+"]} |
For other uses, see Junctional epidermolysis bullosa.
The Belgian Draft Horse is one breed in which JEB occurs
Junctional epidermolysis bullosa (JEB) is an inherited disorder that is also known as red foot disease or hairless foal syndrome.[1] JEB is the result of a genetic mutation that inhibits protein production that is essential for skin adhesion.[2] Therefore, tissues, such as skin and mouth epithelia, are affected.[3] Blisters form over the entire body causing pain and discomfort,[1]and open sores leave newborn foals highly susceptible to secondary infection.[2] The condition can be categorized into two types of mutations: JEB1 and JEB2. JEB1 is found in Belgian Draft horses, as well as other related Draft breeds. In contrast, JEB2 is found in American Saddlebred horses.[1]
## Contents
* 1 Breeds affected
* 2 Humans
* 3 Genetics
* 4 Symptoms
* 5 Diagnosis and testing
* 6 Prognosis
* 7 Treatment and prevention
* 8 References
## Breeds affected[edit]
JEB has documented in Belgian drafts, American Cream Draft, Breton drafts, Comtois, and American Saddlebreds. Of these horses, 12% of Belgians and 4% of Saddlebreds are thought to carry the disorder.[4]
## Humans[edit]
Main article: Junctional epidermolysis bullosa (medicine)
JEB also affects the human population. Symptoms are closely related to those that are seen in horses. Blisters occur over a large portion of the body and are very susceptible to agitation. There are other symptoms associated, such as alopecia (hair loss), abnormalities of fingernails and toenails, and joint deformities.[5] Children born with JEB may not live past the first year of age if the condition is severe enough. Other children that have a less severe case of JEB may live a normal lifespan.[5]
## Genetics[edit]
JEB is an autosomal recessive trait; both parents must carry the recessive gene in order to have an affected offspring. If N represents a normal individual and J represents an affected individual, the following crosses indicate the rate of occurrence among related horses.[6]
(N/J) x (N/J) = 50% N/J, 25% N/N, and 25% J/J
(N/N) x (N/J) = 50% N/N and 50% N/J
Foals which are homozygous recessive (J/J) do not make it to reproductive age, so cannot be a parent. Carriers (N/J) do not display symptoms and have normal skin.[6]
Mutations in the genes LAMB3, LAMC2, and COL17A1, are the cause of JEB. These genes are associated with the protein responsible for skin attachment to the underlying layers, laminin 332.[7] When the genes undergo mutations, the protein is altered, making it dysfunctional. As a result, the skin is very fragile and may be damaged by even minor trauma.[5]
Another protein, called type XVII collagen, is affected by a mutation in COL17A1. Due to this mutation, the defective protein is not able to produce collagen, which provides strength and structure for the skin. For this reason, the skins resistance to trauma is weakened.[5]
## Symptoms[edit]
Foals appear normal immediately after birth. JEB affects tissues including mucous membranes, so one of the first signs is blistering of the gingiva and tongue after the first attempt at nursing. Within the next few days, the foal develops lesions all over the body, especially over pressure points.[2] The proteins affected by the gene mutations are also present in the hooves, causing hooves to slough.[8]
Other symptoms that occur in JEB:
* Corneal lesions
* Dental dysplasia
* Depression
* Oral ulcers
* Suppressed appetite
* Incisors present at birth
## Diagnosis and testing[edit]
Biopsies of the skin may be performed to identify the cleavage that takes place at the dermal-epidermal junction.[9] Another test that can aid in a diagnosis of JEB is the positive Nikolsky’s sign.[10] By applying pressure to the skin, transverse movements can indicate slipping between the dermal and epidermal layers. An easier and more definitive test is through polymerase chain reaction (PCR).[9] This method allows mane and tail samples to be genetically tested for the mutated genes that cause the condition. Hair samples must be pulled, not cut, with roots attached. The test can detect both JEB1 and JEB2. Testing costs around $35.00 US per sample.[1]
## Prognosis[edit]
One of the biggest risks factors faced by the affected foals is susceptibility to secondary infection. Within three to eight days after birth, the foal may die from infection or is euthanized for welfare reasons.[1]
## Treatment and prevention[edit]
Currently, there are no treatments available for JEB. However, the disorder can be prevented through good breeding management. Horses that are carriers of JEB should not be incorporated into breeding programs.[3] Although, if breeders are insistent on breeding a carrier, precautions need to be taken to ensure that the other mate is not a carrier as well. Genetic testing for the disorder is highly recommended among breeding programs for the Draft horse and Saddlebred breeds to determine their carrier status.[8]
## References[edit]
1. ^ a b c d e "Junctional Epidermolysis Bullosa (JEB)". Animal Genetics.
2. ^ a b c Abuterbush, Sameeh M. (2009). Illustrated Guide to Equine Disease. Ames: Blackwell Science.[page needed]
3. ^ a b Robinson, N. Edward (2003). Current Therapy in Equine Medicine. St. Louis: Elsevier Science.[page needed]
4. ^ "Testing for Genetic Diseases." Equus 353. pp 42–43.[verification needed]
5. ^ a b c d Berman, Kevin (November 20, 2012). "Junctional Epidermolysis Bullosa". U.S. National Library of Medicine.
6. ^ a b "Junctional Epidermolysis Bullosa (JEB) Test". UC Davis. 2012.
7. ^ Floyd, Andrea E.; Mansmann, Richard A. (2007). Equine Podiatry. St. Louis: Elsevier Science.[page needed]
8. ^ a b Higgins, Andrew J.; Snyder, Jack R. (2006). The Equine Manual. St. Louis: Elsevier.[page needed]
9. ^ a b McAuliffe, Siobhan B.; Slovis, Nathan M. (2008). Color Atlas of Diseases and Disorders of the Foal. St. Louis: Elseiver.[page needed]
10. ^ Lloyd, D.H.; Littlewood, J.D.; Craig, J.M.; Thomsett, L.R. (2003). Practical Equine Dermatology. Ames: Blackwell Science.[page needed]
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Junctional epidermolysis bullosa (veterinary medicine) | None | 4,010 | wikipedia | https://en.wikipedia.org/wiki/Junctional_epidermolysis_bullosa_(veterinary_medicine) | 2021-01-18T19:09:30 | {"wikidata": ["Q6311810"]} |
A number sign (#) is used with this entry because of evidence that poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP) is caused by heterozygous mutation in the FAM111B gene (615584) on chromosome 11q12.
Description
Poikiloderma, characterized by mottled pigmentation, telangiectasia, and epidermal atrophy, can be accompanied by tendon contractures, myopathy, and progressive pulmonary fibrosis. Clinical manifestations include poikiloderma from early childhood with telangiectasia and pigmentary anomalies on sun-exposed areas, tendon contractures that tend to involve the ankles and feet with gait disturbances, and development of pulmonary fibrosis during the second decade of life resulting in progressive dyspnea and restrictive impairment of lung function. Additional features include heat intolerance, reduced sweating, and thin hair (summary by Mercier et al., 2013).
Clinical Features
Khumalo et al. (2006) described a 2-generation South African family of European descent in which the proband was a 26-year-old woman with a history of heat intolerance and facial skin lesions from early childhood. At 9 years of age she developed Achilles tendon contractures, requiring surgery at 14 years of age. Examination showed telangiectasia, mottled hyper- and hypopigmentation, papules, and epidermal atrophy of the cheeks and face. She had fine scalp hair, thin eyebrows, and virtually no hair on her arms or legs, which also showed variable pigmentation. There was bilateral atrophy of thenar and hypothenar eminences, and limited extension of fingers due to sclerosis, but no Raynaud phenomenon. She exhibited hypohidrosis, but teeth and nails were normal. Pulmonary evaluation showed restrictive impairment of lung function but normal chest x-ray. Her father and older brother had similar skin and tendon abnormalities and had died of diffuse interstitial pulmonary fibrosis at the age of 56 and 30 years, respectively. At autopsy, the brother was found to have tendon contractures, thin tapered limbs with clubbing, truncal obesity and encasement of mediastinal and abdominal organs by excess fat, and scleroderma-like changes of the skin with replacement of adnexal structures by fibrosis. Microscopy of the skin revealed elastic tissue degeneration with formation of elastic globes in the papillary dermis. There was diffuse interstitial fibrosis of the lungs with abnormal airspace formation consistent with usual interstitial pneumonia (178500). Fibrosis of the esophagus and mediastinal lymph nodes was also present, as well as medial mucinous degeneration of the arteries with associated elastic degeneration and medial calcification of the splenic and anterior descending coronary artery, and extensive fatty infiltration of the pancreas and peripheral skeletal muscle. At 31 years of age, another brother had similar skin and limb changes and heat intolerance, but normal lung evaluation. A half sister from their father's previous marriage was also reported to have similar skin changes. Khumalo et al. (2006) proposed the term 'hereditary sclerosing poikiloderma with tendon and pulmonary involvement' for this disorder, and suggested that Weary syndrome (173700) be designated 'hereditary sclerosing poikiloderma with cardiac involvement.'
Mercier et al. (2013) studied 5 families with fibrosing poikiloderma, including the South African family originally reported by Khumalo et al. (2006). The 4 new probands were of French, Italian, Algerian, and French/Moroccan ancestry, and all presented in childhood with poikiloderma, alopecia involving the scalp, eyebrows, and eyelashes, and muscle weakness with fibrosis and adiposis on biopsy. All had tendinous contractures of the distal lower extremities requiring lengthening, and 3 of the 4 also had contractures of the upper limbs. In addition, 3 probands exhibited hypohidrosis and/or heat intolerance, and 2 had documented restrictive disease of the lungs.
Molecular Genetics
Mercier et al. (2013) performed whole-exome sequencing in 3 South African sibs with fibrosing poikiloderma and their unaffected mother, originally reported by Khumalo et al. (2006), and a French boy and his unaffected parents, and identified 2 different heterozygous missense mutations in the FAM111B gene (Y621D, 615584.0001; R627G, 615584.0002) in affected individuals from each family. Sanger sequencing of the FAM111B gene in 3 more families with fibrosing poikiloderma revealed that an Algerian man and an Italian girl also carried the R627G mutation, whereas a girl of French and Moroccan ancestry was heterozygous for an S628N mutation (615584.0003). The patients were known to be negative for mutation in the RECQL4 gene (603780), and the FAM111B mutations were not found in unaffected parents available for testing or in 388 controls, including 96 Algerian, 127 Moroccan, and 165 South African individuals.
INHERITANCE \- Autosomal dominant GROWTH Height \- Growth retardation (in some patients) HEAD & NECK Head \- Scalp hair sparse or absent Face \- Poikiloderma, congenital Eyes \- Eyebrows sparse or absent \- Eyelashes sparse or absent \- Cataract (rare) RESPIRATORY Lung \- Interstitial pulmonary fibrosis \- Restrictive syndrome ABDOMEN Liver \- Hepatomegaly (rare) Pancreas \- Fatty infiltration of pancreas (rare) SKELETAL Spine \- Scoliosis (in some patients) SKIN, NAILS, & HAIR Skin \- Congenital poikiloderma on face and exposed skin \- Telangiectatic lesions \- Hypohidrosis and/or heat intolerance \- Eczema-like lesions (in some patients) \- Erysipelas (in some patients) \- Sclerosis of digits (in some patients) \- Psoriasiform lesions (rare) Skin Histology \- Atrophy of epidermis \- Enlarged and fragmented elastic fibers \- Elastic globules in papillary dermis \- Diffuse collagen sclerosis Nails \- Nail dysplasia (rare) Hair \- Hypotrichosis and/or alopecia, primarily involving scalp hair, eyebrows, and eyelashes MUSCLE, SOFT TISSUES \- Contractures of distal lower limbs \- Contractures of upper limbs (in some patients) \- Muscle weakness of proximal and distal upper and lower limbs \- Muscle wasting \- Myogenic profile on electromyography \- Adiposis on MRI \- Extensive fatty infiltration on biopsy \- Focal lymphocytic and macrophage infiltrates on biopsy \- Loss of lower-limb tendon reflexes \- Lymphedema of upper and/or lower limbs (in some patients) \- Weakness of neck extensors (rare) ENDOCRINE FEATURES \- Delayed puberty (in some patients) LABORATORY ABNORMALITIES \- Elevated serum creatine kinase MISCELLANEOUS \- Patients require Achilles tendon lengthening in first or second decade of life MOLECULAR BASIS \- Caused by mutation in the family with sequence similarity 111, member B gene (FAM111B, 615584.0001 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| POIKILODERMA, HEREDITARY FIBROSING, WITH TENDON CONTRACTURES, MYOPATHY, AND PULMONARY FIBROSIS | c3810325 | 4,011 | omim | https://www.omim.org/entry/615704 | 2019-09-22T15:51:14 | {"omim": ["615704"], "orphanet": ["221043"], "synonyms": ["Alternative titles", "POIKILODERMA, HEREDITARY SCLEROSING, WITH TENDON AND PULMONARY INVOLVEMENT", "POIKTMP syndrome"], "genereviews": ["NBK390610"]} |
A number sign (#) is used with this entry because of evidence that distal hereditary motor neuronopathy type VB (HMN5B) is caused by heterozygous mutation in the REEP1 gene (609139) on chromosome 2p11. One such family has been reported.
Mutation in the REEP1 gene can also cause spastic paraplegia-31 (SPG31; 610250). Some patients with REEP1 mutations can show overlapping signs of HMN5B and SPG31, indicating that there is a phenotypic spectrum of manifestations associated with REEP1 mutations.
Description
Distal hereditary motor neuronopathy type VB is an autosomal dominant neurologic disorder characterized by onset in the first or second decade of distal muscle weakness and atrophy, primarily affecting the intrinsic hand muscles, but also affecting the lower legs, resulting in abnormal gait and pes cavus (summary by Beetz et al., 2012).
For a general phenotypic description and a discussion of genetic heterogeneity of distal HMN (dHMN), see HMN type I (HMN1; 182960).
Clinical Features
Beetz et al. (2012) reported an Austrian family in which 4 adult individuals spanning 3 generations developed a predominant peripheral motor neuronopathy in the first or second decades of life. Three presented with hand muscle weakness and atrophy confined to the thenar and dorsalis interosseus I muscles, and the fourth patient presented with an unstable gait, but also had hand involvement. Three had mild or moderate peroneal atrophy and weakness. All had pes cavus, which ranged from mild to severe. Patellar tendon reflexes were decreased and Achilles tendon reflexes were absent in all patients. None had increased muscle tone or spasticity. Electrophysiologic studies were performed in 3 patients and showed variable results, but mostly decreased amplitude and conduction velocities in the hand and lower legs. Three of the patients were diagnosed with dHMN type V, and 1 with dHMN.
Inheritance
The transmission pattern of dHMN type VB in the family reported by Beetz et al. (2012) was consistent with autosomal dominant inheritance.
Molecular Genetics
By genomewide linkage analysis followed by exome sequencing of a family with dHMN type V, Beetz et al. (2012) identified a heterozygous splice site mutation in the REEP1 gene (609139.0006), resulting in skipping of exon 5 and a mutant protein lacking residues 102-139. The mutant REEP1 protein showed some localization similar to wildtype, but also accumulated in cytoplasmic compact structures of varying sizes, with the largest structures in the perinuclear regions. REEP1 lacking exon 5 showed colocalization with atlastin-1 (ATL1; 606439), including in the abnormal cytoplasmic structures. In contrast, the A20E mutant protein (609139.0004) associated with SPG31 showed severely altered localization to numerous punctate small structures throughout the cytoplasm and no localization to the endoplasmic reticulum. Moreover, A20E did not colocalize with atlastin. These findings suggested a different pathomechanism of these 2 mutations, which may explain the different associated phenotypes. Beetz et al. (2012) postulated that loss-of-function REEP1 mutations (i.e., A20E) may cause upper motor neuron disease, whereas possible gain-of-function mutations (102_139del) may cause lower motor neuron disease. The findings expanded the phenotypic spectrum associated with REEP1 mutations, similar to that observed with BSCL2 (606158).
INHERITANCE \- Autosomal dominant SKELETAL Hands \- Amyotrophy of the intrinsic hand muscles Feet \- Pes cavus MUSCLE, SOFT TISSUES \- Muscle weakness, distal \- Muscle atrophy, distal NEUROLOGIC Central Nervous System \- Unstable gait Peripheral Nervous System \- Decreased motor nerve conduction velocities \- Areflexia \- Hyporeflexia MISCELLANEOUS \- Onset in first or second decade \- One family (4 affected members) has been reported (last curated July 2012) MOLECULAR BASIS \- Caused by mutation in the receptor expression-enhancing protein 1 gene (REEP1, 609139.0006 ) ▲ Close
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| NEURONOPATHY, DISTAL HEREDITARY MOTOR, TYPE VB | c1833308 | 4,012 | omim | https://www.omim.org/entry/614751 | 2019-09-22T15:54:18 | {"doid": ["0111205"], "mesh": ["C563443"], "omim": ["614751"], "orphanet": ["139536"], "synonyms": ["Alternative titles", "HMN VB", "NEUROPATHY, DISTAL HEREDITARY MOTOR, TYPE VB", "DHMN VB", "SPINAL MUSCULAR ATROPHY, DISTAL, TYPE VB"]} |
A rare renal disease characterized by glomerular nephropathy with hematuria progressing to end-stage renal disease (ESRD), frequently associated with sensorineural deafness, and occasionally with ocular anomalies.
## Epidemiology
The global prevalence of Alport syndrome (AS) is unknown. The prevalence at birth in Finland is estimated at 1/53,000. In the USA, Alport syndrome reportedly accounts for up to 2% of new cases of pediatric ESRD.
## Clinical description
The clinical subtypes of AS include X-linked (XL), autosomal recessive (AR) and autosomal dominant (AD) AS and count for about 80%, 15% and 5% of all AS cases, respectively. AS can present anywhere from childhood to elderly age, although it generally manifests earlier (during childhood or adolescence) in XL and AR forms. Males are severely affected in XLAS and present with microhematuria very early in life, followed by micro-albuminuria, macroproteinuria and progression to ESRD before the age of 40 years old. XLAS is highly variable in females, ranging from an asymptomatic disease to lifelong microscopic hematuria (with preserved renal function), or renal failure at a young age. Sensorineural hearing loss is common. Occasional ocular anomalies (e.g. anterior lenticonus, retinal flecks, corneal lesions) may develop in late childhood or early adulthood, males being more commonly affected than females. Rarely, leiomyomatosis (esophagus, tracheobronchial tree or female genitalia) can be associated, forming the X-linked diffuse leiomyomatosis-AS (XL-DLAS). ARAS is similar to XLAS in males, but presents without any gender differentiation in the disease course and the family history. ADAS varies from an asymptomatic disease (mostly presenting as a familial benign hematuria) to AD forms of proteinuria and focal segmental glomerulosclerosis (in cases without hematuria or not as a first line presentation). The progression to ESRD is usually slower than in XLAS, and extra-renal manifestations are less common.
## Etiology
AS involves a structural defect of type IV collagen, an essential component of the glomerular basal membrane. XLAS is due to mutations in COL4A5 (Xq22.3) gene coding for the alpha 5 chain of type IV collagen. ARAS and ADAS are due to mutations in both COL4A3 (2q36.3) and COL4A4 (2q36.3) genes coding for the alpha 3 and 4 chains of type IV collagen, respectively. XL-DLAS is due to COL4A5 (Xq22.3) and COL4A6 (Xq22.3).
## Diagnostic methods
The diagnosis is based on familial history, clinical signs, electron microscopy examination of renal biopsy (showing abnormalities of the glomerular basal membrane), and immunohistochemical findings on renal and cutaneous biopsy (even if it cannot establish the diagnosis in all the patients). Molecular genetic testing can confirm the diagnosis.
## Differential diagnosis
The differential diagnoses include hematuria related to urologic diseases and cancer, IgA nephropathy, nephropathy related to MYH9 mutation, and familial benign hematuria.
## Antenatal diagnosis
A prenatal and pre-implantation diagnosis is possible for at-risk pregnancies, if a causative mutation has been found in a member of the affected family.
## Genetic counseling
Most AS cases follow an X-linked dominant mode of inheritance, but AR and AD cases have also been reported. A genetic counseling should be proposed to affected families.
## Management and treatment
The management of AS is only symptomatic, mainly aiming at slowing the progression to ESRD. It includes angiotensin blockade (e.g. angiotensin converting enzyme inhibitors, angiotensin receptor blockers), diuretics, and a salt-restricted diet. The most severe cases require dialysis and renal replacement therapy. Regular hearing and ocular follow-up are recommended. Hearing aids should be prescribed when needed, and surgical intervention for ocular anomalies can be considered.
## Prognosis
The prognosis of AS is poor due to the progression to ESRD (often affecting young adults). However, renal transplantation is usually successful, since the development of anti-type IV collagen antibodies is a rare event. The extra-renal features can affect the quality of life.
* European Reference Network
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Alport syndrome | c1567741 | 4,013 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=63 | 2021-01-23T17:47:37 | {"gard": ["5785"], "mesh": ["D009394"], "omim": ["104200", "203780", "301050"], "umls": ["C1567741"], "icd-10": ["Q87.8"], "synonyms": ["Alport deafness-nephropathy", "Alport hearing loss-nephropathy"]} |
Substance-induced psychosis
Other namesSubstance-induced psychotic disorder, drug-induced psychosis, substance/medication-induced psychotic disorder, toxic psychosis
SpecialtyPsychiatry, addiction psychiatry
Substance-induced psychosis (commonly known as toxic psychosis or drug-induced psychosis) is a form of psychosis that is attributed to substance use. It is a psychosis that results from the effects of chemicals or drugs, including those produced by the body itself.[citation needed] Various psychoactive substances have been implicated in causing or worsening psychosis in users.
## Contents
* 1 Signs and symptoms
* 2 Transition to schizophrenia
* 3 Substances
* 3.1 International Classification of Diseases
* 3.2 Medication
* 3.3 Other drugs illicit in America
* 3.4 Plants
* 3.5 Nonmedicinal substances
* 4 References
* 5 External links
## Signs and symptoms[edit]
Main article: Psychosis
Psychosis manifests as disorientation, visual hallucinations and/or haptic hallucinations.[1] It is a state in which a person's mental capacity to recognize reality, communicate, and relate to others is impaired, thus interfering with the capacity to deal with life demands.[2] While there are many types of psychosis, substance-induced psychosis can be pinpointed to specific chemicals.
## Transition to schizophrenia[edit]
A 2019 systematic review and meta-analysis by Murrie et al found that the pooled proportion of transition from substance-induced psychosis to schizophrenia was 25% (95% CI 18%–35%), compared with 36% (95% CI 30%–43%) for brief, atypical and not otherwise specified psychoses.[3] Type of substance was the primary predictor of transition from drug-induced psychosis to schizophrenia, with highest rates associated with cannabis (6 studies, 34%, CI 25%–46%), hallucinogens (3 studies, 26%, CI 14%–43%) and amphetamines (5 studies, 22%, CI 14%–34%). Lower rates were reported for opioid (12%), alcohol (10%) and sedative (9%) induced psychoses. Transition rates were slightly lower in older cohorts but were not affected by sex, country of the study, hospital or community location, urban or rural setting, diagnostic methods, or duration of follow-up.[3]
## Substances[edit]
Psychotic states may occur after using a variety of legal and illegal substances. Usually such states are temporary and reversible, with fluoroquinolone-induced psychosis being a notable exception. Drugs whose use, abuse, or withdrawal are implicated in psychosis include the following:
### International Classification of Diseases[edit]
Psychoactive substance-induced psychotic disorders outlined within the ICD-10 codes F10.5—F19.5:
* F10.5 alcohol:[4][5][6] Alcohol is a common cause of psychotic disorders or episodes, which may occur through acute intoxication, chronic alcoholism, withdrawal, exacerbation of existing disorders, or acute idiosyncratic reactions.[4] Research has shown that alcohol abuse causes an 8-fold increased risk of psychotic disorders in men and a 3 fold increased risk of psychotic disorders in women.[7][8] While the vast majority of cases are acute and resolve fairly quickly upon treatment and/or abstinence, they can occasionally become chronic and persistent.[4] Alcoholic psychosis is sometimes misdiagnosed as another mental illness such as schizophrenia.[9]
* F11.5 opioid: Studies show stronger opioids such as Fentanyl are more likely to cause psychosis and hallucinations[10]
* F12.5 cannabinoid: Some studies indicate that cannabis may trigger full-blown psychosis.[11] Recent studies have found an increase in risk for psychosis in cannabis users.[12]
* F13.5 sedatives/hypnotics (barbiturates;[13][14] benzodiazepines[15][16][17]): It is also important to this topic to understand the paradoxical effects of some sedative drugs.[18] Serious complications can occur in conjunction with the use of sedatives creating the opposite effect as to that intended. Malcolm Lader at the Institute of Psychiatry in London estimates the incidence of these adverse reactions at about 5%, even in short-term use of the drugs.[19] The paradoxical reactions may consist of depression, with or without suicidal tendencies, phobias, aggressiveness, violent behavior and symptoms sometimes misdiagnosed as psychosis.[20][21] However, psychosis is more commonly related to the benzodiazepine withdrawal syndrome.[22]
* F14.5 cocaine[23]
* F15.5 other stimulants: amphetamines;[24][pages needed] methamphetamine;[24] methylphenidate.[24] See also stimulant psychosis.
* F16.5 hallucinogens (LSD and others)[citation needed]
* F18.5 volatile solvents (volatile inhalants);[25]
* Toluene,[26][27] found in glue, paint, thinner, etc. See also toluene toxicity.
* Butane[28]
* Gasoline (petrol)[29]
F17.5 is reserved for tobacco-induced psychosis, but is traditionally not associated with the induction of psychosis.
The code F15.5 also includes caffeine-induced psychosis, despite not being specifically listed in the DSM-IV. However, there is evidence that caffeine, in extreme acute doses or when severely abused for long periods of time, may induce psychosis.[30][31]
### Medication[edit]
* Fluoroquinolone drugs, fluoroquinolone use has been linked to serious cases of toxic psychosis that have been reported to be irreversible and permanent, see adverse effects of fluoroquinolones[32][33][34][35][36][37][38][39] The related quinoline derivative mefloquine (Lariam) has also been associated with psychosis.[40][41]
* some over-the-counter drugs, including:
* Dextromethorphan (DXM) at high doses.[42][43]
* Certain antihistamines at high doses.[44][45][46][47]
* Cold Medications[48] (i.e. containing Phenylpropanolamine, or PPA)
* prescription drugs:
* Prednisone and other corticosteroids[49]
* Isotretinoin[50]
* Anticholinergic drugs
* atropine[51][52]
* scopolamine[53]
* antidepressants[54]
* L-dopa[55]
* antiepileptics[56]
* antipsychotics, in an idiosyncratic reaction
* antimalarials
* mepacrine[57]
### Other drugs illicit in America[edit]
Other drugs illegal in America (not listed above), including:
* MDMA (ecstasy)[58]
* Phencyclidine (PCP)[59]
* Ketamine
* Synthetic research chemicals used recreationally, including:
* JWH-018 and some other synthetic cannabinoids, or mixtures containing them (e.g. "Spice", "Kronic", "MNG" or "Mr. Nice Guy", "Relaxinol", etc.).[60][permanent dead link] Various "JWH-XXX" compounds in "Spice" or "Incense" have also been found and have been found to cause psychosis in some people.[61][62][63]
* Mephedrone and related amphetamine-like drugs sold as "bath salts" or "plant food".[64]
### Plants[edit]
Plants:
* Hawaiian baby woodrose (contains ergine)
* Morning glory seeds (contains ergine)
* Jimson weed[65] (Datura, angel's trumpet, thorn apple)
* Belladonna (deadly nightshade)
* Salvia divinorum[66]
### Nonmedicinal substances[edit]
Substances chiefly nonmedicinal as to source:
* Carbon monoxide (T58†[clarification needed]),[67] carbon dioxide (T59.7†),[67] carbon disulfide (T65.4†);
* heavy metals;
* organophosphate insecticides (T60.0†);[67]
* sarin and other nerve gases;[67]
* tetraethyllead (T56.0†);
* aniline (T65.3†);
* acetone and other ketones (T52.4†);
* antifreeze – a mixture of ethylene glycol and other glycols (T51.8†);
* arsenic and its compounds (T57.0†).
## References[edit]
1. ^ Pitts, Ferris N; Allen, Robert E; Aniline, Orm; Burgoyne, Rodney W (August 1982). "The Dilemma of the Toxic Psychosis: Differential Diagnosis and the PCP Psychosis". Psychiatric Annals. 12 (8): 762–8. doi:10.3928/0048-5713-19820801-07. OCLC 5584879101.
2. ^ "toxic psychosis". TheFreeDictionary.com. Archived from the original on 2019-04-25. Retrieved 2020-01-21.
3. ^ a b Murrie, Benjamin; Lappin, Julia; Large, Matthew; Sara, Grant (16 October 2019). "Transition of Substance-Induced, Brief, and Atypical Psychoses to Schizophrenia: A Systematic Review and Meta-analysis". Schizophrenia Bulletin. 46 (3): 505–516. doi:10.1093/schbul/sbz102. PMC 7147575. PMID 31618428.
4. ^ a b c Alcohol-Related Psychosis at eMedicine
5. ^ Soyka, Michael (March 1990). "Psychopathological characteristics in alcohol hallucinosis and paranoid schizophrenia". Acta Psychiatrica Scandinavica. 81 (3): 255–9. doi:10.1111/j.1600-0447.1990.tb06491.x. PMID 2343749.
6. ^ Delirium Tremens (DTs) at eMedicine
7. ^ Tien, Allen Y.; Anthony, James C. (August 1990). "Epidemiological Analysis of Alcohol and Drug Use as Risk Factors for Psychotic Experiences". The Journal of Nervous and Mental Disease. 178 (8): 473–480. doi:10.1097/00005053-199017880-00001. PMID 2380692.
8. ^ Cargiulo, Thomas (1 March 2007). "Understanding the health impact of alcohol dependence". American Journal of Health-System Pharmacy. 64 (5 Supplement 3): S5–S11. doi:10.2146/ajhp060647. PMID 17322182.
9. ^ Schuckit, Marc A. (November 1983). "Alcoholism and Other Psychiatric Disorders". Psychiatric Services. 34 (11): 1022–1027. doi:10.1176/ps.34.11.1022. PMID 6642446.
10. ^ Sivanesan, Eellan; Gitlin, Melvin C.; Candiotti, Keith A. (October 2016). "Opioid-induced Hallucinations". Anesthesia & Analgesia. 123 (4): 836–843. doi:10.1213/ANE.0000000000001417. PMC 6482381. PMID 27258073.
11. ^ Degenhardt L (January 2003). "The link between cannabis use and psychosis: furthering the debate". Psychological Medicine. 33 (1): 3–6. doi:10.1017/S0033291702007080. PMID 12537030.
12. ^ Moore TH, Zammit S, Lingford-Hughes A, et al. (July 2007). "Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review" (PDF). Lancet. 370 (9584): 319–28. doi:10.1016/S0140-6736(07)61162-3. PMID 17662880. S2CID 41595474.
13. ^ de Paola L, Mäder MJ, Germiniani FM, et al. (June 2004). "Bizarre behavior during intracarotid sodium amytal testing (Wada test): are they predictable?". Arquivos de Neuro-Psiquiatria. 62 (2B): 444–8. doi:10.1590/S0004-282X2004000300012. PMID 15273841.
14. ^ Sarrecchia C, Sordillo P, Conte G, Rocchi G (1998). "[Barbiturate withdrawal syndrome: a case associated with the abuse of a headache medication]". Annali Italiani di Medicina Interna (in Italian). 13 (4): 237–9. PMID 10349206.
15. ^ White MC, Silverman JJ, Harbison JW (February 1982). "Psychosis associated with clonazepam therapy for blepharospasm". The Journal of Nervous and Mental Disease. 170 (2): 117–9. doi:10.1097/00005053-198202000-00010. PMID 7057171.
16. ^ Jaffe R, Gibson E (June 1986). "Clonazepam withdrawal psychosis". Journal of Clinical Psychopharmacology. 6 (3): 193. doi:10.1097/00004714-198606000-00021. PMID 3711371.
17. ^ Hallberg RJ, Lessler K, Kane FJ (August 1964). "Korsakoff-Like Psychosis Associated With Benzodiazepine Overdosage". The American Journal of Psychiatry. 121 (2): 188–9. doi:10.1176/ajp.121.2.188. PMID 14194223.
18. ^ Hall RC, Zisook S (1981). "Paradoxical reactions to benzodiazepines". British Journal of Clinical Pharmacology. 11 (Suppl 1): 99S–104S. doi:10.1111/j.1365-2125.1981.tb01844.x. PMC 1401636. PMID 6133541.
19. ^ Lader M, Morton S (1991). "Benzodiazepine Problems". British Journal of Addiction. 86 (7): 823–828. doi:10.1111/j.1360-0443.1991.tb01831.x. PMID 1680514.
20. ^ Benzodiazepines: Paradoxical Reactions & Long-Term Side-Effects
21. ^ Hansson O, Tonnby B (1976). "Serious Psychological Symptoms Caused by Clonazepam". Läkartidningen. 73 (13): 1210–1211. PMID 1263638.
22. ^ Pétursson H (November 1994). "The benzodiazepine withdrawal syndrome". Addiction. 89 (11): 1455–9. doi:10.1111/j.1360-0443.1994.tb03743.x. PMID 7841856.
23. ^ Brady, K. T.; R. B. Lydiard; R. Malcolm; J. C. Ballenger (December 1991). "Cocaine-induced psychosis". Journal of Clinical Psychiatry. 52 (12): 509–512. PMID 1752853.
24. ^ a b c Diaz, Jaime. How Drugs Influence Behavior. Englewood Cliffs: Prentice Hall, 1996.
25. ^ Wada K, Nakayama K, Koishikawa H, Katayama M, Hirai S, Yabana T, et al. (2005). "揮発性溶剤誘発性精神病の症候学的構造 「溶剤性精神病」は識別可能な症候群か?" [Symptomatological structure of volatile solvent-induced psychosis: is "solvent psychosis" a discernible syndrome?]. 日本アルコール・薬物医学会雑誌 = [Japanese Journal of Alcohol Studies & Drug Dependence] (in Japanese). 40 (5): 471–484. PMID 16316074.
26. ^ Tarsh, M.J. (1979). "Schizophreniform Psychosis caused by Sniffing Toluene". Occupational Medicine. 29 (4): 131–133. doi:10.1093/occmed/29.4.131. PMID 513663.
27. ^ Rao, Naren P.; Arun Gupta; K. Sreejayan; Prabhat K. Chand; Vivek Benegal; Pratima Murthy (2009). "Toluene associated schizophrenia-like psychosis". Indian Journal of Psychiatry. 51 (4): 329–330. doi:10.4103/0019-5545.58307. PMC 2802388. PMID 20048466.
28. ^ Jung IK, Lee HJ, Cho BH (December 2004). "Persistent psychotic disorder in an adolescent with a past history of butane gas dependence". European Psychiatry. 19 (8): 519–20. doi:10.1016/j.eurpsy.2004.09.010. PMID 15589716.
29. ^ Hernandez-Avila, Carlos A.; Hector A. Ortega-Soto; Antonio Jasso; Cecilia A. Hasfura-Buenaga; Henry R. Kranzler (1998). "Treatment of Inhalant-Induced Psychotic Disorder With Carbamazepine Versus Haloperidol". Psychiatric Services. 49 (6): 812–815. doi:10.1176/ps.49.6.812. PMID 9634163.
30. ^ Hedges DW, Woon FL, Hoopes SP (March 2009). "Caffeine-induced psychosis". CNS Spectrums. 14 (3): 127–9. doi:10.1017/S1092852900020101. PMID 19407709.
31. ^ Cerimele JM, Stern AP, Jutras-Aswad D (March 2010). "Psychosis following excessive ingestion of energy drinks in a patient with schizophrenia". The American Journal of Psychiatry. 167 (3): 353. doi:10.1176/appi.ajp.2009.09101456. PMID 20194494.
32. ^ Cohen JS (December 2001). "Peripheral Neuropathy Associated with Fluoroquinolones" (PDF). Ann Pharmacother. 35 (12): 1540–7. doi:10.1345/aph.1Z429. PMID 11793615. S2CID 12589772.
33. ^ Adams M, Tavakoli H (2006). "Gatifloxacin-induced hallucinations in a 19-year-old man". Psychosomatics. 47 (4): 360. doi:10.1176/appi.psy.47.4.360. PMID 16844899.
34. ^ Mulhall JP, Bergmann LS (July 1995). "Ciprofloxacin-induced acute psychosis". Urology. 46 (1): 102–3. doi:10.1016/S0090-4295(99)80171-X. PMID 7604468.
35. ^ Reeves RR (1992). "Ciprofloxacin-induced psychosis". Ann Pharmacother. 26 (7–8): 930–1. doi:10.1177/106002809202600716. PMID 1504404. S2CID 29848723.
36. ^ Yasuda H, Yoshida A, Masuda Y, Fukayama M, Kita Y, Inamatsu T (March 1999). "Levofloxacin-Induced Neurological Adverse Effects such as Convulsion, Involuntary Movement (Tremor, Myoclonus and Chorea Like), Visual Hallucination in Two Elderly Patients" [Levofloxacin-induced neurological adverse effects such as convulsion, involuntary movement (tremor, myoclonus and chorea like), visual hallucination in two elderly patients]. Nippon Ronen Igakkai Zasshi (in Japanese). 36 (3): 213–7. doi:10.3143/geriatrics.36.213. PMID 10388331.
37. ^ Azar S, Ramjiani A, Van Gerpen JA (April 2005). "Ciprofloxacin-induced chorea". Mov. Disord. 20 (4): 513–4, author reply 514. doi:10.1002/mds.20425. PMID 15739219.
38. ^ Kukushkin ML, Igonkina SI, Guskova TA (April 2004). "Mechanisms of pefloxacin-induced pain". Bull. Exp. Biol. Med. 137 (4): 336–8. doi:10.1023/B:BEBM.0000035122.45148.93. PMID 15452594. S2CID 20357078.
39. ^ Christie MJ, Wong K, Ting RH, Tam PY, Sikaneta TG (May 2005). "Generalized seizure and toxic epidermal necrolysis following levofloxacin exposure". Ann Pharmacother. 39 (5): 953–5. doi:10.1345/aph.1E587. PMID 15827068. S2CID 8470095.
40. ^ Marsepoil T, Petithory J, Faucher JM, Ho P, Viriot E, Benaiche F (1993). "[Encephalopathy and memory disorders during treatments with mefloquine]". Rev Méd Interne (in French). 14 (8): 788–91. doi:10.1016/S0248-8663(05)81426-2. PMID 8191092.
41. ^ Phillips-Howard PA, ter Kuile FO (June 1995). "CNS adverse events associated with antimalarial agents. Fact or fiction?". Drug Saf. 12 (6): 370–83. doi:10.2165/00002018-199512060-00003. PMID 8527012. S2CID 23907268.
42. ^ Price, L. H.; Lebel, J (1 February 2000). "Dextromethorphan-Induced Psychosis". American Journal of Psychiatry. 157 (2): 304. doi:10.1176/appi.ajp.157.2.304. PMID 10671422.
43. ^ Lachover, L. (2007). "Deciphering a Psychosis: A Case of Dextromethorphan-Induced Symptoms". Primary Psychiatry. 14 (1): 70–72.
44. ^ Sexton, J. D.; Pronchik, D. J. (1997). "Diphenhydramine-induced psychosis with therapeutic doses". The American Journal of Emergency Medicine. 15 (5): 548–549. doi:10.1016/S0735-6757(97)90212-6. PMID 9270406.
45. ^ Lang, K.; Sigusch, H.; Müller, S. (1995). "Anticholinergisches Syndrom mit halluzinatorischer Psychose nach Diphenhydramin-Intoxikation" [An anticholinergic syndrome with hallucinatory psychosis after diphenhydramine poisoning]. Deutsche Medizinische Wochenschrift (in German). 120 (49): 1695–1698. doi:10.1055/s-2008-1055530. PMID 7497894.
46. ^ Schreiber, W.; Pauls, A. M.; Krieg, J. C. (1988). "Toxische Psychose als Akutmanifestation der Diphenhydraminvergiftung" [Toxic psychosis as an acute manifestation of diphenhydramine poisoning]. Deutsche Medizinische Wochenschrift (in German). 113 (5): 180–183. doi:10.1055/s-2008-1067616. PMID 3338401.
47. ^ Timnak, C.; Gleason, O. (2004). "Promethazine-Induced Psychosis in a 16-Year-Old Girl". Psychosomatics. 45 (1): 89–90. doi:10.1176/appi.psy.45.1.89. PMID 14709767.
48. ^ Gunn, V. L.; Taha, S. H.; Liebelt, E. L.; Serwint, J. R. (1 September 2001). "Toxicity of Over-the-Counter Cough and Cold Medications". Pediatrics. 108 (3): e52. CiteSeerX 10.1.1.536.6102. doi:10.1542/peds.108.3.e52. PMID 11533370.
49. ^ Hall, R. C.; Popkin, M. K.; Stickney, S. K.; Gardner, E. R. (1979). "Presentation of the steroid psychoses". The Journal of Nervous and Mental Disease. 167 (4): 229–236. doi:10.1097/00005053-197904000-00006. PMID 438794. S2CID 45515092.
50. ^ Hull P. R.; D'Arcy C. (2003). "Isotretinoin Use and Subsequent Depression and Suicide: Presenting the Evidence". American Journal of Clinical Dermatology. 4 (7): 493–505. doi:10.2165/00128071-200304070-00005. PMID 12814338. S2CID 36042481.
51. ^ Bergman, K. R.; Pearson, C.; Waltz, G. W.; Evans R. III (1980). "Atropine-induced psychosis. An unusual complication of therapy with inhaled atropine sulfate". Chest. 78 (6): 891–893. doi:10.1378/chest.78.6.891. PMID 7449475.
52. ^ Varghese, S.; Vettath, N.; Iyer, K.; Puliyel, J. M.; Puliyel, M. M. (1990). "Ocular atropine induced psychosis--is there a direct access route to the brain?". Journal of the Association of Physicians of India. 38 (6): 444–445. PMID 2384469.
53. ^ Barak, Segev; Weiner, I. (2006). "Scopolamine Induces Disruption of Latent Inhibition Which is Prevented by Antipsychotic Drugs and an Acetylcholinesterase Inhibitor". Neuropsychopharmacology. 32 (5): 989–999. doi:10.1038/sj.npp.1301208. PMID 16971898.
54. ^ Ellison Gaylord (1995). "The N-methyl-d-aspartate antagonists phencyclidine, ketamine and dizocilpine as both behavioral and anatomical models of the dementias". Brain Research Reviews. 20 (2): 250–267. doi:10.1016/0165-0173(94)00014-G. PMID 7795658. S2CID 24071513.
55. ^ Carey, R. J.; Pinheiro-Carrera, M.; Dai, H.; Tomaz, C.; Huston, J. P. (1995). "l-DOPA and psychosis: Evidence for l-DOPA-induced increases in prefrontal cortex dopamine and in serum corticosterone". Biological Psychiatry. 38 (10): 669–676. doi:10.1016/0006-3223(94)00378-5. PMID 8555378. S2CID 26029044.
56. ^ Ettinger, A. B. (2006). "Psychotropic effects of antiepileptic drugs". Neurology. 67 (11): 1916–1925. doi:10.1212/01.wnl.0000247045.85646.c0. PMID 17159095. S2CID 29007335.
57. ^ Perk, David (2018). "Mepacrine Psychosis". Journal of Mental Science. 93 (393): 756–771. doi:10.1192/bjp.93.393.756. ISSN 0368-315X. PMID 18916870.
58. ^ Creighton, FJ; Black, DL; Hyde, CE (November 1991). "'Ecstasy' psychosis and flashbacks". Br J Psychiatry. 159 (5): 713–5. doi:10.1192/bjp.159.5.713. PMID 1684523. Archived from the original on 2018-12-10.
59. ^ http://www.minddisorders.com/Py-Z/Substance-induced-psychotic-disorder.html Substance-induced psychotic disorder
60. ^ http://www.airforcetimes.com/news/2011/06/air-force-spice-users-risk-psychosis-says-doctor-061111w/ Spice users risk psychosis, doctor says By Gidget Fuentes - Staff writer Accessed 06-25-2011
61. ^ Shalit, Nadav; Barzilay, Ran; Shoval, Gal; Shlosberg, Dan; Mor, Nofar; Zweigenhaft, Nofar; Weizman, Abraham; Krivoy, Amir (24 August 2016). "Characteristics of Synthetic Cannabinoid and Cannabis Users Admitted to a Psychiatric Hospital". The Journal of Clinical Psychiatry. 77 (8): e989–e995. doi:10.4088/JCP.15m09938. PMID 27379411.
62. ^ Every-Palmer S (2010). "Warning: legal synthetic cannabinoid-receptor agonists such as JWH-018 may precipitate psychosis in vulnerable individuals". Addiction. 105 (10): 1859–60. doi:10.1111/j.1360-0443.2010.03119.x. PMID 20840203.
63. ^ Müller H, et al. (2010). "The synthetic cannabinoid Spice as a trigger for an acute exacerbation of cannabis induced recurrent psychotic episodes". Schizophr. Res. 118 (1–3): 309–10. doi:10.1016/j.schres.2009.12.001. PMID 20056392. S2CID 205066297.
64. ^ https://www.addictions.com/bath-salts/ Bath Salt Addiction, Accessed 06-25-2011
65. ^ Kurzbaum, Alberto; Claudia Simsolo; Ludmilla Kvasha; Arnon Blum (July 2001). "Toxic Delirium due to Datura Stramonium" (PDF). Israel Medical Association Journal. 3 (7): 538–539. PMID 11791426. Archived from the original (PDF) on 2007-06-14. Retrieved 2006-10-17.
66. ^ Przekop, Peter; Lee, Timothy (July 2009). "Persistent Psychosis Associated With Salvia Divinorum Use". American Journal of Psychiatry. 166 (7): 832. doi:10.1176/appi.ajp.2009.08121759. PMID 19570943.
67. ^ a b c d American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Arlington, VA: American Psychiatric Publishing. p. 113. doi:10.1176/appi.books.9780890425596. ISBN 978-0-89042-554-1.
## External links[edit]
Classification
D
* ICD-10: F10.5—F19.5
* ICD-9-CM: 292.1
* MeSH: D011605
* v
* t
* e
Psychoactive substance-related disorder
General
* SID
* Substance intoxication / Drug overdose
* Substance-induced psychosis
* Withdrawal:
* Craving
* Neonatal withdrawal
* Post-acute-withdrawal syndrome (PAWS)
* SUD
* Substance abuse / Substance-related disorders
* Physical dependence / Psychological dependence / Substance dependence
Combined
substance use
* SUD
* Polysubstance dependence
* SID
* Combined drug intoxication (CDI)
Alcohol
SID
Cardiovascular diseases
* Alcoholic cardiomyopathy
* Alcohol flush reaction (AFR)
Gastrointestinal diseases
* Alcoholic liver disease (ALD):
* Alcoholic hepatitis
* Auto-brewery syndrome (ABS)
Endocrine diseases
* Alcoholic ketoacidosis (AKA)
Nervous
system diseases
* Alcohol-related dementia (ARD)
* Alcohol intoxication
* Hangover
Neurological
disorders
* Alcoholic hallucinosis
* Alcoholic polyneuropathy
* Alcohol-related brain damage
* Alcohol withdrawal syndrome (AWS):
* Alcoholic hallucinosis
* Delirium tremens (DTs)
* Fetal alcohol spectrum disorder (FASD)
* Fetal alcohol syndrome (FAS)
* Korsakoff syndrome
* Positional alcohol nystagmus (PAN)
* Wernicke–Korsakoff syndrome (WKS, Korsakoff psychosis)
* Wernicke encephalopathy (WE)
Respiratory tract diseases
* Alcohol-induced respiratory reactions
* Alcoholic lung disease
SUD
* Alcoholism (alcohol use disorder (AUD))
* Binge drinking
Caffeine
* SID
* Caffeine-induced anxiety disorder
* Caffeine-induced sleep disorder
* Caffeinism
* SUD
* Caffeine dependence
Cannabis
* SID
* Cannabis arteritis
* Cannabinoid hyperemesis syndrome (CHS)
* SUD
* Amotivational syndrome
* Cannabis use disorder (CUD)
* Synthetic cannabinoid use disorder
Cocaine
* SID
* Cocaine intoxication
* Prenatal cocaine exposure (PCE)
* SUD
* Cocaine dependence
Hallucinogen
* SID
* Acute intoxication from hallucinogens (bad trip)
* Hallucinogen persisting perception disorder (HPPD)
Nicotine
* SID
* Nicotine poisoning
* Nicotine withdrawal
* SUD
* Nicotine dependence
Opioids
* SID
* Opioid overdose
* SUD
* Opioid use disorder (OUD)
Sedative /
hypnotic
* SID
* Kindling (sedative–hypnotic withdrawal)
* benzodiazepine: SID
* Benzodiazepine overdose
* Benzodiazepine withdrawal
* SUD
* Benzodiazepine use disorder (BUD)
* Benzodiazepine dependence
* barbiturate: SID
* Barbiturate overdose
* SUD
* Barbiturate dependence
Stimulants
* SID
* Stimulant psychosis
* amphetamine: SUD
* Amphetamine dependence
Volatile
solvent
* SID
* Sudden sniffing death syndrome (SSDS)
* Toluene toxicity
* SUD
* Inhalant abuse
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Substance-induced psychosis | c0154334 | 4,014 | wikipedia | https://en.wikipedia.org/wiki/Substance-induced_psychosis | 2021-01-18T19:06:17 | {"umls": ["C0154334"], "icd-9": ["292"], "icd-10": ["F06", "F10-F19"], "wikidata": ["Q2151786"]} |
Combined pancreatic lipase-colipase deficiency is a disorder of lipid absorption and transport characterized by steatorrhea with foul-smelling stools from birth, diminished serum carotene and vitamin E and a combined deficiency of the pancreatic enzymes lipase and colipase. Patients are otherwise healthy and develop normally with no apparent pancreatic disease. There have been no further descriptions in the literature since 1990.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Combined pancreatic lipase-colipase deficiency | c3280527 | 4,015 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=309111 | 2021-01-23T17:16:03 | {"omim": ["614338"], "icd-10": ["K90.3"]} |
This article is about a military-related term. For the band, see Thousand Yard Stare (band). For the Chicane album, see Thousand Mile Stare.
War artist Thomas Lea's The Two-Thousand Yard Stare
The thousand-yard stare or two-thousand-yard stare is a phrase often used to describe the blank, unfocused gaze of combatants who have become emotionally detached from the horrors around them. It is also sometimes used more generally to describe the look of dissociation among victims of other types of trauma.
## Origin[edit]
The phrase was popularized after Life magazine published the painting Marines Call It That 2,000 Yard Stare by World War II artist and correspondent Tom Lea,[1] although the painting was not referred to with that title in the 1945 magazine article. The painting, a 1944 portrait of a nameless Marine at the Battle of Peleliu, is now held by the United States Army Center of Military History in Fort Lesley J. McNair, Washington, D.C.[2] About the real-life Marine who was his subject, Lea said:
> He left the States 31 months ago. He was wounded in his first campaign. He has had tropical diseases. He half-sleeps at night and gouges Japs out of holes all day. Two-thirds of his company has been killed or wounded. He will return to attack this morning. How much can a human being endure?[3]
When recounting his arrival in Vietnam in 1965, then-Corporal Joe Houle (director of the Marine Corps Museum of the Carolinas in 2002) said he saw no emotion in the eyes of his new squad: "The look in their eyes was like the life was sucked out of them," later learning that the term for their condition was "the 1,000-yard stare". "After I lost my first friend, I felt it was best to be detached," he explained.[4]
## See also[edit]
* Afghan Girl
* Catatonia
* Defence mechanisms
* Hypervigilance
* James Blake Miller
* Shell shock
## References[edit]
Wikimedia Commons has media related to Thousand-yard stare.
1. ^ Life magazine, 6/11/1945, p. 65. link
2. ^ Jones, James, and Tom Lea (illustration), (1975). - "Two-Thousand-Yard Stare" Archived 2006-11-09 at the Wayback Machine. - WW II. - (c/o Military History Network). - Grosset and Dunlap. - pp.113,116. - ISBN 0-448-11896-3
3. ^ Host: Rear Admiral Gene LaRocque (USN, Ret.); Interviewer & narrator: Sanford Gottlieb; Producers: Matthew Hansen, Nick Moore, Lori McRea, Daniel Sagalyn (1991). "War through the eyes of artists". America's Defense Monitor, Program Number 438. Center for Defense Information. Archived from the original (Transcript of televised broadcast) on 2006-10-26. Retrieved 2006-10-27.CS1 maint: multiple names: authors list (link)
4. ^ Stone, Sgt. Arthur L. (2002-05-02). "Retired Sgt. Maj. Joe Houle recounts Vietnam tour". Marine Corps News. Archived from the original on 2015-07-07. Retrieved 2015-07-07.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Thousand-yard stare | None | 4,016 | wikipedia | https://en.wikipedia.org/wiki/Thousand-yard_stare | 2021-01-18T18:58:07 | {"wikidata": ["Q841743"]} |
A rare syndromic, inherited form of sideroblastic anemia characterized by mild to moderate anemia (with hypochromia and microcytosis) and early-onset, non- or slowly progressive spinocerebellar ataxia.
## Epidemiology
X-linked sideroblastic anemia and ataxia (XLSA-A) prevalence is unknown. Less than 20 genetically confirmed patients have been reported to date.
## Clinical description
.XLSA-A usually presents before the age of 3 years. Anemia is usually asymptomatic. In males, spinocerebellar symptoms are apparent in childhood and can include delayed walking, predominantly truncal ataxia, dysmetria and dysdiadochokinesis. Dysarthria and intention tremor are sometimes present. Ataxia may improve over time, but in the fifth to sixth decade of life a slow deterioration of walking is noted. Upper motor neuron signs in the legs such as equivocal or extensor plantar responses, brisk deep tendon reflexes and unsustained ankle clonus are sometimes present. Strabismus, as well as mild learning disability and depression, have also been reported in some, but intellectual abilities are generally within the normal range. Hepatic and systemic iron overload does not occur. Females are clinically asymptomatic.
## Etiology
XLSA-A is caused by mutations in the ABCB7 gene (Xq13.3), encoding a mitochondrial ATP-binding cassette (ABC) transporter protein, which plays a role in heme production and iron homeostasis. A pathogenic variant in this gene alters the availability of reduced iron and therefore disrupts heme biosynthesis. The ABCB7 gene is highly expressed in both the bone marrow and the cerebellum, which may explain ataxia.
## Diagnostic methods
Diagnosis is based on the presence of characteristic neurological and blood test findings. Mild to moderate hypochromic, microcytic anemia is noted in all males and both whole blood total erythrocyte protoporphyrin (TEP) and zinc erythrocyte protoporphyrin (ZnEP) are elevated. Bone marrow examination demonstrates the presence of increased iron stores with ring sideroblasts and peripheral blood smear reveals Pappenheimer bodies. In the majority of cases magnetic resonance imaging (MRI) shows cerebellar atrophy/hypoplasia. Female carriers display hematological abnormalities. Molecular genetic testing identifies a ABCB7 gene variation, confirming the diagnosis.
## Differential diagnosis
The main differential diagnosis includes other forms/causes of ataxia that typically present before the age of 3 years such as ataxia-telangiectasia, infantile-onset spinocerebellar ataxia, congenital disorder of glycosylation, and cerebellar malformations (e.g. Dandy-Walker malformation). Ataxia with vitamin E deficiency, Friedreich ataxia, ataxia - oculomotor apraxia type 1 and 2, and X linked sideroblastic anemia , the most common form of congenital sideroblastic anemia (without ataxia), should also be excluded.
## Antenatal diagnosis
Prenatal testing is possible in families with a known ABCB7 mutation.
## Genetic counseling
The pattern of inheritance is X-linked recessive and gentic counselling should be offerend to affected families. Where the female is a carrier, the risk to male offspring inheriting the disease is 50%, female offspring have a 50% risk of being carriers. Where a male is affected, female offspring are obligate carriers, and male offspring do not inherit the pathogenic mutation.
## Management and treatment
There is no cure for XLSA-A and treatment is symptomatic. Anemia does not require treatment. Early physical therapy may aid in the acquisition of gross motor skills. Ankle fixation orthoses and walkers may be required to aid with mobility. Weighted eating utensils promote independent skills in children. Speech therapy is recommended for those with dysarthria. Crutches or a wheelchair may be needed by some patients.
## Prognosis
While prognosis information is limited due to very few existing reports, XLSA-A does not appear to have a significant impact on life expectancy. Quality of life, however, can be significantly affected.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| X-linked sideroblastic anemia and spinocerebellar ataxia | c1845028 | 4,017 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2802 | 2021-01-23T18:10:35 | {"gard": ["668"], "mesh": ["C536358"], "omim": ["301310"], "umls": ["C1845028"], "icd-10": ["D64.0"], "synonyms": ["Pagon-Bird-Detter syndrome", "X-linked sideroblastic anemia with ataxia", "XLSA-A"]} |
Spermatocytic seminoma (SS) is an extremely rare form of testicular cancer distinguished from testicular seminomatous germ cell tumors (see this term) by a very low rate of metastasis and lack of an ovarian equivalent.
## Epidemiology
SS accounts for around 1- 2% of all cases of testicular germ cell tumors (see this term). Annual incidence in Europe is 1/3,300,000.
## Clinical description
SS presents in males in their fifth to sixth decade of life. A painless mass in the scrotum or an interscrotal mass are indicative of disease. A long-standing hydrocele may be noted causing a feeling of heaviness in the testicle. Gynecomastia and back and flank pain are symptoms that are seen in some patients. The invasion of seminoma into the blood vessels, tunica albuginea and epididymus is rarely seen. In extremely rare instances a sarcomatous transformation can occur which causes the tumor size to rapidly increase along with its propensity for metastasis. In the very few cases that metastasis occurs, this aggressive form of tumor is referred to as metastatic spermatocytic seminoma.
## Etiology
The etiology of SS is unknown. It is thought to originate from a premeiotic germ cell.
## Diagnostic methods
Clinical findings orientate the diagnosis and measurement of tumor marker levels (alpha-fetoprotein) help in the precision of SS diagnosis. Testicular sonogram is also performed while bone scan and magnetic resonance imaging (MRI) of the central nervous system is only needed when symptoms of involvement in those areas are seen. Histopathological examination of the testicular mass biopsy confirms SS with the presence of three characteristic cell types: small cells (7-8 µm) with dark nuclei, medium sized cells (15 µm) with granular chromatin and eosinophilic cytoplasm in round nuclei and large multinucleated cells (up to 100 µm).
## Differential diagnosis
Differential diagnoses include testicular seminomatous germ cell tumors and all types of lymphoma (see these terms).
## Management and treatment
Treatment of SS is similar to that of testicular seminomatous germ cell tumors which involves an orchidectomy. As this form of seminoma rarely metastasizes there is usually no further treatment needed but surveillance following surgery is necessary. Patients with the rare metastatic form are given additional chemotherapy (carboplatin) and radiotherapy but no specific treatment regimen has yet been established. Due to cosmetic and psychological reasons, patients may be offered testicular prostheses after an orchidectomy.
## Prognosis
The prognosis for SS is very good as once an orchidectomy is performed most patients are cured.
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Spermatocytic seminoma | c0334517 | 4,018 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99865 | 2021-01-23T17:02:17 | {"omim": ["273300"], "umls": ["C0334517"], "icd-10": ["C62.9"]} |
A number sign (#) is used with this entry because of evidence that lipid storage myopathy due to FLAD1 deficiency (LSMFLAD) is caused by homozygous or compound heterozygous mutation in the FLAD1 gene (610595) on chromosome 1q21.
Description
Lipid storage myopathy due to FLAD1 deficiency is an autosomal recessive inborn error of metabolism that includes variable mitochondrial dysfunction. The phenotype is extremely heterogeneous: some patients have a severe disorder with onset in infancy and cardiac and respiratory insufficiency resulting in early death, whereas others have a milder course with onset of muscle weakness in adulthood. Some patients show significant improvement with riboflavin treatment (summary by Olsen et al., 2016).
Clinical Features
Taylor et al. (2014) reported a Turkish boy (patient 30), born of consanguineous parents, who presented at age 4 months with respiratory insufficiency and lipid myopathy. Skeletal muscle biopsy showed global COX defect and decreased activities of mitochondrial complexes I and IV. He died at 8 months of age.
Olsen et al. (2016) reported 9 patients from 7 unrelated families, recruited from metabolic centers in 6 countries, with a metabolic myopathy variably associated with mitochondrial respiratory chain deficiencies. Seven patients had a severe disorder with onset of hypotonia, swallowing and feeding difficulties, and respiratory insufficiency in infancy. Analysis of skeletal muscle showed multiple mitochondrial respiratory chain deficiency in most patients. Muscle biopsy showed a lipid storage myopathy in most patients. Laboratory studies were variable, but tended to show elevation of multiple acylcarnitines, as well as increased urinary organic acids, including ethylmalonic acid and adipic acid. The biochemical abnormalities resembled those observed in multiple acyl-CoA dehydrogenase deficiency (MADD; 231680). Four patients died within the first year of life. In 1 consanguineous family, a boy died at age 3 days, whereas his sister was still alive at age 22 years. She had been treated for cardiomyopathy in the first year of life and had a pacing/defibrillator device; riboflavin treatment resulted in a favorable response. Two additional unrelated women had a much milder disease course, with onset of significant muscle weakness at ages 20 and 45 years, respectively. The first patient had an exacerbation of muscle weakness during pregnancy at age 30 associated with increased C8- and C10-acylcarnitine species and a lipid storage myopathy on muscle biopsy. The other woman had proximal muscle weakness of the upper and lower limbs, abnormal acylcarnitine profile, and lipid storage myopathy. Both of these patients had decreased activities of multiple respiratory chain enzymes. Riboflavin treatment in both women resulted in almost complete resolution of muscle weakness and biochemical abnormalities. None of the patients had progressive neurologic signs: there was no hearing or visual impairment and also no peripheral neuropathy. One consanguineous family experienced 4 miscarriages.
Inheritance
The transmission pattern of lipid-storage myopathy due to FLAD1 deficiency in the families reported by Olsen et al. (2016) was consistent with autosomal recessive inheritance.
Molecular Genetics
In a Turkish boy (patient 30), born of consanguineous parents, with lipid myopathy resulting in death in infancy, Taylor et al. (2014) identified a homozygous truncating mutation in the FLAD1 gene (610595.0001). The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. The patient was part of a cohort of 53 individuals with biochemical evidence of multiple respiratory chain complex defects who underwent whole-exome sequencing. Functional studies of the variant and studies of patient cells were not performed.
In 9 patients from 7 unrelated families with lipid-storage myopathy due to FLAD1 deficiency, Olsen et al. (2016) identified homozygous or compound heterozygous mutations in the FLAD1 gene (see, e.g., 610595.0002-610595.0006). The mutations in 2 patients were found by whole-exome sequencing; mutations in other patients were found by sequencing of candidate genes associated with fatty acid oxidation and/or mitochondrial disorders, as well as genes involved in riboflavin uptake and metabolism. Fibroblasts derived from some of the patients showed residual FADS activity. Those with mutations affecting a single residue (Ser495del, 610595.0002 and R530C, 610595.0003) had a less severe phenotype than those with biallelic truncating mutations. However, even those with truncating mutations had some residual FADS activity, which Olsen et al. (2016) speculated resulted from the compensatory use of alternative isoforms encoding only the FADS domain.
History
Bradley et al. (1969) described the case of a 25-year-old woman, offspring of first-cousin parents, with myopathy involving the muscles of the neck and proximal limbs. Muscle biopsy showed interfibrillar and subsarcolemmal vacuoles; histochemical study showed normal type-II muscle fibers with excessive neutral fat and free fatty acids in type-I fibers; and electron microscopy showed degenerate mitochondria. The defect may reside in the pathway of free fatty acid oxidation.
INHERITANCE \- Autosomal recessive CARDIOVASCULAR Heart \- Cardiomyopathy (in some patients) \- Supraventricular tachycardia (in some patients) RESPIRATORY \- Respiratory insufficiency ABDOMEN Gastrointestinal \- Feeding difficulties \- Swallowing difficulties SKELETAL Spine \- Scoliosis (in some patients) MUSCLE, SOFT TISSUES \- Hypotonia \- Muscle weakness \- Proximal limb muscle weakness \- Exercise intolerance \- Lipid storage myopathy \- Variable decrease in multiple mitochondrial respiratory complex activities LABORATORY ABNORMALITIES \- Increased plasma acylcarnitine species \- Increased urinary ethylmalonic acid \- Increased urinary adipic acid \- Organic aciduria \- Increased serum creatine kinase (in some patients) MISCELLANEOUS \- Highly variable phenotype \- Some patients present in infancy with a severe disorder that may result in early death \- Some patients have adult-onset of myopathy \- Some patients may respond well to riboflavin supplementation MOLECULAR BASIS \- Caused by mutation in the flavin adenine dinucleotide synthetase 1 gene (FLAD1, 610595.0001 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| LIPID STORAGE MYOPATHY DUE TO FLAVIN ADENINE DINUCLEOTIDE SYNTHETASE DEFICIENCY | c4310822 | 4,019 | omim | https://www.omim.org/entry/255100 | 2019-09-22T16:24:37 | {"omim": ["255100"], "orphanet": ["394529", "394532"], "synonyms": ["MAD deficiency, severe neonatal type", "Glutaric aciduria type 2, mild type", "Glutaric aciduria type 2, severe neonatal type", "MAD deficiency, mild type", "MADD, mild type", "MADD, severe neonatal type"]} |
An inflammatory myofibroblastic tumor (IMT) is an uncommon, usually benign (non-cancerous) tumor made up of cells called myofibroblastic spindle cells. It usually develops in children or young adults, but can affect people of any age. An IMT can occur in almost any part of the body but is most commonly found in the lung, orbit (eye socket), peritoneum (lining of the abdominal cavity and internal organs), and mesentery. Signs and symptoms vary depending on the site of the tumor. Some people with an IMT are asymptomatic, while others may have nonspecific respiratory symptoms, fever, or pain. IMTs may recur, and become locally invasive and/or spread (metastasize) to other parts of the body. However, malignant (cancerous) IMTs are rare. The underlying cause of IMTs is poorly understood. Some cases have been linked to translocations involving the ALK gene. Treatment involves surgical removal when possible, although there are reports of treatment with oral steroids and radiation therapy.
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Inflammatory myofibroblastic tumor | c0334121 | 4,020 | gard | https://rarediseases.info.nih.gov/diseases/7146/inflammatory-myofibroblastic-tumor | 2021-01-18T17:59:46 | {"mesh": ["D006104"], "umls": ["C0334121"], "orphanet": ["178342"], "synonyms": ["Inflammatory fibrosarcoma"]} |
Hirschsprung disease (HSCR) is a disease of the large intestine or colon. People with this disease do not have the nerve cells in the intestine required to pass stools from the body normally. Symptoms of Hirschsprung disease usually start in very young children, but may occur later. The symptoms may vary with age, but often involve constipation and/or obstruction of the bowel. Other signs and symptoms include vomiting, abdominal pain or swelling, diarrhea, poor feeding, malnutrition, and slow growth. There are two main types of Hirschsprung disease, known as short-segment disease and long-segment disease, defined by the region of the intestine lacking nerve cells (aganglionic segments). HSCR is considered a neurocristopathy, a disorder of cells and tissues derived from the neural crest, (a group of embryonic cells of the neural tube that forms several structures, of the body). HSCR may occur as an isolated finding or as part of a another disorder. Isolated HSCR is associated with mutations in several genes. Treatment is with surgery, removing the aganglionic intestinal segment.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Hirschsprung disease | c0019569 | 4,021 | gard | https://rarediseases.info.nih.gov/diseases/6660/hirschsprung-disease | 2021-01-18T18:00:00 | {"mesh": ["D006627"], "omim": ["142623"], "orphanet": ["388"], "synonyms": ["HSCR", "Hirschsprung disease 1", "HSCR 1", "Aganglionic megacolon", "Hirschsprung disease type 1"]} |
A number sign (#) is used with this entry because of evidence that autosomal recessive deafness-61 (DFNB61) is caused by compound heterozygous mutation in the SLC26A5 (PRES) gene (604943) on chromosome 7q22. One such family has been reported.
Clinical Features
Liu et al. (2003) reported 2 unrelated families segregating nonsyndromic autosomal recessive deafness. One of the probands was born to consanguineous parents in a multiplex sibship, whereas the other was born to nonconsanguineous parents in a simplex sibship. Both probands had a severe profound bilateral hearing loss that appeared to have been congenital with no evidence of progression.
Mutai et al. (2013) reported 2 sisters, aged 6 and 9 years, who had moderate to severe hearing loss and mutation in the SLC26A5 gene (see MOLECULAR GENETICS).
Molecular Genetics
In 2 of 220 hearing-impaired Caucasian probands, Liu et al. (2003) identified an A-to-G transition at the intron 2/exon 3 junction of the SLC26A5 gene (604943.0001). In addition, heterozygosity for this mutation was observed in 7 (3%) of the 220 probands, suggesting the possibility of semidominant influence of the mutation in causing hearing loss. However, based on allele frequency in 8,595 controls from 12 populations (maximum minor allele frequency = 0.0156), Shearer et al. (2014) recategorized this intronic variant as benign.
In 2 sisters, aged 6 and 9 years, who had moderate to severe hearing loss, Mutai et al. (2013) identified compound heterozygous mutations in the SLC26A5 gene: a W70X substitution (604943.0003) inherited from their father and an R130S substitution (604943.0002) inherited from their mother.
INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Hearing loss, bilateral, moderate-to-profound MISCELLANEOUS \- Limited clinical information provided \- One family with compound heterozygous SLC26A5 mutation has been reported (last curated October 2015) MOLECULAR BASIS \- Caused by mutation in the solute carrier family 26, member 5 gene (SLC26A5, 604943.0002 ) ▲ Close
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| DEAFNESS, AUTOSOMAL RECESSIVE 61 | c3151230 | 4,022 | omim | https://www.omim.org/entry/613865 | 2019-09-22T15:57:07 | {"doid": ["0110513"], "omim": ["613865"], "orphanet": ["90636"], "synonyms": ["Autosomal recessive isolated neurosensory deafness type DFNB", "Autosomal recessive isolated sensorineural deafness type DFNB", "Autosomal recessive non-syndromic neurosensory deafness type DFNB"]} |
Junctional epidermolysis bullosa (JEB) is a major form of epidermolysis bullosa, a group of genetic conditions that cause the skin to be very fragile and to blister easily. Blisters and areas of skin loss (erosions) form in response to minor injury or friction, such as rubbing or scratching. Researchers classify junctional epidermolysis bullosa into two main types: JEB generalized severe (formerly known as Herlitz JEB) and JEB generalized intermediate (formerly known as non-Herlitz JEB). Although the types differ in severity, their features overlap significantly, and they can be caused by mutations in the same genes.
JEB generalized severe is the more serious form of the condition. From birth or early infancy, affected individuals have blistering over large regions of the body. Blistering also affects the mucous membranes, such as the moist lining of the mouth and digestive tract, which can make it difficult to eat and digest food. As a result, many affected children are undernourished and grow slowly. The extensive blistering leads to scarring and the formation of red, bumpy patches called granulation tissue. Granulation tissue bleeds easily and profusely, making affected infants susceptible to serious infections and loss of necessary proteins, minerals, and fluids. Additionally, a buildup of granulation tissue in the airway can lead to a weak, hoarse cry and difficulty breathing.
Other complications of JEB generalized severe can include fusion of the fingers and toes, abnormalities of the fingernails and toenails, joint deformities (contractures) that limit movement, hair loss (alopecia), and thinning of the protective outer layer (enamel) of the teeth. Because the signs and symptoms of JEB generalized severe are so serious, infants with this condition usually do not survive beyond the first year of life.
The milder form of junctional epidermolysis bullosa is called JEB generalized intermediate. The blistering associated with JEB generalized intermediate may be limited to the hands, feet, knees, and elbows, and it often improves after the newborn period. Other characteristic features of this form of the condition include hair loss, abnormal fingernails and toenails, and irregular tooth enamel. Most affected individuals do not have extensive scarring or granulation tissue formation, so breathing difficulties and other severe complications are rare. JEB generalized intermediate is typically associated with a normal lifespan.
## Frequency
Both types of junctional epidermolysis bullosa are rare, together affecting approximately 3 per million people per year in the United States.
## Causes
Junctional epidermolysis bullosa most commonly results from mutations in the LAMA3, LAMB3, LAMC2, and COL17A1 genes. Mutations in each of these genes can cause JEB generalized severe or JEB generalized intermediate. LAMB3 gene mutations are the most common, causing about 70 percent of all cases of junctional epidermolysis bullosa.
The LAMA3, LAMB3, and LAMC2 genes each provide instructions for making one part (subunit) of a protein called laminin 332. This protein plays an important role in strengthening and stabilizing the skin by helping to attach the top layer of skin (the epidermis) to underlying layers. Mutations in any of the three laminin 332 genes lead to the production of a defective or nonfunctional version of this protein. Without functional laminin 332, cells in the epidermis are fragile and easily damaged. Friction or other minor trauma can cause the skin layers to separate, leading to the formation of blisters.
The COL17A1 gene provides instructions for making a protein that is used to assemble type XVII collagen. Collagens are molecules that give structure and strength to connective tissues, such as skin, tendons, and ligaments, throughout the body. Type XVII collagen helps attach the epidermis to underlying layers of skin, making the skin strong and flexible. Mutations in the COL17A1 gene prevent the normal formation of collagen XVII. As a result, the skin is less resistant to friction and minor trauma and blisters easily. Most COL17A1 gene mutations cause JEB generalized intermediate, although a few individuals with mutations in this gene have had the more serious JEB generalized severe.
Very rarely, junctional epidermolysis bullosa is caused by mutations in another gene that provides instructions for making a different protein that helps attach the top layer of skin to underlying layers.
### Learn more about the genes associated with Junctional epidermolysis bullosa
* COL17A1
* ITGB4
* LAMA3
* LAMB3
* LAMC2
## Inheritance Pattern
Both types of junctional epidermolysis bullosa are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Rarely, people with one mutated copy of the COL17A1, LAMA3, or LAMB3 gene have irregular tooth enamel.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Junctional epidermolysis bullosa | c0079683 | 4,023 | medlineplus | https://medlineplus.gov/genetics/condition/junctional-epidermolysis-bullosa/ | 2021-01-27T08:25:46 | {"gard": ["6359", "2152"], "mesh": ["D016109"], "omim": ["226700", "226650"], "synonyms": []} |
A very rare, syndromic genetic deafness characterized by mild to moderate conductive hearing loss, dysmorphic pinnae and lip pits or dimples. The pinnae are usually small, cup-shaped, with helix folded forward, and hearing loss is associated with malformed ossicles and displacement of the external auditory canal.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Conductive deafness-malformed external ear syndrome | c1857341 | 4,024 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3216 | 2021-01-23T17:39:55 | {"gard": ["1460"], "mesh": ["C565644"], "omim": ["221300"], "umls": ["C1857341", "C2931454"], "synonyms": ["Conductive hearing loss-malformed external ear syndrome", "Mengel-Konigsmark syndrome"]} |
Cardiofaciocutaneous (CFC) syndrome is a disorder that affects many parts of the body, particularly the heart, face, skin, and hair. People with this condition also have developmental delay and intellectual disability, usually ranging from moderate to severe. The signs and symptoms of CFC syndrome overlap significantly with those of two other conditions, Costello syndrome and Noonan syndrome. These syndromes belong to a group of related conditions called the RASopathies, which are distinguished by their genetic causes and specific pattern of features. It can sometimes be hard to tell these conditions apart in infancy. CFC syndrome is usually caused by a mutation in the BRAF gene, but can also be due to a mutation in the MAP2K1, MAP2K2 or KRAS gene. It is an autosomal dominant condition, but most cases are not inherited, due to a new mutation that occurs for the first time in an affected person. Treatment depends on the symptoms in each person and may include surgery for heart defects.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Cardiofaciocutaneous syndrome | c1275081 | 4,025 | gard | https://rarediseases.info.nih.gov/diseases/9146/cardiofaciocutaneous-syndrome | 2021-01-18T18:01:38 | {"mesh": ["C535579"], "omim": ["115150"], "umls": ["C1275081"], "orphanet": ["1340"], "synonyms": ["CFC syndrome", "Congenital heart defects characteristic facial appearance ectodermal abnormalities and growth failure", "Cardio-facio-cutaneous syndrome"]} |
"Wry neck" redirects here. For the bird, see Wryneck.
Torticollis
Other namesCrick in the neck, wry neck, stiff neck, loxia[note 1]
The muscles involved with torticollis
SpecialtyOrthopedics
Torticollis, also known as wry neck, is a dystonic condition defined by an abnormal, asymmetrical head or neck position, which may be due to a variety of causes. The term torticollis is derived from the Latin words tortus for twisted and collum for neck.[1][2]
The most common case has no obvious cause, and the pain and difficulty with turning the head usually goes away after a few days, even without treatment.[3]
## Contents
* 1 Signs and symptoms
* 2 Causes
* 2.1 Congenital muscular torticollis
* 2.2 Acquired torticollis
* 2.3 Spasmodic torticollis
* 2.4 Trochlear torticollis
* 3 Anatomy
* 4 Diagnosis
* 5 Treatment
* 5.1 Physical therapy
* 5.2 Microcurrent therapy
* 5.3 Surgery
* 6 Prognosis
* 7 Other animals
* 7.1 Head tilt
* 8 Notes
* 9 References
* 10 External links
## Signs and symptoms[edit]
Torticollis is a fixed or dynamic tilt, rotation, with flexion or extension of the head and/or neck. The type of torticollis can be described depending on the positions of the head and neck.[1][4][5]
* laterocollis : the head is tipped toward the shoulder
* rotational torticollis : the head rotates along the longitudinal axis
* anterocollis : forward flexion of the head and neck[6]
* retrocollis : hyperextension of head and neck backward[7]
A combination of these movements may often be observed. Torticollis can be a disorder in itself as well as a symptom in other conditions.
Other symptoms include:[8][9]
* Neck pain
* Occasional formation of a mass
* Thickened or tight sternocleidomastoid muscle
* Tenderness on the cervical spine
* Tremor in head
* Unequal shoulder heights
* Decreased neck movement
## Causes[edit]
A multitude of conditions may lead to the development of torticollis including: muscular fibrosis, congenital spine abnormalities, or toxic or traumatic brain injury.[2] A rough categorization discerns between congenital torticollis and acquired torticollis.
Other categories include:[10]
* Osseous
* Traumatic
* CNS/PNS
* Ocular
* Non-muscular soft tissue
* Spasmodic
* Drug induced
### Congenital muscular torticollis[edit]
The congenital muscular torticollis is the most common torticollis which is present at birth.[11] The cause of congenital muscular torticollis is unclear. Birth trauma or intrauterine malposition is considered to be the cause of damage to the sternocleidomastoid muscle in the neck.[2] Other alterations to the muscle tissue arise from repetitive microtrauma within the womb or a sudden change in the calcium concentration in the body which causes a prolonged period of muscle contraction.[12]
Any of these mechanisms can result in a shortening or excessive contraction of the sternocleidomastoid muscle, which curtails its range of motion in both rotation and lateral bending. The head typically is tilted in lateral bending toward the affected muscle and rotated toward the opposite side. In other words, the head itself is tilted in the direction towards the shortened muscle with the chin tilted in the opposite direction.[10]
Congenital Torticollis is presented at 1–4 weeks of age, and a hard mass usually develops. It is normally diagnosed using ultrasonography and a colour histogram or clinically through evaluating the infant's passive cervical range of motion.[13]
Congenital torticollis constitutes the majority of cases seen in clinical practice.[10] The reported incidence of congenital torticollis is 0.3-2.0%.[14] Sometimes a mass, such as a sternocleidomastoid tumor, is noted in the affected muscle at the age of two to four weeks. Gradually it disappears, usually by the age of eight months, but the muscle is left fibrotic.[2]
### Acquired torticollis[edit]
Noncongenital muscular torticollis may result from scarring or disease of cervical vertebrae, adenitis, tonsillitis, rheumatism, enlarged cervical glands, retropharyngeal abscess, or cerebellar tumors. It may be spasmodic (clonic) or permanent (tonic). The latter type may be due to Pott's Disease (tuberculosis of the spine).[citation needed]
* A self-limiting spontaneously occurring form of torticollis with one or more painful neck muscles is by far the most common ('stiff neck') and will pass spontaneously in 1–4 weeks. Usually the sternocleidomastoid muscle or the trapezius muscle is involved. Sometimes draughts, colds, or unusual postures are implicated; however, in many cases, no clear cause is found. These episodes are commonly seen by physicians.[citation needed]
* Tumors of the skull base (posterior fossa tumors) can compress the nerve supply to the neck and cause torticollis, and these problems must be treated surgically.[citation needed]
* Infections in the posterior pharynx can irritate the nerves supplying the neck muscles and cause torticollis, and these infections may be treated with antibiotics if they are not too severe, but could require surgical debridement in intractable cases.
* Ear infections and surgical removal of the adenoids can cause an entity known as Grisel's syndrome, a subluxation of the upper cervical joints, mostly the atlantoaxial joint, due to inflammatory laxity of the ligaments caused by an infection.[15]
* The use of certain drugs, such as antipsychotics, can cause torticollis.[16]
* Antiemetics - Neuroleptic Class - Phenothiazines
* There are many other rare causes of torticollis. A very rare cause of acquired torticollis is fibrodysplasia ossificans progressiva (FOP), the hallmark of which is malformed great toes.
### Spasmodic torticollis[edit]
Main article: Spasmodic torticollis
Torticollis with recurrent, but transient contraction of the muscles of the neck and especially of the sternocleidomastoid, is called spasmodic torticollis. Synonyms are "intermittent torticollis", "cervical dystonia" or "idiopathic cervical dystonia", depending on cause.[citation needed]
### Trochlear torticollis[edit]
Main article: Congenital fourth nerve palsy
Torticollis may be unrelated to the sternocleidomastoid muscle, instead caused by damage to the trochlear nerve (fourth cranial nerve), which supplies the superior oblique muscle of the eye. The superior oblique muscle is involved in depression, abduction, and intorsion of the eye. When the trochlear nerve is damaged, the eye is extorted because the superior oblique is not functioning. The affected person will have vision problems unless they turn their head away from the side that is affected, causing intorsion of the eye and balancing out the extorsion of the eye. This can be diagnosed by the Bielchowsky test, also called the head-tilt test, where the head is turned to the affected side. A positive test occurs when the affected eye elevates, seeming to float up.[17]
## Anatomy[edit]
The underlying anatomical distortion causing torticollis is a shortened sternocleidomastoid muscle. This is the muscle of the neck that originates at the sternum and clavicle and inserts on the mastoid process of the temporal bone on the same side.[10] There are two sternocleidomastoid muscles in the human body and when they both contract, the neck is flexed. The main blood supply for these muscles come from the occipital artery, superior thyroid artery, transverse scapular artery and transverse cervical artery.[10] The main innervation to these muscles is from cranial nerve XI (the accessory nerve) but the second, third and fourth cervical nerves are also involved.[10] Pathologies in these blood and nerve supplies can lead to torticollis.[citation needed]
## Diagnosis[edit]
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Evaluation of a child with torticollis begins with history taking to determine circumstances surrounding birth and any possibility of trauma or associated symptoms. Physical examination reveals decreased rotation and bending to the side opposite from the affected muscle. Some[who?] say that congenital cases more often involve the right side, but there is not complete agreement about this in published studies. Evaluation should include a thorough neurologic examination, and the possibility of associated conditions such as developmental dysplasia of the hip and clubfoot should be examined. Radiographs of the cervical spine should be obtained to rule out obvious bony abnormality, and MRI should be considered if there is concern about structural problems or other conditions.
Ultrasonography can be used to visualize muscle tissue, with a colour histogram generated to determine cross-sectional area and thickness of the muscle.[18]
Evaluation by an optometrist or an ophthalmologist should be considered in children to ensure that the torticollis is not caused by vision problems (IV cranial nerve palsy, nystagmus-associated "null position," etc.).
Differential diagnosis for torticollis includes[10][19]
* Cranial nerve IV palsy
* Spasmus nutans
* Sandifer syndrome
* Myasthenia gravis
* Cerebrospinal fluid leak
Cervical dystonia appearing in adulthood has been believed to be idiopathic in nature, as specific imaging techniques most often find no specific cause.[20]
## Treatment[edit]
Initially, the condition is treated with physical therapies, such as stretching to release tightness, strengthening exercises to improve muscular balance, and handling to stimulate symmetry. A TOT collar is sometimes applied. Early initiation of treatment is very important for full recovery and to decrease chance of relapse.[10]
### Physical therapy[edit]
Physical therapy is an option for treating torticollis in a non-invasive and cost-effective manner.[21] In the children above 1 year of age, surgical release of the tight sternocleidomastoid muscle is indicated along with aggressive therapy and appropriate splinting. Occupational therapy rehabilitation in Congenital muscular torticollis concentrates on observation, orthosis, gentle stretching, myofascial release techniques, parents’ counseling-training, and home exercise program. While outpatient infant physiotherapy is effective, home therapy performed by a parent or guardian is just as effective in reversing the effects of congenital torticollis.[12] It is important for physical therapists to educate parents on the importance of their role in the treatment and to create a home treatment plan together with them for the best results for their child. Five components have been recognized as the "first choice intervention" in PT for treatment of torticollis and include neck passive range of motion, neck and trunk active range of motion, development of symmetrical movement, environmental adaptations, and caregiver education. In therapy, parents or guardians should expect their child to be provided with these important components, explained in detail below.[22] Lateral neck flexion and overall range of motion can be regained quicker in newborns when parents conduct physical therapy exercises several times a day.[12]
Physical therapists should teach parents and guardians to perform the following exercises:[12]
* Stretching the neck and trunk muscles actively. Parents can help promote this stretching at home with infant positioning.[22] For example, prone positioning will encourage the child to lift their chin off the ground, thereby strengthening their bilateral neck and spine extensor muscles, and stretching their neck flexor muscles.[22] Active rotation exercises in supine, sitting or prone position by using toys, lights and sounds to attract infant's attention to turn neck and look toward the non-affected side.[22]
* Stretching the muscle in a prone position passively.[22] Passive stretching is manual, and does not include infant involvement. Two people can be involved in these stretches, one person stabilizing the infant while the other holds the head and slowly brings it through the available range of motion.[22] Passive stretching should not be painful to the child, and should be stopped if the child resists.[22] Also, discontinue the stretch if changes in breathing or circulation are seen or felt.[22]
* Stretching the muscle in a lateral position supported by a pillow (have infant lie on the side with the neck supported by pillow). Affected side should be against the pillow to deviate the neck towards the non-affected side.[citation needed]
* Environmental adaptations can control posture in strollers, car seats and swings (using U-shaped neck pillow or blankets to hold neck in neutral position)[citation needed]
* Passive cervical rotation (much like stretching when being supported by a pillow, have affected side down)[citation needed]
* Position infant in the crib with affected side by the wall so they must turn to the non-affected side to face out[citation needed]
Physical therapists often encourage parents and caregivers of children with torticollis to modify the environment to improve neck movements and position. Modifications may include:
* Adding neck supports to the car seat to attain optimal neck alignment
* Reducing time spent in a single position
* Using toys to encourage the child to look in the direction of limited neck movement
* Alternating sides when bottle or breastfeeding[22]
* Encouraging prone playtime (tummy time). Although the Back to Sleep campaign promotes infants sleeping on their backs to avoid sudden infant death syndrome during sleep, parents should still ensure that their infants spend some waking hours on their stomachs.[22]
### Microcurrent therapy[edit]
A Korean study has recently[when?] introduced an additional treatment called microcurrent therapy that may be effective in treating congenital torticollis. For this therapy to be effective the children should be under three months of age and have torticollis involving the entire sternocleidomastoid muscle with a palpable mass and a muscle thickness over 10 mm. Microcurrent therapy sends minute electrical signals into tissue to restore the normal frequencies in cells.[18] Microcurrent therapy is completely painless and children can only feel the probe from the machine on their skin.[18]
Microcurrent therapy is thought to increase ATP and protein synthesis as well as enhance blood flow, reduce muscle spasms and decrease pain along with inflammation.[18] It should be used in addition to regular stretching exercises and ultrasound diathermy. Ultrasound diathermy generates heat deep within body tissues to help with contractures, pain and muscle spasms as well as decrease inflammation. This combination of treatments shows remarkable outcomes in the duration of time children are kept in rehabilitation programs: Micocurrent therapy can cut the length of a rehabilitation program almost in half with a full recovery seen after 2.6 months.[18]
About 5–10% of cases fail to respond to stretching and require surgical release of the muscle.[23][24]
### Surgery[edit]
Surgical release involves the two heads of the sternocleidomastoid muscle being dissected free. This surgery can be minimally invasive and done laparoscopically. Usually surgery is performed on those who are over 12 months old. The surgery is for those who do not respond to physical therapy or botulinum toxin injection or have a very fibrotic sternocleidomastoid muscle.[8] After surgery the child will be required to wear a soft neck collar (also called a Callot's cast). There will be an intense physiotherapy program for 3–4 months as well as strengthening exercises for the neck muscles.[25]
Other treatments include:[12]
* Rest and analgesics for acute cases
* Diazepam or other muscle relaxants
* Botulinum toxin[26][27]
* Encouraging active movements for children 6–8 months of age
* Ultrasound diathermy
## Prognosis[edit]
Studies and evidence from clinical practice show that 85–90% of cases of congenital torticollis are resolved with conservative treatment such as physical therapy.[22] Earlier intervention is shown to be more effective and faster than later treatments. More than 98% of infants with torticollis treated before 1 month of age recover by 2.5 months of age.[22] Infants between 1 and 6 months usually require about 6 months of treatment.[22] After that point, therapy will take closer to 9 months, and it is less likely that the torticollis will be fully resolved.[22] It is possible that torticollis will resolve spontaneously, but chance of relapse is possible.[10] For this reason, infants should be reassessed by their physical therapist or other provider 3–12 months after their symptoms have resolved.[22]
## Other animals[edit]
A guinea pig with a head-tilt
In veterinary literature usually only the lateral bend of head and neck is termed torticollis, whereas the analogon to the rotatory torticollis in humans is called a head tilt. The most frequently encountered form of torticollis in domestic pets is the head tilt, but occasionally a lateral bend of the head and neck to one side is encountered.[citation needed]
### Head tilt[edit]
Causes for a head tilt in domestic animals are either diseases of the central or peripheral vestibular system or relieving posture due to neck pain. Known causes for head tilt in domestic animals include:
* Encephalitozoon cuniculi (or E. cuniculi) infection in rabbits[28]
* Inner ear infection
* Hypothyroidism in dogs[29]
* Disease of the VIIIth cranial nerve the N. Vestibulocochlearis through trauma, infection, inflammation or neoplasia
* Disease of the brain stem through either stroke, trauma or neoplasia
* Damage to the vestibular organ due to toxicity, inflammation or impaired blood supply
* Geriatric vestibular syndrome in dogs
## Notes[edit]
1. ^ Not be confused with the genus Loxia covering those bird species known as "crossbills", which was assigned by Swiss naturalist Conrad Gesner because of the obvious similarities.
## References[edit]
1. ^ a b Dauer, W.; Burke, RE; Greene, P; Fahn, S (1998). "Current concepts on the clinical features, aetiology and management of idiopathic cervical dystonia". Brain. 121 (4): 547–60. doi:10.1093/brain/121.4.547. PMID 9577384.
2. ^ a b c d Cooperman, Daniel R. (1997). Karmel-Ross, Karen (ed.). The Differential Diagnosis of Torticollis in Children. Physical & Occupational Therapy in Pediatrics. 17. pp. 1–11. doi:10.1080/J006v17n02_01. ISBN 978-0-7890-0316-4.
3. ^ Bartleson, J. D.; Deen, H. Gordon (2009-07-23). Spine Disorders: Medical and Surgical Management. Cambridge University Press. p. 46. ISBN 9780521889414. "Many patients for no apparent reason will awaken in the morning with a “wry” neck or a “crick” in the neck. They may have trouble moving the neck and often have acute muscle spasm. Their pain and limited range of motion subside typically in a matter of a few days without or perhaps more quickly with treatment."
4. ^ Velickovic, M; Benabou, R; Brin, MF (2001). "Cervical dystonia pathophysiology and treatment options". Drugs. 61 (13): 1921–43. doi:10.2165/00003495-200161130-00004. PMID 11708764. S2CID 46954613.
5. ^ "Cervical dystonia - Symptoms and causes - Mayo Clinic". www.mayoclinic.org. Retrieved 2017-11-02.
6. ^ Papapetropoulos, S; Tuchman, A; Sengun, C; Russell, A; Mitsi, G; Singer, C (2008). "Anterocollis: Clinical features and treatment options". Medical Science Monitor. 14 (9): CR427–30. PMID 18758411.
7. ^ Papapetropoulos, Spiridon; Baez, Sheila; Zitser, Jennifer; Sengun, Cenk; Singer, Carlos (2008). "Retrocollis: Classification, Clinical Phenotype, Treatment Outcomes and Risk Factors". European Neurology. 59 (1–2): 71–5. doi:10.1159/000109265. PMID 17917462. S2CID 30159732.
8. ^ a b Saxena, Amulya (2015). "Pediatric torticollis surgery treatment & management". Medscape.
9. ^ "Torticollis: MedlinePlus Medical Encyclopedia". medlineplus.gov.
10. ^ a b c d e f g h i Tomczak, K (2013). "Torticollis". Journal of Child Neurology. 28 (3): 365–378. doi:10.1177/0883073812469294. PMID 23271760. S2CID 216099695.
11. ^ 2013, Boston Childrens Hospital. "Torticollis | Boston Children's Hospital". www.childrenshospital.org. Retrieved 2017-09-21.CS1 maint: numeric names: authors list (link)
12. ^ a b c d e Carenzio, G (2015). "Early rehabilitation treatment in newborns with congenital muscular torticollis". Phys Rehabil Med. 51 (5): 539–45. PMID 25692687.
13. ^ Boricean, ID (2011). "Understanding ocular torticollis in children". Oftalmologia (Bucharest, Romania : 1990). 55 (1): 10–26. PMID 21774381.
14. ^ Cheng, JC; Wong, MW; Tang, SP; Chen, TM; Shum, SL; Wong, EM (2001). "Clinical determinants of the outcome of manual stretching in the treatment of congenital muscular torticollis in infants. A prospective study of eight hundred and twenty-one cases". The Journal of Bone and Joint Surgery. American Volume. 83-A (5): 679–87. doi:10.2106/00004623-200105000-00006. PMID 11379737. S2CID 999791.
15. ^ Bocciolini, C; Dall’Olio, D; Cunsolo, E; Cavazzuti, PP; Laudadio, P (August 2005). "Grisel's syndrome: a rare complication following adenoidectomy". Acta Otorhinolaryngologica Italica. 25 (4): 245–249. ISSN 0392-100X. PMC 2639892. PMID 16482983.
16. ^ Dressler, D.; Benecke, R. (2005). "Diagnosis and management of acute movement disorders". Journal of Neurology. 252 (11): 1299–306. doi:10.1007/s00415-005-0006-x. PMID 16208529. S2CID 189867541.
17. ^ "Trochlear Nerve Palsy: Background, History of the Procedure, Problem". 2016-08-12. Cite journal requires `|journal=` (help)
18. ^ a b c d e Kwon, D.R. (2014). "Efficacy of micro current therapy in infants with congenital muscular torticollis involving the entire sternocleidomastoid muscle". Clinical Rehabilitation. 28 (10): 983–91. doi:10.1177/0269215513511341. PMID 24240061. S2CID 206484848.
19. ^ Mokri, Bahram (December 2014). "Movement disorders associated with spontaneous CSF leaks: a case series". Cephalalgia: An International Journal of Headache. 34 (14): 1134–1141. doi:10.1177/0333102414531154. ISSN 1468-2982. PMID 24728303. S2CID 3100453.
20. ^ Crowner, Beth E. (2007-11-01). "Cervical Dystonia: Disease Profile and Clinical Management". Physical Therapy. 87 (11): 1511–1526. doi:10.2522/ptj.20060272. ISSN 0031-9023. PMID 17878433.
21. ^ Kaplan, Sandra L.; Coulter, Colleen; Fetters, Linda (2013). "Physical Therapy Management of Congenital Muscular Torticollis". Pediatric Physical Therapy. 25 (4): 348–394. doi:10.1097/pep.0b013e3182a778d2. PMID 24076627.
22. ^ a b c d e f g h i j k l m n o Kaplan, Sandra L.; Coulter, Colleen; Sargent, Barbara (October 2018). "Physical Therapy Management of Congenital Muscular Torticollis: A 2018 Evidence-Based Clinical Practice Guideline From the APTA Academy of Pediatric Physical Therapy". Pediatric Physical Therapy. 30 (4): 240–290. doi:10.1097/PEP.0000000000000544. ISSN 0898-5669. PMID 30277962. S2CID 52909510.
23. ^ Tang, SF; Hsu, KH; Wong, AM; Hsu, CC; Chang, CH (2002). "Longitudinal followup study of ultrasonography in congenital muscular torticollis". Clinical Orthopaedics and Related Research. 403 (403): 179–85. doi:10.1097/00003086-200210000-00026. PMID 12360024. S2CID 20606626.
24. ^ Hsu, Tsz-Ching; Wang, Chung-Li; Wong, May-Kuen; Hsu, Kuang-Hung; Tang, Fuk-Tan; Chen, Huan-Tang (1999). "Correlation of clinical and ultrasonographic features in congenital muscular torticollis". Archives of Physical Medicine and Rehabilitation. 80 (6): 637–41. doi:10.1016/S0003-9993(99)90165-X. PMID 10378488.
25. ^ Seung, Seo (2015). "Change of facial asymmetry in patients". Medscape.
26. ^ Samotus, Olivia; Lee, Jack; Jog, Mandar (2018-03-20). "Personalized botulinum toxin type A therapy for cervical dystonia based on kinematic guidance". Journal of Neurology. 265 (6): 1269–1278. doi:10.1007/s00415-018-8819-6. ISSN 1432-1459. PMID 29557988. S2CID 4043479.
27. ^ Safarpour, Yasaman; Jabbari, Bahman (2018-02-24). "Botulinum Toxin Treatment of Movement Disorders". Current Treatment Options in Neurology. 20 (2): 4. doi:10.1007/s11940-018-0488-3. ISSN 1092-8480. PMID 29478149. S2CID 3502413.
28. ^ Künzel, Frank; Joachim, Anja (2009). "Encephalitozoonosis in rabbits". Parasitology Research. 106 (2): 299–309. doi:10.1007/s00436-009-1679-3. PMID 19921257. S2CID 11727371.
29. ^ Jaggy, André; Oliver, John E.; Ferguson, Duncan C.; Mahaffey, E. A.; Glaus Jr, T. Glaus (1994). "Neurological Manifestations of Hypothyroidism: A Retrospective Study of 29 Dogs". Journal of Veterinary Internal Medicine. 8 (5): 328–36. doi:10.1111/j.1939-1676.1994.tb03245.x. PMID 7837108.
## External links[edit]
* Head Tilt: Causes and Treatment
Classification
D
* ICD-10: M43.6
* ICD-9-CM: 723.5
* MeSH: D014103
* DiseasesDB: 31866
External resources
* MedlinePlus: 000749
* eMedicine: emerg/597 orthoped/452
* Patient UK: Torticollis
Wikimedia Commons has media related to Torticollis.
* v
* t
* e
Spinal disease
Deforming
Spinal curvature
* Kyphosis
* Lordosis
* Scoliosis
Other
* Scheuermann's disease
* Torticollis
Spondylopathy
inflammatory
* Spondylitis
* Ankylosing spondylitis
* Sacroiliitis
* Discitis
* Spondylodiscitis
* Pott disease
non inflammatory
* Spondylosis
* Spondylolysis
* Spondylolisthesis
* Retrolisthesis
* Spinal stenosis
* Facet syndrome
Back pain
* Neck pain
* Upper back pain
* Low back pain
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Intervertebral disc disorder
* Schmorl's nodes
* Degenerative disc disease
* Spinal disc herniation
* Facet joint arthrosis
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Torticollis | c0040485 | 4,026 | wikipedia | https://en.wikipedia.org/wiki/Torticollis | 2021-01-18T19:09:13 | {"mesh": ["D014103"], "umls": ["C0040485"], "icd-9": ["723.5"], "icd-10": ["M43.6"], "wikidata": ["Q615363"]} |
PMM2-congenital disorder of glycosylation (PMM2-CDG, also known as congenital disorder of glycosylation type Ia) is an inherited condition that affects many parts of the body. The type and severity of problems associated with PMM2-CDG vary widely among affected individuals, sometimes even among members of the same family.
Individuals with PMM2-CDG typically develop signs and symptoms of the condition during infancy. Affected infants may have weak muscle tone (hypotonia), retracted (inverted) nipples, an abnormal distribution of fat, eyes that do not look in the same direction (strabismus), developmental delay, and a failure to gain weight and grow at the expected rate (failure to thrive). Infants with PMM2-CDG also frequently have an underdeveloped cerebellum, which is the part of the brain that coordinates movement. Distinctive facial features are sometimes present in affected individuals, including a high forehead, a triangular face, large ears, and a thin upper lip. Children with PMM2-CDG may also have elevated liver function test results, seizures, fluid around the heart (pericardial effusion), and blood clotting disorders. About 20 percent of affected infants do not survive the first year of life due to multiple organ failure.
The most severe cases of PMM2-CDG are characterized by hydrops fetalis, a condition in which excess fluid builds up in the body before birth. Most babies with hydrops fetalis are stillborn or die soon after birth.
People with PMM2-CDG who survive infancy may have moderate intellectual disability, and some are unable to walk independently. Affected individuals may also experience stroke-like episodes that involve an extreme lack of energy (lethargy) and temporary paralysis. Recovery from these episodes usually occurs over a period of a few weeks to several months.
During adolescence or adulthood, individuals with PMM2-CDG have reduced sensation and weakness in their arms and legs (peripheral neuropathy), an abnormal curvature of the spine (kyphoscoliosis), impaired muscle coordination (ataxia), and joint deformities (contractures). Some affected individuals have an eye disorder called retinitis pigmentosa that causes vision loss. Females with PMM2-CDG have hypergonadotropic hypogonadism, which affects the production of hormones that direct sexual development. As a result, females with PMM2-CDG do not go through puberty. Affected males experience normal puberty but often have small testes.
## Frequency
More than 800 individuals with PMM2-CDG have been identified worldwide.
## Causes
PMM2-CDG is caused by mutations in the PMM2 gene. This gene provides instructions for making an enzyme called phosphomannomutase 2 (PMM2). The PMM2 enzyme is involved in a process called glycosylation, which attaches groups of sugar molecules (oligosaccharides) to proteins. Glycosylation modifies proteins so they can perform a wider variety of functions. Mutations in the PMM2 gene lead to the production of an abnormal PMM2 enzyme with reduced activity. Without a properly functioning PMM2 enzyme, glycosylation cannot proceed normally. As a result, incorrect oligosaccharides are produced and attached to proteins. The wide variety of signs and symptoms in PMM2-CDG are likely due to the production of abnormally glycosylated proteins in many organs and tissues.
### Learn more about the gene associated with PMM2-congenital disorder of glycosylation
* PMM2
## Inheritance Pattern
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| PMM2-congenital disorder of glycosylation | c0349653 | 4,027 | medlineplus | https://medlineplus.gov/genetics/condition/pmm2-congenital-disorder-of-glycosylation/ | 2021-01-27T08:25:29 | {"gard": ["9826"], "mesh": ["C535739"], "omim": ["212065"], "synonyms": []} |
## Description
Idiopathic scoliosis, an abnormality of the vertebral column in which patients develop lateral curvature of the spine of at least 10 degrees, affects approximately 2 to 3% of the worldwide population and has a heritable component (summary by Bashiardes et al., 2004).
For a discussion of genetic heterogeneity of isolated scoliosis, see IS1 (181800).
Cytogenetics
Bashiardes et al. (2004) described a family in which a pericentric inversion of chromosome 8 cosegregated with idiopathic scoliosis. The long arm break did not interrupt any known gene and occurred in a region of highly repetitive sequence elements. On the short arm, the break occurred in a 32-kb region between exons 10 and 11 of the SNTG1 gene (608714). Mutation analysis of SNTG1 exons in 152 sporadic idiopathic scoliosis patients revealed a 6-bp deletion in exon 10 in 1 patient and a 2-bp insertion/deletion mutation occurring in a polypyrimidine tract of intronic sequence approximately 20 bp upstream of the SNTG1 exon 5 splice site in 2 patients. These changes were not seen in a screen of 480 control chromosomes. Because SNTG1 expression appeared to be restricted to neural lineages, the authors could not directly measure SNTG1 splice forms in any of the patients.
Mapping
Gao et al. (2007) studied a cohort of 52 families ascertained through probands who had received a confirmed diagnosis of idiopathic scoliosis and had reported additional family history of idiopathic scoliosis. Genomewide scans produced evidence of linkage and association with 8q12 loci (multipoint lod = 2.77; P = 0.0028). Further fine mapping in the region revealed significant evidence of disease-associated haplotypes centering over exons 2 through 4 of the CHD7 gene (608892), which had been found to be mutant in the CHARGE syndrome of multiple anomalies (214800).
Molecular Genetics
For discussion of a possible association between variation in the CHD7 gene and susceptibility to idiopathic scoliosis mapping to chromosome 8q12, see 608892.0009.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| SCOLIOSIS, ISOLATED, SUSCEPTIBILITY TO, 3 | c1837461 | 4,028 | omim | https://www.omim.org/entry/608765 | 2019-09-22T16:07:20 | {"omim": ["608765"]} |
Siegel-Bartlet et al. (2002) reported 2 female sibs with congenital heart defects: one with atrial and ventricular septal defects, which were surgically repaired, and the other with a ventricular septal defect that closed spontaneously. Both sibs also had a sacral neural tube defect with tethered cord requiring surgical repair. Other common features included bilateral hyperopia, rapid onset of cataracts, aphakic glaucoma, and abnormal facial features with low anterior hairline, short philtrum with full lips, prominent widely spaced central incisors, and micrognathia. There was generalized growth and developmental delay. Siegel-Bartlet et al. (2002) distinguished the disorder from Kousseff syndrome (see 188400) by the presence of cataracts. They suggested that the apparently autosomal recessive MCA/MR disorder in their family might be caused by a metabolic derangement.
INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Low anterior hairline \- Micrognathia \- Short philtrum Eyes \- Hyperopia \- Cataracts, rapid-onset \- Aphakic glaucoma Mouth \- Full lips Teeth \- Prominent widely-spaced incisors CARDIOVASCULAR Heart \- Atrial septal defect \- Ventricular septal defect CHEST Breasts \- Inverted nipples SKELETAL \- Decreased bone density \- Delayed bone age Spine \- Tethered spinal cord \- Compression deformities of the spine \- Scoliosis SKIN, NAILS, & HAIR Skin \- Sacral dimple Hair \- Low anterior hairline NEUROLOGIC Central Nervous System \- Developmental delay \- Central hypotonia \- Peripheral hypertonia ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| CRANIOFACIAL ABNORMALITIES, CATARACTS, CONGENITAL HEART DISEASE, SACRAL NEURAL TUBE DEFECTS, AND GROWTH AND DEVELOPMENTAL RETARDATION | c1842363 | 4,029 | omim | https://www.omim.org/entry/608227 | 2019-09-22T16:08:07 | {"mesh": ["C564271"], "omim": ["608227"], "orphanet": ["314993"], "synonyms": []} |
A number sign (#) is used with this entry because immunodeficiency-centromeric instability-facial anomalies syndrome-2 (ICF2) is caused by homozygous or compound heterozygous mutation in the ZBTB24 gene (614064) on chromosome 6q21.
Description
Immunodeficiency, centromeric instability, and facial dysmorphism (ICF) syndrome is a rare autosomal recessive disorder characterized by facial dysmorphism, immunoglobulin deficiency resulting in recurrent infections, and mental retardation. Laboratory studies of patient cells show hypomethylation of satellite regions of chromosomes 1, 9, and 16, as well as pericentromeric chromosomal instability in response to phytohemagglutinin stimulation (summary by de Greef et al., 2011).
For a discussion of genetic heterogeneity of immunodeficiency-centromeric instability-facial anomalies syndrome, see ICF1 (242860).
Clinical Features
De Greef et al. (2011) reported 7 patients from 6 families with agammaglobulinemia, facial anomalies, and mental retardation. Facial anomalies included broad, flat nasal bridge, hypertelorism, and epicanthal folds. Four of the patients also had motor delay. Five of the patients had previously been reported by Hagleitner et al. (2008). All had recurrent infections, sometimes leading to early death. While there were no apparent clinical differences between ICF1 and ICF2. cells from patients with ICF2 showed hypomethylation of the alpha-satellite repeat on chromosome 9.
Chouery et al. (2012) reported 3 Lebanese brothers with ICF2. The parents originated from the same village, but denied consanguinity. The boys showed delayed psychomotor development and recurrent respiratory infections from infancy. They had a round face, high-arched palate, small chin, retrognathism, and everted lower lip. Head circumferences were between the 5th and 15th percentiles, and height was below the 5th percentile. Karyotype analysis showed 30 to 40% cells with whole-arm deletions and pericentromeric breaks of chromosomes 1, 9, and 16; multibranched chromosomes containing 3 or more arms of 1, 9, and 16 joined in the vicinity of the centromere; and/or decondensation in the 1qh and 16qh regions. Methylation studies showed a lack of methylation of the alpha satellite in 2 patients, thus leading to the diagnosis. Laboratory studies showed decreased IgM and IgG; IgA was normal. Absolute and relative numbers of B and T cells were normal, but there was absence of memory B cells and a decrease in memory T cells.
Inheritance
The transmission pattern of ICF2 in the families reported by de Greef et al. (2011) was consistent with autosomal recessive inheritance. Five of 6 reported families were consanguineous.
Molecular Genetics
By homozygosity mapping of 5 patients with ICF2, born of consanguineous parents, followed by exome sequencing in 1 patient, de Greef et al. (2011) identified a homozygous truncating mutation in the ZBTB24 gene (R320X; 614064.0001). Homozygous mutations in the ZBTB24 gene were subsequently identified in 3 of the 4 remaining consanguineous families, as well as in an additional consanguineous family (see, e.g., S16X; 614064.0002 and R457X; 614064.0005). An affected sib pair of nonconsanguineous descent was compound heterozygous for ZBTB24 mutations (S278X; 614064.0003 and C408G; 614064.0004). Mutations in this gene were not identified in 4 remaining patients with a similar phenotype, indicating further genetic heterogeneity. All but 1 of the mutations created a premature stop codon, indicating that ICF2 is caused by ZBTB24 loss of function.
Chouery et al. (2012) identified a homozygous 2-bp deletion in the ZBTB24 gene (396delTA; 614064.0006) in 3 Lebanese brothers with ICF2. The molecular studies indicated a loss-of-function effect. The unaffected parents were heterozygous for the mutation, which was found by Sanger sequencing after no mutations were found in the DNMT3B gene.
Genotype/Phenotype Correlations
Among 44 patients with a clinical diagnosis of ICF, Weemaes et al. (2013) found that 23 (52%) had mutations in the DNMT3B gene and 13 (30%) had mutations in the ZBTB24 gene. A genetic defect was not identified in 8 patients. Although the phenotype was relatively homogeneous, systematic phenotypic evaluation showed that humoral immunodeficiency was generally more pronounced in ICF1 patients and ICF2 patients had a significantly higher incidence of intellectual disability. Both T- and B-cell compartments were involved in ICF1 and ICF2. A few patients from both groups had congenital malformations including cardiac defects, cleft lip, clinodactyly, choanal stenosis, hip dislocation, and cerebral malformations.
INHERITANCE \- Autosomal recessive GROWTH Other \- Poor growth HEAD & NECK Face \- Round face \- Retrognathia \- Small chin Ears \- Low-set ears Eyes \- Epicanthal folds \- Hypertelorism Nose \- Flat nasal bridge \- Small nose \- Upturned nose Mouth \- High-arched palate RESPIRATORY Airways \- Chronic bronchitis Lung \- Pneumonia ABDOMEN Gastrointestinal \- Gastroenteritis NEUROLOGIC Central Nervous System \- Mental retardation \- Delayed motor development IMMUNOLOGY \- Recurrent infections \- Opportunistic infections \- Hypogammaglobulinemia \- Normal numbers of absolute B cells \- Reduced number of memory B cells LABORATORY ABNORMALITIES \- Hypomethylation of alpha-satellite repeats on chromosome 9 \- Hypomethylation of satellite repeats on chromosome 1, 9, and 16 \- Chromosomal breakage and abnormalities of the juxtacentromeric regions of chromosomes 1, 9, and 16 MISCELLANEOUS \- Onset at birth \- Death in childhood may occur due to infection MOLECULAR BASIS \- Caused by mutation in the zinc finger- and BTB domain-containing protein 24 gene (ZBTB24, 614064.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| IMMUNODEFICIENCY-CENTROMERIC INSTABILITY-FACIAL ANOMALIES SYNDROME 2 | c3279748 | 4,030 | omim | https://www.omim.org/entry/614069 | 2019-09-22T15:56:39 | {"doid": ["0090009"], "omim": ["614069"], "orphanet": ["2268"], "synonyms": ["Immunodeficiency-centromeric instability-facial anomalies syndrome"]} |
Sooty blotch and flyspeck (SBFS) or apple summer disease is a plant disease caused by a complex of saprophytic fungi which colonize the epicuticular wax layer of apple (Malus x domestica Borkh.). It is found worldwide in regions with moist growing seasons.[1]
## Contents
* 1 Description
* 2 Risk factors
* 3 Biology
* 3.1 History of discovery
* 3.2 Diversity
* 4 Effect
* 5 Control
* 6 See also
* 7 References
## Description[edit]
Haralson with its typical peel coloration from sooty blotch and flyspeck
Sooty blotch and flyspeck is a descriptive term for a condition of darkly pigmented blemishes and smudges caused by a number of different fungi affecting fruit including apples, pear, persimmon, banana, papaya, and several other cultivated tree and vine crops. The greenish black coating resembling soot or flyspeck-like dots grow into irregular stains and blotches during the summer or growing season. They can grow into each other and may cover the entire fruit surface. Frequently blotches run down in a track resembling tears (German: "Regenfleckenkrankheit"). The blotches can be removed by vigorous rubbing or be scratched off revealing a normal peel. Symptoms can be seen particularly well when apples are light or green colored. Late varieties are more susceptible, because the disease builds over a longer growing period.[2]
## Risk factors[edit]
Moist and cool weather favors the infection. Orchards with shade or regions near bodies of water with frequent morning dew are especially prone to disease. Infections can occur from June until autumn. Secondary infections are caused by conidia, which are transported by wind and rain onto other developing fruit. The first visible signs of SBFS colonies appear about 3 weeks after infection.[2]
## Biology[edit]
Microscopically, the flyspeck-like spots and sooty blemishes are fungal mycelium adhering to fruit. The fungi live as saprophytes on the wax layer surface of apples and do not invade the peel. The hyphae, fruiting bodies, and survival structures of these fungi become melanized over time. SBFS fungi also grow on the surfaces of stems, twigs, leaves, and fruit of a wide range of wild plants.[3]
### History of discovery[edit]
In an 1832 paper written in Latin and published in Philadelphia, Ludwig Schweinitz described the first sooty blotch species as a fungus he named 'Dothidea pomigena'. It remained the sole species established as a cause until the beginning of the 1990s. In 1920, sooty blotch and flyspeck were mentioned together for the first time, blotch caused by Dothidea, renamed as Gloeodes pomigena and flyspeck caused by Schizothyrium pomi, respectively. Over the next 80 years various different looks of mycelia, that is morphologies were described.[4]
By the end of the 20th century three more fungal species had been identified as causes of sooty blotch on North Carolina apples, still based on their morphological type: Peltaster fructicola, Geastrumia polystigmatis and Leptodontium elatius.[5] The authors broke ground after 160 years of "confusion", stating that "sooty blotch fungi are difficult to isolate due to many contaminating microorganisms on the surface of plant parts".[5]:94 Also, fruiting structures -a major part of morphological identification- are rare on apple peels. The authors went back to the original historical deposits at the herbarium of the Academy of Natural Sciences in Philadelphia and found no conidia. They coined the term 'apple sooty blotch complex' for this group of fungi, which they suspected would include more.[5]:94
As soon as DNA sequence-based methods were used, many more fungi were found and new species and genera described. A sample from nine orchards in four Midwestern states near the cities of Indianola, Pella, Iowa Falls in Iowa, Rockford, Illinois, Simpson and Chester in Illinois, Mooresville and New Franklin in Missouri and New Munster, Wisconsin grew 422 isolates. Their 1 month old DNA was extracted and two regions, ITS1 and 28S ribosomal RNA sequenced.Parsimony analysis, bootstrapping and the minimum evolution principle led to groups of species, further described by conidial and colony morphology. The species were re-inoculated into apples grown at an Iowa State University research station in Gilbert, Iowa, re-isolated, sequenced, and morphology compared. Thirty isolates fulfilled Koch’s postulates as new species, all Dothideomycetes, 27 were within Dothideales, one was within Pleosporales and two with undetermined ordinal level. Only 2 species (Peltaster fructicola and Zygophiala jamaicensis) had previously been associated with SBFS [4]
A 2008 publication of the same sample plus a 2005 sample of 30 more orchards in 10 eastern U.S. states, (39 US apple orchards in 14 states) speciated by DNA- and phylogenetic analyses reported 58 putative species belonging to the Dothideomycetes, 52 of which were Capnodiales, and 36 were part of the Mycosphaerellaceae. Thus the SBFS species diversity had been underestimated by more than tenfold. The number of species per orchard varied from 2 to 15, with a higher diversity the longer an orchard had not been sprayed with fungicide.with blotch and flyspeck signs, reported four species of Zygophiala (Schizothyriaceae, Capnodiales), three of them newly identified. Schizothyrium pomi, Peltaster fructicola, and Pseudocercosporella sp. RH1, were found in nearly every geographic region. Species, such as Stomiopeltis sp. RS5.2, Phialophora sessilis, and Geastrumia polystigmatis, were found only in certain regions, leading to the conclusion that SBFS species differ geographically.[6]
Since then, slow-growing epiphytic fungi often belonging to the Capnodiales have been identified (Gleason et al. 2011), and a new species in 2014, Peltaster cerophilus from Europe.[7]
### Diversity[edit]
Most fungi are part of the Ascomycetes. The composition of the fungal complex varies depending on the region. Their complete life cycle is as of yet unknown. The fungi are hibernating on wild plants like willow, ash or brambles, which are the locus of primary infections.[5] Whether fungi stay within apple orchards is unknown. They probably thrive on apple juice, which exits through minute tears of the cuticula during growth.[2]
Flyspeck disease is caused by Schizothyrium pomi. It causes sharply demarcated grey blotches consisting of many small black flyspeck like dots. They can be rubbed off like sooty blotch, but no tear formation occurs. Fruit develop normally. Flyspeck frequently occurs in older trees with light colored peels (Golden Delicious, etc.). Because of their similarity the two diseases are often combined as sooty blotch and flyspeck ("Regenfleckenkrankheit" in German).[2]
## Effect[edit]
The blotches are cosmetic damage "unacceptable to consumers"[4] and downgrade fruit from premium fresh-market grade to processing use, i.e. reduce its market value, but leaf and fruit development are not affected.[2]
## Control[edit]
Preventive measures are pruning which allows light and air to enter the tree, to achieve fast drying. Strong growth within the root area dams up moisture and facilitates infection.[2]
A prognostic model called Sooty Blotch RIMpro has been developed, which still awaits validation. Similar to the apple scab model it numerically grades risk and degree of infection and can serve as a warning system. It allows conventional growers to spray more targeted. The parameters for calculation are wetness of leaves, amount of rain fall and temperature.[8]
Conventional orchards that spray fungicides against apple scab, treat soot blotch and flyspeck at the same time. Therefore, the problem is not seen in conventional non-resistant varieties. However, scab-resistant varieties, which are not sprayed frequently show the infection. In organic orchards, spraying 4–5 with lime sulphur or coco soap during the main infectious periods is recommended.[2]
## See also[edit]
* Sooty mold
* Apple scab
## References[edit]
1. ^ Williamson, S. M.; Turner S. B. (2000). "Sooty Blotch and Flyspeck of Apple: Etiology, Biology, and Control". Plant Disease. 84 (7): 714–724. doi:10.1094/pdis.2000.84.7.714.
2. ^ a b c d e f g Rußflecken Kompetenzzentrum Obstbau-Bodensee in Bavendorf (KOB), not dated, retrieved 25 October 2015
3. ^ Gleason, Mark L.; Batzer, Jean C.; Sun, Guangyu; Zhang, Rong; Arias, Maria M. Díaz; Sutton, Turner B.; et al. (2011). "A New View of Sooty Blotch and Flyspeck". Plant Disease. 95 (4): 368–383. doi:10.1094/PDIS-08-10-0590. ISSN 0191-2917. PMID 30743360.
4. ^ a b c Batzer, JC; Gleason, ML; Harrington, TC; Tiffany, LH (2005). "Expansion of the sooty blotch and flyspeck complex on apples based on analysis of ribosomal DNA gene sequences and morphology". Mycologia. 97 (6): 1268–86. doi:10.3852/mycologia.97.6.1268. PMID 16722219.
5. ^ a b c d Johnson, EM; Sutton, TB; Hodges, CS (1997). "Etiology of apple sooty blotch disease in north Carolina". Phytopathology. 87 (1): 88–95. doi:10.1094/PHYTO.1997.87.1.88. PMID 18945159.
6. ^ Batzer, JC; Arias, MM; Harrington, TC; Gleason, ML; Groenewald, JZ; Crous, PW (2008). "Four species of Zygophiala (Schizothyriaceae, Capnodiales) are associated with the sooty blotch and flyspeck complex on apple". Mycologia. 100 (2): 246–58. doi:10.3852/mycologia.100.2.246. PMID 18592899.
7. ^ Medjedović, A; Frank, J; Schroers, HJ; Oertel, B; Batzer, JC (2014). "Peltaster cerophilus is a new species of the apple sooty blotch complex from Europe". Mycologia. 106: 525–536. doi:10.3852/13-226.
8. ^ RIMpro forecast model "Sooty Blotch" Fruitwebinfo, not dated, retrieved 25 October 2015
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*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Sooty blotch and flyspeck | None | 4,031 | wikipedia | https://en.wikipedia.org/wiki/Sooty_blotch_and_flyspeck | 2021-01-18T19:08:49 | {"wikidata": ["Q7562791"]} |
Willard et al. (1986) described a general strategy for the detection of high-frequency restriction fragment length polymorphisms in the centromeric regions of human chromosomes by molecular analysis of alpha satellite DNA. Alpha satellite DNA represents a diverse family of randomly repeated DNA located near the centromeres of all chromosomes. Its organization is chromosome specific. Willard et al. (1986) described multiple high-frequency RFLPs for the centromeric region of chromosome 17 and the X chromosome. The X-linked polymorphisms were particularly informative and constituted a virtually unique marker for each X chromosome studied. Waye and Willard (1986) found in hybridization experiments that the sequences on chromosome 17 and the X chromosome are more similar to each other than to the sequences on several other chromosomes. Thus, they may be members of an alphoid subfamily that evolved from a common ancestral repeat. The alphoid family of repetitive DNA is found exclusively in primates. Different families of this repeat probably arose before the emergence of several of these species, after which the alphoid families have remained relatively unchanged. Although the separation of the branches leading to great apes and humans took place 6 to 8 million years ago, the most significant human evolution has probably taken place within the last few million years. One might therefore expect to find within the human genome families of the alphoid repeat that have been amplified relatively recently. Chromosome specificity of subfamilies of alphoid DNA implies that transfer of sequences between nonhomologous human chromosomes occurs very rarely. However, the nucleolus-organizing (NOR) chromosomes appear to undergo recombination between nonhomologs more frequently than do other chromosomes. This may account for the fact that Jorgensen et al. (1987) found related subfamilies of alphoid sequences in 3 NOR-bearing chromosomes--13, 21, and 22. Waye et al. (1988) found that, under conditions of high stringency, a cloned alpha satellite sequence called p82H hybridizes solely to a low-copy or single-copy alphoid domain located at or near the centromere of chromosome 14.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| DNA, SATELLITE, ALPHA TYPE | c1852038 | 4,032 | omim | https://www.omim.org/entry/126410 | 2019-09-22T16:42:11 | {"omim": ["126410"]} |
A number sign (#) is used with this entry because of evidence that recurrent metabolic crises with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration (MECRCN) is caused by homozygous or compound heterozygous mutation in the TANGO2 gene (616830) on chromosome 22q11.
Description
Recurrent metabolic crises with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration (MECRCN) is an autosomal recessive disorder characterized by episodic metabolic degeneration affecting skeletal muscle, cardiac muscle, and the nervous system. Affected individuals usually present in childhood with acute encephalomyopathic features, including rhabdomyolysis, hypotonia, and neurologic regression, although most patients have delayed psychomotor development before the acute onset. The overall disease course is characterized by progressive neurodegeneration with epilepsy, cognitive impairment, pyramidal and cerebellar signs, and loss of expressive language. Cardiac involvement with severe arrhythmias is a consistent and potentially life-threatening manifestation (summary by Lalani et al., 2016 and Kremer et al., 2016).
Clinical Features
Lalani et al. (2016) studied 12 affected individuals from 9 families with episodic rhabdomyolysis, hypoglycemia, hyperammonemia, and susceptibility to cardiac tachyarrhythmias. Acute rhabdomyolysis was the presentation in 10 of the 12 patients, with onset between 5 months and 8 years of age. Neurodevelopmental problems were observed in all affected individuals by early childhood, and muscle weakness, gait abnormality, or poor coordination were reported in most patients prior to the acute presentation of myoglobinuria. Seizures were present in 9 of 12 patients. The acute clinical presentation ranged from profound muscle weakness, ataxia, and/or disorientation to a comatose state, frequently precipitated by an acute illness. During these metabolic crises, hypoglycemia, hyperlactacidemia, and mild hyperammonemia were repeatedly observed. Elevated transaminases were also noted, indicative of muscle injury. Acylcarnitine profiles during acute episodes showed elevated C14:1 in at least 3 patients; another patient had elevated C10 species during the acute episode, and another showed elevated C3 (propionyl-carnitine) and C10 species. Life-threatening cardiac tachyarrhythmia presented as torsade de pointes or ventricular tachycardia in 4 (33%) of 12 patients, and intermittent prolonged QTc interval was seen in 6 (50%) of patients. The QT interval often reverted to normal between episodes, and metabolic abnormalities typically normalized outside the critical period of crises. Mitochondrial studies and muscle biopsies were essentially normal. Structural brain abnormalities, seen in 7 of 10 patients who underwent imaging, mostly reflected varying degrees of cerebral atrophy or volume loss. Gait disturbances, dysarthria, and myopathic facies were observed in most patients outside the crisis episodes. Hypothyroidism was diagnosed in 4 of 12 patients. In 1 family, affected twins from a dichorionic diamniotic pregnancy died at 2 years of age, the boy during an episode of hypoglycemia and lactic acidemia, and the girl due to worsening cardiomyopathy. In another family, 1 sib from an affected monozygotic twin pair died at 7 years of age during an acute rhabdomyolytic crisis, whereas his twin brother was alive at 11 years of age. The oldest living patient in the study cohort was 27.
Kremer et al. (2016) reported 3 unrelated individuals with recurrent encephalomyopathic crises characterized by hypoglycemia, elevated plasma creatine kinase activity, lactic acidosis, and increased acylcarnitines, as well as massive urinary excretion of lactate, ketones, and dicarboxylic acids. Prior to the first crisis, global developmental delay as well as cortical signs were observed. Although the clinical condition stabilized between episodes, the overall disease course was one of neurodegeneration, including epilepsy, cognitive impairment, pyramidal and cerebellar signs, and loss of expressive language. Optic atrophy and sensorineural hearing impairment were each seen in 1 patient. Cardiac involvement, with severe arrhythmias including torsade de pointes and long QT syndrome, was a consistent and potentially life-threatening condition. Increased TSH levels indicating hypothyroidism were documented in all 3 patients.
Molecular Genetics
Lalani et al. (2016) performed whole-exome sequencing in 12 patients from 9 families with recurrent metabolic encephalomyopathic crises associated with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, who were negative for mutation in rhabdomyolysis-associated genes. A recurrent homozygous missense mutation in the TANGO2 gene (G154R; 616830.0001) was identified in 4 unrelated Hispanic probands, and homozygous deletion of exons 3-9 (616830.0002) was identified in 4 probands from 2 families of European origin. In addition, the proband from a mixed Hispanic/European family was compound heterozygous for G154R and the exon 3-9 deletion. In another Hispanic family, the proband was homozygous for a splice site mutation (616830.0003), and 2 affected sibs from a Saudi Arabian family carried a homozygous deletion of exons 4-6 (616830.0004). The mutations segregated fully with disease in the families, and none of the variants was present in homozygosity in control databases.
Kremer et al. (2016) performed whole-exome sequencing in 3 unrelated individuals with recurrent metabolic encephalomyopathic crises associated with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, and identified homozygosity or compound heterozygosity for mutations in the TANGO2 gene in all 3 patients: 1 patient was homozygous for deletion of exons 3-9, another was compound heterozygous for the exon 3-9 deletion and a 1-bp deletion (616830.0005), and the third patient was homozygous for a nonsense mutation (R140X; 616830.0006). The mutations segregated with disease in each of the families, and none of the variants had been reported in homozygous state in public databases.
INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Microcephaly (in some patients) Face \- Myopathic facies Ears \- Hearing loss, sensorineural (in some patients) Eyes \- Optic atrophy (rare) Mouth \- Drooling \- Oropharyngeal dysphagia CARDIOVASCULAR Heart \- Long QTc interval, intermittent \- Premature ventricular contraction \- Ventricular tachycardia \- Torsade de pointes \- Ventricular fibrillation \- Cardiac arrest \- Brugada pattern on electrocardiogram (rare) \- Cardiomyopathy, hypertrophic (in some patients) CHEST Breasts \- Premature thelarche (rare) SKELETAL Skull \- Microcephaly (in some patients) MUSCLE, SOFT TISSUES \- Muscle weakness \- Rhabdomyolysis, episodic \- Normal respiratory chain studies seen on muscle biopsy \- Normal histopathology seen on muscle biopsy (in some patients) \- Nonspecific myopathic changes seen on biopsy (in some patients) \- Neurogenic atrophy of muscle fibers seen on biopsy (in some patients) \- Hemihypertrophy of right arm and leg (rare) NEUROLOGIC Central Nervous System \- Neurodegeneration, progressive \- Global developmental delay \- Mental retardation \- Absent speech/nonverbal \- Seizures \- Dysarthric speech \- Hypotonia \- Weakness in lower extremities \- Ataxic gait \- Scissoring gait \- Brisk deep tendon reflexes \- Positive Babinski sign, bilateral \- Clonus \- Dystonia (in some patients) \- Spasticity of lower extremities (in some patients) \- Spastic diplegia (in some patients) \- Spastic quadriplegia (rare) \- Cerebral atrophy, mild diffuse \- Cerebellar volume loss, mild \- Wallerian degeneration of cerebral peduncles (in some patients) METABOLIC FEATURES \- Hypoglycemia, intermittent severe \- Metabolic acidosis \- Lactic acidemia \- Excretion of dicarboxylic acids \- Normalization of metabolic parameters in between crises ENDOCRINE FEATURES \- Elevated TSH \- Hypothyroidism \- Premature pubarche (rare) LABORATORY ABNORMALITIES \- Hypoglycemia, intermittent severe \- Myoglobinuria \- Ketonuria \- Elevated serum creatine phosphokinase (CPK) levels \- Elevated serum ammonia \- Elevated serum transaminases \- Elevated serum acylcarnitines \- Elevated aldolase MISCELLANEOUS \- Metabolic encephalomyopathic crises often triggered by infection MOLECULAR BASIS \- Caused by mutation in the transport and Golgi organization 2 homolog gene (TANGO2, 616830.0001 ) ▲ Close
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| METABOLIC CRISES, RECURRENT, WITH RHABDOMYOLYSIS, CARDIAC ARRHYTHMIAS, AND NEURODEGENERATION | c4225171 | 4,033 | omim | https://www.omim.org/entry/616878 | 2019-09-22T15:47:39 | {"omim": ["616878"], "orphanet": ["480864"], "synonyms": [], "genereviews": ["NBK476443"]} |
Lichen planus (LP) pigmentosus is a rare variant of cutaneous lichen planus (see this term) characterized by the presence of hyperpigmented lichenoid lesions in sun-exposed or flexural areas of the body.
## Epidemiology
LP pigmentosus is a rare disease in Europe but it is common in Indian populations and in the Middle East. The overall prevalence is unknown. There is no difference in distribution between males and females.
## Clinical description
The disease usually appears in the third and fourth decade of life. The lesions are asymptomatic or mildly pruritic. Skin changes are dark brown or slate grey macules or papules with, in most cases, a diffuse pigmentation pattern. They most commonly affect the face, neck and upper limbs. Predominantly a intertriginous disease, usually in the axillae and groin (described mostly in Caucasians), it has also been termed as lichen planus pigmentosus inversus. The scalp, nails or mucosa are not affected. LP pigmentosus can exist in association with typical LP lesions.
## Etiology
Etiology is unknown but various factors (e.g. viral infections and certain topical agents including mustard oil, amla oil and henna hair dyes) can trigger the disease. One case has been reported in association with Bazex syndrome (see this term).
## Diagnostic methods
Histological features of LP pigmentosus are similar but milder than classic LP, with a lichenoid interface reaction, vacuolar change and apoptotic keratinocytes. Melanin incontinence is prominent, and may be the only feature of older lesions; it may extend deeper into the dermis than typical post-inflammatory pigmentation.
## Prognosis
Lichen planus pigmentosa seems to follow a chronic progressive course.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Lichen planus pigmentosus | c0406366 | 4,034 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=254463 | 2021-01-23T17:49:17 | {"gard": ["10816"], "umls": ["C0406366"], "icd-10": ["L43.8"], "synonyms": ["LP pigmentosa", "LP pigmentosus", "Lichen planus pigmentosa", "Lichen planus pigmentosus inversus"]} |
## Description
Familial juvenile hypertrophy of the breast (JHB) is a rare condition characterized by gigantomastia in peripubertal females. The pathology is limited to the breast with otherwise normal growth and development (summary by Genzer-Nir et al., 2010).
A syndrome has been described in which affected females display JHB in association with onychodystrophy/anonychia and abnormalities of the distal phalanges (ODP; see 106995), whereas males have only ODP (mammary-digital-nail syndrome; 613689).
Clinical Features
Badejo (1984) observed unilateral giant breast in 4 of 7 female children from 2 unrelated families in Nigeria. Males were unaffected. All 4 affected females noted the development around age 8 years, which resulted in great social embarrassment throughout their lives. Unilateral breast enlargement was suspected in the 4-year-old child of an affected female. Three of the women had breast reduction surgery, and histology showed no evidence of malignancy. One of the patients developed hypertrophy of the other breast after surgery. The condition had been described before by surgeons in Africa who attributed it to lymphedema or considered it to be related in part to pregnancy. However, onset occurred well before pregnancy in this study. Badejo (1984) suspected that the father in each family might be a carrier of a sex-limited autosomal dominant gene.
Kupfer et al. (1992) reported a mother and daughter with the condition. The mother developed rapid massive enlargement of both breasts at age 11 years. As a consequence, she developed kyphosis and lordosis necessitating breast reduction surgery. Histologic examination showed hyperplasia of stromal and epithelial elements. Her daughter developed similar bilateral massive breast enlargement following normal menarche at age 11.5 years. Kupfer et al. (1992) provided a review of the literature and stated that 29 cases had been reported, including their 2. Juvenile hypertrophy of the breast was characterized by rapid, bilateral, and often asymmetrical enlargement of the breasts in the peripubertal period. The pathologic mechanism was postulated to represent an end-organ hypersensitivity to normal estrogen stimuli.
Misirlioglu and Akoz (2005) reported 2 affected adult sisters who had onset of the disorder in adolescence.
Dancey et al. (2008) provided a review of gigantomastia and proposed a classification scheme based on the cause, management, and prognosis of the disease. Among a total of 115 patients gleaned from the literature and their practice, the authors identified 57 as having juvenile gigantomastia. The juvenile form was considered to be distinct from pregnancy-induced gigantomastia, although both forms likely result from aberrant endogenous hormone stimulation.
Thorax \- Unilateral giant breast Inheritance \- Sex-limited autosomal dominant ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| HYPERTROPHY OF THE BREAST, JUVENILE | c0405471 | 4,035 | omim | https://www.omim.org/entry/113670 | 2019-09-22T16:43:56 | {"mesh": ["C536821"], "omim": ["113670"], "orphanet": ["180176"], "synonyms": ["Virginal breast hypertrophy", "Alternative titles", "Familial juvenile gigantomastia", "GIGANTOMASTIA, JUVENILE"]} |
Chemotherapy-induced peripheral neuropathy
Other namesCIPN
SpecialtyNeurology
Chemotherapy-induced peripheral neuropathy is a progressive, enduring, and often irreversible condition featuring pain, numbness, tingling and sensitivity to cold in the hands and feet (sometimes progressing to the arms and legs) that afflicts between 30% and 40% of patients undergoing chemotherapy.[1]
## Contents
* 1 Symptoms
* 2 Causes
* 3 Research
* 3.1 Antidepressants
* 3.2 Valproate
* 3.3 Interleukin-6
* 3.4 Dietary supplements
* 3.4.1 Glutathione
* 3.4.2 Intravenous calcium and magnesium
* 3.4.3 Acetyl-L-carnitine
* 3.4.4 Others
* 4 References
## Symptoms[edit]
Though the symptoms are mainly sensory – pain, tingling, numbness and temperature sensitivity – in some cases motor nerves are affected, and occasionally, also, the autonomic nervous system.[2] CIPN often follows the first chemotherapy dose and increases in severity as treatment continues, but this progression usually levels off at completion of treatment. The platinum-based drugs are the exception; with these drugs, sensation may continue to deteriorate for several months after the end of treatment.[3] Some CIPN appears to be irreversible.[3]
CIPN disrupts leisure, work, and family relations, and the pain of CIPN is often accompanied by sleep and mood disturbance, fatigue and functional difficulties. A 2007 American Cancer Society study found that most patients did not recall being told to expect CIPN, and doctors monitoring the condition rarely asked how it affects daily living but focused on practical effects such as dexterity and gait.[4]
## Causes[edit]
Chemotherapy drugs associated with CIPN include thalidomide, the epothilones such as ixabepilone, the vinca alkaloids vincristine and vinblastine, the taxanes paclitaxel and docetaxel, the proteasome inhibitors such as bortezomib, and the platinum-based drugs cisplatin, oxaliplatin and carboplatin.[1][5][6] Whether CIPN arises, and to what degree, is determined by the choice of drug, duration of use, the total amount received and whether the patient already has peripheral neuropathy.
It is not known what causes the condition, but microtubule and mitochondrial damage, and leaky blood vessels near nerve cells are some of the possibilities being explored.[3] One of the more promising theories is that chemotherapeutic drugs act by disrupting microtubules of the mitotic spindle during cell division, causing the disruption of microtubule based axonal transport of neurons.[7] Also, the nervous system has programmed cell death pathways that are particularly sensitive to DNA damage induced by many chemotherapeutic agents. Pain can often be helped with drug or other treatment but the numbness is usually resistant to treatment.[8]
## Research[edit]
### Antidepressants[edit]
Venlafaxine
Forty eight patients experiencing acute neurotoxicity during oxaliplatin treatment were given either the antidepressant venlafaxine or placebo. Of those given venlafaxine, 31.3 percent experienced complete relief of symptoms as opposed to 5.3 percent of those on placebo. After three months, 38.5 percent of the venlafaxine-treated patients had no neuropathy, vs. 5.6 percent of those on placebo, and while 33.3 percent of the placebo-treated patients had grade 3 neuropathy after 3 months, none of the venlafaxine-treated patients did.[9][10]
Duloxetine
A trial of the antidepressant duloxetine suggested it may be useful in controlling the pain of neurotoxicity due to taxane or platinum treatment.[10][11]
### Valproate[edit]
The anticonvulsant valproate, an effective treatment for diabetic neuropathy, appeared to offer some protection against cisplatin-induced neuropathy in rats.[9]
### Interleukin-6[edit]
Interleukin-6 prevented peripheral nerve damage in animals without inhibiting the anti-cancer effect.[9]
### Dietary supplements[edit]
As possible preventative interventions, the American National Cancer Institute Symptom Management and Health-related Quality of Life Steering Committee recommends continued investigation of several dietary supplements, including glutathione, and intravenous calcium and magnesium, which have shown early promise in limited human trials; acetyl-L-carnitine, which was effective in animal models and on diabetes and HIV patients; and the anti-oxidant alpha-lipoic acid.[1]
#### Glutathione[edit]
Glutathione was studied in two large double-blind placebo-controlled trials and seemed to reduce neurotoxicity without interfering with the therapeutic effect, but shortcomings in the trial designs make confident interpretation of the results impossible. As of September 2013, patients are being recruited for a more definitive study.[9]
#### Intravenous calcium and magnesium[edit]
In a study of patients receiving oxaliplatin treatment, only 4 percent of those also receiving intravenous calcium and magnesium (ca/mg) before and after each oxaliplatin dose had to discontinue treatment due to neurotoxicity, compared to 33 percent who were receiving intravenous placebo; onset of neuropathy was also significantly delayed in the ca/mg patients, and only 22 percent of the ca/mg patients had long-term CIPN of grade 2 or worse compared with 41 percent of those on placebo. Overall, trials of ca/mg infusion suggest there are no serious harmful side effects and it may be an effective preventative therapy — the number of patients so far studied is small, however, and confident conclusions cannot be drawn.[9][12]
#### Acetyl-L-carnitine[edit]
Though preclinical trials and a phase II trial of acetyl-L-carnitine indicated it may be effective for CIPN, a 2013 review concluded there is no solid evidence to support its use; and the 2013 report of a randomized double-blind placebo-controlled trial (409 patients) of acetyl-L-carnitine for the prevention of taxane-induced neuropathy found "no evidence that ALC affected CIPN at 12 weeks; however, ALC significantly increased CIPN by 24 weeks."[13][14]
#### Others[edit]
Two small randomized controlled trials (RCTs) and one larger RCT (86 subjects) tested glutamine in the prevention of platinum treatment-induced neuropathy and showed promise. As of September 2013 a larger, placebo-controlled trial is running.[9]
A 2013 systematic review of the use of acetyl-L-carnitine, glutamine, vitamin E, glutathione, vitamin B6, omega-3 fatty acids, magnesium, calcium, alpha lipoic acid and n-acetyl cysteine as anti-CIPN adjuvants concluded that "currently no agent has shown solid beneficial evidence to be recommended for the treatment or prophylaxis of CIPN."[13]
## References[edit]
1. ^ a b c del Pino BM. Chemotherapy-induced Peripheral Neuropathy. NCI Cancer Bulletin. Feb 23, 2010 [archived October 6, 2014];7(4):6.
2. ^ Beijers AJM, Jongen, JLM & Vreugdenhil1 G. [1]. The Netherlands Journal of Medicine. January 2012 [archived 2013-12-03];70(1). PMID 22271810.
3. ^ a b c Windebank AJ & Grisold W. Chemotherapy-induced neuropathy. Journal of the Peripheral Nervous System. 2008 Mar;13(1):27–46. doi:10.1111/j.1529-8027.2008.00156.x. PMID 18346229.
4. ^ Paice JA, Ferrell B. The management of cancer pain. CA – A Cancer Journal for Clinicians. 2011;61(3):157–82. doi:10.3322/caac.20112. PMID 21543825.
5. ^ Grisold W, Oberndorfer S, Windebank AJ. Chemotherapy and polyneuropathies. European Association of Neurooncology Magazine. 2012;12(1).
6. ^ "Peripheral sensory neuropathy and Herceptin - a study from real-world data | eHealthMe".
7. ^ Windebank, Anthony J.; Grisold, Wolfgang (2008). "Chemotherapy-induced neuropathy". Journal of the Peripheral Nervous System. 13 (1): 27–46. doi:10.1111/j.1529-8027.2008.00156.x. PMID 18346229.
8. ^ Savage L. Chemotherapy-induced pain puzzles scientists. Journal of the National Cancer Institute. 2007;99(14):1070–1071. doi:10.1093/jnci/djm072. PMID 17623791.
9. ^ a b c d e f Sherry, Victoria (10 September 2013). "Chemotherapy-Induced Peripheral Neuropathy (CIPN): Scientific and Clinical Perspectives". The Abramson Cancer Center of the University of Pennsylvania. Archived from the original on 21 February 2014.
10. ^ a b Maxwell T. Vergo; Axel Grothey; Julia Minocha; Jonathan Cotliar (28 October 2013). "Management of systemic treatment-induced toxicities". In Benson, Al; Chakravarthy, A. Bapsi; Hamilton, Stanley; Sigurdson, Elin (eds.). Cancers of the Colon and Rectum: A Multidisciplinary Approach to Diagnosis and Management. Demos Medical Publishing. p. 233. ISBN 978-1-936287-58-1.
11. ^ Smith, EM; Pang, H; Cirrincione, C; Fleishman, S; Paskett, ED; Ahles, T; Bressler, LR; Fadul, CE; Knox, C; Le-Lindqwister, N; Gilman, PB; Shapiro, CL; Alliance for Clinical Trials in, Oncology (3 April 2013). "Effect of duloxetine on pain, function, and quality of life among patients with chemotherapy-induced painful peripheral neuropathy: a randomized clinical trial". JAMA. 309 (13): 1359–67. doi:10.1001/jama.2013.2813. PMC 3912515. PMID 23549581.
12. ^ Mellar P. Davis; Petra Feyer; Petra Ortner; Camilla Zimmermann (11 February 2011). Supportive Oncology: Expert Consult. Elsevier Health Sciences. ISBN 9781437710151. Archived from the original on 25 February 2014. Retrieved 9 October 2013.
13. ^ a b Schloss, JM.; Colosimo, M.; Airey, C.; Masci, PP.; Linnane, AW.; Vitetta, L. (Apr 2013). "Nutraceuticals and chemotherapy induced peripheral neuropathy (CIPN): A systematic review". Clin Nutr. 32 (6): 888–93. doi:10.1016/j.clnu.2013.04.007. PMID 23647723.
14. ^ Hutchinson, L. (Aug 2013). "Chemotherapy: Supplements--for better or worse?". Nat Rev Clin Oncol. 10 (8): 426. doi:10.1038/nrclinonc.2013.106. PMID 23774646.
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| Chemotherapy-induced peripheral neuropathy | c3873567 | 4,036 | wikipedia | https://en.wikipedia.org/wiki/Chemotherapy-induced_peripheral_neuropathy | 2021-01-18T18:36:11 | {"umls": ["C3873567"], "wikidata": ["Q17153857"]} |
Dehydrated hereditary stomatocytosis (DHS) is a rare hemolytic anemia characterized by a decreased red cell osmotic fragility due to a defect in cation permeability, resulting in red cell dehydration and mild to moderate compensated hemolysis. Pseudohyperkalemia (loss of potassium ions from red cells on storage at room temperature) is sometimes observed.
## Epidemiology
The prevalence of DHS is unknown but to date, about 20 families with DHS have been described in the literature.
## Clinical description
The clinical presentation of the disease is very heterogeneous. Onset of DHS may occur during the perinatal period with occurrence of edema and ascites (most often not related to an underlying anemia) that usually resolve spontaneously during the first weeks of life but may rarely lead to hydrops fetalis (see this term). Most adult patients present a mild anemia or a totally compensated hemolysis, with fatigue, icterus, splenomegaly and risks of secondary complications including cholelithiasis. Patients can also be referred for unexplained hemochromatosis, since iron overload is frequently associated with the disease. Thrombotic complications (arterial and venous events, including portal vein thrombosis (see this term) and pulmonary hypertension) have been described at a high rate after splenectomy.
## Etiology
Most reported DHS cases are caused by gain-of-function mutations in the gene PIEZO1 (16q24.3) which encodes part of a mechanosensitive ion channel. This results in increased red cell membrane permeability for cations that consequently leads to cation depletion, dehydration and shortened red cell survival. Rare atypical forms have been associated with mutations in SLC4A1 (17q21.31), coding for the Band 3 anion transport protein, or KCNN4 (19q13.2) which codes for the putative Gardos channel.
## Diagnostic methods
Diagnosis relies on laboratory findings. The typical presentation includes normal hemoglobin level or mild anemia, normal mean cell volume (MCV) or mild macrocytosis, normal or elevated mean corpuscular hemoglobin concentration (MCHC), elevated reticulocytosis, and a small number of stomatocytes (<10% of red cells). A diagnosis of DHS must be evoked in patients with unexplained iron overload, even if hemoglobin levels are normal, as well as in patients with unexplained hemolysis (before splenectomy) or those presenting with thrombotic events, if already splenectomized. Osmolar gradient ektacytometry is the best phenotypic diagnosis method, showing a leftward shift of the bell-shaped curve with a normal maximum deformability index and a decreased hypo and hyper-osmotic point, reflecting decreased osmotic fragility and cell dehydration, respectively. In some cases, an increased serum potassium level is observed, which results from in vitro leakage and is clinically irrelevant. Measurement of ferritin level and liver magnetic resonance imaging (MRI) are performed to evaluate iron overload. Genetic screening of the causative genes can be performed after phenotypic investigations.
## Differential diagnosis
Differential diagnoses include other causes of hemolysis, including hereditary spherocytosis, overhydrated hereditary stomatocytosis, hemoglobinopathy or red cell enzyme deficiencies such as hemolytic anemia due to red cell pyruvate kinase deficiency (see these terms).
## Genetic counseling
Transmission is autosomal dominant and genetic counseling should be offered to affected families.
## Management and treatment
Treatment is mainly symptomatic. Occurrence of cholelithiasis should be regularly monitored. Folic acid supplementation should be proposed in case of anemia. Pregnancy should be closely monitored. Iron status should be regularly monitored by serum ferritinemia and liver MRI. Iron depletion, most often by phlebotomy, is proposed when ferritinemia reaches the threshold of 1000 ng/ml or when iron liver overload is present. Splenectomy is contraindicated in DHS due to an elevated risk of life threatening arterial and venous thrombotic events.
## Prognosis
Overall prognosis is favorable in well managed patients (not splenectomized and with regular monitoring of their iron status). Splenectomized patients are at risk of early or late thrombotic events.
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*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
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*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Dehydrated hereditary stomatocytosis | c0272051 | 4,037 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3202 | 2021-01-23T18:57:52 | {"gard": ["5623"], "mesh": ["C536764"], "omim": ["194380", "616689"], "umls": ["C0272051"], "icd-10": ["D58.8"], "synonyms": ["Hereditary xerocytosis"]} |
Stacks or aggregations of red blood cells
This article is about red blood cell stacks. "Rouleaux" is a plural form for "Rouleau". For people, see Rouleau (surname). For other uses, see Rouleau.
This article needs attention from an expert in biology. Please add a reason or a talk parameter to this template to explain the issue with the article. WikiProject Biology may be able to help recruit an expert. (May 2008)
Rouleaux formation in a peripheral blood smear from a patient with plasma cell myeloma.
Rouleaux (singular is rouleau) are stacks or aggregations of red blood cells (RBCs) that form because of the unique discoid shape of the cells in vertebrates. The flat surface of the discoid RBCs gives them a large surface area to make contact with and stick to each other; thus forming a rouleau. They occur when the plasma protein concentration is high, and, because of them, the ESR (erythrocyte sedimentation rate) is also increased. This is a nonspecific indicator of the presence of disease.[1]
Conversely, the presence of rouleaux is a cause of disease because it will restrict the flow of blood throughout the body because capillaries can only accept free-flowing singular and independent red blood cells. The aggregations, also known as "clumping," form as an allergic reaction to certain antibiotics and not necessarily because of disease.
Conditions that cause rouleaux formation include infections, multiple myeloma, Waldenström's macroglobulinemia, inflammatory and connective tissue disorders, and cancers. It also occurs in diabetes mellitus and is one of the causative factors for microvascular occlusion in diabetic retinopathy.
Acute-phase proteins, particularly fibrinogen, interact with sialic acid on the surface of RBCs to facilitate the formation of rouleaux. An increase in the ratio of RBCs to plasma volume, as seen in the setting of polycythemia and hypovolemia, increases rouleaux formation and accelerates sedimentation. Rouleaux formation is retarded by albumin proteins.
Rouleaux formations are also adopted by spermatozoa as a means of cooperation between genetically similar gametocytes so as to improve reproductive success through enhanced motility and, therefore, fertilization capacity—e.g., the guinea pig.
Typical mammalian erythrocytes: (a) seen from surface; (b) in profile, forming rouleaux.
## Contents
* 1 Kinetics of Linear Rouleaux Formation
* 2 See also
* 3 References
* 4 Further reading
## Kinetics of Linear Rouleaux Formation[edit]
According to Smoluchowski aggregation, the kinetics of colloids is based on the assumption that each particle is surrounded by a "sphere influence". Single spherical particles which undergo Brownian motion collide and sticking of particles happens. As aggregation proceeds, the average diffusion constant of the aggregate population decreases. The aggregation of red blood cells progresses in the same manner except that cells are biconcave rather than spherical.
## See also[edit]
* Hemorheology
* Agglutinin
Wikimedia Commons has media related to Rouleaux.
## References[edit]
1. ^ Oxford Textbook of Medicine
## Further reading[edit]
* Stoltz, J.F.; Gaillard, S.; Paulus, F.; Henri, O.; Dixneuf, P.; Stoltz, J.F.; Puchelle, E. (1 December 1984). "Experimental approach to rouleau formation. Comparison of three methods". Biorheology. 23 (s1): 221–226. doi:10.3233/BIR-1984-23S138.
* Huang, C.R.; Pan, W.D.; Chen, H.Q.; Copley, A.L. (1 December 1987). "Thixotropic properties of whole blood from healthy human subjects". Biorheology. 24 (6): 795–801. doi:10.3233/BIR-1987-24630. PMID 3502773.
* Samsel, R.W.; Perelson, A.S. (February 1982). "Kinetics of rouleau formation. I. A mass action approach with geometric features". Biophysical Journal. 37 (2): 493–514. Bibcode:1982BpJ....37..493S. doi:10.1016/S0006-3495(82)84696-1. PMC 1328832. PMID 7059652.
* Samsel, R.W.; Perelson, A.S. (April 1984). "Kinetics of rouleau formation. II. Reversible reactions". Biophysical Journal. 45 (4): 805–824. Bibcode:1984BpJ....45..805S. doi:10.1016/S0006-3495(84)84225-3. PMC 1434900. PMID 6426540.
* Stoltz, J.F.; Gaillard, S.; Paulus, F.; Henri, O.; Dixneuf, P.; Stoltz, J.F.; Puchelle, E. (1 December 1984). "Experimental approach to rouleau formation. Comparison of three methods". Biorheology. 23 (s1): 221–226. doi:10.3233/BIR-1984-23S138.
* Fabry, T. L. (1 November 1987). "Mechanism of erythrocyte aggregation and sedimentation". Blood. 70 (5): 1572–1576. PMID 3663946.
* American Society of Hematology (1 June 2006). "Rouleaux formation". Blood. 107 (11): 4205. PMID 16739263.</ref>
* Barshtein, G.; Wajnblum, D.; Yedgar, S. (May 2000). "Kinetics of Linear Rouleaux Formation Studied by Visual Monitoring of Red Cell Dynamic Organization". Biophysical Journal. 78 (5): 2470–2474. Bibcode:2000BpJ....78.2470B. doi:10.1016/S0006-3495(00)76791-9. PMC 1300836. PMID 10777743.
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*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Rouleaux | c0221285 | 4,038 | wikipedia | https://en.wikipedia.org/wiki/Rouleaux | 2021-01-18T18:41:16 | {"umls": ["C0221285"], "wikidata": ["Q682542"]} |
Intermediate maple syrup urine disease (intermediate MSUD) is a milder form of MSUD (see this term) characterized by persistently raised branched-chain amino acids (BCAAs) and ketoacids, but fewer or no acute episodes of decompensation.
## Epidemiology
The estimated birth prevalence of MSUD is 1/ 150,000. Around 30% of cases are believed to be of the intermediate type.
## Clinical description
Symptom onset of intermediate MSUD varies between the early months and the early years of childhood. Infants may have feeding problems, poor growth, maple syrup odor in urine and developmental delay. Older children usually present with learning difficulties. Like classic MSUD (see this term), catabolic stress can result in acute decompensation with anorexia, vomiting, ataxia (in infants/toddlers), cognitive impairment, sleep disturbances, hallucinations, hyperactivity, mood swings, acute dystonia, choreoathetosis (in adults), stupor, coma and cerebral edema, if untreated.
## Etiology
MSUD is due to mutations in genes encoding 3 of the 4 subunits of the branched chain 2-ketoacid dehydrogenase (BCKAD) complex. The genes are BCKDHA (19q13.1-q13.2), encoding E1a, BCKDHB (6q14.1), encoding E1b, and DBT (1p31), encoding E2 respectively. Mutations lead to accumulation of BCAAs (especially leucine) and branched-chain alpha-ketoacids. In intermediate MSUD mutations in BCKDHB and DBT predominate. A mutation in the PPM1K gene (4q22.1) was found in one case.
## Diagnostic methods
Intermediate MSUD can be diagnosed by tandem mass spectrometry newborn screening. Otherwise, plasma amino acid analysis is diagnostic. Plasma leucine levels are increased while isoleucine and valine levels may be normal or increased. Patients have 3-30% BCKAD activity so their levels of plasma BCAAs are not as high as those seen in classic MSUD (see this term). Molecular genetic testing can identify a disease causing mutation, equally confirming diagnosis.
## Differential diagnosis
Differential diagnoses of the presenting symptoms include other inborn errors of intermediary metabolism such as NAGS deficiency, ornithine transcarbamylase deficiency, argininosuccinic aciduria (and other urea cycle defects), neonatal glycine encephalopathy, propionic acidemia, methylmalonic acidemia, and beta-ketothiolase deficiency (see these terms).
## Antenatal diagnosis
Prenatal diagnosis is possible in families with a known disease-causing mutation.
## Genetic counseling
Intermediate MSUD is inherited autosomal recessively and genetic counseling is possible.
## Management and treatment
Treatment of intermediate MSUD is similar to classic MSUD. Infants require high calorie BCAA-free formulas, dietary leucine restriction and close outpatient monitoring at a metabolic clinic. Management of acute decompensation requires aggressive enhancement of protein anabolism using glucose plus insulin, intravenous lipids, plasma amino acid monitoring, and isoleucine and valine supplements. Patients must adhere to a strict life-long diet to avoid episodes of acute decompensation. Special monitoring during pregnancy is vital.
## Prognosis
With early diagnosis and appropriate therapy the prognosis is good, but because the disorder is mild, diagnostic delay is common and some neurological damage may be sustained.
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*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Intermediate maple syrup urine disease | c1621920 | 4,039 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=268162 | 2021-01-23T17:37:34 | {"mesh": ["D008375"], "omim": ["248600", "615135"], "umls": ["C1621920"], "icd-10": ["E71.0"], "synonyms": ["Intermediate BCKD deficiency", "Intermediate MSUD", "Intermediate branched-chain alpha-ketoacid dehydrogenase deficiency"]} |
Jugular vein ectasia
Pronunciation
* vascular specialist/surgeorn
Jugular vein ectasia is a venous anomaly that commonly presents itself as a unilateral neck swelling in children and adults. It is rare to have bilateral neck swelling due to internal jugular vein ectasia.[1]
## References[edit]
1. ^ Gendeh, BS; Dhillon MK; Hamzah M. (March 1994). "Bilateral internal jugular vein ectasia: a report of two cases". J Laryngol Otol. 108 (3): 256–260. doi:10.1017/s0022215100126465. PMID 8169515.
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D
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*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Jugular vein ectasia | None | 4,040 | wikipedia | https://en.wikipedia.org/wiki/Jugular_vein_ectasia | 2021-01-18T18:42:01 | {"wikidata": ["Q16943887"]} |
A number sign (#) is used with this entry because Wieacker-Wolff syndrome (WRWF) is caused by mutation in the ZC4H2 gene (300897) on chromosome Xq11.
Description
Wieacker-Wolff syndrome is a severe X-linked recessive neurodevelopmental disorder affecting the central and peripheral nervous systems. It is characterized by onset of muscle weakness in utero (fetal akinesia). Affected boys are born with severe contractures, known as arthrogryposis, and have delayed motor development, facial and bulbar weakness, characteristic dysmorphic facial features, and skeletal abnormalities, such as hip dislocation, scoliosis, and pes equinovarus. Those that survive infancy show mental retardation. Carrier females may have mild features of the disorder (summary by Hirata et al., 2013).
Clinical Features
Wieacker et al. (1985) described an apparently novel X-linked syndrome in 6 men in 4 sibships of 3 generations of a family, genealogically connected through presumably carrier females. All had congenital contractures of the feet at birth, a slowly progressive predominantly distal muscle atrophy, dyspraxia of the eyes, face and tongue muscles, and mild mental retardation. Hirata et al. (2013) provided follow-up of the family reported by Wieacker et al. (1985). Affected males showed signs of a developmental defect of neuromuscular transmission, as evidenced by congenital equinovarus foot deformity and ptosis.
In 4 generations of a Missouri kindred, Miles and Carpenter (1991) observed 3 brothers and a male cousin with mental retardation in association with exotropia, microcephaly, distal muscle wasting, and 10 low digital arches. Six women who might represent heterozygotes were found to have 8 to 10 low digital arches; 5 of these women had exotropia. May et al. (2015) reported follow-up of the family (K8070) reported by Miles and Carpenter (1991). Additional features noted in the males included short stature, high-arched palate, narrow shoulders and thorax, kyphosis/lordosis/scoliosis, delayed motor development, hypotonia, camptodactyly, ulnar deviation of the fingers, knee or elbow contractures, and foot abnormalities such as club foot, rocker-bottom feet, or flat feet. All had distal muscle weakness and 3 had spasticity and hyperreflexia. More variable features included poor feeding, ptosis, long philtrum, carp-shaped mouth, and broad alveolar ridges. Only 1 had seizures. Carrier females were more mildly affected and showed some similar features.
Hirata et al. (2013) identified a second family with a similar, but more severe phenotype. Affected individuals presented with neonatal respiratory distress, arthrogryposis multiplex congenita, muscle weakness, and ptosis, suggesting dysfunction of neuromuscular transmission in utero. Histologic investigation did not show evidence of a demyelinating or axonal neuropathy or a myopathy. As development progressed, it became clear that the affected boys were also severely intellectually disabled. In both families, central neurologic dysfunction was manifest as intellectual disability, spasticity, and seizures. Heterozygous females showed mild intellectual disability; some showed minor dysmorphic signs, such as camptodactyly and equinovarus feet.
A third family identified by Hirata et al. (2013) had previously been reported by Hennekam et al. (1991). That family had 5 affected males in 3 sibships connected through females. Affected males had severe arthrogryposis and muscle weakness in the pre- and postnatal periods, resulting in death within the first weeks or months of life. The 1 surviving boy was severely mentally retarded. Features included respiratory insufficiency, swallowing difficulties, multiple contractures of the hands and limbs, clubfeet, kyphoscoliosis, hip dislocation, and chest deformities. Facial features included carp-like mouth, narrow palate, micrognathia, long philtrum, upturned nares, and short neck. Several female carriers showed mild features in the form of clubfoot, contractures, hyperkyphosis, and slight muscle weakness. One manifesting carrier was affected more severely with mental retardation. Muscle biopsy suggested a degenerative muscle disorder. Two more families with a similar disorder were subsequently identified by Hirata et al. (2013); 1 had been ascertained due to a diagnosis of cerebral palsy. Cranial MRI of several patients in the whole cohort studied by Hirata et al. (2013) showed several abnormalities, including delayed myelination, cerebral atrophy, and gyral disorganization.
May et al. (2015) reported 3 previously unreported families with X-linked syndromic mental retardation. There were 10 affected males and 10 carrier females. There was phenotypic variability between the families, but all male patients had intellectual disability. Common features in affected males included short stature, microcephaly, delayed motor development, contractures, spinal deformities, foot abnormalities, and high-arched palate. Variable neuromuscular features included distal muscles weakness, spasticity, drooling, hypotonia, and seizures, all of which tended to run within families. Affected males in 1 family showed palmar hyperkeratosis and small testes/penis. Females in some of the families showed milder features.
Inheritance
The transmission pattern of congenital arthrogryposis in the families reported by Wieacker et al. (1985), Hennekam et al. (1991), and Hirata et al. (2013) was consistent with X-linked recessive inheritance. However, carrier females showed mild manifestations of the disorder.
Mapping
Wieacker et al. (1985) excluded close linkage of the disorder to the Xg locus on Xp and to a DNA polymorphism on Xq. Wieacker et al. (1987) found a maximum lod score of 3.225 at a recombination fraction of 0.0 between the disorder and DXYS1. This places the syndrome in the proximal part of the long arm of the X chromosome. Kloos et al. (1997) used highly polymorphic short terminal repeat markers between Xp21 and Xq24 to refine the localization of the Wieacker syndrome locus. Recombinant events placed the locus in the pericentromeric region between PFC and DXS339, a critical segment of approximately 8 cM.
By linkage analysis of a 4-generation Missouri kindred with MRXS4, Miles and Carpenter (1991) found linkage to a locus near Xq21.31 (peak lod score of 2.78 at theta = 0.0 was calculated for linkage of the syndrome locus and DXYS1). HGM11 stated the probable location as Xq13-q22.
Molecular Genetics
In affected members of 5 unrelated families with Wieacker-Wolff syndrome, including the families reported by Wieacker et al. (1985) and Hennekam et al. (1991), Hirata et al. (2013) identified 4 different missense mutations in the ZC4H2 gene (300897.0001-300897.0004). The mutations were found by exome sequencing in some of the families. Expression of 3 of the mutations in mouse primary neurons caused a significant decrease in synapse number and density, and none of the mutations was able to rescue the swimming defect of zebrafish morphants. The findings indicated that mutations in the ZC4H2 gene cause a clinically variable broad-spectrum neurodevelopmental disorder of the central and peripheral nervous systems.
In affected members of 4 unrelated families with WRWF, including the original family reported by Miles and Carpenter (1991) as having Miles-Carpenter syndrome, May et al. (2015) identified mutations in the ZC4H2 gene (300897.0004-300897.0007). The mutations were found by various methods, including whole-genome sequencing, X-chromosome exome sequencing, and direct sequencing of the ZC4H2 gene: all mutations were confirmed by Sanger sequencing and segregated with the disorder in the families. There were 3 missense and 1 splice site mutations. Molecular modeling of the mutant proteins suggested that all the missense mutations would destabilize the protein and result in a loss of function. Based on knockdown of the gene in zebrafish (see ANIMAL MODEL), May et al. (2015) suggested that ZC4H2 mutations adversely affect interneuron fate and connectivity throughout the brain and spinal cord, including a loss of GABAergic neurons. Clinical variability likely results from mutations affecting different isoforms as well as having different effects on the protein.
Cytogenetics
In a boy with sporadic occurrence of WRWF, Hirata et al. (2013) identified a de novo paracentric inversion on the X chromosome with breakpoints at Xq11.2, involving ZC4H2, and Xq28, which did not contain any known genes. RT-PCR on patient cells showed no detectable ZC4H2 transcripts, indicating that the rearrangement abolished ZC4H2 expression. In addition, whole-genome microarray analysis identified small heterozygous deletions at Xq11.2 in 2 mildly affected girls. The girls had distal muscle weakness, camptodactyly, equinovarus foot deformity or contracture of the Achilles tendon, language deficits, and intellectual disability. The deletions were 826 and 321 Kb, respectively, and included ZC4H2, but no adjacent genes. These findings indicated that heterozygous deletions of ZC4H2 can result in a clinical phenotype, even in females.
Zanzottera et al. (2017) reported a girl with a severe Wiecker-Wolff phenotype who had a 429-kb deletion on 11q11.2 that included ZC4H2 as the only known gene. The girl, born to healthy nonconsanguineous parents, had severe neurodevelopmental impairment, distinctive hand creases, and unusual electrophysiological At birth, she showed normal growth parameters, micrognathia, strabismus, and arthrogryposis multiplex congenita. She had bilateral hip subluxation, severe swallowing difficulties requiring tube feeding, and delayed motor and cognitive development. At age 13 years, she was not able to stand and language was restricted to a small number of single words. Height was below the 3rd centile with normal weight and head circumference. She had an unusual face (brachycephaly, low insertion of the columella, mild retrognathia, abnormal helix, ptosis, prominent nose, thin upper vermilion, downturned corners of the mouth). She also had small hands with decreased creases and contractures, ulnar and radial deviations of fingers, fixed extension of knees and clubfeet webbing of fingers, and decreased palmar creases. Neurologic exam showed hypotonia with lower limb spasticity, brisk deep tendon reflexes of the upper limbs, and marked ankle hyperreflexia with clonus. MRI of her vertebral column showed stenosis of her spinal canal and a markedly pointed and anteriorly curved coccyx. Testing of X-inactivation in lymphocytes from the patient demonstrated random (not skewed) inactivation. Zanzottera et al. (2017) suggested that females with ZC4H2 deletions can be as severely affected as males with Wieacker-Wolff syndrome. They also noted that the variable phenotype found in affected individuals with Wieacker-Wolff syndrome make clinical recognition a challenge.
Okubo et al. (2018) reported a 4-year-old girl, born to healthy nonconsanguineous parents, with a severe phenotype with features of Wiecker-Wolff syndrome who had a 395-kb deletion on 11q11.2 that included ZC4H2 as the only known gene. At birth the patient had multiple joint contractures at elbows, knees, shoulders, and hips, with overlapping fingers and toes, congenital clubfeet, and cleft palate. She had poor feeding requiring placement of a G-tube. At age 6 months, she had no head control with truncal hypotonia, and exaggerated deep tendon reflexes with ankle clonus, consistent with spastic quadriplegia. Brain MRI at 6 months showed enlarged posterior horns of the lateral ventricles, thinning of the corpus callosum, and mildly delayed myelination; by age 2 years, the MRI showed no apparent delayed myelination, but progressive diffuse cerebral atrophy, suggesting a progressive nature of cerebral dysfunction associated with this condition. At age 4 years, she was noted to have profound developmental delay and remarkable physical findings including prominent facial palsy, strabismus, carp-shaped mouth, ptosis, cleft palate, kyphoscoliosis, overlapping fingers and toes, and multiple contractures. EEG showed no epileptic discharges, but disorganized theta range activities during wakefulness and no spindles at sleep.
Animal Model
May et al. (2015) found expression of the zc4h2 zebrafish ortholog in the developing central nervous system, mainly in differentiating progenitors and mature neurons and/or glia. Expression was localized mainly in the nucleus. Zc4h2-null zebrafish showed abnormal flexion of the pectoral fins and active movements of the pectoral fins, continuous swimming movements, and balance problems. They also had abnormally positioned eyes, an open mouth, and continuous jaw movements. These abnormalities were associated with a loss of markers of the V2a and V2b interneurons in the hindbrain and spinal cord, as well as a significant reduction in the number of GABAergic interneurons in the midbrain tegmentum, as demonstrated by decreased gad1 (605363) expression. Wildtype human ZC4H2 was able to restore the behavioral abnormalities of mutant fish as well as gad1 expression.
INHERITANCE \- X-linked recessive GROWTH Height \- Short stature HEAD & NECK Head \- Microcephaly Face \- Facial weakness \- Micrognathia \- Retrognathia \- Flat philtrum \- Long philtrum Ears \- Low-set ears Eyes \- Upslanting palpebral fissures \- Ptosis \- Exotropia \- Oculomotor apraxia (in some patients) Nose \- Upturned nares Mouth \- Carp-shaped mouth \- High-arched palate \- Drooling \- Broad alveolar ridges Neck \- Short neck RESPIRATORY \- Neonatal respiratory distress \- Apnea CHEST External Features \- Narrow thorax \- Narrow shoulders ABDOMEN Gastrointestinal \- Poor feeding SKELETAL \- Arthrogryposis, congenital \- Joint contractures Spine \- Kyphosis \- Scoliosis \- Lordosis Pelvis \- Hip dislocation Hands \- Proximally placed thumbs \- Camptodactyly \- Ulnar deviation of the fingers Feet \- Proximally placed toes \- Club feet \- Equinovarus SKIN, NAILS, & HAIR Skin \- Low fingerprint arches \- Palmar hyperkeratosis Hair \- High anterior hairline MUSCLE, SOFT TISSUES \- Muscle weakness, severe \- Fat pads on the hands and feet NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Hypotonia \- Mental retardation \- Speech delay \- Dystonia \- Spasticity \- Seizures \- Delayed myelination \- Gyral disorganization \- Cerebral atrophy Peripheral Nervous System \- Areflexia PRENATAL MANIFESTATIONS Movement \- Decreased fetal movements MISCELLANEOUS \- Onset in utero \- Carrier females may show mild features, such as mild contractures, club feet, and intellectual disability \- Two females with large deletions (429 kb and 395 kb) on 11q11.2 that include ZC4H2 as the only known gene have been reported with severe features of Wiecker-Wolff syndrome MOLECULAR BASIS \- Caused by mutation in the zinc finger C4H2 domain-containing protein gene (ZC4H2, 300897.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| WIEACKER-WOLFF SYNDROME | c1839735 | 4,041 | omim | https://www.omim.org/entry/314580 | 2019-09-22T16:17:04 | {"doid": ["0060815"], "mesh": ["C537472"], "omim": ["314580"], "orphanet": ["85283", "3454"], "synonyms": ["Alternative titles", "WIEACKER SYNDROME", "CONTRACTURES OF FEET, MUSCLE ATROPHY, AND OCULOMOTOR APRAXIA", "APRAXIA, OCULOMOTOR, WITH CONGENITAL CONTRACTURES AND MUSCLE ATROPHY", "MILES-CARPENTER X-LINKED MENTAL RETARDATION SYNDROME", "MENTAL RETARDATION, X-LINKED, SYNDROMIC 4", "MENTAL RETARDATION, X-LINKED, WITH CONGENITAL CONTRACTURES AND LOW FINGERTIP ARCHES"]} |
For a phenotypic description and a discussion of genetic heterogeneity of postaxial polydactyly, see 174200.
Galjaard et al. (2003) described an autosomal dominant postaxial polydactyly and partial cutaneous syndactyly syndrome in a 31-member, 6-generation Dutch kindred with 11 affected individuals. Although the PAPA phenotype predominated, the expression of the polydactyly and syndactyly phenotypes was variable with respect to involvement of upper/lower limbs, right/left sides, PAPA and/or PAPB phenotype expression, interdigital space (IDS), and extent of syndactyly, especially in 2 branches of the family. No other associated anomalies were observed. Galjaard et al. (2003) performed a whole-genome screen in this family and detected positive lod scores for markers on chromosome 7q, with a maximum 2-point lod score of 3.18 at theta = 0 with D7S1799. Individuals with PAPA/B and one with partial cutaneous syndactyly of IDS2 shared a common haplotype between markers D7S1799 and D7S495 (50 cM). They also shared a haplotype between GATA63F08 and D7S2513 (3.7 cM) with 2 clinically normal individuals and a patient with only syndactyly. Galjaard et al. (2003) concluded that PAP and syndactyly in this family are genetically heterogeneous with high penetrance, the only nonpenetrant individual being the patient with the PAPB-only phenotype.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| POLYDACTYLY, POSTAXIAL, TYPE A4 | c3887487 | 4,042 | omim | https://www.omim.org/entry/608562 | 2019-09-22T16:07:39 | {"mesh": ["C562429"], "omim": ["608562"], "orphanet": ["93334"], "synonyms": ["Alternative titles", "PAPA4", "POSTAXIAL POLYDACTYLY, TYPE A4"]} |
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Ovarian disease
SpecialtyGynecology
Ovarian diseases are conditions that happen to young women[1] which can affect their reproductive system and general health.
These can be classified[by whom?] as endocrine disorders or as a disorders of the reproductive system.
If the egg fails to release from the follicle in the ovary an ovarian cyst may form. Small ovarian cysts are common in healthy women. Some women have more follicles than usual (polycystic ovary syndrome), which inhibits the follicles to grow normally and this will cause cycle irregularities.
Various types of ovarian diseases exist. Some of the ovarian diseases or disorders include:
1. Endometriosis.
2. Ovarian cysts.
3. Ovarian Epithelial Cancer.
4. Ovarian Germ Cell Tumors.
5. Ovarian Low Malignant Potential Tumors.
6. Polycystic Ovary Syndrome (PCOS).
## Contents
* 1 Endometriosis
* 2 Ovarian cysts
* 3 Ovarian epithelial cancer
* 4 Ovarian Germ Cell Tumors
* 5 Ovarian Low Malignant Potential Tumors
* 6 Polycystic ovary syndrome
* 7 References
* 8 External links
## Endometriosis[edit]
Endometriosis is a condition in which tissues lining the uterus (endometrial stroma and gland) grows abnormally beyond the uterus that may become quite painful. In simpler terms, it means that the tissue lining the uterus develops in different parts outside of it. It can be either at ovary, fallopian tubes, or peritoneal spaces.[2]
There is no exact cause of endometriosis.[3]
Symptoms:
Menstrual cramps, heavy menstrual bleeding, bowel or urinary problems, nausea, vomiting, blood with stools, painful intercourse, fatigues, spotting or bleeding between periods. [2]
Treatment:
1. Surgery at extreme situations
2. Hormonal treatments using birth controls.
3. Healthier lifestyle.[2]
## Ovarian cysts[edit]
It is common for many women to develop one cyst in their lifetime[1]. At times, these can go unnoticed without pain or visible symptoms. A cyst may develop in either of the ovaries that are responsible for producing hormones and carrying eggs in the bodies of women. Ovarian cysts can be of various types like dermoid cysts, endometrioma cysts and the functional cyst being the most common one [2]
Symptoms:
1. Abdominal bloating or swelling.
2. Painful bowel movement.
3. Pelvic pain before or after the menstrual cycle.
4. Painful intercourse.
5. Pain in the lower back or thighs.
6. Breast tenderness.
7. Nausea and vomiting.
8. Fever.
9. Rapid breathing.
10. Faintness or dizziness.
11. Sharp pelvic pain.
Treatment:
1. Taking of oral contraceptives or birth control pills as prescribed by the doctor.
2. Laparoscopy: Surgery to remove the cyst.
3. Hysterectomy in case the cyst is cancerous.
## Ovarian epithelial cancer[edit]
It is one of the common ovarian cancers that affect women worldwide.[4] It develops outside the ovaries and ultimately spreads outside and can affect other organs.
Causes:
It may happen if there is a family medical history of breast cancer, colon cancer, rectal cancer or uterine cancer, or Lynch syndrome. If someone is under Estrogen Replacement Therapy for a long time. Smoking habits may also lead to the same. [3]
Treatment:[citation needed]
1. Surgery to remove the uterus.
2. Chemotherapy.
## Ovarian Germ Cell Tumors[edit]
Ovarian germ cell tumors are common among teenagers and young women. It is a growth in the ovaries. [4]
Causes:
Though the exact causes are not known, it may happen owing to certain birth defects affecting the genitals, nervous system or the urinary tract. There may be genetic conditions affecting the sex chromosomes that result in these kind of tumors as well.[5]
Symptoms[citation needed]
1. Belly swelling.
2. Pain or pressure in the belly.
3. Swollen abdomen.
4. Vaginal bleeding after menopause.
Treatment:[citation needed]
1. Surgery to remove the tumor, or the Fallopian tubes or one or more ovaries.
2. Hysterectomy.
3. Chemotherapy in case the tumor is cancerous.
4. Radiation therapy to prevent the cancerous cells from developing.
## Ovarian Low Malignant Potential Tumors[edit]
The tumor forms in the ovaries and gradually spreads to the outside of ovary. This mostly affects younger women and also hinders the reproductive system. [6]
Causes:
Causes are debatable and these may occur to both pregnant women and women who do not opt for pregnancy
Symptoms:[citation needed]
1. Abdominal pain or swelling.
2. Bowel problems or constipation.
Treatment:
Depending on the size of the tumor, choice of pregnancy, the spreading of the tumor, age and choices, removing the affected ovary is the most common treatment. In rare situations, the tumor is taken out of the ovary. Also, hysterectomy can be an option. [6]
## Polycystic ovary syndrome[edit]
This is a hormonal imbalance, where androgens (also called male hormones) are elevated. [7]
The increased level of androgens may result in irregular menstrual cycle and diabetes and heart problem in the long run. It also affects the body in various ways like problem getting pregnant, sleep apnea, depression and anxiety, can enhance the risk of endometrial cancer.
Symptoms:
1. Irregular periods.
2. Heavy bleeding during periods.
3. Excess hair growth on face and other parts of the body like chest, back, belly.
4. Acne.
5. Weight gain.
6. Darkening of skin.
7. Headaches.
Treatment:
1. Oral contraceptives to promote regular periods
2. Healthier lifestyle.[8]
Other conditions include:
* Ovarian cancer
* Luteoma
* Hypogonadism
* Hyperthecosis
## References[edit]
1. ^ Compare: Holmes, Timothy; Packard, John Hooker, eds. (1881). A System of Surgery, Theoretical and Practical. 2 (revised ed.). Philadelphia: H.C. Lea's Son & Company. p. 1022. Retrieved 22 August 2020. "Ovarian disease may occur at any age, from infancy upwards. It is of tolerable frequency during the whole period of sexual activity, but most so during the latter half, i.e., from thirty to forty-five. It is very rare in childhood, [...] and decidedly infrequent after the complete cessation of the menstrual function."
2. ^ a b c "Endometriosis: Symptoms, causes, and treatments". Medical News Today. Retrieved 2018-10-27.
3. ^ "Endometriosis - Symptoms and causes". Mayo Clinic. Retrieved 2018-10-27.
4. ^ "What Is Ovarian Epithelial Cancer?". WebMD. Retrieved 2018-10-27.
5. ^ PDQ Adult Treatment Editorial Board (2002), "Ovarian Germ Cell Tumors Treatment (PDQ®): Patient Version", PDQ Cancer Information Summaries, National Cancer Institute (US), PMID 26389363, retrieved 2018-10-27
6. ^ a b "What Are Ovarian Low Malignant Potential Tumors?". WebMD. Retrieved 2018-10-27.
7. ^ "Polycystic Ovary Syndrome (PCOS): Symptoms, Causes, and Treatment". Healthline. Retrieved 2018-10-27.
8. ^ "Polycystic ovary syndrome (PCOS) - Diagnosis and treatment - Mayo Clinic". www.mayoclinic.org. Retrieved 2018-10-27.
## External links[edit]
Classification
D
* ICD-10: E28, N83
* ICD-9-CM: 256, 620.0-620
* MeSH: D010049
* v
* t
* e
Gonadal disorder
Ovarian
* Polycystic ovary syndrome
* Premature ovarian failure
* Estrogen insensitivity syndrome
* Hyperthecosis
Testicular
Enzymatic
* 5α-reductase deficiency
* 17β-hydroxysteroid dehydrogenase deficiency
* aromatase excess syndrome
Androgen receptor
* Androgen insensitivity syndrome
* Familial male-limited precocious puberty
* Partial androgen insensitivity syndrome
Other
* Sertoli cell-only syndrome
General
* Hypogonadism
* Delayed puberty
* Hypergonadism
* Precocious puberty
* Hypoandrogenism
* Hypoestrogenism
* Hyperandrogenism
* Hyperestrogenism
* Postorgasmic illness syndrome
* Cytochrome P450 oxidoreductase deficiency
* Cytochrome b5 deficiency
* Androgen-dependent condition
* Aromatase deficiency
* Complete androgen insensitivity syndrome
* Mild androgen insensitivity syndrome
* Hypergonadotropic hypogonadism
* Hypogonadotropic hypogonadism
* Fertile eunuch syndrome
* Estrogen-dependent condition
* Premature thelarche
* Gonadotropin insensitivity
* Hypergonadotropic hypergonadism
* v
* t
* e
Female diseases of the pelvis and genitals
Internal
Adnexa
Ovary
* Endometriosis of ovary
* Female infertility
* Anovulation
* Poor ovarian reserve
* Mittelschmerz
* Oophoritis
* Ovarian apoplexy
* Ovarian cyst
* Corpus luteum cyst
* Follicular cyst of ovary
* Theca lutein cyst
* Ovarian hyperstimulation syndrome
* Ovarian torsion
Fallopian tube
* Female infertility
* Fallopian tube obstruction
* Hematosalpinx
* Hydrosalpinx
* Salpingitis
Uterus
Endometrium
* Asherman's syndrome
* Dysfunctional uterine bleeding
* Endometrial hyperplasia
* Endometrial polyp
* Endometriosis
* Endometritis
Menstruation
* Flow
* Amenorrhoea
* Hypomenorrhea
* Oligomenorrhea
* Pain
* Dysmenorrhea
* PMS
* Timing
* Menometrorrhagia
* Menorrhagia
* Metrorrhagia
* Female infertility
* Recurrent miscarriage
Myometrium
* Adenomyosis
Parametrium
* Parametritis
Cervix
* Cervical dysplasia
* Cervical incompetence
* Cervical polyp
* Cervicitis
* Female infertility
* Cervical stenosis
* Nabothian cyst
General
* Hematometra / Pyometra
* Retroverted uterus
Vagina
* Hematocolpos / Hydrocolpos
* Leukorrhea / Vaginal discharge
* Vaginitis
* Atrophic vaginitis
* Bacterial vaginosis
* Candidal vulvovaginitis
* Hydrocolpos
Sexual dysfunction
* Dyspareunia
* Hypoactive sexual desire disorder
* Sexual arousal disorder
* Vaginismus
* Urogenital fistulas
* Ureterovaginal
* Vesicovaginal
* Obstetric fistula
* Rectovaginal fistula
* Prolapse
* Cystocele
* Enterocele
* Rectocele
* Sigmoidocele
* Urethrocele
* Vaginal bleeding
* Postcoital bleeding
Other / general
* Pelvic congestion syndrome
* Pelvic inflammatory disease
External
Vulva
* Bartholin's cyst
* Kraurosis vulvae
* Vestibular papillomatosis
* Vulvitis
* Vulvodynia
Clitoral hood or clitoris
* Persistent genital arousal disorder
This women's health related article is a stub. You can help Wikipedia by expanding it.
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*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
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*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Ovarian disease | c0029928 | 4,043 | wikipedia | https://en.wikipedia.org/wiki/Ovarian_disease | 2021-01-18T18:56:39 | {"mesh": ["D010049"], "umls": ["C0029928", "C4021818"], "icd-9": ["620.0", "256", "620"], "icd-10": ["E28", "N83"], "wikidata": ["Q7113244"]} |
The Immunodeficiency, Centromeric region instability, Facial anomalies syndrome (ICF) is a rare autosomal recessive disease characterized by immunodeficiency, although B cells are present, and by characteristic rearrangements in the vicinity of the centromeres (the juxtacentromeric heterochromatin) of chromosomes 1 and 16 and sometimes 9.
## Epidemiology
ICF has been described in about 50 patients worldwide.
## Clinical description
Other variable symptoms of this probably under-diagnosed syndrome include mild facial dysmorphism, growth retardation, failure to thrive, and psychomotor retardation. Serum levels of IgG, IgM, IgE, and/or IgA are low, although the type of immunoglobulin deficiency is variable. Recurrent infections are the presenting symptom, usually in early childhood.
## Etiology
ICF always involves limited hypomethylation of DNA and often arises from mutations in one of the DNA methyltransferase genes (DNMT3B). Much of this DNA hypomethylation is in the 1qh, 9qh, and 16qh, regions that are the site of whole-arm deletions, chromatid and chromosome breaks, stretching (decondensation), and multiradial chromosome junctions in mitogen-stimulated lymphocytes. By an unknown mechanism, the DNMT3B deficiency that causes ICF interferes with lymphogenesis (at a step after class switching) or lymphocyte activation.
## Antenatal diagnosis
With the identification of DNMT3B as the affected gene in a majority of ICF patients, prenatal diagnosis of ICF is possible. However, given the variety of DNMT3B mutations, a first-degree affected relative should first have both alleles of this gene sequenced.
## Management and treatment
Treatment almost always includes regular infusions of immunoglobulins, mostly intravenously. Recently, bone marrow transplantation has been tried.
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*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| ICF syndrome | c0398788 | 4,044 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2268 | 2021-01-23T18:25:44 | {"gard": ["2945"], "mesh": ["C537362"], "omim": ["242860", "614069", "616910", "616911"], "icd-10": ["D84.8"], "synonyms": ["Immunodeficiency-centromeric instability-facial anomalies syndrome"]} |
Neuronal ceroid lipofuscinosis (NCL) refers to a group of conditions that affect the nervous system. Signs and symptoms vary widely between the forms but generally include a combination of dementia, vision loss, and epilepsy. Although the NCLs were historically classified according to their age of onset and clinical symptoms, the most recent classification system is primarily based on their underlying genetic cause. Most forms are inherited in an autosomal recessive manner; however, autosomal dominant inheritance has been reported in one adult-onset form (neuronal ceroid lipofuscinosis 4B). Treatment options are limited to therapies that can help relieve some of the symptoms.
The Batten Disease Support and Research Association (BDSRA) has more information about the different types of NCL.
* BDSRA: Summary of new classification nomenclature of the NCLs
Please note: Batten disease originally referred specifically to the juvenile and most common form of NCL, now known as CLN3. However, the term Batten disease is increasingly used to describe all forms of NCL. All types of NCL also belong to a larger group of diseases known as lysosomal storage disorders.
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*[c.]: circa
*[AA]: Adrenergic agonist
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*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Neuronal ceroid lipofuscinosis | c0027877 | 4,045 | gard | https://rarediseases.info.nih.gov/diseases/10739/neuronal-ceroid-lipofuscinosis | 2021-01-18T17:58:44 | {"mesh": ["D009472"], "umls": ["C0027877"], "orphanet": ["216"], "synonyms": ["Batten disease", "NCL"]} |
This article is written like a personal reflection, personal essay, or argumentative essay that states a Wikipedia editor's personal feelings or presents an original argument about a topic. Please help improve it by rewriting it in an encyclopedic style. (March 2009) (Learn how and when to remove this template message)
Other specified feeding or eating disorder
Other namesSleep-related eating disorder (SRED), sleep eating, somnambulistic eating
SpecialtyPsychiatry, sleep medicine
Nocturnal sleep-related eating disorder (NSRED) is a combination of a parasomnia and an eating disorder. It is a NREM parasomnia.[1] It is described as being in a specific category within somnambulism or a state of sleepwalking that includes behaviors connected to a person's conscious wishes or wants.[2] Thus many times NSRED is a person's fulfilling of their conscious wants that they suppress; however, this disorder is difficult to distinguish from other similar types of disorders.
## Contents
* 1 Comparison with night eating syndrome
* 2 Signs and symptoms
* 3 Diagnosis
* 3.1 Criteria
* 4 Treatment
* 5 History
* 6 See also
* 7 References
* 8 External links
## Comparison with night eating syndrome[edit]
NSRED is closely related to night eating syndrome (NES) except for the fact that those suffering from NES are completely awake and aware of their eating and bingeing at night while those suffering from NSRED are sleeping and unaware of what they are doing. NES is primarily considered an eating disorder while NSRED is primarily considered a parasomnia; however, both are a combination of parasomnia and eating disorders since those suffering from NES usually have insomnia or difficulty sleeping and those suffering from NSRED experience symptoms similar to binge eating. Some even argue over whether NES and NSRED are the same or distinct disorders.[3][4][5] Even though there have been debates over these two disorders, specialists have examined them to try to determine the differences. Dr. J. Winkelman noted several features of the two disorders that were similar, but he gave one important factor that make these disorders different. In his article "Sleep-Related Eating Disorder and Night Eating Syndrome: Sleep Disorders, Eating Disorders, Or both", Winkelman said, "Both [disorders] involve nearly nightly binging at multiple nocturnal awakenings, defined as excess calorie intake or loss of control over consumption."[2] He also reported that both disorders have a common occurrence of approximately one to five percent of adults, have been predominantly found in women, with a young adult onset, have a chronic course, have a primary morbidity of weight gain, sleep disruption, and shame over loss of control over food intake, have familial bases, and have been observed to have comorbid depression and daytime eating disorders. However, Winkelman said, "The most prominent cited distinction between NES and SRED is the level of consciousness during nighttime eating episodes."[2] Therefore, these two disorders are extremely similar with only one distinction between them. Doctors and psychologists have difficulty differentiating between NES and NSRED, but the distinction of a person's level of consciousness is what doctors chiefly rely on to make a diagnosis. One mistake that is often made is the misdiagnosis of NSRED for NES.[2] However, even though NSRED is not a commonly known and diagnosed disease, many people suffer from it in differing ways while doctors work to find a treatment that works for everyone; several studies have been done on NSRED, such as the one conducted by Schenck and Mahowald.[4] These studies, in turn, provide the basic information on this disorder including the symptoms, behaviors, and possible treatments that doctors are using today.
## Signs and symptoms[edit]
Over the past 30 years, several studies have found that those afflicted with NSRED all have different symptoms and behaviors specific to them, yet they also all have similar characteristics that doctors and psychologists have identified to distinguish NSRED from other combinations of sleep and eating disorders such as night eating syndrome. Winkelman says that typical behaviors for patients with NSRED include: "Partial arousals from sleep, usually within 2 to 3 hours of sleep onset, and subsequent ingestion of food in a rapid or 'out of control' manner."[5] They also will attempt to eat bizarre amalgamations of foods and even potentially harmful substances such as glue, wood, or other toxic materials.[5] In addition, Schenck and Mahowald noted that their patients mainly ate sweets, pastas, both hot and cold meals, improper substances such as "raw, frozen, or spoiled foods; salt or sugar sandwiches; buttered cigarettes; and odd mixtures prepared in a blender."[4]
During the handling of this food, patients with NSRED distinguish themselves, as they are usually messy or harmful to themselves. Some eat their food with their bare hands while others attempt to eat it with utensils. This occasionally results in injuries to the person as well as other injuries. After completing their studies, Schenck and Mahowald said, "Injuries resulted from the careless cutting of food or opening of cans; consumption of scalding fluids (coffee) or solids (hot oatmeal); and frenzied running into walls, kitchen counters, and furniture."[4] A few of the more notable symptoms of this disorder include large amounts of weight gain over short periods of time, particularly in women; irritability during the day, due to lack of restful sleep; and vivid dreams at night. It is easily distinguished from regular sleepwalking by the typical behavioral sequence consisting of "rapid, 'automatic' arising from bed, and immediate entry into the kitchen." In addition, throughout all of the studies done, doctors and psychiatrists discovered that these symptoms are invariant across weekdays, weekends, and vacations as well as the eating excursions being erratically spread throughout a sleep cycle. Most people that suffer from this disease retain no control over when they arise and consume food in their sleep. Although some have been able to restrain themselves from indulging in their unconscious appetites, some have not and must turn to alternative methods of stopping this disorder.[5] It is important for trained physicians to recognize these symptoms in their patients as quickly as possible, so those with NSRED may be treated before they injure themselves.
## Diagnosis[edit]
### Criteria[edit]
The diagnostic criteria utilized by the International Classification of Sleep Disorders-Third Edition (ICSD-3) include some dysfunctional eating when the person wake up during the main sleep period, eating unusual or toxic food, negative health consequences.[6] The patient could be injured during these episodes and he might not be conscious and won’t remember them.[6] This criterion differentiates SRED from Night eating syndrome(NES).[7] Patients with NES are conscious during the episode.[7]
## Treatment[edit]
For those patients who have not been able to stop this disorder on their own, doctors have been working to discover a treatment that will work for everyone. One treatment that Schenck and Mahowald studied consisted of psychotherapy combined with "environmental manipulation". This was usually done separately from the weight-reducing diets. However, during this study only 10 percent of the patients were able to lose more than one third of their initial excess weight, which was not a viable percentage. In addition, they reported that many of the patients experienced "major depression" and "severe anxiety" during the attempted treatments.[4] This was not one of the most successful attempts to help those with NSRED.
However, Dr. R. Auger reported on another trial treatment where patients were treated utilizing pramipexole. Those conducting the treatment noticed how the nocturnal median motor activity was decreased, as was assessed by actigraphy, and individual progress of sleep quality was reported. Nevertheless, Augur also said, "27 percent of subjects had RLS (restless legs syndrome, a condition known to respond to this medication), and number and duration of waking episodes related to eating behaviors were unchanged."[3] Encouraged by the positive response verified in the above-mentioned trial treatment, doctors and psychiatrists conducted a more recent study described by Auger as "efficacy of topiramate [an antiepileptic drug associated with weight loss] in 17 consecutive patients with NSRED." Out of the 65 percent of patients who continued to take the medication on a regular basis, all confirmed either considerable development or absolute remission of "night-eating" in addition to "significant weight loss" being achieved.[3] This has been one of the most effective treatments discovered so far, but many patients still suffered from NSRED. Therefore, other treatments were sought after.
Such treatments include those targeted to associated sleep disorders with the hope that it would play an essential part of the treatment process of NSRED. In Schenck and Mahowald's series, combinations of cardibopa/L-dopa, codeine, and clonazepam were used to treat five patients with RLS and one patient with somnambulism and PLMS (periodic limb movements in sleep). These patients all were suffering from NSRED as well as these other disorders, and they all experienced a remission of their NSRED as a result of taking these drugs. Two patients with OSA (obstructive sleep apnea) and NSRED also reported as having a "resolution of their symptoms with nasal continuous positive airway pressure (nCPAP) therapy." Clonazepam monotherapy was also found to be successful in 50 percent of patients with simultaneous somnambulism.[4] Dopaminergic agents such as monotherapy were effective in 25 percent of the NSRED subgroup. Success with combinations of dopaminergic and opioid drugs, with the occasional addition of sedatives, also was found in seven patients without associated sleep disorders. In those for whom opioids and sedatives are relatively contraindicated (e.g., in those with histories of substance abuse), two case reports were described as meeting with success with a combination of bupropion, levodopa, and trazodone.[4] Notably, hypnotherapy, psychotherapy, and various behavioral techniques, including environmental manipulation, were not effective on the majority of the patients studied. Nevertheless, Auger argue that behavioral strategies should complement the overall treatment plan and should include deliberate placement of food to avoid indiscriminate wandering, maintenance of a safe sleep environment, and education regarding proper sleep hygiene and stress management.[3] Even with their extensive studies, Schenck and Mahowald did not find the success as Auger found by treating his patients with topiramate.
## History[edit]
The first case of NSRED was reported in 1955, but over the next 36 years, only nine more reports were made of this syndrome. Seven of these reports were single-case studies and the other two instances were seen during objective sleep studies, all done by psychiatrists and doctors.[4] Schenck and Mahowald were the first to a major study on this disorder. They started their study of NSRED in 1985 and continued until 1993 with several cases among a total of 38 other various sleep-related disorders. Many of the cases they observed had symptoms that overlapped with those of NES, but this study was the first to discover that NSRED was different from NES in the fact that those suffering from NSRED were either partially or completely unaware of their actions at night while those with NES were aware.[4] Schenck and Mahowald also discovered that none of the patients had any eating instability before their problems at night while sleeping. In their 1993 report, they summarized the major findings with the idea that women encompass at least two thirds of the patients and that the majority of these patients had become overweight. They also discovered that while the patients' night-eating normally started during early adulthood, this wasn't always the case as it started as early as childhood to as late as middle adulthood. These patients not only had NSRED, but many of them had also been suffering from other nighttime behaviors such as sleep terrors for several years.[4] This revolutionized the way people saw NSRED.[citation needed] With the technological age growing and more people becoming obese, Schenck and Mahowald's discovery of NSRED causing a large weight increase helped doctors more easily identify this disorder. As seen in Table 1 below, almost half of Schenck and Mahowald's patients were significantly obese. According to body mass index's criteria, no patient was emaciated. Schenck and Mahowald said, "virtually all patients had accurate non-distorted appraisals of their body size, shape, and weight. Furthermore, unlike the patients in Stunkard's series, none of our patients had problematic eating in the evening between dinner and bedtime; sleep onset insomnia was not present; and sleep latency was usually brief, apart from several patients with RLS."[4] After realizing what was wrong with them, many of Schenck and Mahowald's patients with NSRED restricted their day eating and over exercised.[4] This table summary identifies the first initial findings concerning NSRED, and it shows how NSRED is a random malady that affects many different types of people in individual ways.
## See also[edit]
* Night eating syndrome
## References[edit]
1. ^ Inoue, Y. (2015). Sleep-related eating disorder and its associated conditions. Psychiatry and clinical neurosciences, 69(6), 309–320.
2. ^ a b c d Winkelman, John W (2006). "Sleep-Related Eating Disorder and Night Eating Syndrome: Sleep Disorders, Eating Disorders, Or both?". Sleep. 29 (7): 876–7. doi:10.1093/sleep/29.7.876. PMID 16895252.
3. ^ a b c d Auger, Robert R. (2006). "Sleep-Related Eating Disorders". Psychiatry. 3 (11): 64–70. ISSN 1550-5952. PMC 2945843. PMID 20877520.
4. ^ a b c d e f g h i j k l Schenck, Carlos H.; Mahowald, Mark W. (1994). "Review of Nocturnal Sleep-Related Eating Disorders". International Journal of Eating Disorders. 15 (4): 343–56. doi:10.1002/eat.2260150405.
5. ^ a b c d Winkelman, J. W. (1998). "Clinical and Polysomnographic Features of Sleep-Related Eating Disorder". The Journal of Clinical Psychiatry. 59 (1): 14–9. doi:10.4088/jcp.v59n0104. PMID 9491060.
6. ^ a b American Academy of Sleep Medicine (2014) International classification of sleep disorders, 3rd edn. American Academy of Sleep Medicine, Darien
7. ^ a b Avidan, A. Y. (2017). Non–Rapid Eye Movement Parasomnias: Clinical Spectrum, Diagnostic Features, and Management. In Principles and Practice of Sleep Medicine (p. 981–992). Elsevier
## External links[edit]
Classification
D
* ICD-9-CM: 307.50
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Nocturnal sleep-related eating disorder | c1319848 | 4,046 | wikipedia | https://en.wikipedia.org/wiki/Nocturnal_sleep-related_eating_disorder | 2021-01-18T18:47:59 | {"wikidata": ["Q11583761"]} |
A rare multisystemic genetic disorder characterized by a characteristic facial features with macrocephaly, overgrowth in infancy, intellectual disability and behavioral problems including anxieties and aggressiveness.
## Epidemiology
Approximatively 80 patients have been reported in the literature to date.
## Clinical description
Malan syndrome is an overgrowth disorder characterized by postnatal overgrowth (in infancy and childhood), developmental delay, moderate to severe intellectual disability and unusual behavior (i.e. anxieties, noise sensitivity, hetero/auto-aggressive behavior). It is worth noting that overgrowth is less marked in adulthood. The most characteristic facial features include macrocephaly, long, triangular face, prominent forehead, depressed nasal bridge, deeply set eyes, downslanting palpebral fissures, short nose with anteverted nares, small mouth with an everted lower lip and a prominent chin. Additional variable manifestations comprise musculoskeletal abnormalities with slender habitus, scoliosis and pectus excavatum as well as long hands. Visual problems are frequent, especially strabismus, myopia, hypermetropia, nystagmus and underdeveloped optic nerves. Structural brain imaging abnormalities (i.e. enlarged ventricles, hypoplasia of the corpus callosum, cortical dysplasia and periventricular nodular heterotopia) have also been reported. Some patients have seizures and/or electroencephalogram abnormalities. The increased prevalence of epilepsy in individuals with deletions of NFIX may be explained by the presence of a contiguous gene disorder.
## Etiology
NFIX (Nuclear factor I X) haploinsufficiency is responsible for this syndrome and may be the result of heterozygous loss-of-function variants in the NFIX (Nuclear Factor I X (19p13.13) gene or 19p13 microdeletions encompassing the gene NFIX.
## Diagnostic methods
Malan syndrome is a clinically recognizable overgrowth syndrome. The diagnosis is based on the major clinical findings including postnatal overgrowth, facial dysmorphism with macrocephaly, intellectual disability and behaviorally anxiety. The genetic diagnosis is established by identification of a heterozygous pathogenic variant in NFIX or a deletion encompassing this gene. Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing and multigene panel) and/or comprehensive genomic testing (chromosomal microarray analysis, exome sequencing, genome sequencing).
## Differential diagnosis
The differential diagnoses include Sotos syndrome, Weaver syndrome and Marfan or Marfan-like syndromes. In case of large 19p13 deletions, other clinical signs are reported corresponding to the 19p13.13 microdeletion syndrome.
## Antenatal diagnosis
Prenatal diagnosis is possible if the disease-causing variant has been identified in the family. The recent implementation of prenatal whole exome sequencing could lead to molecular diagnostics during pregnancy.
## Genetic counseling
Malan syndrome is inherited in an autosomal dominant manner. In the majority of cases, the pathogenic variants or deletions occur de novo. In this situation, the risk to sibs of the proband is very low due to a possible germinal mosaicism (<1%). In the rare familial cases, there is a 50% risk of transmitting the disease from an affected individual to offspring.
## Management and treatment
Management of Malan syndrome requires a multidisciplinary approach with appropriate medical specialists for intellectual disability, seizures, musculoskeletal and ocular abnormalities. Special education training along with behavioral intervention therapy may also be required.
## Prognosis
Malan syndrome has significant impact on quality of life.
* European Reference Network
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Malan overgrowth syndrome | c3553660 | 4,047 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=420179 | 2021-01-23T18:22:33 | {"omim": ["614753"], "icd-10": ["Q87.3"], "synonyms": ["Sotos syndrome 2"]} |
Vibratory urticaria is a rare, genetic urticaria characterized by the development of localized, short-lasting (resolving within 1 hour), pruritic, erythematous, edematous hives in response to repetitive frictional or vibratory stimulation of the skin, which in some cases is accompanied by facial flushing, headache or the sensation of a metallic taste. Concomitant local mast cell degranulation and increased histamine serum levels are additional typical findings.
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Vibratory urticaria | c1852146 | 4,048 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=493342 | 2021-01-23T19:12:57 | {"mesh": ["C536612"], "omim": ["125630"]} |
A rare neurologic disease characterized by seizures that are triggered by acoustic stimulation, which can be simple (as in startle epilepsy) or complex (e.g. musicogenic seizures, seizures triggered by the voice).
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Audiogenic seizures | c0751791 | 4,049 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=166415 | 2021-01-23T17:09:15 | {"mesh": ["D020195"], "umls": ["C0751791"], "icd-10": ["G40.5"]} |
This documentation needs attention from an expert in medicine. Please add a reason or a talk parameter to this template to explain the issue with the documentation. WikiProject Medicine may be able to help recruit an expert. (February 2009)
Tropical diseases are diseases that are prevalent in or unique to tropical and subtropical regions.[1] The diseases are less prevalent in temperate climates, due in part to the occurrence of a cold season, which controls the insect population by forcing hibernation. However, many were present in northern Europe and northern America in the 17th and 18th centuries before modern understanding of disease causation. The initial impetus for tropical medicine was to protect the health of colonial settlers, notably in India under the British Raj.[2] Insects such as mosquitoes and flies are by far the most common disease carrier, or vector. These insects may carry a parasite, bacterium or virus that is infectious to humans and animals. Most often disease is transmitted by an insect "bite", which causes transmission of the infectious agent through subcutaneous blood exchange. Vaccines are not available for most of the diseases listed here, and many do not have cures.
Human exploration of tropical rainforests, deforestation, rising immigration and increased international air travel and other tourism to tropical regions has led to an increased incidence of such diseases to non-tropical countries.[3][4]
## Contents
* 1 Health programmes
* 2 Other neglected tropical diseases
* 3 Relation of climate to tropical diseases
* 4 Prevention and treatment
* 4.1 Vector-borne diseases
* 4.2 Sexually transmitted diseases
* 4.3 Community approaches
* 4.4 Other approaches
* 5 See also
* 6 References
* 7 Further reading
* 7.1 Books
* 7.2 Journals
* 7.3 Websites
* 8 External links
## Health programmes[edit]
In 1975 the Special Programme for Research and Training in Tropical Diseases (TDR) was established to focus on neglected infectious diseases which disproportionately affect poor and marginalized populations in developing regions of Africa, Asia, Central America and North South America. It was established at the World Health Organization, which is the executing agency, and is co-sponsored by the United Nations Children's Fund, United Nations Development Programme, the World Bank and the World Health Organization.
TDR's vision is to foster an effective global research effort on infectious diseases of poverty in which disease endemic countries play a pivotal role. It has a dual mission of developing new tools and strategies against these diseases, and to develop the research and leadership capacity in the countries where the diseases occur. The TDR secretariat is based in Geneva, Switzerland, but the work is conducted throughout the world through many partners and funded grants.
Some examples of work include helping to develop new treatments for diseases, such as ivermectin for onchocerciasis (river blindness); showing how packaging can improve use of artemesinin-combination treatment (ACT) for malaria; demonstrating the effectiveness of bednets to prevent mosquito bites and malaria; and documenting how community-based and community-led programmes increases distribution of multiple treatments. TDR history
The current TDR disease portfolio includes the following entries:[5]
Historical TDR disease portfolio Disease When added Pathogen Primary vector Primary endemic areas Frequency Annual deaths Symptoms Complications
Malaria 1975 Plasmodium falciparum and four other Plasmodium species of protazoa Anopheles mosquitoes throughout the tropics 228 million (2018) 405,000 (2018) fever, tiredness, vomiting, headache yellow skin, seizures, coma, death
Schistosomiasis /ˌʃɪstəsəˈmaɪəsɪs/[6][7] (snail fever, bilharzia, "schisto") 1975 Schistosoma flatworms (blood flukes) freshwater snails throughout the tropics 252 million (2015) 4,400–200,000 abdominal pain, diarrhea, bloody stool, blood in the urine. In children, it may cause poor growth and learning difficulty. Liver damage, kidney failure, infertility, bladder cancer
Lymphatic filariasis 1975 Wuchereria bancrofti, Brugia malayi, and Brugia timori filarial worms mosquitoes throughout the tropics 38.5 million (2015) few lymphoedema, elephantiasis, hydrocele
Onchocerciasis /ˌɒŋkoʊsɜːrˈkaɪəsɪs, -ˈsaɪ-/[8][9] (river blindness) 1975 Onchocerca volvulus filarial worms[10] Simuliidae black flies sub-Saharan Africa 15.5 million (2015) 0 itching, papules edema, lymphadenopathy, visual impairment, blindness
Chagas disease (American trypanosomiasis) 1975 Trypanosoma cruzi protozoa Triatominae kissing bugs South America 6.2 million (2017) 7,900 (2017) fever, swollen lymph nodes, headache heart failure, enlarged esophagus, enlarged colon
African trypanosomiasis (sleeping sickness) 1975 Trypanosoma brucei gambiense and T. b. rhodesiense protozoa Glossina tsetse flies sub-Saharan Africa 11,000 (2015) 3,500 (2015) first stage: fever, headache, itchiness, joint pain
second stage: insomnia, confusion, ataxia, hemiparesis, paralysis
anemia, endocrine disfunction, cardiac disfunction, kidney dysfunction, coma, death
Leishmaniasis 1975 Leishmania protozoa Phlebotominae sandflies throughout the tropics 4–12 million 24,200 (2015) skin ulcers fever, anemia, enlarged liver, enlarged spleen, death
Leprosy† (Hansen's disease) 1975 Mycobacterium leprae and M. lepromatosis mycobacteria extensive contact (probably airborne disease) throughout the tropics 209,000 (2018) few skin lesions,[11] numbness permanent damage to the skin, nerves, limbs, and eyes
Dengue fever 1999 dengue virus Aedes aegypti and other Aedes mosquitoes tropical Asia 390 million (2020) 40,000 fever, headache, muscle and joint pain, rash, vomiting, diarrhea low levels of blood platelets, hypotension, hemorrhage, shock
Tuberculosis† (TB, consumption) 1999 Mycobacterium tuberculosis mycobacteria airborne disease worldwide 10 million (active, 2018),
2 billion (latent, 2018)
1.5 million (2018) chronic cough, fever, cough with bloody mucus, weight loss death
TB-HIV coinfection‡ 1999 HIV \+ Mycobacterium tuberculosis sexual contact \+ airborne disease Africa 1.2 million (2015) 251,000 (2018)
Sexually transmitted infections (notably syphilis, gonorrhoea, chlamydia, trichomoniasis, hepatitis B, HSV, HIV, and HPV) 2000 bacteria, parasite, viruses sexual contact worldwide various various
† Although leprosy and tuberculosis are not exclusively tropical diseases, their high incidence in the tropics justifies their inclusion.
‡ People living with HIV are 19 (15-22) times more likely to develop active TB disease than people without HIV.
## Other neglected tropical diseases[edit]
Additional neglected tropical diseases include:[12]
Disease Causative Agent Comments
Hookworm Ancylostoma duodenale and Necator americanus
Trichuriasis Trichuris trichiura
Treponematoses Treponema pallidum pertenue, Treponema pallidum endemicum, Treponema pallidum carateum, Treponema pallidum pallidum
Buruli ulcer Mycobacterium ulcerans
Dracunculiasis Dracunculus medinensis
Leptospirosis Leptospira
Strongyloidiasis Strongyloides stercoralis
Foodborne trematodiases Trematoda
Neurocysticercosis Taenia solium
Scabies Sarcoptes scabiei
Flavivirus Infections Yellow fever virus, West Nile virus, dengue virus, Tick-borne encephalitis virus, Zika virus
Some tropical diseases are very rare, but may occur in sudden epidemics, such as the Ebola hemorrhagic fever, Lassa fever and the Marburg virus. There are hundreds of different tropical diseases which are less known or rarer, but that, nonetheless, have importance for public health.
## Relation of climate to tropical diseases[edit]
The so-called "exotic" diseases in the tropics have long been noted both by travelers, explorers, etc., as well as by physicians. One obvious reason is that the hot climate present during all the year and the larger volume of rains directly affect the formation of breeding grounds, the larger number and variety of natural reservoirs and animal diseases that can be transmitted to humans (zoonosis), the largest number of possible insect vectors of diseases. It is possible also that higher temperatures may favor the replication of pathogenic agents both inside and outside biological organisms. Socio-economic factors may be also in operation, since most of the poorest nations of the world are in the tropics. Tropical countries like Brazil, which have improved their socio-economic situation and invested in hygiene, public health and the combat of transmissible diseases have achieved dramatic results in relation to the elimination or decrease of many endemic tropical diseases in their territory.[citation needed]
Climate change, global warming caused by the greenhouse effect, and the resulting increase in global temperatures, are possibly causing tropical diseases and vectors to spread to higher altitudes in mountainous regions, and to higher latitudes that were previously spared, such as the Southern United States, the Mediterranean area, etc.[13][14] For example, in the Monteverde cloud forest of Costa Rica, global warming enabled Chytridiomycosis, a tropical disease, to flourish and thus force into decline amphibian populations of the Monteverde Harlequin frog.[15] Here, global warming raised the heights of orographic cloud formation, and thus produced cloud cover that would facilitate optimum growth conditions for the implicated pathogen, B. dendrobatidis.
## Prevention and treatment[edit]
Disability-adjusted life year for tropical diseases per 100,000 inhabitants. These include trypanosomiasis, chagas disease, schistosomiasis, leishmaniasis, lymphatic filariasis, onchocerciasis.
no data
≤100
100-200
200-300
300-400
400-500
500-600
600-700
700-800
800-900
900-1000
1000-1500
≥1500
### Vector-borne diseases[edit]
Vectors are living organisms that pass disease between humans or from animal to human. The vector carrying the highest number of diseases is the mosquito, which is responsible for the tropical diseases dengue and malaria.[16] Many different approaches have been taken to treat and prevent these diseases. NIH-funded research has produced genetically modify mosquitoes that are unable to spread diseases such as malaria.[17] An issue with this approach is global accessibility to genetic engineering technology; Approximately 50% of scientists in the field do not have access to information on genetically modified mosquito trials being conducted.[18]
Other prevention methods include:
* Draining wetlands to reduce populations of insects and other vectors, or introducing natural predators of the vectors.
* The application of insecticides and/or insect repellents) to strategic surfaces such as clothing, skin, buildings, insect habitats, and bed nets.
* The use of a mosquito net over a bed (also known as a "bed net") to reduce nighttime transmission, since certain species of tropical mosquitoes feed mainly at night.
### Sexually transmitted diseases[edit]
Both pharmacologic pre-exposure prophylaxis (to prevent disease before exposure to the environment and/or vector) and pharmacologic post-exposure prophylaxis (to prevent disease after exposure to the environment and/or vector) are used to prevent and treat HIV[citation needed]
### Community approaches[edit]
Assisting with economic development in endemic regions can contribute to prevention and treatment of tropical diseases. For example, microloans enable communities to invest in health programs that lead to more effective disease treatment and prevention technology.[19]
Educational campaigns can aid in the prevention of various diseases. Educating children about how diseases spread and how they can be prevented has proven to be effective in practicing preventative measures.[20] Educational campaigns can yield significant benefits at low costs.
### Other approaches[edit]
* Use of water wells, and/or water filtration, water filters, or water treatment with water tablets to produce drinking water free of parasites.
* Sanitation to prevent transmission through human waste.
* Development and use of vaccines to promote disease immunity.
* Pharmacologic treatment (to treat disease after infection or infestation).
## See also[edit]
* Hospital for Tropical Diseases
* Tropical medicine
* Infectious disease
* Neglected diseases
* List of epidemics
* Waterborne diseases
* Globalization and disease
## References[edit]
1. ^ Farrar, Jeremy; Hotez, Peter J; Junghanss, Thomas; Kang, Gagandeep; Lalloo, David; White, Nicholas (2013). Manson's tropical diseases (New ed.). Philadelphia: Saunders [Imprint]. ISBN 9780702051012.
2. ^ Farley, John (2003). Bilharzia : a history of imperial tropical medicine (1. paperback ed.). [S.l.]: Cambridge Univ Press. ISBN 0521530601.
3. ^ "Deforestation Boosts Malaria Rates, Study Finds". npr.org. Archived from the original on 3 January 2018. Retrieved 4 May 2018.
4. ^ UK 'faces tropical disease threat' Archived 2006-06-15 at the Wayback Machine, BBC News
5. ^ "Disease portfolio". Special Programme for Research and Training in Tropical Diseases. Archived from the original on 2008-01-13. Retrieved 2009-08-01.
6. ^ "Schistosomiasis". Oxford Dictionaries UK Dictionary. Oxford University Press. Retrieved 2016-01-21.
7. ^ "Schistosomiasis". Merriam-Webster Dictionary. Retrieved 2016-01-21.
8. ^ "Onchocerciasis". Merriam-Webster Dictionary. Retrieved 2016-01-21.
9. ^ "Onchocerciasis". Oxford Dictionaries UK Dictionary. Oxford University Press. Retrieved 2016-01-21.
10. ^ "Archived copy". Archived from the original on 2008-03-24. Retrieved 2008-03-24.CS1 maint: archived copy as title (link) The World Bank | Global Partnership to Eliminate Riverblindness. Retrieved 2007-11-04.
11. ^ Kenneth J. Ryan and C. George Ray, Sherris Medical Microbiology Fourth Edition McGraw Hill 2004.
12. ^ Hotez, P. J.; Molyneux, DH; Fenwick, A; Kumaresan, J; Sachs, SE; Sachs, JD; Savioli, L (September 2007). "Control of Neglected Tropical Diseases". The New England Journal of Medicine. 357 (10): 1018–1027. doi:10.1056/NEJMra064142. ISSN 0028-4793. PMID 17804846. 17804846.
13. ^ Climate change brings malaria back to Italy Archived 2016-03-05 at the Wayback Machine The Guardian 6 January 2007
14. ^ BBC Climate link to African malaria Archived 2006-06-16 at the Wayback Machine 20 March 2006.
15. ^ Pounds, J. Alan et al. "Widespread Amphibian Extinctions from Epidemic Deisease Driven by Global Warming." Nature 439.12 (2006) 161-67
16. ^ "Vector-borne diseases". www.who.int. Retrieved 2020-05-04.
17. ^ "Engineering malaria resistance in mosquitoes". National Institutes of Health (NIH). 2017-10-23. Retrieved 2020-05-04.
18. ^ Boëte, Christophe; Beisel, Uli; Reis Castro, Luísa; Césard, Nicolas; Reeves, R. Guy (2015-08-10). "Engaging scientists: An online survey exploring the experience of innovative biotechnological approaches to controlling vector-borne diseases". Parasites & Vectors. 8 (1): 414. doi:10.1186/s13071-015-0996-x. ISSN 1756-3305. PMC 4530488. PMID 26259589.
19. ^ "WHO | Linking health to microfinance to reduce poverty". WHO. Retrieved 2020-05-04.
20. ^ LaBeaud, A. Desiree; Glinka, Allison; Kippes, Christopher; King, Charles Harding (October 2009). "School-Based Health Promotion for Mosquito-Borne Disease Prevention in Children". The Journal of Pediatrics. 155 (4): 590–592.e1. doi:10.1016/j.jpeds.2009.03.009. ISSN 0022-3476. PMC 3104726. PMID 19773005.
## Further reading[edit]
### Books[edit]
* TDR at a glance - fostering an effective global research effort on diseases of poverty
* Le TDR en un coup d’oeilLe TDR en un coup d’oeil - favoriser un eff ort mondial de recherche eff icace sur les maladies liées à la pauvreté
* TDR annual report - 2009
* Monitoring and evaluation tool kit for indoor residual spraying
* Indicators for monitoring and evaluation of the kala-azar elimination programme
* Malaria Rapid Diagnostic Test Performance - results of WHO product testing of malaria RDTs: Round 2- 2009
* Quality Practices in Basic Biomedical Research (QPBR) training manual: Trainer
* Quality Practices in Basic Biomedical Research (QPBR) training manual: Trainee
* Progress and prospects for the use of genetically modified mosquitoes to inhibit disease transmission
* Use of Influenza Rapid Diagnostic Tests
* Manson's Tropical Diseases
* Mandell's Principles and Practice of Infectious Diseases or this site
### Journals[edit]
* American Journal of Tropical Medicine and Hygiene
* Japanese Journal of Tropical Medicine and Hygiene
* Tropical Medicine and International Health[permanent dead link]
* The Southeast Asian Journal of Tropical Medicine and Public Health
* Revista do Instituto de Medicina Tropical de São Paulo
* Revista da Sociedade Brasileira de Medicina Tropical
* Journal of Venomous Animals and Toxins including Tropical Diseases
### Websites[edit]
* Special Programme for Research and Training in Tropical Diseases -TDR
* GIDEON-Global Infectious Disease Epidemiology Network
## External links[edit]
Wikivoyage has a travel guide for Tropical diseases.
* WHO Neglected Tropical Diseases
* WHO Operational research in tropical and other communicable diseases
* European Bioinformatics Institute
* open source drug discovery
* Drugs for Neglected Diseases Initiative
* Tropical diseases from Maya Paradise, The Guatemala Information Web Site
* American Society for Tropical Medicine and Hygiene
* Treating Tropical Diseases U.S. Food and Drug Administration
* Travelers' Health \- National Center for Infectious Diseases - Centers for Disease Control and Prevention
* Professor Andrew Speilman, Harvard School of Tropical Medicine Freeview Malaria video by the Vega Science Trust.
* Rob Hutchingson, Entomolgoist, London School of Tropical Medicine, Mosquitoes Freeview 'Snapshot' video by the Vega Science Trust.
* Links to pictures of tropical diseases (Hardin MD/Univ of Iowa)
* Tulane University School of Public Health and Tropical Medicine \- New Orleans, Louisiana, USA
* Tropical Diseases Web Ring
* Tropicology Library. In Portuguese.
* Institute for Tropical Medicine \- Antwerp - Belgium
* Lecture Notes ITM \- Antwerp - Belgium
* Faculty of Tropical Medicine, Mahidol University \- Bangkok - Thailand
* 'Conquest and Disease or Colonisation and Health', lecture by Professor Frank Cox on the history of tropical disease, given at Gresham College, 17 September 2007 (available for download as video and audio files, as well as a text file).
* NIH/National Institute of Allergy and Infectious Diseases (2007, December 28). "Neglected Tropical Diseases Burden Those Overseas, But Travelers Also At Risk". ScienceDaily. Retrieved 2007-12-28.
* Colombian Institute of Tropical Medicine ICMT-CES University
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*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Tropical disease | c1336827 | 4,050 | wikipedia | https://en.wikipedia.org/wiki/Tropical_disease | 2021-01-18T19:02:33 | {"wikidata": ["Q1345671"]} |
An extremely rare form of oculocutaneous albinism type 1 characterized by temperature sensitive hair pigmentation leading to dark hair on the hands, feet, legs, arms and chest (cooler body areas) and white or pale yellow hair on the scalp, axilla and pubic area (warmer body areas). Nystagmus and reduced visual acuity are also noted.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Temperature-sensitive oculocutaneous albinism type 1 | c1847132 | 4,051 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=352737 | 2021-01-23T18:27:59 | {"mesh": ["C564645"], "omim": ["606952"], "umls": ["C1847132"], "icd-10": ["E70.3"], "synonyms": ["OCA1-TS", "TS OCA type 1"]} |
Ebstein's anomaly is a rare heart defect in which parts of the tricuspid valve (which separates the right ventricle from the right atrium) are abnormal. The abnormality causes the tricuspid valve to leak blood backwards into the right atrium. The backup of blood flow can lead to heart swelling and fluid buildup in the lungs or liver. Sometimes, not enough blood gets out of the heart into the lungs and the person may appear blue. Symptoms range from mild to very severe. Treatment depends on the severity of the defect and may include medications, oxygen therapy, or surgery.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Ebstein's anomaly | c0013481 | 4,052 | gard | https://rarediseases.info.nih.gov/diseases/6313/ebsteins-anomaly | 2021-01-18T18:00:45 | {"mesh": ["D004437"], "omim": ["224700"], "umls": ["C0013481"], "orphanet": ["1880"], "synonyms": ["Ebstein's malformation", "Ebstein anomaly"]} |
Pancreatic serous cystadenoma
Other namesSerous cystadenoma of the pancreas, serous microcystic adenoma
Micrograph showing a pancreatic serous cystadenoma. H&E stain.
SpecialtyGeneral surgery, gastroenterology
SymptomsUsually asymptomatic
Usual onset50-60 years of age
Risk factorsFemale gender
TreatmentSurgical resection (if symptomatic)
Deaths0.1%[1]
Pancreatic serous cystadenoma is a benign tumour of pancreas. It is usually found in the tail of the pancreas,[2] and may be associated with von Hippel-Lindau syndrome.[3]
In contrast to some of the other cyst-forming tumors of the pancreas (such as the intraductal papillary mucinous neoplasm and the mucinous cystic neoplasm), serous cystic neoplasms are almost always entirely benign. There are some exceptions; rare case reports have described isolated malignant serous cystadenocarcinomas.[4] In addition, serous cystic neoplasms slowly grow, and if they grow large enough they can press on adjacent organs and cause symptoms.
## Contents
* 1 Signs and symptoms
* 2 Classification
* 3 Pathology
* 4 Treatment
* 5 Epidemiology
* 6 See also
* 7 References
* 8 External links
## Signs and symptoms[edit]
In most cases, serous cystadenomas of the pancreas are asymptomatic.[5] However, large cysts may cause symptoms related to their size.[5]
## Classification[edit]
Pathologists classify serous cystic neoplasms into two broad groups. Those that are benign, that have not spread to other organs, are designated "serous cystadenoma".[6] Serous cystadenomas can be further sub-typed into microcystic, oligocystic (or macrocystic), solid, mixed serous-endocrine neoplasm, and VHL-associated serous cystic neoplasm. This latter classification scheme is useful because it highlights the range of appearances and the clinical associations of these neoplasms. Serous cystic neoplasms that have spread ("metastasized") to another organ are considered malignant and are designated "serous cystadenocarcinoma".[citation needed]
## Pathology[edit]
* * * * * *
## Treatment[edit]
These lesions rarely require surgery unless they are symptomatic or the diagnosis is in question. Since these lesions do not have malignant potential, long-term observation with imaging surveillance is unnecessary.[5] Surgery can include the removal of the head of the pancreas (a pancreaticoduodenectomy), removal of the body and tail of the pancreas (a distal pancreatectomy), or rarely removal of the entire pancreas (a total pancreatectomy).[7] In selected cases the surgery can be performed using minimally invasive techniques such as laparoscopy.[8]
## Epidemiology[edit]
Serous cystadenomas of the pancreas are more common in women.[5] SCAs are usually diagnosed in people 50-60 years of age.[5]
## See also[edit]
* Ovarian serous cystadenoma
* Pancreatic mucinous cystadenoma
* Solid pseudopapillary neoplasm
## References[edit]
1. ^ Jais, B; Rebours, V; Malleo, G; Salvia, R; Fontana, M; Maggino, L; Bassi, C; Manfredi, R; Moran, R; Lennon, AM; Zaheer, A; Wolfgang, C; Hruban, R; Marchegiani, G; Fernández Del Castillo, C; Brugge, W; Ha, Y; Kim, MH; Oh, D; Hirai, I; Kimura, W; Jang, JY; Kim, SW; Jung, W; Kang, H; Song, SY; Kang, CM; Lee, WJ; Crippa, S; Falconi, M; Gomatos, I; Neoptolemos, J; Milanetto, AC; Sperti, C; Ricci, C; Casadei, R; Bissolati, M; Balzano, G; Frigerio, I; Girelli, R; Delhaye, M; Bernier, B; Wang, H; Jang, KT; Song, DH; Huggett, MT; Oppong, KW; Pererva, L; Kopchak, KV; Del Chiaro, M; Segersvard, R; Lee, LS; Conwell, D; Osvaldt, A; Campos, V; Aguero Garcete, G; Napoleon, B; Matsumoto, I; Shinzeki, M; Bolado, F; Fernandez, JM; Keane, MG; Pereira, SP; Acuna, IA; Vaquero, EC; Angiolini, MR; Zerbi, A; Tang, J; Leong, RW; Faccinetto, A; Morana, G; Petrone, MC; Arcidiacono, PG; Moon, JH; Choi, HJ; Gill, RS; Pavey, D; Ouaïssi, M; Sastre, B; Spandre, M; De Angelis, CG; Rios-Vives, MA; Concepcion-Martin, M; Ikeura, T; Okazaki, K; Frulloni, L; Messina, O; Lévy, P (February 2016). "Serous cystic neoplasm of the pancreas: a multinational study of 2622 patients under the auspices of the International Association of Pancreatology and European Pancreatic Club (European Study Group on Cystic Tumors of the Pancreas)". Gut. 65 (2): 305–12. doi:10.1136/gutjnl-2015-309638. hdl:11577/3187425. PMID 26045140.
2. ^ Colonna, J.; Plaza, JA.; Frankel, WL.; Yearsley, M.; Bloomston, M.; Marsh, WL. (2008). "Serous cystadenoma of the pancreas: clinical and pathological features in 33 patients". Pancreatology. 8 (2): 135–41. doi:10.1159/000123606. PMID 18382099. S2CID 28918883.
3. ^ Eras, M.; Yenigun, M.; Acar, C.; Kumbasar, B.; Sar, F.; Bilge, T. (2004). "Pancreatic involvement in Von Hippel-Lindau disease". Indian J Cancer. 41 (4): 159–61. PMID 15659868.
4. ^ Galanis C, Zamani A, Cameron JL, et al. (July 2007). "Resected serous cystic neoplasms of the pancreas: a review of 158 patients with recommendations for treatment". J. Gastrointest. Surg. 11 (7): 820–6. doi:10.1007/s11605-007-0157-4. PMID 17440789. S2CID 32023143.
5. ^ a b c d e Elta, GH; Enestvedt, BK; Sauer, BG; Lennon, AM (April 2018). "ACG Clinical Guideline: Diagnosis and Management of Pancreatic Cysts". The American Journal of Gastroenterology. 113 (4): 464–479. doi:10.1038/ajg.2018.14. PMID 29485131. S2CID 3584079.
6. ^ "Pathology of Neoplasms of the Pancreas". Johns Hopkins University. Retrieved 25 April 2010.
7. ^ "Pancreatic Surgery". Johns Hopkins University. Retrieved 25 April 2010.
8. ^ "Laproscopic Pancreatic Surgery". Johns Hopkins University. Retrieved 25 April 2010.
## External links[edit]
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| Pancreatic serous cystadenoma | c1335316 | 4,053 | wikipedia | https://en.wikipedia.org/wiki/Pancreatic_serous_cystadenoma | 2021-01-18T18:34:33 | {"umls": ["C1335316"], "wikidata": ["Q7130420"]} |
## Description
Multiple symmetric lipomatosis (MSL) is a rare disorder characterized by the growth of uncapsulated masses of adipose tissue. It is associated with high ethanol intake and may be complicated by somatic and autonomic neuropathy and by the infiltration of the adipose tissue at the mediastinal level (summary by Enzi et al., 2002).
Clinical Features
McKusick (1962) described 3 brothers with a collar of fat around the neck in the submandibular area and involving the nape of the neck. The age of onset was said to be 45, 39, and 29 years in the 3 patients. The mother was said to be definitely unaffected, having died at age 61, but 2 sisters and a maternal aunt were also affected. In advanced stages the process extended into the upper mediastinum. In 3 of those affected, lipomata of conventional type were present (e.g., in the epitrochlear area, back, axillae, and internal aspect of forearm).
Lyon (1910) reported a striking case which was familial. Michon and Rose (1935) observed familial cases.
Cervical lipomatosis was associated with gout and hyperlipoproteinemia type IV in the sisters reported by Greene et al. (1970). Oligomenorrhea, muscle cramps, pes cavus, and extensor plantar reflexes were also described.
Because fat cells are smaller than normal in this disorder, Enzi et al. (1977) concluded that lipomata are attributable to neoformation of adipocytes. In their studies of 10 affected males, reduced glucose tolerance and hyperlipoproteinemia were no more frequent than in controls. In lipomatous tissue but not in normal fat tissue from these subjects, in vitro insensitivity to the lipolytic effect of catecholamines was demonstrated. The block appeared to be proximal to cyclic AMP formation because theophylline induced a prompt and significant decrease in intracellular ATP in lipomatous tissue.
Enzi et al. (1985) documented the high frequency of somatic and autonomic neuropathies. In 28 of 33 male patients changes varying from vibratory sensory loss to incapacitating trophic ulcers or Charcot arthropathy were found. High density lipoprotein was increased, consistent with the diagnosis of hyperalphalipoproteinemia, and low density lipoprotein fractions were reduced with a marked enhancement of lipoprotein lipase activity in adipose tissue.
Pollock et al. (1988) pointed out that, with increasing age, peripheral neuropathy becomes more common in multiple symmetric lipomatosis and is a principal cause of severe disability. The peripheral neuropathy is often attributed to alcoholism, but the pathologic findings of Pollock et al. (1988) led them to conclude that the neuropathy is in fact an integral part of the syndrome. Biochemical observations suggested a defect in catecholamine-stimulated lipolysis at the level of cell membranes. Chalk et al. (1990) also thought that alcoholism could be excluded. Sural nerve biopsy in 1 patient showed nerve fiber loss, predominantly affecting large myelinated fibers. The relationship between myelin sheath thickness and axon diameter was normal, arguing that this neuropathy is not due to primary axonal atrophy.
Zancanaro et al. (1990) presented studies suggesting that multiple symmetric lipomatosis may be a neoplastic disease that originates in brown fat.
Williams et al. (1993) described the findings on magnetic resonance imaging in 2 unrelated women, aged 27 and 48 years. Tizian et al. (1983) had described malignant degeneration within the lipomatosis tissue. This must be very rare inasmuch as Williams et al. (1993) could find no other report of this complication.
Klopstock et al. (1994) pointed out that ragged-red fibers are occasionally found in muscle of patients with multiple symmetric lipomatosis, suggesting a mitochondrial abnormality. They studied 11 unrelated patients with this disorder by means of neurophysiology, muscle morphology, muscle biochemistry, Southern blot, and PCR analysis of mitochondrial DNA. All patients were men, aged 41 to 63 years. Clinical or electrophysiologic signs of sensorimotor polyneuropathy were present in 9 patients, 8 of whom had a history of alcoholism. In muscle biopsy specimens, the most prominent feature was pathologic subsarcolemmal accumulations of mitochondria. Biochemical analysis of respiratory chain enzymes revealed a moderate but significant decrease of cytochrome c oxidase activity as compared with age-matched controls. In 1 patient, Southern blot analysis showed multiple deletions of mitochondrial DNA.
In a longitudinal study of 31 patients with MLS (mean follow-up of 14.5 +/- 5.0 years), Enzi et al. (2002) confirmed the association of the disorder with high ethanol intake. Onset was usually in the fourth or fifth decade. Eight patients (25.8%) died during follow-up, none of whom had signs or symptoms of coronary heart disease. In addition to this high fatality rate, a substantial morbidity related to the occupation of the mediastinal space by the lipomatous tissue and to somatic neuropathy was observed.
Inheritance
Enzi (1984) studied 34 patients with MLS, 3 of whom had other affected family members: a brother in 2 instances and a father and son in the third. The other patients declared that none of their sibs (34 brothers, 28 sisters) or parents was affected.
Chalk et al. (1990) described coexisting peripheral neuropathy and multiple symmetric lipomatosis in 4 of 7 sibs, 3 female and 1 male. They favored autosomal recessive inheritance because of absence of either condition in 3 other generations of this family.
Population Genetics
Enzi et al. (1985) suggested that MSL is not unusual in Mediterranean areas and that the frequency in Italy is about 1 per 25,000 males.
Clinical Management
Taylor et al. (1961) described surgical procedures adopted in a case similar to those reported by McKusick (1962).
Williams et al. (1993) commented that the standard treatment is surgical debulking, but prognosis is guarded because of frequent recurrences.
In a longitudinal follow-up of patients with MLS, Enzi et al. (2002) found that alcohol discontinuation was associated with a slight regression of lipomatous depots and that an increase in ethanol consumption seemed to accelerate the lipomatous growth.
Molecular Genetics
Holme et al. (1993) reported a woman with multiple symmetric lipomas in the neck and shoulder area associated with a heteroplasmic c.8344A-G mutation in the MTTK gene (590060.0001). Her son, who also carried the mutation, had MERRF syndrome (545000); the mother had no signs of MERRF syndrome. The fraction of mutant mtDNA in the woman varied between 62% and 80% in cultured skin fibroblasts, lymphocytes, normal adipose tissue, and muscle, whereas the fraction of mutant mtDNA in the lipomas ranged from 90 to 94%. Ultrastructural examination of the lipomas revealed numerous mitochondria and electron-dense inclusions in some adipocytes. Holme et al. (1993) concluded that the mutation may either directly or indirectly perturb the maturation process of the adipocytes, increasing the risk of lipoma formation.
Gamez et al. (1998) identified a heteroplasmic c.8344A-G mutation in the MTTK gene in 6 members of a family with multiple symmetric lipomatosis. The 36-year-old female proband had a history of progressive muscle weakness associated with peripheral polyneuropathy, neurosensory hypoacusis, and symmetric confluent large lipomas over the neck and upper trunk. She developed dysarthria, dysphagia, and ptosis, suggestive of a stroke, and subsequently had lactic acidosis with multiorgan failure; some of these features are found in MERRF syndrome. Muscle biopsy of the proband showed both ragged-red and COX-negative fibers. The proportion of mutated mtDNA was higher in lipomas than in muscle and blood. Five maternal relatives had multiple symmetric lipomatosis but no neuromuscular involvement; only the proband's affected mother had hearing loss.
History
Brodie (1846) is said to have first described diffuse symmetrical lipomatosis with predilection for the neck. It was called 'Fetthals" (fat neck) by Madelung (1888).
Inheritance \- Autosomal dominant Neuro \- Somatic and autonomic neuropathy Skin \- Neck collar of fat \- Multiple lipomata ▲ Close
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
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*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| LIPOMATOSIS, MULTIPLE SYMMETRIC | c2931642 | 4,054 | omim | https://www.omim.org/entry/151800 | 2019-09-22T16:38:50 | {"doid": ["14116"], "mesh": ["C537837"], "omim": ["151800"], "orphanet": ["2398"], "synonyms": ["Alternative titles", "LIPOMATOSIS, FAMILIAL BENIGN CERVICAL", "LIPODYSTROPHY, CEPHALOTHORACIC"]} |
Diamond-Blackfan anemia is an inherited blood disorder that affects the ability of the bone marrow to produce red blood cells. Symptoms may include a shortage of red blood cells (anemia), physical abnormalities such as small head size (microcephaly) characteristic facial features, cleft palate, cleft lip, short and webbed neck, small shoulder blades, and defects of the hands (mostly of the thumbs), as well as defects of the genitalia, urinary tract, eyes and heart. In some cases there is also short stature.
Diamond-Blackfan anemia is caused by mutations in several genes, some of which have been identified and some of which have not. Identified genes include but are not limited to: RPS19, RPL5, RPS10, RPL11, RPL35A, RPS7, RPS17, RPS24, RPS26 and GATA1 genes. Different subtypes exist and are divided based on the specific gene mutated; however, they have similar features. Patients with mutations in the RPL5 gene have more serious symptoms and about 45% have cleft palate and are smaller than average size. Patients with mutations in the RPL11 gene have thumb anomalies more frequently than people with the other types. Mutations in the GATA1 gene are associated with severe anemia. Most cases are isolated, but about 45% of people with Diamond-Blackfan anemia inherit this condition from a parent. Inheritance is typically autosomal dominant , but can rarely be X-linked.
Treatment may involve corticosteroids, blood transfusions, a bone marrow transplant or stem cell transplantation. The severity of the disease is very varied. People with Diamond-Blackfan anemia may have an increased risk of having diseases related to a bone marrow defect, such as myelodysplastic syndrome, and certain cancers. Adults with the disease may have hormonal problems in later life, specially adrenal insufficiency, hypogonadism and hypothyroidism.
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*[AA]: Adrenergic agonist
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*[DOR]: δ-opioid receptor
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*[NET]: Norepinephrine transporter
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*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
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*[CEEs]: conjugated estrogens
| Diamond-Blackfan anemia | c1260899 | 4,055 | gard | https://rarediseases.info.nih.gov/diseases/6274/diamond-blackfan-anemia | 2021-01-18T18:00:54 | {"mesh": ["D029503"], "icd-10": ["D61.0"], "orphanet": ["124"], "synonyms": ["DBA", "Anemia Diamond Blackfan type", "Blackfan Diamond syndrome", "BDS", "Anemia congenital erythroid hypoplastic", "Aregenerative anemia chronic congenital", "Erythrogenesis imperfecta", "Red cell aplasia, pure hereditary", "Congenital hypoplastic anemia", "Aase syndrome", "Blackfan-Diamond anemia", "Aase-Smith II syndrome", "Congenital PRCA", "Congenital hypoplastic anemia, Blackfan-Diamond type", "Congenital pure red cell aplasia"]} |
Not to be confused with Dipsomania.
This article needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the article and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed.
Find sources: "Potomania" – news · newspapers · books · scholar · JSTOR (September 2020)
Potomania
Other namesBeer potomania, Beer drinker's potomania, Beer drinker's hyponatremia, Frat boy syndrome
Annual beer consumption per capita.
SymptomsAlcoholism
Potomania is a specific hypo-osmolality syndrome related to massive consumption of beer, which is poor in solutes and electrolytes. With little food or other sources of electrolytes, consumption of large amounts of beer or other dilute alcoholic drinks leads to electrolyte disturbances, where the body does not have enough nutrients known as electrolytes, namely sodium, potassium, and magnesium. The symptoms of potomania are similar to other causes of hyponatremia and include dizziness, muscular weakness, neurological impairment and seizures, all related to hyponatremia and hypokalaemia. While the symptoms of potomania are similar to other causes of hyponatremia and acute water intoxication, it should be considered an independent clinical entity because of its often chronic nature of onset, pathophysiology, and presentation of symptoms.
## Contents
* 1 Pathophysiology
* 2 Diagnosis
* 3 Treatment
* 4 See also
* 5 References
## Pathophysiology[edit]
The normal human kidney, through suppression of anti-diuretic hormone, is normally able to excrete vast amounts of dilute urine. Thus a normal adult can drink up to 20 liters per day of water without becoming hyponatremic. However, the intake of solutes is also necessary to excrete free water. Under normal circumstances, this is clinically irrelevant. In the lack of proper solute intake, the amount of free water excretion can be severely limited. Without adequate solute intake, the normal functioning electrolyte gradient that pulls water into urine will be effectively destroyed.
Briefly, to excrete free water from urine, the urine flow (which is solute clearance + free water clearance) will equal the rate of solute excretion divided by the urine osmolality. With a diet of only solute poor beer, only about 200–300 mOSM (normal 750 mOSM to greater than 900 mOSM) of solute will be excreted per day, capping the amount of free water excretion at four liters. Any intake above 4 liters would lead to a dilution of the serum sodium concentration and thus hyponatremia.
Any vomiting or GI absorptive problems due to alcohol intoxication can also compound the effect of potomania due to additional electrolyte and acid-base disturbances.
## Diagnosis[edit]
This section is empty. You can help by adding to it. (March 2019)
## Treatment[edit]
As with all cases of hyponatremia, extreme caution must be taken to avoid the fatal consequences of rapidly correcting electrolytes (e.g. central pontine myelinolysis, edema). Special considerations with the treatment of potomania are needed. Because this could be a chronic condition, low sodium may be normal for the patient, so an especially careful correction is warranted. It is also very important to note that due to the normal kidney function, and lack of other intrinsic or toxic cause of the electrolyte disturbance, restoration of dietary solutes will correct the electrolytes to normal serum levels. This again must be done with caution.
## See also[edit]
* Hyponatremia
* Primary polydipsia
* Water intoxication
## References[edit]
This article includes a list of references, related reading or external links, but its sources remain unclear because it lacks inline citations. Please help to improve this article by introducing more precise citations. (May 2015) (Learn how and when to remove this template message)
* Hilden, T; Svendsen, T. L. (1975). "ELECTROLYTE DISTURBANCES IN BEER DRINKERS a Specific 'Hypo-osmolality Syndrome'". The Lancet. 306 (7928): 245–6. doi:10.1016/S0140-6736(75)90961-7. PMID 49796. S2CID 12873417.)
* Harrow, A. S. (1989). "Beer potomania syndrome in an alcoholic". Virginia Medical. 116 (6): 270–1. PMID 2763635.
* http://renalfellow.blogspot.com/2009/03/beer-potomania.html[full citation needed]
* Berl, T. (2008). "Impact of Solute Intake on Urine Flow and Water Excretion". Journal of the American Society of Nephrology. 19 (6): 1076–8. doi:10.1681/ASN.2007091042. PMID 18337482.
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*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Potomania | c1167939 | 4,056 | wikipedia | https://en.wikipedia.org/wiki/Potomania | 2021-01-18T19:06:04 | {"wikidata": ["Q7235099"]} |
Mastitis
Other namesMammitis
A drawing of mastitis from the early 1900s
Pronunciation
* /mæstˈaɪtɪs/
SpecialtyGynecology
SymptomsLocalized breast pain and redness, fever[1]
ComplicationsAbscess[2]
Usual onsetRapid[1]
Diagnostic methodBased on symptoms[2]
Differential diagnosisPlugged milk duct,[3] breast engorgement,[4] breast cancer (rare)[1]
PreventionFrequent breastfeeding with good technique[2]
TreatmentAntibiotics (cephalexin), ibuprofen[2][1]
Frequency10% of breastfeeding women[2]
Mastitis is inflammation of the breast or udder, usually associated with breastfeeding.[1][5][6] Symptoms typically include local pain and redness.[1] There is often an associated fever and general soreness.[1] Onset is typically fairly rapid and usually occurs within the first few months of delivery.[1] Complications can include abscess formation.[2]
Risk factors include poor latch, cracked nipples, use of a breast pump, and weaning.[1] The bacteria most commonly involved are Staphylococcus and Streptococci.[1] Diagnosis is typically based on symptoms.[2] Ultrasound may be useful for detecting a potential abscess.[1]
Prevention is by proper breastfeeding techniques.[2] When infection is present, antibiotics such as cephalexin may be recommended.[2] Breastfeeding should typically be continued, as emptying the breast is important for healing.[2][1] Tentative evidence supports benefits from probiotics.[1] About 10% of breastfeeding women are affected.[2]
## Contents
* 1 Signs and symptoms
* 1.1 Breast abscess
* 2 Causes
* 2.1 Risk factors
* 2.2 Infection
* 3 Types
* 3.1 Pregnancy related
* 3.2 Non pregnancy related
* 4 Diagnosis
* 4.1 Differential diagnosis
* 5 Treatment
* 5.1 Antibiotics
* 5.2 Breast abscess
* 6 Prognosis
* 7 Epidemiology
* 8 Terminology
* 8.1 Etymology and pronunciation
* 9 Other animals
* 10 References
* 11 External links
## Signs and symptoms[edit]
Mastitis localized on the underside of the breast, with a large area of inflammation.
Lactation mastitis usually affects only one breast and the symptoms can develop quickly.[7] The signs and symptoms usually appear suddenly and they include:
* Breast tenderness or warmth to the touch
* General malaise or feeling ill
* Swelling of the breast
* Pain or a burning sensation continuously or while breast-feeding
* Skin redness, often in a wedge-shaped pattern
* Fever of 101 F (38.3 C) or greater[8]
* The affected breast can then start to appear lumpy and red.
Some women may also experience flu-like symptoms such as:
* Aches
* Shivering and chills
* Feeling anxious or stressed
* Fatigue[9]
Contact should be made with a health care provider with special breastfeeding competence as soon as the patient recognizes the combination of signs and symptoms. Most of the women first experience the flu-like symptoms and just after they may notice a sore red area on the breast. Also, women should seek medical care if they notice any abnormal discharge from the nipples, if breast pain is making it difficult to function each day, or they have prolonged, unexplained breast pain.
### Breast abscess[edit]
A breast abscess is a collection of pus that develops into the breast with different causes.[10] During lactation, breast abscess develops only rarely, most sources cite about 0.4–0.5% of breastfeeding women.[11] Known risk factors are age over 30, primiparous and late delivery. No correlation was found with smoking status; however, this may be in part because far fewer smoking women choose to breastfeed.[12] Antibiotics were not shown effective in prevention of lactation abscess but are useful to treat a secondary infection (see the section on the treatment of breast abscess in this article).
Keratinizing squamous metaplasia of lactiferous ducts may play a similar[clarification needed] role in the pathogenesis of nonpuerperal subareolar abscess.
## Causes[edit]
Since the 1980s mastitis has often been divided into non-infectious and infectious sub-groups. However, recent research [13] suggests that it may not be feasible to make divisions in this way. It has been shown that types and amounts of potentially pathogenic bacteria in breast milk are not correlated to the severity of symptoms. Moreover, although only 15% of women with mastitis in Kvist et al.'s study were given antibiotics, all recovered and few had recurring symptoms. Many healthy breastfeeding women wishing to donate breast milk have potentially pathogenic bacteria in their milk but have no symptoms of mastitis.
### Risk factors[edit]
Mastitis typically develops when the milk is not properly removed from the breast. Milk stasis can lead to the milk ducts in the breasts becoming blocked, as the breast milk is not being properly and regularly expressed.[14] It has also been suggested that blocked milk ducts can occur as a result of pressure on the breast, such as tight-fitting clothing or an over-restrictive bra, although there is sparse evidence for this supposition. Mastitis may occur when the baby is not appropriately attached to the breast while feeding, when the baby has infrequent feeds or has problems suckling the milk out of the breast.
The presence of cracks or sores on the nipples increases the likelihood of infection. Tight clothing or ill-fitting bras may also cause problems as they compress the breasts. There is a possibility that infants carrying infectious pathogens in their noses can infect their mothers;[15] the clinical significance of this finding is still unknown.
Mastitis, as well as breast abscess, can also be caused by direct trauma to the breast. Such injury can occur for example during sports activities[16] or due to seat belt injury.
Mastitis can also develop due to contamination of a breast implant or any other foreign body, for example after nipple piercing. In such cases, the removal of the foreign body is indicated.[17]
Women who are breastfeeding are at risk for developing mastitis especially if they have sore or cracked nipples or have had mastitis before while breastfeeding another baby. Also, the chances of getting mastitis increases if women use only one position to breastfeed or wear a tight-fitting bra, which may restrict milk flow [18] Difficulties in getting a nursing infant to latch on to the breast can also increase the risk for mastitis.[19]
Women with diabetes, chronic illness, AIDS, or an impaired immune system may be more susceptible to the development of mastitis.[20]
### Infection[edit]
Some women (approximately 15%)[13] will require antibiotic treatment for infection which is usually caused by bacteria from the skin or the baby's mouth that entering the milk ducts through skin lesions of the nipple or through the opening of the nipple.[21] Infection is usually caused by Staphylococcus aureus.[22] Infectious pathogens commonly associated with mastitis are Staphylococcus aureus, Streptococcus spp., and Gram-negative bacilli such as Escherichia coli. Salmonella spp., mycobacteria, and fungi such as Candida and Cryptococcus have been identified in rare instances.[11]
Recent research suggests that infectious pathogens play a much smaller role in the pathogenesis than was commonly assumed only a few years ago. Most detected pathogens are very common species that are natural part of the breast fauna and simple detection of their presence is not sufficient to prove a causative role. Furthermore, there are indications that treatment with antibiotics may have minimal impact,[23][24] and over-all there is insufficient evidence to confirm or refute the effectiveness of antibiotic therapy for treating lactational mastitis.[25]
## Types[edit]
When it occurs in breastfeeding mothers, it is known as puerperal mastitis, lactation mastitis, or lactational mastitis. When it occurs in non breastfeeding women it is known as non-puerperal or nonlactational. Mastitis can, in rare cases, occur in men. Inflammatory breast cancer has symptoms very similar to mastitis and must be ruled out.
The symptoms are similar for puerperal and nonpuerperal mastitis but predisposing factors and treatment can be very different.
### Pregnancy related[edit]
An ultrasound image of puerperal mastitis
Puerperal mastitis is the inflammation of the breast in connection with pregnancy, breastfeeding or weaning. Since one of the most prominent symptoms is tension and engorgement of the breast, it is thought to be caused by blocked milk ducts or milk excess. It is relatively common; estimates range depending on methodology between 5–33%. However, only about 0.4–0.5% of breastfeeding mothers develop an abscess.[11]
Some predisposing factors are known but their predictive value is minimal. It appears that proper breastfeeding technique, frequent breastfeeding and avoidance of stress are the most important factors that can be influenced.
Light cases of mastitis are often called breast engorgement; the distinction is overlapping and possibly arbitrary or subject to regional variations.
### Non pregnancy related[edit]
Main article: Nonpuerperal mastitis
The term nonpuerperal mastitis describes inflammatory lesions of the breast occurring unrelated to pregnancy and breastfeeding. This article includes description of mastitis as well as various kinds of mammary abscesses. Skin related conditions like dermatitis and foliculitis are a separate entity.
Names for non-puerperal mastitis are not used very consistently and include mastitis, subareolar abscess, duct ectasia, periductal inflammation, Zuska's disease and others.
Periductal mastitis is a form of nonlactational mastitis, and is characterized by inflammation of the subareolar ducts. Although the cause of periductal mastitis is currently unknown, it is predicted that smoking may be related. This condition is mainly seen in young women but can also be seen in men.[26]
## Diagnosis[edit]
The diagnosis of mastitis and breast abscess can usually be made based on a physical examination.[22] The doctor will also take into account the signs and symptoms of the condition.
However, if the doctor is not sure whether the mass is an abscess or a tumor, a breast ultrasound may be performed. The ultrasound provides a clear image of the breast tissue and may be helpful in distinguishing between simple mastitis and abscess or in diagnosing an abscess deep in the breast. The test consists of placing an ultrasound probe over the breast.
In cases of infectious mastitis, cultures may be needed in order to determine what type of organism is causing the infection. Cultures are helpful in deciding the specific type of antibiotics that will be used in curing the disease. These cultures may be taken either from the breast milk or of the material aspirated from an abscess.
Mammograms or breast biopsies are normally performed on women who do not respond to treatment or on non-breastfeeding women. This type of tests is sometimes ordered to exclude the possibility of a rare type of breast cancer which causes symptoms similar to those of mastitis.
### Differential diagnosis[edit]
Breast cancer may coincide with or mimic symptoms of mastitis. Only full resolution of symptoms and careful examination are sufficient to exclude the diagnosis of breast cancer.
Lifetime risk for breast cancer is significantly reduced for women who were pregnant and breastfeeding. Mastitis episodes do not appear to influence lifetime risk of breast cancer.
Mastitis does however cause great difficulties in diagnosis of breast cancer and delayed diagnosis and treatment can result in worse outcome.
Breast cancer may coincide with mastitis or develop shortly afterwards. All suspicious symptoms that do not completely disappear within 5 weeks must be investigated.
Breast cancer incidence during pregnancy and lactation is assumed to be the same as in controls. Course and prognosis are also very similar to age matched controls.[27][28] However diagnosis during lactation is particularly problematic, often leading to delayed diagnosis and treatment.
Some data suggest that noninflammatory breast cancer incidence is increased within a year following episodes of nonpuerperal mastitis and special care is required for follow-up cancer prevention screening.[29] So far only data from short term observation is available and total risk increase can not be judged. Because of the very short time between presentation of mastitis and breast cancer in this study it is considered very unlikely that the inflammation had any substantial role in carcinogenesis, rather it would appear that some precancerous lesions may increase the risk of inflammation (hyperplasia causing duct obstruction, hypersensitivity to cytokines or hormones) or the lesions may have common predisposing factors.
A very serious type of breast cancer called inflammatory breast cancer presents with similar symptoms as mastitis (both puerperal and nonpuerperal). It is the most aggressive type of breast cancer with the highest mortality rate. The inflammatory phenotype of IBC is thought to be mostly caused by invasion and blocking of dermal lymphatics, however it was recently shown that NF-κB target genes activation may significantly contribute to the inflammatory phenotype. Case reports show that inflammatory breast cancer symptoms can flare up following injury or inflammation making it even more likely to be mistaken for mastitis. Symptoms are also known to partially respond to progesterone and antibiotics, reaction to other common medications can not be ruled out at this point.[30][31][32][33][34]
## Treatment[edit]
In lactation mastitis, frequent emptying of both breasts by breastfeeding is essential. Also essential is adequate fluid supply for the mother and baby.
For breastfeeding women with light mastitis, massage and application of heat prior to feeding can help as this may aid unblocking the ducts. However, in more severe cases of mastitis heat or massage could make the symptoms worse and cold compresses are better suited to contain the inflammation.
Nonpuerperal mastitis is treated by medication and possibly aspiration or drainage (see in particular treatment of subareolar abscess and treatment of granulomatous mastitis). According to a BMJ best practice report, antibiotics are generally to be used in all nonpuerperal mastitis cases, with replacement of the antibiotics by an antifungal agent such as fluconazole in cases of deep fungal infections, and corticosteroids are to be used in case of granulomatous mastitis (with differential diagnosis to tuberculosis infection of the breast).[17]
In idiopathic granulomatous mastitis, successful treatment includes invasive surgical procedures or less invasive treatment with steroid medications.[35]
### Antibiotics[edit]
In lactational mastitis, antibiotics are not needed in the overwhelming majority of cases and should be used only for bacterial infections.[23] For people with nonsevere infections, dicloxacillin or cephalexin are recommended.[36] For people with severe infections, vancomycin is recommended.[37] The length of antibiotic treatment ranges anywhere from 5–14 days.[38] The effects of antibiotics has not been well studied as of 2013.[39]
### Breast abscess[edit]
An abscess (or suspected abscess) in the breast may be treated by ultrasound-guided fine-needle aspiration (percutaneous aspiration) or by surgical incision and drainage; each of these approaches is performed under antibiotic coverage. In case of puerperal breast abscess, breastfeeding from the affected breast should be continued where possible.[23][40]
For small breast abscesses, ultrasound-guided fine needle aspiration such as to completely drain the abscess is widely recognized as a preferred initial management.[41]
One recommended treatment includes antibiotics, ultrasound evaluation and, if fluid is present, ultrasound-guided fine needle aspiration of the abscess with an 18 gauge needle, under saline lavage until clear.[42] The exudate is then sent for microbiological analysis for identification of the pathogen and determination of its antibiotic sensitivity profile,[43] which may in turn give an indication for changing the antibiotics. At follow-up, a mammography is performed if the condition has resolved; otherwise the ultrasound-guided fine-needle aspiration with lavage and microbiological analysis is repeated.[44] If three to five aspirations still do not resolve the condition, percutaneous drainage in combination with placement of an indwelling catheter is indicated, and only if several attempts at ultrasound-guided drainage fail, surgical resection of the inflamed lactiferous ducts (preferably performed after the acute episode is over).[45] It is noted, however, that even the excision of the affected ducts does not necessarily prevent recurrence.[45]
Nonpuerperal breast abscesses have a higher rate of recurrence compared to puerperal breast abscesses.[46] There is a high statistical correlation of nonpuerperal breast abscess with diabetes mellitus (DM). On this basis, it has recently been suggested that diabetes screening should be performed on patients with such abscess.[47][48]
Although there are a number of recommendations regarding the treatment of breast abscesses, a 2015 review found not enough evidence regarding if needle aspiration is comparable to incision and drainage, or if antibiotics should generally be given to women undergoing incision and drainage.[49]
## Prognosis[edit]
Temperature and severity of symptoms at presentation do not predict outcome; women with sore or damaged nipples may need special attention.[50][51]
## Epidemiology[edit]
Mastitis is quite common among breastfeeding women. The WHO estimates that although incidences vary between 2.6% and 33%, the prevalence globally is approximately 10% of breastfeeding women. Most mothers who develop mastitis usually do so within the first few weeks after delivery. Most breast infections occur within the first or second month after delivery or at the time of weaning.[20] However, in rare cases it affects women who are not breastfeeding.[52]
## Terminology[edit]
Popular usage of the term mastitis varies by geographic region. Outside the US it is commonly used for puerperal and nonpuerperal cases, in the US the term nonpuerperal mastitis is rarely used and alternative names such as duct ectasia, subareolar abscess and plasma cell mastitis are more frequently used.
Chronic cystic mastitis is an older name for fibrocystic disease.
American usage: mastitis usually refers to puerperal (occurring to breastfeeding mothers) mastitis with symptoms of systemic infection. Lighter cases of puerperal mastitis are often called breast engorgement.
In this Wikipedia article, "mastitis" is used in the original sense of the definition as inflammation of the breast with additional qualifiers where appropriate.
### Etymology and pronunciation[edit]
The word mastitis (/mæstˈaɪtɪs/) uses combining forms of mast- \+ -itis. The word mammitis (/mæmˈaɪtɪs/) uses combining forms of mamm- \+ -itis. They are synonymous in modern usage, and mastitis is the more commonly used synonym.
## Other animals[edit]
See also: Mastitis in dairy cattle
Mastitis occurs in other animals as in humans, and is especially a concern in livestock, since milk from the affected udders of livestock may enter the food supply and pose a health risk.
It is a major condition in some species, like dairy cows. It is the cause of much unwanted suffering for the dairy cows. It is of tremendous economic importance for the dairy industry, and it is also of concern for public health. The same considerations apply to mastitis in sheep and goats and other milk-producing females. It is also of economic importance in the sow, but, in this species, it is not related to public health. In other domestic females (queen, mare, etc.), it is more an individual illness dealt with by veterinary practitioners.
* Udder of a Roux du Valais sheep after a healed mastitis, one teat was lost due to the disease.
* Serous exudate from bovine udder in E. coli mastitis[53] at left. Normal milk at right.
* Gangrenous mastitis in a dairy cow.
## References[edit]
1. ^ a b c d e f g h i j k l m Berens PD (December 2015). "Breast Pain: Engorgement, Nipple Pain, and Mastitis". Clinical Obstetrics and Gynecology. 58 (4): 902–14. doi:10.1097/GRF.0000000000000153. PMID 26512442. S2CID 13006527.
2. ^ a b c d e f g h i j k Spencer JP (September 2008). "Management of mastitis in breastfeeding women". American Family Physician. 78 (6): 727–31. PMID 18819238.
3. ^ Ferri, Fred F. (2009). Ferri's Clinical Advisor 2010 E-Book: 5 Books in 1. Elsevier Health Sciences. p. 593. ISBN 9780323076852.
4. ^ Buttaro TM, Trybulski J, Bailey PP, Sandberg-Cook J (2007). Primary Care: A Collaborative Practice. Elsevier Health Sciences. p. PT1608. ISBN 978-0323078412.
5. ^ The Worldwatch Institute (2015). State of the World 2006: Special Focus: China and India. Island Press. p. 36. ISBN 9781610916332.
6. ^ Ratcliffe, Stephen D. (2008). Family Medicine Obstetrics. Elsevier Health Sciences. p. 634. ISBN 978-0323043069.
7. ^ "Symptoms of mastitis". Retrieved 2010-04-20.
8. ^ "Symptoms". Retrieved 2010-04-20.
9. ^ "Breast Infection Symptoms". Retrieved 2010-04-20.
10. ^ Segura-Sampedro JJ, Jiménez-Rodríguez R, Camacho-Marente V, Pareja-Ciuró F, Padillo-Ruiz J (May 2016). "Breast abscess and sepsis arising from oral infection". Cirugia Espanola. 94 (5): 308–9. doi:10.1016/j.ciresp.2015.05.007. PMID 26148851.
11. ^ a b c Michie C, Lockie F, Lynn W (September 2003). "The challenge of mastitis". Archives of Disease in Childhood. 88 (9): 818–21. doi:10.1136/adc.88.9.818. PMC 1719627. PMID 12937109.
12. ^ Cusack L, Brennan M (December 2011). "Lactational mastitis and breast abscess - diagnosis and management in general practice". Australian Family Physician. 40 (12): 976–9. PMID 22146325.
13. ^ a b Kvist LJ, Larsson BW, Hall-Lord ML, Steen A, Schalén C (April 2008). "The role of bacteria in lactational mastitis and some considerations of the use of antibiotic treatment". International Breastfeeding Journal. 3 (1): 6. doi:10.1186/1746-4358-3-6. PMC 2322959. PMID 18394188.
14. ^ "Non-infectious mastitis and milk stasis". Retrieved 2010-04-20.
15. ^ Amir LH, Garland SM, Lumley J (October 2006). "A case-control study of mastitis: nasal carriage of Staphylococcus aureus". BMC Family Practice. 7: 57. doi:10.1186/1471-2296-7-57. PMC 1630426. PMID 17032458.
16. ^ Patel DR, Greydanus DE (2010). Adolescents and Sports. Elsevier Health Sciences. p. 711. ISBN 978-1-4377-2006-8.
17. ^ a b Mastitis and breast abscess, BMJ Best Practice (last updated 5 September 2014) (subscription-limited access)
18. ^ "Risk factors". Retrieved 2010-04-20.
19. ^ "Common questions about breastfeeding and pain". womenshealth.gov. Retrieved 4 August 2017. This article incorporates text from this source, which is in the public domain.
20. ^ a b "Breast Infection Causes". Retrieved 2010-04-20.
21. ^ "Breastfeeding Mastitis Causes and Symptoms". Retrieved 2010-04-20.
22. ^ a b "Exams and Tests". Retrieved 2010-04-20.
23. ^ a b c Peters J (April 2004). "[Mastitis puerperalis - causes and therapy]". Zentralblatt für Gynakologie (in German). 126 (2): 73–6. doi:10.1055/s-2004-44880. PMID 15112132.
24. ^ Barbosa-Cesnik C, Schwartz K, Foxman B (April 2003). "Lactation mastitis". JAMA. 289 (13): 1609–12. doi:10.1001/jama.289.13.1609. PMID 12672715.
25. ^ Antibiotics for mastitis in breastfeeding women. Cochrane Database of Systematic Reviews, PubMed Health. Review published 2013; Review content assessed as up-to-date: November 23, 2012.
26. ^ Dixon, J Michael; Pariser, Kenneth M. "Nonlactational mastitis in adults". UpToDate. Retrieved 2019-08-02.
27. ^ Middleton LP, Amin M, Gwyn K, Theriault R, Sahin A (September 2003). "Breast carcinoma in pregnant women: assessment of clinicopathologic and immunohistochemical features". Cancer. 98 (5): 1055–60. doi:10.1002/cncr.11614. PMID 12942575. S2CID 21424443.
28. ^ Shousha S (July 2000). "Breast carcinoma presenting during or shortly after pregnancy and lactation". Archives of Pathology & Laboratory Medicine. 124 (7): 1053–60. doi:10.1043/0003-9985(2000)124<1053:BCPDOS>2.0.CO;2 (inactive 2020-12-22). PMID 10888783.CS1 maint: DOI inactive as of December 2020 (link)
29. ^ Peters F, Kiesslich A, Pahnke V (October 2002). "Coincidence of nonpuerperal mastitis and noninflammatory breast cancer". European Journal of Obstetrics, Gynecology, and Reproductive Biology. 105 (1): 59–63. doi:10.1016/S0301-2115(02)00109-4. PMID 12270566.
30. ^ Kusama M, Koyanagi Y, Sekine M, Serizawa H, Ebihara Y, Hirota T, Nakamura Y, Matsunaga T (September 1994). "[A case of inflammatory breast cancer successfully treated with 5'-DFUR and MPA]". Gan to Kagaku Ryoho. Cancer & Chemotherapy (in Japanese). 21 (12): 2049–52. PMID 8085857.
31. ^ Yamada T, Okazaki M, Okazaki A, Sato H, Watanabe Y, Toda K, Okazaki Y, Asaishi K, Hirata K, Narimatsu E (September 1992). "[A case of inflammatory breast cancer treated with medroxyprogesterone acetate (MPA) in combination with intra-arterial infusion chemotherapy]". Gan to Kagaku Ryoho. Cancer & Chemotherapy (in Japanese). 19 (11): 1923–5. PMID 1387777.
32. ^ Van Laere SJ, Van der Auwera I, Van den Eynden GG, Elst HJ, Weyler J, Harris AL, van Dam P, Van Marck EA, Vermeulen PB, Dirix LY (June 2006). "Nuclear factor-kappaB signature of inflammatory breast cancer by cDNA microarray validated by quantitative real-time reverse transcription-PCR, immunohistochemistry, and nuclear factor-kappaB DNA-binding". Clinical Cancer Research. 12 (11 Pt 1): 3249–56. doi:10.1158/1078-0432.CCR-05-2800. PMID 16740744. S2CID 86034806.
33. ^ Van Laere SJ, Van der Auwera I, Van den Eynden GG, van Dam P, Van Marck EA, Vermeulen PB, Dirix LY (September 2007). "NF-kappaB activation in inflammatory breast cancer is associated with oestrogen receptor downregulation, secondary to EGFR and/or ErbB2 overexpression and MAPK hyperactivation". British Journal of Cancer. 97 (5): 659–69. doi:10.1038/sj.bjc.6603906. PMC 2360371. PMID 17700572.
34. ^ van der Burg B, van der Saag PT (June 1996). "Nuclear factor-kappa-B/steroid hormone receptor interactions as a functional basis of anti-inflammatory action of steroids in reproductive organs". Molecular Human Reproduction. 2 (6): 433–8. doi:10.1093/molehr/2.6.433. PMID 9238713.
35. ^ Lei, Xin; Chen, Kai; Zhu, Liling; Song, Erwei; Su, Fengxi; Li, Shunrong (2017-07-21). "Treatments for Idiopathic Granulomatous Mastitis: Systematic Review and Meta-Analysis". Breastfeeding Medicine. 12 (7): 415–421. doi:10.1089/bfm.2017.0030. ISSN 1556-8253. PMID 28731822.
36. ^ Spencer JP (September 2008). "Management of mastitis in breastfeeding women". American Family Physician (review). 78 (6): 727–31. PMID 18819238.
37. ^ David, Michael Z.; Daum, Robert S. (2017), Bagnoli, Fabio; Rappuoli, Rino; Grandi, Guido (eds.), "Treatment of Staphylococcus aureus Infections", Staphylococcus aureus, Springer International Publishing, 409, pp. 325–383, doi:10.1007/82_2017_42, ISBN 9783319720616, PMID 28900682
38. ^ Jahanfar, Shayesteh; Ng, Chirk Jenn; Teng, Cheong Lieng (2016). "Antibiotics for mastitis in breastfeeding women". Sao Paulo Medical Journal. 134 (3): 273. doi:10.1590/1516-3180.20161343T1. ISSN 1516-3180. PMID 27355802.
39. ^ Jahanfar S, Ng CJ, Teng CL (February 2013). "Antibiotics for mastitis in breastfeeding women". The Cochrane Database of Systematic Reviews (2): CD005458. doi:10.1002/14651858.CD005458.pub3. PMID 23450563.
40. ^ Trop I, Dugas A, David J, El Khoury M, Boileau JF, Larouche N, Lalonde L (October 2011). "Breast abscesses: evidence-based algorithms for diagnosis, management, and follow-up". Radiographics (review). 31 (6): 1683–99. doi:10.1148/rg.316115521. PMID 21997989., p. 1684
41. ^ Silberman H, Silberman AW (28 March 2012). Principles and Practice of Surgical Oncology: A Multidisciplinary Approach to Difficult Problems. Lippincott Williams & Wilkins. p. 301. ISBN 978-1-4511-5323-1.
42. ^ Trop I, Dugas A, David J, El Khoury M, Boileau JF, Larouche N, Lalonde L (October 2011). "Breast abscesses: evidence-based algorithms for diagnosis, management, and follow-up". Radiographics (review). 31 (6): 1683–99. doi:10.1148/rg.316115521. PMID 21997989., Fig. 9 on p. 1696
43. ^ Trop I, Dugas A, David J, El Khoury M, Boileau JF, Larouche N, Lalonde L (October 2011). "Breast abscesses: evidence-based algorithms for diagnosis, management, and follow-up". Radiographics (review). 31 (6): 1683–99. doi:10.1148/rg.316115521. PMID 21997989., p. 1691
44. ^ Trop I, Dugas A, David J, El Khoury M, Boileau JF, Larouche N, Lalonde L (October 2011). "Breast abscesses: evidence-based algorithms for diagnosis, management, and follow-up". Radiographics (review). 31 (6): 1683–99. doi:10.1148/rg.316115521. PMID 21997989., p. 1692–1693
45. ^ a b Trop I, Dugas A, David J, El Khoury M, Boileau JF, Larouche N, Lalonde L (October 2011). "Breast abscesses: evidence-based algorithms for diagnosis, management, and follow-up". Radiographics (review). 31 (6): 1683–99. doi:10.1148/rg.316115521. PMID 21997989., p. 1694
46. ^ Trop I, Dugas A, David J, El Khoury M, Boileau JF, Larouche N, Lalonde L (October 2011). "Breast abscesses: evidence-based algorithms for diagnosis, management, and follow-up". Radiographics (review). 31 (6): 1683–99. doi:10.1148/rg.316115521. PMID 21997989., abstract
47. ^ Rizzo M, Gabram S, Staley C, Peng L, Frisch A, Jurado M, Umpierrez G (March 2010). "Management of breast abscesses in nonlactating women". The American Surgeon. 76 (3): 292–5. doi:10.1177/000313481007600310. PMID 20349659. S2CID 25120670.
48. ^ Verghese BG, Ravikanth R (May 2012). "Breast abscess, an early indicator for diabetes mellitus in non-lactating women: a retrospective study from rural India". World Journal of Surgery. 36 (5): 1195–8. doi:10.1007/s00268-012-1502-7. PMID 22395343. S2CID 23073438.
49. ^ Irusen H, Rohwer AC, Steyn DW, Young T (August 2015). "Treatments for breast abscesses in breastfeeding women". The Cochrane Database of Systematic Reviews. 8 (8): CD010490. doi:10.1002/14651858.CD010490.pub2. hdl:10019.1/104306. PMID 26279276.
50. ^ Kvist LJ, Hall-Lord ML, Larsson BW (January 2007). "A descriptive study of Swedish women with symptoms of breast inflammation during lactation and their perceptions of the quality of care given at a breastfeeding clinic". International Breastfeeding Journal. 2: 2. doi:10.1186/1746-4358-2-2. PMC 1784075. PMID 17244353.
51. ^ Kvist LJ, Hall-Lord ML, Rydhstroem H, Larsson BW (June 2007). "A randomised-controlled trial in Sweden of acupuncture and care interventions for the relief of inflammatory symptoms of the breast during lactation". Midwifery. 23 (2): 184–95. doi:10.1016/j.midw.2006.02.003. PMID 17052823.
52. ^ "Causes of mastitis". NHS. Retrieved 2010-04-20.
53. ^ Kandasamy S, Green BB, Benjamin AL, Kerr DE (Dec 2011). "Between-cow variation in dermal fibroblast response to lipopolysaccharide reflected in resolution of inflammation during Escherichia coli mastitis". J. Dairy Sci. 94 (12): 5963–75. doi:10.3168/jds.2011-4288. PMID 22118085.CS1 maint: multiple names: authors list (link)
## External links[edit]
Classification
D
* ICD-10: N61
* ICD-9-CM: 611.0
* MeSH: D008413
* DiseasesDB: 7861
* SNOMED CT: 45198002
External resources
* MedlinePlus: 001490
* Mastitis on mayoclinic.com
* Australian Breastfeeding Association
* v
* t
* e
Breast disease
Inflammation
* Mastitis
* Nonpuerperal mastitis
* Subareolar abscess
* Granulomatous mastitis
Physiological changes
and conditions
* Benign mammary dysplasia
* Duct ectasia of breast
* Chronic cystic mastitis
* Mammoplasia
* Gynecomastia
* Adipomastia (lipomastia, pseudogynecomastia)
* Breast hypertrophy
* Breast atrophy
* Micromastia
* Amastia
* Anisomastia
* Breast engorgement
Nipple
* Nipple discharge
* Galactorrhea
* Inverted nipple
* Cracked nipples
* Nipple pigmentation
Masses
* Galactocele
* Breast cyst
* Breast hematoma
* Breast lump
* Pseudoangiomatous stromal hyperplasia
Other
* Pain
* Tension
* Ptosis
* Fat necrosis
* Amazia
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Mastitis | c0024894 | 4,057 | wikipedia | https://en.wikipedia.org/wiki/Mastitis | 2021-01-18T19:06:48 | {"mesh": ["D008413"], "umls": ["C0024894"], "icd-10": ["N61"], "wikidata": ["Q835061"]} |
Uncombable hair syndrome (UHS) is a rare disorder of the hair shaft of the scalp. It is usually characterized by silvery-blond or straw-colored hair that is disorderly; stands out from the scalp; and cannot be combed flat. It may first become apparent from 3 months of age to 12 years of age. Most cases are isolated, but in some cases it has been described in association with other diseases, such as ectodermal dysplasias, Bork syndrome and Angel-shaped phalangoepiphyseal dysplasia. The syndrome has been found to be caused by mutations in the genes PADI3, TGM3, and TCHH. These three genes code for proteins that are involved in hair shaft formation. The syndrome appears to be inherited in an autosomal recessive fashion; however, cases inherited in an autosomal dominant manner may also exist, as there are other genes involved in hair formation. The condition often spontaneously regresses in late childhood. Some published studies suggest that biotin may improve the condition.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Uncombable hair syndrome | c0432347 | 4,058 | gard | https://rarediseases.info.nih.gov/diseases/5404/uncombable-hair-syndrome | 2021-01-18T17:57:14 | {"mesh": ["C536939"], "omim": ["191480"], "umls": ["C0432347"], "orphanet": ["1410"], "synonyms": ["Pili trianguli et Canaliculi", "Cheveux incoiffables", "Unmanageable hair syndrome", "Spun glass hair"]} |
Giant cell arteritis (GCA) is a form of vasculitis, a group of disorders that cause inflammation of blood vessels. GCA most commonly affects the arteries of the head (especially the temporal arteries, located on each side of the head), but arteries in other areas of the body can also become inflamed. The inflammation causes the arteries to narrow, resulting in poor blood flow. Signs and symptoms when arteries in the head are involved may include a throbbing headache on one side or the back of the head, tenderness of the scalp, flu-like symptoms, and/or problems with eyesight. Symptoms when other arteries are involved depend on the location of those arteries. The cause of GCA is still being studied, but it is thought to involve the immune system mistakenly attacking the artery walls. Several genetic and environmental factors may increase a person's risk to develop GCA. Complications of GCA may include permanent vision loss or a stroke, so treating the condition is important. Treatment may include corticosteroids and/or other medications that suppress the immune system.
GCA may develop with or after another inflammatory disorder known as polymyalgia rheumatica, which occurs in about 40% to 50% of people with GCA.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Giant cell arteritis | c0039483 | 4,059 | gard | https://rarediseases.info.nih.gov/diseases/9615/giant-cell-arteritis | 2021-01-18T18:00:20 | {"mesh": ["D013700"], "omim": ["187360"], "orphanet": ["397"], "synonyms": ["GCA", "Temporal arteritis", "Cranial arteritis", "Horton’s disease", "Horton's arteritis", "Horton's giant cell arteritis", "Horton’s syndrome", "Horton's temporal arteritis", "Arteritis temporalis", "Arteritis cranialis"]} |
Breast cyst
Ultrasound scan showing a small cyst in the breast
SpecialtyGeneral surgery
A breast cyst is a fluid-filled sac within the breast. One breast can have one or more breast cysts. They are often described as round or oval lumps with distinct edges. In texture, a breast cyst usually feels like a soft grape or a water-filled balloon, but sometimes a breast cyst feels firm.[1]
Breast cysts can be painful and may be worrisome but are generally benign. They are most common in pre-menopausal women in their 30s or 40s. They usually disappear after menopause, but may persist or reappear when using hormone therapy.[1] They are also common in adolescents.[2] Breast cysts can be part of fibrocystic disease. The pain and swelling is usually worse in the second half of the menstrual cycle or during pregnancy.
Treating breast cysts is usually not necessary unless they are painful or cause discomfort. In most cases, the discomfort they cause may be alleviated by draining the fluid from the cyst. The cysts form as a result of the growth of the milk glands and their size may range from smaller than a pea to larger than a ping pong ball.[3] Small cysts cannot be felt during a physical examination, and some large cysts feel like lumps. However, most cysts, regardless of their size cannot be identified during physical exams.
Breast cysts are not to be confused with "milk cysts" (galactoceles), which usually appear during weaning.
## Contents
* 1 Signs and symptoms
* 2 Diagnosis
* 3 Prevention
* 4 Treatment
* 5 Epidemiology
* 6 Cysts and bra support
* 7 References
* 8 External links
## Signs and symptoms[edit]
Signs and symptoms of breast cysts include:
* A smooth, easily movable round or oval breast lump with distinct edges
* Breast pain or tenderness in the area of the lump
* Increased lump size and tenderness just before menstruation
* Decreased lump size and resolution of other signs and symptoms after menstruation
* Having one or many simple breast cysts does not increase a person's risk of breast cancer.[4]
Lumps in the breast are often not found during self-examinations or physical exams. However, in some cases they can be felt at touch, especially if they are larger.
Breasts are usually lumpy or nodular as a result of the hormonal changes that women go through during their menstrual cycle. However, new breast lumps should always be referred to a specialist.
Cysts can also be confused with infections that form on the nipple or the areola. A common cyst look-alike is a localised infection of a duct in the nipple. These can happen whether you're breast feeding or not, (if you are breast feeding it could also be a bleb) this becomes a bump that may then start to look yellow and white (pus filled). Check with your doctor if you are unsure or have other symptoms that are worrying you.
Fluid leaking from a cyst, as may happen due to puncture or vigorous compression during mammography, or due to seat belt injury in the course of an automobile accident, may trigger an aseptic inflammation in the surrounding breast tissue.[5]
## Diagnosis[edit]
Needle biopsy being performed to determine nature of lump either fluid-filled cyst or solid tumor
The cystic nature of a breast lump can be confirmed by ultrasound examination, aspiration[6] (removal of contents with needle), or mammogram. Ultrasound can also show if the cyst contains solid nodules, a sign that the lesion may be pre-cancerous or cancerous. Examination by a cytopathologist of the fluid aspirated from the cyst may also help with this diagnosis. In particular, it should be sent to a laboratory for testing if it is blood-stained.
Commonly, cysts are detected with the help of mammograms. However, the medical history and physical examination also play an important role in establishing an accurate diagnosis. During these tests, the doctor will try to find out as much information as possible regarding the symptoms the patient has experienced, their intensity and duration and the physical examination is performed regularly to check for other abnormalities that may exist within the breast.
As mentioned above, cysts are often undetectable at touch. Therefore, a mammogram can provide valuable and clear images of the breast tissue. Generally, if there is any abnormality within the breast tissue, it will be shown on the mammogram. There are two types of mammograms available. One of them is primarily used in screening, and are ordered for patients who do not show any symptoms and these are called screening mammograms. Diagnostic mammograms are used on patients who developed certain symptoms of a breast condition or in patients whose screening mammograms showed abnormalities.
Patients suspected of breast cysts will normally be given a diagnosing mammogram, although they are not suspected of cancer. This type of mammogram provides the doctor with the possibility of performing a breast ultrasound at the same time and this is the reason why they are often preferred over the screening mammograms. Breast ultrasound is considered the best option when diagnosing breast cysts because it is 95 to 100% accurate, it provides a clear image on the cyst's appearance (simple or complex) and it may also distinguish between solid lumps and fluid-filled cysts, which a mammogram cannot do.[7] Breast ultrasounds are performed with the help of a handheld medical instrument which is placed on the skin, after a special type of fluid has been applied on it. The instruments picks up the echo resulted from the sound waves it sends to the breast. These echoes are transmitted to a computer which translates it into a picture.
Breast cysts may remain stable for many years or may resolve spontaneously.[8] Most simple cysts are benign and do not require any treatment or further diagnostic workup. Some complex cysts may require further diagnostic measures such as fine needle aspiration or biopsy to exclude breast cancer however the overwhelming majority is of benign nature.[6][9] Aspiration both diagnoses and removes cysts at the same time. That is, cysts will usually resolve on their own after the fluid is drained. Otherwise, if the lump is not a cyst, the fluid aspirated may contain blood or there may not be fluid at all. Whereas in the first case, the fluid is sent to the laboratory for further examination, the latter circumstance is a sign that the breast lump is solid. This type of tumor needs to be biopsied in order to determine whether it is malignant or benign.
## Prevention[edit]
The development of breast cysts may be prevented to some degree, according to the majority of the specialists. The recommended measures one is able to take in order to avoid the formation of the cysts include practicing good health and avoiding certain medications, eating a balanced diet, taking necessary vitamins and supplements, getting exercise, and avoiding stress.[10][unreliable source?]
Although caffeine consumption does not have a scientifically proved connection with the process of cyst development, many women claim that their symptoms are relieved if avoiding it. Some doctors recommend reducing the amount of caffeine in one's diet in terms of both beverages and foods (such as chocolate). Also reducing salt intake may help in alleviating the symptoms of breast cysts, although, again, there is no scientific linkage between these two. Excessive sugar consumption as well as undetected food allergies, such as to gluten or lactose, may also contribute to cyst development.
## Treatment[edit]
Breast cysts do not require treatment unless a cyst is large and painful or otherwise uncomfortable. In that case, draining the fluid from a breast cyst can ease symptoms.[1]
Nipple cysts (commonly duct infections) would benefit from a hot compress to draw out the pus, antibacterial cream, and keeping it clean. Doctors have suggested these infected ducts will clear up within a few days. If there are other symptoms that are worrying you please see your Doctor.
Typical treatment involves a Needle aspiration biopsy which is typically done with a 10 cc syringe attached to a fine needle aspiration needle. [11] Fine needle aspiration allows retrieval of cytological samples that can be sent for pathological review to determine if the cyst is benign or malignant. [12] Aspirated cysts often recur (come back); definitive treatment may require surgery. During an excisional biopsy an incision is made around the mass creating a superior and inferior flap. The mass is dissected out followed by confirmation of hemostasis. Once hemostasis is confirmed the wound is closed with an absorbable suture. The mass is then sent to pathology for review. Pathology can help determine if the surgeon needs to dissect a bigger margin. [13]
Draining the fluid and then waiting for the cyst to resolve is the main treatment applied in these cases. Moreover, if cysts are aspirated and the fluid looks normal, they do not require any other medical attention apart from following-up to make sure they have completely disappeared. Hormone therapy, by the means of oral contraceptives, is sometimes prescribed to reduce their recurrence and to regulate the menstrual cycle of the patient (which is likely to cause them in the first place). Danazol may also be prescribed to treat this condition and it is usually considered in patients on whom the non-medical treatment fails and the symptoms are intense.
Surgical removal of a breast cyst is necessary only in a few unusual circumstances. If an uncomfortable breast cyst recurs month after month, or if a breast cyst contains blood-tinged fluid and displays other worrisome signs, surgery may be considered.[14]
## Epidemiology[edit]
It is estimated that 7% of women in the western world develop palpable breast cysts.[15]
In males, the occurrence of breast cysts is rare[16] and may (but need not) be an indication of malignancy.[17]
## Cysts and bra support[edit]
Some women experience breast pain, especially when engaging in vigorous physical activity. A properly fitted sports bra, which compresses or encapsulates breast tissue, is designed to reduce pain caused by exercise.[18][19][20]
## References[edit]
1. ^ a b c Mayo Clinic Staff (9 November 2012). "Breast cysts". Mayo Clinic. Retrieved 2015-05-16.
2. ^ Victor C. Strasburger (2006). Adolescent Medicine: A Handbook for Primary Care. Lippincott Williams & Wilkins. p. 228. ISBN 978-0-7817-5315-9.
3. ^ "Breast Cysts". Retrieved 2010-06-25.
4. ^ Mayo Clinic Staff (9 November 2012). "Breast cysts Symptoms". Mayo Clinic. Archived from the original on 26 July 2015. Retrieved 2015-05-16.
5. ^ Daniel J. Dronkers; J. H. C. L. Hendriks (1 January 2011). Practice of Mammography: Pathology - Technique - Interpretation - Adjunct Modalities. Thieme. p. 130. ISBN 978-3-13-160601-3.
6. ^ a b Daly CP, Bailey JE, Klein KA, Helvie MA (May 2008). "Complicated breast cysts on sonography: is aspiration necessary to exclude malignancy?". Acad Radiol. 15 (5): 610–7. doi:10.1016/j.acra.2007.12.018. PMID 18423318.
7. ^ "What are breast cysts?". Retrieved 2010-06-25.
8. ^ Veena Chowdhury; Arun Kumar Gupta; Niranjan Khandelwal; et al., eds. (2012). Diagnostic Radiology: Musculoskeletal and Breast Imaging. JP Medical Ltd. p. 484. ISBN 978-93-5025-883-5.
9. ^ "Tests and diagnosis". Retrieved 2010-06-25.
10. ^ "Breast Cyst Treatment Alternatives". Archived from the original on 2010-06-28. Retrieved 2010-06-25.
11. ^ [1], Cruz C, Villamin J, Ranjan D, Suntay M, Henry J. Fine-Needle Aspiration Biopsy and Excision Biopsy of a Cystic Mass in the Right Breast (Male). J Med Ins. 2019;2019(268.3) doi:https://jomi.com/article/268.3
12. ^ [2], Cruz C, Villamin J, Ranjan D, Suntay M, Henry J. Fine-Needle Aspiration Biopsy and Excision Biopsy of a Cystic Mass in the Right Breast (Male). J Med Ins. 2019;2019(268.3) doi:https://jomi.com/article/268.3
13. ^ [3], Cruz C, Villamin J, Ranjan D, Suntay M, Henry J. Fine-Needle Aspiration Biopsy and Excision Biopsy of a Cystic Mass in the Right Breast (Male). J Med Ins. 2019;2019(268.3) doi:https://jomi.com/article/268.3
14. ^ "Treatments and drugs". Retrieved 2010-06-25.
15. ^ Dixon JM, McDonald C, Elton RA, Miller WR (May 1999). "Risk of breast cancer in women with palpable breast cysts: a prospective study. Edinburgh Breast Group". Lancet. 353 (9166): 1742–5. doi:10.1016/s0140-6736(98)06408-3. PMID 10347986. S2CID 54392159.
16. ^ Alexander N. Sencha (24 October 2014). Imaging of Male Breast Cancer. Springer. p. 115. ISBN 978-3-319-06050-7.
17. ^ Chen L, Chantra PK, Larsen LH, Barton P, Rohitopakarn M, Zhu EQ, Bassett LW (2006). "Imaging characteristics of malignant lesions of the male breast". Radiographics (Review). 26 (4): 993–1006. doi:10.1148/rg.264055116. PMID 16844928.
18. ^ Greenbaum AR, Heslop T, Morris J, Dunn KW (April 2003). "An investigation of the suitability of bra fit in women referred for reduction mammaplasty". British Journal of Plastic Surgery. 56 (3): 230–6. doi:10.1016/S0007-1226(03)00122-X. PMID 12859918.
19. ^ Hadi MS (November 2000). "Sports Brassiere: Is It a Solution for Mastalgia?". The Breast Journal. 6 (6): 407–409. doi:10.1046/j.1524-4741.2000.20018.x. PMID 11348400. S2CID 46191435.
20. ^ Mason BR, Page KA, Fallon K (June 1999). "An analysis of movement and discomfort of the female breast during exercise and the effects of breast support in three cases". Journal of Science and Medicine in Sport. 2 (2): 134–44. doi:10.1016/S1440-2440(99)80193-5. PMID 10476977.
## External links[edit]
Classification
D
* ICD-10: N60.0
* ICD-9-CM: 610.0
* MeSH: D047688
* v
* t
* e
Breast disease
Inflammation
* Mastitis
* Nonpuerperal mastitis
* Subareolar abscess
* Granulomatous mastitis
Physiological changes
and conditions
* Benign mammary dysplasia
* Duct ectasia of breast
* Chronic cystic mastitis
* Mammoplasia
* Gynecomastia
* Adipomastia (lipomastia, pseudogynecomastia)
* Breast hypertrophy
* Breast atrophy
* Micromastia
* Amastia
* Anisomastia
* Breast engorgement
Nipple
* Nipple discharge
* Galactorrhea
* Inverted nipple
* Cracked nipples
* Nipple pigmentation
Masses
* Galactocele
* Breast cyst
* Breast hematoma
* Breast lump
* Pseudoangiomatous stromal hyperplasia
Other
* Pain
* Tension
* Ptosis
* Fat necrosis
* Amazia
* v
* t
* e
Cystic diseases
Respiratory system
* Langerhans cell histiocytosis
* Lymphangioleiomyomatosis
* Cystic bronchiectasis
Skin
* stratified squamous: follicular infundibulum
* Epidermoid cyst and Proliferating epidermoid cyst
* Milia
* Eruptive vellus hair cyst
* outer root sheath
* Trichilemmal cyst and Pilar cyst and Proliferating trichilemmal cyst and Malignant trichilemmal cyst
* sebaceous duct
* Steatocystoma multiplex and Steatocystoma simplex
* Keratocyst
* nonstratified squamous: Cutaneous ciliated cyst
* Hidrocystoma
* no epithelium: Pseudocyst of the auricle
* Mucocele
* other and ungrouped: Cutaneous columnar cyst
* Keratin implantation cyst
* Verrucous cyst
* Adenoid cystic carcinoma
* Breast cyst
Human musculoskeletal system
* Cystic hygroma
Human digestive system
* oral cavity: Cysts of the jaws
* Odontogenic cyst
* Periapical cyst
* Dentigerous cyst
* Odontogenic keratocyst
* Nasopalatine duct cyst
* liver: Polycystic liver disease
* Congenital hepatic fibrosis
* Peliosis hepatis
* bile duct: Biliary hamartomas
* Caroli disease
* Choledochal cysts
* Bile duct hamartoma
Nervous system
* Cystic leukoencephalopathy
Genitourinary system
* Polycystic kidney disease
* Autosomal dominant polycystic kidney
* Autosomal recessive polycystic kidney
* Medullary cystic kidney disease
* Nephronophthisis
* Congenital cystic dysplasia
Other conditions
* Hydatid cyst
* Von Hippel–Lindau disease
* Tuberous sclerosis
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Breast cyst | c0006144 | 4,060 | wikipedia | https://en.wikipedia.org/wiki/Breast_cyst | 2021-01-18T18:45:51 | {"mesh": ["D047688"], "umls": ["C0006144"], "icd-9": ["610.0"], "wikidata": ["Q1647794"]} |
For the island, see Bone Island.
Enostosis
Other namesBone island
Osteopoikilosis results in multiple enostoses.
SpecialtyOrthopedic
An enostosis is a small area of compact bone within the cancellous bone.[1][2] They are commonly seen as an incidental finding on radiographs or CT scans. They are typically very small and do not cause any symptoms.[3] Their radiodensity is generally similar to cortical bone.[4] No treatment is necessary. Multiple enostoses are present in osteopoikilosis.[5]
## Contents
* 1 Spine
* 2 References
* 3 Further reading
* 4 External links
## Spine[edit]
Enostosis is usually found in T1 to T7 for the thoracic spine and L2 to L3 in the lumbar spine. It is consisting of cortical bone merging with medullary bone with irregular margins. The shape of the lesion is round or oval with thornlike margin, up to 2 cm in diameter. In both T1 and T2-weighted imaging, it shows low signal intensity. It is usually presented as a single lesion.[6]
## References[edit]
1. ^ Ingle, John Ide; Bakland, Leif K. (2002). Endodontics. PMPH-USA. p. 197. ISBN 9781550091885. Retrieved 23 November 2017.
2. ^ Davies, A. Mark; Sundaram, Murali; James, Steven J. (2009). Imaging of Bone Tumors and Tumor-Like Lesions: Techniques and Applications. Springer Science & Business Media. p. 253. ISBN 9783540779841. Retrieved 23 November 2017.
3. ^ Mann, Robert W.; Hunt, David R. (2013). PHOTOGRAPHIC REGIONAL ATLAS OF BONE DISEASE: A Guide to Pathologic and Normal Variation in the Human Skeleton (3rd Ed.). Charles C Thomas Publisher. p. 284. ISBN 9780398088279. Retrieved 23 November 2017.
4. ^ Page 1900 in: Albert L. Baert (2008). Encyclopedia of Imaging, Volume 2. Springer Science & Business Media. ISBN 9783540352785.
5. ^ Algra, Paul R.; Valk, Jaap; Heimans, Jan J. (2013). Diagnosis and Therapy of Spinal Tumors. Springer. p. 96. ISBN 9783642602542. Retrieved 23 November 2017.
6. ^ Orguc, Sebnem; Arkun, Remide (2014-06-04). "Primary Tumors of the Spine". Seminars in Musculoskeletal Radiology. 18 (03): 280–299. doi:10.1055/s-0034-1375570. ISSN 1089-7860.
## Further reading[edit]
* Greenspan, A (Feb 1995). "Bone island (enostosis): current concept--a review". Skeletal Radiology. 24 (2): 111–5. doi:10.1007/bf00198072. PMID 7747175.
## External links[edit]
* Media related to Enostosis at Wikimedia Commons
Classification
D
* SNOMED CT: 25994006
External resources
* eMedicine: article/387758
This article about a disease of musculoskeletal and connective tissue is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Enostosis | c0265512 | 4,061 | wikipedia | https://en.wikipedia.org/wiki/Enostosis | 2021-01-18T18:51:31 | {"umls": ["C0265512"], "wikidata": ["Q1343590"]} |
## Summary
### Clinical characteristics.
CYLD cutaneous syndrome (CCS) typically manifests in the second or third decade with the appearance of multiple skin tumors including cylindromas, spiradenomas, trichoepitheliomas, and rarely, membranous basal cell adenoma of the salivary gland. The first tumor typically develops at puberty and tumors progressively accumulate through adulthood. Females often have more tumors than males. Tumors typically arise on the scalp and face but can also arise on the torso and sun-protected sites, such as the genital and axillary skin. A minority of individuals develop salivary gland tumors. Rarely, pulmonary cylindromas can develop in large airways and compromise breathing. Although the tumors are usually benign, malignant transformation is recognized.
### Diagnosis / testing.
The diagnosis of CYLD cutaneous syndrome is established in a proband with multiple skin tumors (histologically confirmed cylindromas, spiradenomas, and/or trichoepitheliomas) and/or by identification of a germline heterozygous pathogenic variant in CYLD by molecular genetic testing.
### Management.
Treatment of manifestations: Removal of cylindromas, spiradenomas, and trichoepitheliomas is by conventional surgery. Ideally, as much normal scalp and skin should be preserved. "Scalp-sparing" strategies include early primary excision with direct skin closure, tumor enucleation followed by direct skin closure, and excision followed by secondary intention healing techniques. Hyfrecation or laser ablation of selected small tumors may be considered. Mohs micrographic surgery for recurrence of tumors after failure of primary surgical excision may have limited benefit. Multidisciplinary team management of tumors that have undergone malignant transformation is recommended.
Prevention of primary manifestations: Appropriate precautions against UV-related skin damage are recommended.
Surveillance: Annual or more frequent full skin examination by a dermatologist, with assessment of tumor burden and rate of new tumor development, and for signs/symptoms of malignant transformation (rapid tumor growth, bleeding, ulceration, or appearance that is different from an affected individual's usual tumors).
Agents/circumstances to avoid: Radiotherapy should be avoided as it causes DNA damage and may result in further tumor formation or malignant transformation of existing lesions.
Evaluation of relatives at risk: It is appropriate to clarify the genetic status of apparently asymptomatic older and younger at-risk relatives of an affected individual in order to identify as early as possible those who would benefit from prompt initiation of treatment and preventive measures.
### Genetic counseling.
Germline pathogenic variants in CYLD are inherited in an autosomal dominant manner. Most individuals with CYLD cutaneous syndrome inherit it from a parent. The degree of severity can vary within families; for example, a mildly affected parent may have a more severely affected child or vice versa. Offspring of an individual with CYLD cutaneous syndrome have a 50% chance of inheriting the variant. Prenatal testing is possible for pregnancies at increased risk if the CYLD pathogenic variant in the family is known; however, requests for prenatal diagnosis of later-onset diseases are uncommon and require careful genetic counseling.
## Diagnosis
Formal diagnostic criteria for CYLD cutaneous syndrome (CCS) have not been established.
### Suggestive Findings
CYLD cutaneous syndrome should be suspected in an individual with the following findings:
* The presence of one or more cylindromas or spiradenomas on the face and scalp, perinasal trichoepitheliomas, or a combination of these tumor types in an individual
Cylindromas, spiradenomas, and trichoepitheliomas can be diagnosed clinically but may mimic other skin tumors, thus requiring confirmatory skin biopsy.
* A cylindroma or spiradenoma on the scalp or torso incidentally identified during an imaging study (CT, MRI, and/or PET scan) [Serra et al 1996, Brown et al 2018a]
* A membranous basal cell adenoma-type salivary gland tumor in an individual with a single cylindroma, spiradenoma, or trichoepithelioma
Clinical genetic testing for a germline heterozygous CYLD pathogenic variant should be considered in an individual with the following [Dubois et al 2015]:
* Two or more biopsy-confirmed cylindromas, spiradenomas, or trichoepitheliomas
* A single biopsy-confirmed cylindroma, spiradenoma, or trichoepithelioma in the setting of a first-degree relative who has any one of these biopsy-confirmed tumors
### Establishing the Diagnosis
The diagnosis of CYLD cutaneous syndrome is established in a proband with multiple skin tumors (histologically confirmed cylindromas, spiradenomas, and/or trichoepitheliomas) and/or by identification of a germline heterozygous pathogenic variant in CYLD by molecular genetic testing [Dubois et al 2015] (see Table 1).
When the phenotypic and laboratory findings suggest the diagnosis of CYLD cutaneous syndrome, molecular genetic testing approaches include single-gene testing or use of a multigene panel.
Single-gene testing. Sequence analysis of CYLD detects small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. Perform sequence analysis on a peripheral blood sample first.
* If no pathogenic variant is found, and there is no known family history of this condition, it is possible that the proband has mosaicism for a CYLD pathogenic variant.
If mosaicism is suspected, sequence analysis of CYLD can be performed on two or more skin tumors [Arefi et al 2019].
* Gene-targeted deletion/duplication analysis to detect intragenic deletions or duplications may also be considered, although intragenic deletions and duplications are rare (see Table 1).
A hereditary cancer multigene panel that includes CYLD and other genes of interest (see Differential Diagnosis) may also be considered. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
### Table 1.
Molecular Genetic Testing Used in CYLD Cutaneous Syndrome
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Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method
CYLDSequence analysis 340%-100% 4, 5, 6
Gene-targeted deletion/duplication analysis 7Rare 8
1\.
See Table A. Genes and Databases for chromosome locus and protein.
2\.
See Molecular Genetics for information on allelic variants detected in this gene.
3\.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
4\.
A single test center performing CYLD testing over a five-year period detected pathogenic CYLD variants in ∼70% of 56 probands who fulfilled previously published testing criteria using Sanger sequencing of coding exons [ESHG 2019].
5\.
In a smaller study of 25 probands, the presence of cylindromas raised the likelihood of pathogenic variant detection to between 86% and 100% [Saggar et al 2008].
6\.
In probands with only trichoepitheliomas, the rate of pathogenic variant detection was as low as 40% [Saggar et al 2008].
7\.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.
8\.
Vanecek et al [2014] reported two affected individuals with large deletions of CYLD out of 13 affected individuals who did not demonstrate a pathogenic CYLD variant using Sanger sequencing.
## Clinical Characteristics
### Clinical Description
CYLD cutaneous syndrome (CCS) encompasses the clinical phenotypes described in individuals with germline pathogenic CYLD variants. Historically descriptive names including Brooke-Spiegler syndrome (BSS), familial cylindromatosis (FC), and multiple familial trichoepithelioma (MFT) were assigned on the basis of the predominant tumor type and location; these conditions are now recognized to constitute a clinical spectrum. Individuals with the clinical phenotypes of BSS, FC, and MFT can all present in a single family, and the lack of prognostication offered by these historical labels favors the use of CYLD cutaneous syndrome as a diagnostic term for those with this single gene disorder.
### Table 2.
Features of CYLD Cutaneous Syndrome
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Feature 1# of Persons w/FeatureComment
Phenotype of predominantly
cylindromas/spiradenomas14/26 (∼54%)
Phenotype of predominantly trichoepitheliomas8/26 (∼30%)
Phenotype of mixed cylindroma/spiradenoma/
trichoepithelioma4/26 (∼15%)
Severe phenotype
necessitating
complete scalp excision6/26 (∼23%)In a further study of a Hungarian pedigree, 2 5/21 individuals w/a germline pathogenic CYLD variant had this severe phenotype.
Salivary gland tumors~5%
Pulmonary cylindromas3 persons 3May result in respiratory compromise if lesion affects the large airways
Except where otherwise noted, the table summarizes a single study by Rajan et al [2009a], which analyzed the clinical features of 26 individuals with germline pathogenic CYLD variants.
1\.
While by definition most individuals with CYLD cutaneous syndrome will be affected by one of more of the characteristic tumors, precise detail about frequency of the clinical features is lacking in most published studies.
2\.
Nagy et al [2013]
3\.
Vernon et al [1988], Brown et al [2018b]
To date, more than 100 pedigrees have been identified with a germline pathogenic variant in CYLD, most of whom have family-specific pathogenic variants with few mutational hot spots identified [Rajan et al 2009a, Grossmann et al 2013, Nagy et al 2015]. The following description of the phenotypic features associated with this condition is based on these reports.
CYLD cutaneous syndrome typically manifests in the second or third decade with the appearance of multiple skin tumors including cylindromas, spiradenomas, and trichoepitheliomas. The first tumor typically presents at puberty, but tumors have been reported to present in children as young as age eight years. Tumors progressively accumulate through adulthood. A female preponderance was reported in early studies of small pedigrees; however, assessment of larger pedigrees supports equal penetrance in both males and females, with increased expressivity in females. The presence of tumors at sites of secondary sexual hair development, the timing of onset, and the gender disparity in severity in females with cylindromas suggest a role of hormonal factors in tumor pathogenesis [Rajan et al 2009b].
Natural history studies in CYLD cutaneous syndrome are limited, but a recent study that followed three affected individuals with a combined total of 32 skin tumors visible on serial CT scans (6.7-23.5 mm across) showed progressive growth in 30 out of 32 lesions over a period of one year [Brown et al 2018b]. The progressive growth of these benign tumors supports the case for considering early excision of skin lesions rather than waiting until a more extensive procedure is required (see Table 5). Affected individuals frequently need repeated procedures due to the development of new tumors and, in some cases, the recurrence of incompletely excised tumors.
Individuals with CYLD cutaneous syndrome may present with more than one tumor type discussed below.
* Tumors typically arise on the scalp and face but can also arise on the torso and sun-protected sites, such as the genital and axillary skin.
* Tumors are often painful and may cause sexual dysfunction when they arise on genital skin.
* Tumors arising within the ear (a favored site for tumor formation) can occlude the external auditory canal and result in conductive hearing loss.
* Although the tumors are usually benign, malignant transformation is recognized, and affected individuals should be guided to report tumors which are rapidly growing, bleeding, ulcerating, or different in appearance from their usual tumors.
#### Cylindromas
Cylindromas are well-circumscribed, smooth, pale pink nodular tumors, often with arborizing vessels visible. The tumors are slow growing and vary in size from a few millimeters to >5 mm (see Figure 1a). The finding of mixed cylindroma and spiradenoma histology within a single tumor is common in CYLD cutaneous syndrome, and the two terms have been used to describe variants of the same tumor [Rajan et al 2011a].
#### Figure 1
A. Cylindroma demonstrating a well-circumscribed pink nodular lesion with arborizing blood vessels visible on the surface B. Confluent scalp cylindromas in a severely affected individual with CYLD cutaneous syndrome
Confluent scalp tumors. In severe cases, tumors may cover most of the scalp, referred to as confluent scalp tumors (see Figure 1b).
* Early surgical intervention may prevent or delay confluent scalp tumors.
* One study of two families reported that confluent scalp tumors affected up to one in four individuals with a heterozygous germline pathogenic CYLD variant [Rajan et al 2009a].
Pulmonary cylindromas. Single or multiple pulmonary cylindromas that originate from the skin have been described in three individuals with CYLD cutaneous syndrome [Vernon et al 1988, Brown et al 2018b]. In these cases, there is no history of a primary malignant cutaneous cylindroma in the skin, lymph node disease is absent, and pulmonary histology is benign, leading them to be categorized as "benign" metastases.
* One individual presented at age 64 with breathlessness on exertion and was found to have multiple pulmonary tumors. This individual required serial monitoring with pulmonary imaging, and received endocopic laser ablation to maintain large airway patency.
* A second individual had four asymptomatic pulmonary tumors discovered incidentally on a chest radiograph at age 80 years. The tumors were histologically confirmed on autopsy.
* Whole-exome and genome sequencing have shown pulmonary cylindromas to harbor an additional pathogenic variant in AKT1 and a UV mutation signature confirming cutaneous origin [Davies et al 2019].
* The true prevalence of pulmonary cylindromas in individuals with CYLD cutaneous syndrome is not known, as prospective radiologic imaging studies of large numbers of affected individuals have yet to be performed.
* Currently, there are no routine surveillance imaging guidelines that can be recommended; however clinicians who care for individuals with CYLD cutaneous syndrome need to be aware that these tumors do arise and may need to be monitored to determine rate of growth, and that surgical interventions may be necessary to ablate pulmonary tumors that threaten large airway patency.
Histopathology. The histologic appearance of well-circumscribed cylindrical nests of basaloid cells in the dermis led to the term "cylindroma." Each cluster consists of darker, basophilic cells at the periphery, and larger pale cells centrally and is surrounded by a thick, hyaline membrane consisting of extracellular matrix proteins (including collagen IV and VII and laminin-332) in the basement membrane of the skin (see Figure 2a).
#### Figure 2
A. Histopathology of cylindroma B. Histopathology of spiradenoma
#### Spiradenomas
Spiradenomas are nodular tumors that are often blue/black in color. They tend to be painful and can grow up to 10 cm in diameter (see Figure 3).
#### Figure 3.
Spiradenoma: a well-circumscribed nodular lesion (excision specimen) with characteristic blue/black appearance Rajan & Ashworth [2015]; republished with permission of author.
Histopathology. Spiradenomas are relatively disorganized histologically when compared to cylindromas and consist of sheets of epithelial cells associated with a lymphocytic infiltrate (mixed T and B cells). Some affected individuals present with histologic features of both cylindroma and spiradenoma within a single tumor specimen, giving rise to the term spiradenocylindroma. In addition, there is evidence that histologically organized cylindroma and histologically disorganized spiradenoma represent extremes of a spectrum of histophenotype of the same tumor [Rajan et al 2011a] (see Figure 2b).
#### Trichoepitheliomas
Trichoepitheliomas are skin-colored papules or firm nodules, mainly found on the central face (see Figure 4). They are often symmetrically distributed and usually no more than 2-5 mm across.
#### Figure 4.
Trichoepithelioma: small skin-colored papules with a predilection for the central face Rajan & Ashworth [2015]; republished with permission of author.
Histopathology. Trichepitheliomas demonstrate clusters of basaloid germinative cells with keratinizing cystic spaces and superficial follicular differentiation surrounded by a fibrocytic stroma. Intra-stromal clefts and mesenchymal papillary buds may be seen.
#### Other Findings
Salivary lesions. Affected individuals are also at risk of developing tumors of the salivary glands, typically membranous basal cell adenoma (MBCA) [Jungehülsing et al 1999] usually after age 40 years.
* These tumors typically present as a lump in the parotid gland, may be bilateral, and warrant a biopsy to confirm the diagnosis.
* MBCA is a benign entity which may be managed surgically, but recurs in up to 25% of affected individuals [Zarbo 2002] (see also Malignant transformation).
Malignant transformation has been (rarely) reported in preexisting spiradenomas, cylindromas, spiradenocylindromas, and MBCA [Hyman et al 1988, Kazakov 2016]. Malignant tumors tend to be aggressive carcinomas with frequent local infiltrative growth or metastases.
* Transcalvarial invasion is uncommon, but has been observed [Serracino & Kleinschmidt-Demasters 2013].
* Malignant metastases to bone, lung, and liver have been reported [Gerretsen et al 1993].
* Death from metastatic disease has been described in affected individuals in the early fifth decade [Kazakov et al 2009].
* Malignant histopathology. Four diverse histologic patterns of malignant cylindroma or spiradenoma have been described [Kazakov et al 2009], including:
* Salivary gland type basal cell adenocarcinoma-like pattern, low-grade
* Salivary gland type basal cell adenocarcinoma-like pattern, high-grade
* Invasive adenocarcinoma, not otherwise specified
* Sarcomatoid (metaplastic) carcinoma
Other skin lesions and malignancies
* Affected individuals may also develop small milia cysts on the skin of the face [Bajwa et al 2018].
* Vulval cysts consisting histologically of multiple epidermal inclusion cysts and milia were reported in one affected female [Dubois et al 2017].
* Squamous cell carcinoma [Ganguly et al 2012, Ma et al 2016] and follicular squamous cell carcinoma [Dubois et al 2018] arising in individuals with CYLD cutaneous syndrome have been described in isolated reports.
* Basal cell carcinoma (BCC) is the most common human cancer, and coexistence in individuals with CYLD cutaneous syndrome may be coincidental or related to overlap in the appearance of each under the microscope. However, in a recent study of a large South American family with CYLD cutaneous syndrome, BCC was a reported in 25% of affected family members from this kindred [Arruda et al 2019].
Segmental disease due to mosaic pathogenic CYLD variants should be considered when individuals develop unilateral clusters of any cylindromas, spiradenomas, or trichoepitheliomas [Arefi et al 2019]. Findings may include skin lesions arranged in a linear fashion [Furuichi et al 2012] following embryologic skin development lines (lines of Blaschko). The presentation of unilateral clusters may reflect either a pathogenic CYLD variant in the skin alone (late postzygotic mosaicism) or a pathogenic variant in both the blood and the skin (early postzygotic mosaicism) (see Figure 5 below) [Arefi et al 2019].
#### Figure 5.
Mosaic presentations of CYLD cutaneous syndrome Arefi et al [2019]; published under Creative Commons license.
### Genotype-Phenotype Correlations
No convincing genotype-phenotype correlations have been identified. There is a suggestion that individuals with pathogenic missense variants may have a milder phenotype; however, as missense variants constitute a minority of pathogenic variants in affected individuals (most have pathogenic truncating variants, which can also result in a mild phenotype), further studies are needed to investigate this hypothesis [Nagy et al 2015].
### Nomenclature
Historically, descriptive names including Brooke-Spiegler syndrome (BSS), familial cylindromatosis (FC), and multiple familial trichoepithelioma (MFT) were assigned on the basis of the predominant tumor type and location. These conditions are now recognized to constitute a clinical spectrum and individuals with the clinical phenotypes of BSS, FC, and MFT can all present in a single family. The lack of prognostication offered by these historic labels favors the use of CYLD cutaneous syndrome as a diagnostic term for individuals with this single-gene disorder.
Outdated terms previously used in the literature to refer to CYLD cutaneous syndrome include the following:
* Ancell-Spiegler cylindromas
* Dermal eccrine cylindroma
* Turban tumor syndrome (now denoted as confluent scalp tumors)
### Prevalence
The true prevalence of CYLD cutaneous syndrome is unknown but may be in the order of more than 1:100,000 population [Rajan & Ashworth 2015].
## Differential Diagnosis
Disorders with multiple facial papules in the differential diagnosis of CYLD cutaneous syndrome (CCS) are summarized in Table 3.
### Table 3.
Disorders with Multiple Facial Papules in the Differential Diagnosis of CYLD Cutaneous Syndrome (CCS)
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Gene(s)Disorder 1Distinguishing Histologic Features in Differential DisorderComment
FLCNBirt-Hogg-Dubé syndromeFibrofolliculomas
NF1Neurofibromatosis 1 (NF1)NeurofibromasBoth NF1 & CCS are assoc w/lesions on the torso
PTENCowden syndrome (see PTEN Hamartoma Tumor Syndrome)Trichilemmomas
TSC1
TSC2Tuberous sclerosis complexAngiofibromas
HRMarie Unna hypotrichosis 1 (MUHH1) (OMIM 146550)Trichoepitheliomas 2Severe hair breakage/loss & absence of cylindromas in MUHH1 further distinguishes MUHH1 from CCS.
PTCH1Basal cell nevus syndromeBasal cell neviMacrocephaly, broad nasal root & jaw cysts
UnknownMultiple syringomas (OMIM 186600)Syringomas
1\.
All of the disorders listed are inherited in an autosomal dominant manner.
2\.
Huang et al [2019]
Pilar (trichilemmal) cysts. Pilar cysts are common keratin-filled cysts that often affect the scalp in multiple numbers, either sporadically or inherited as an autosomal dominant trait associated with heterozygous variants in PLCD1 [Hörer et al 2019]. They may mimic scalp cylindromas, but clinically, the skin overlying these scalp lesions is normal, while in cylindromas there is frequently loss of overlying hair and thinning of the skin, giving it a pink translucent appearance.
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with CYLD cutaneous syndrome (CCS), the evaluations summarized in Table 4 (if not performed as part of the evaluation that led to the diagnosis) are recommended.
### Table 4.
Recommended Evaluations Following Initial Diagnosis in Individuals with CYLD Cutaneous Syndrome
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System/ConcernEvaluationComment
SkinSkin examination by dermatologist
* Full skin examination incl skin of the genitalia
* Painful tumors should be identified & prioritized for excision (see Table 5).
* Education about signs & symptoms of malignant transformation 1
Histologic examinationOf tumors that are rapidly growing, have a distinct appearance, or are ulcerated or bleeding
Imaging, if clinically indicated
* Routine imaging not currently recommended
* If malignant transformation is suspected in a scalp tumor, consider radiologic imaging (preferably MRI), given the possibility of intracranial invasion.
* Little evidence is available as to when staging imaging should be considered for malignant tumors; consult specialist skin cancer multidisciplinary team. 2
Ears/HearingEvaluation of external auditory canals w/otoscope
* To screen for tumors that occlude the external auditory canal
* When present, clinical assessment for conductive hearing loss may be considered.
OralClinical exam of parotid glandsTo screen for salivary lesions
RespiratoryAssessment for signs of respiratory compromise in those w/new onset of shortness of breath, cough, or stridorIf present, radiologic imaging may be necessary to evaluate for pulmonary lesions.
Genetic
counselingConsultation w/clinical geneticist &/or genetic counselorTo incl genetic counseling & cascade testing where needed
1\.
Including tumors that are rapidly growing, bleeding, ulcerating or appear different than an affected individual's usual tumors.
2\.
This team typically includes a dermatologist, plastic surgeon, radiologist, oncologist and pathologist, all of whom can guide a consensus decision making process.
### Treatment of Manifestations
### Table 5.
Treatment of Manifestations in Individuals with CYLD Cutaneous Syndrome
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Manifestation/
ConcernTreatmentConsiderations/Other
Cylindroma, spiradenoma, trichoepitheliomaRemoval of tumors by conventional surgery
* Repeated surgical procedures to ↓ tumor burden typically required 1,2
* "Scalp-sparing" strategies incl early primary excision, tumor enucleation, & excision followed by secondary intention healing techniques recommended; 3 avoid removing large areas of scalp.
* Complete scalp excision to be used only when no feasible alternatives 4
HyfrecationFor selected small tumors, such as trichoepithelioma on the nasolabial skin 5
Laser
* Ablative laser resurfacing of smaller lesions (i.e., perinasal trichoepitheliomas) can yield good cosmetic results. 6
* However, the advantage of laser treatment for large cylindromas & spiradenomas over standard excision is not clear. Laser treatment also precludes histologic assessment.
Mohs micrographic surgery 7
* Technique allows dermatologic surgeon to track invasive tumor cells & confirm histologic clearance before closing the skin defect. 8
* Mohs may be of limited benefit in CCS, as it may be difficult to obtain tumor-negative margins, leading to large defects.
Malignant tumorsMultidisciplinary team input required to develop management plan
* At least 8 different types of malignant tumors are seen in affected individuals; w/the exception of BCC, these would be considered rare cancers & require appropriate evaluation following histopathologic assessment (see Clinical Characteristics).
* Each case may need to be assessed & staged; decision should be made by a skin cancer multidisciplinary team w/support from dermatologists, oncologists, pathologists, plastic surgeons, & radiologists.
BCC = basal cell carcinoma; CCS = CYLD cutaneous syndrome
1\.
Tumors progressively grow over time such that early treatment may reduce the need for extensive surgical procedures and also allow for the use of local anesthetic.
2\.
Benign lesions removed for cosmetic reasons should have narrow margins to leave as much normal healthy tissue as possible.
3\.
Rajan et al [2009b], Brass et al [2014]
4\.
Complete scalp excision is not curative. Often tumors develop from follicles within the graft, and individuals can have significant tumors at other sites, such as on the trunk.
5\.
Histologic assessment of a representative lesion may be useful prior to ablative procedures. If there is a clinical suspicion of basal cell carcinoma, a biopsy should be performed prior to initiating ablative procedures.
6\.
Repeated treatments are often needed and may not be cost effective.
7\.
This technique has been used to treat sporadic cylindroma and spiradenoma where recurrence has occurred after primary surgical excision.
8\.
Mohs may be best reserved for sporadic cases.
### Prevention of Primary Manifestations
The role of UV light in the pathogenesis of the tumors seen in CYLD cutaneous syndrome is unclear. As with all skin cancer predisposition syndromes, appropriate precautions against UV-related skin damage are recommended [Davies et al 2019].
### Surveillance
It is recommended that individuals with CYLD cutaneous syndrome undergo at least annual full skin examination by a dermatologist, with some affected individuals requiring skin review every three to four months.
* An assessment of tumor burden and rate of new tumor development can be made, and existing tumors can also be monitored for any signs of malignant transformation.
* Annual monitoring will guide the frequency and interval of surgical procedures.
* Between appointments, affected individuals should be asked to report growing, ulcerated, or bleeding tumors or tumors that appear different from existing lesions so that they can be assessed to determine if urgent excision is warranted.
### Agents/Circumstances to Avoid
Radiotherapy should be avoided as it causes DNA damage and may result in further tumor formation or malignant transformation of existing lesions [Crain & Helwig 1961, Rajan & Ashworth 2015].
### Evaluation of Relatives at Risk
It is appropriate to clarify the genetic status of apparently asymptomatic older and younger at-risk relatives of an affected individual in order to identify as early as possible those who would benefit from prompt initiation of treatment and preventive measures.
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Therapies Under Investigation
Treatment for CYLD cutaneous syndrome is largely surgical. The first placebo-controlled early-phase trial of a topical targeted kinase inhibitor (tropomyosin receptor kinase) showed short-term safety [Danilenko et al 2018]; a dose escalation study is needed to determine efficacy.
It is important to recognize that tumors in CYLD cutaneous syndrome lack a curative medical therapy, and any treatments will likely need to be repeated over the affected individual's lifetime. Isolated case reports of topical or intralesional therapeutic interventions must be interpreted with caution as all have some or all of the following limitations:
* They are not placebo controlled.
* No objective measures were used to assess improvement.
* Only short-term follow-up data are presented.
* No long-term safety data regarding the repeated use of these agents in treatment of CYLD cutaneous syndrome are available.
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| CYLD Cutaneous Syndrome | None | 4,062 | gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK555820/ | 2021-01-18T21:37:24 | {"synonyms": ["Brooke-Spiegler Syndrome (BSS)", "Familial Cylindromatosis (FC)", "Multiple Familial Trichoepithelioma (MFT)"]} |
## Description
Familial progressive hyperpigmentation (FPH) is a rare autosomal dominant disorder characterized by patches of hyperpigmentation in the skin, which are present at birth or in early infancy and increase in size and number with age (summary by Zhang et al., 2006).
Also see familial progressive hyperpigmentation with or without hypopigmentation (FPHH; 145250).
Clinical Features
Zhang et al. (2006) described a 3-generation Han Chinese family in which 6 members had progressive hyperpigmentation. The family resided in a rural area of Hubei Province in central China. The earliest onset of the disease was at age 5 years. The proband, aged 32 years, had typical manifestations and a history of FPH. Hyperpigmentation was present on the hands, forehead, back of feet, and trunk. The disease progressed with age, with the lesions slowly increasing in size and number and becoming darker. Hair, sweating, and sensation were normal.
Inheritance
The inheritance pattern of hyperpigmentation in the family reported by Zhang et al. (2006) was autosomal dominant; there was 1 instance of male-to-male transmission.
Mapping
Using a genome screening with 182 STR markers from autosomes in a 3-generation Han Chinese family with progressive hyperpigmentation, Zhang et al. (2006) identified a locus in a region spanning 48.48 cM between 19pter and D19S593 (19pter-p13.1).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| HYPERPIGMENTATION, FAMILIAL PROGRESSIVE, 1 | c1840392 | 4,063 | omim | https://www.omim.org/entry/614233 | 2019-09-22T15:55:57 | {"mesh": ["C564163"], "omim": ["614233"], "orphanet": ["79146"], "synonyms": ["Alternative titles", "FPH"]} |
Tylosis with esophageal cancer
SpecialtyMedical genetics
Howel–Evans syndrome is an extremely rare condition involving thickening of the skin in the palms of the hands and the soles of the feet (hyperkeratosis). This familial disease is associated with a high lifetime risk of esophageal cancer. For this reason, it is sometimes known as tylosis with oesophageal cancer (TOC).[1]
The condition is inherited in an autosomal dominant manner, and it has been linked to a mutation in the RHBDF2 gene. It was first described in 1958.[2]
## Contents
* 1 Presentation
* 2 Genetics
* 3 Molecular biology
* 3.1 Other associations
* 3.2 Related genes
* 4 Diagnosis
* 4.1 Differential diagnosis
* 5 Treatment
* 6 Terminology
* 7 See also
* 8 References
* 9 External links
## Presentation[edit]
This condition is inherited as an autosomal dominant syndrome and characterized by palmoplantar keratoderma, oral precursor lesions particularly on the gums (leukoplakia) and a high lifetime risk of esophageal cancer (95% develop esophageal cancer by the age of 65).[3] Relapsing cutaneous horns of the lips has been reported in this condition.[4]
There are several types of this condition have been described – epidermolytic (Vörner type) and non-epidermolytic. Another classification divides these into an early onset type (type B) which occurs in the first year of life and is usually benign and a type A tylosis which occurs between the ages of 5 and 15 years and is strongly associated with esophageal cancer.[5]
Cytoglobin gene expression in oesphageal biopsies is significantly reduced (70% reduction) in this condition.[6] The mechanism of this change is not known.
## Genetics[edit]
The gene responsible is RHBDF2 (Rhomboid family member 2), which is located on the long arm of chromosome 17 (at 17q25).[7] The mutation responsible for the disease was detected in Finnish, German, UK and US families. The RHBDF2 protein is a member of the intramembranous serine proteases. It is thought to play an important role in the epithelial response to injury in the esophagus and skin. RHBDF2 is involved in the regulation of the secretion of several ligands of the epidermal growth factor receptor.
## Molecular biology[edit]
The rhomboid proteases – the first known intramembranous serine proteases[8] – were discovered in 1988.[9] The first rhomboid protease was cloned in 1990[10] Rhomboid proteases have a core of six transmembrane helices with the active site residues lying in a hydrophilic cavity. Rhomboid family members are widely conserved and found in all three kingdoms of life.[11]
RHBDF2 associates with the rhomboid like protease 2 (RHBDL2) and inhibits its activity.
Mutations in RHBDF2 inhibit tumour necrosis factor alpha.
RHBDL2 also acts on Epidermal growth factor and EphrinB3.
Thrombomodulin – a membrane glycoprotein – is upregulated in neoepidermis during cutaneous wound healing. RHBDL2 cleaves thrombomodulin at the transmembrane domain and causes the release of soluble thrombomodulin.
### Other associations[edit]
RHBDF2 may also play a role in ovarian epithelial cancer.[12]
Possible associations with gastric cancer[13][14] and lung cancer[15][16][17][18] have been suggested. Other possible associations include corneal defects, congenital pulmonary stenosis,[19] total anomalous pulmonary venous connection[20] deafness[21] and optic atrophy.[22]
### Related genes[edit]
A related gene – Rhomboid domain containing 2 (RHBDD2) – appears to be important in breast cancer.[23]
A second related gene – rhomboid family 1 (RHBDF1) – appears to be important in head and neck cancer.[24]
A third member of this family – RHBDD1 – cleaves Bcl-2-interacting killer (BIK) – a proapoptotic member of the B cell lymphoma 2 (Bcl-2) family.[25]
These proteins may also have a role in diabetes.[26]
## Diagnosis[edit]
### Differential diagnosis[edit]
The differential diagnosis is quite extensive and includes[27][28]
* Buschke–Fischer–Brauer disease
* Curth–Macklin ichthyosis
* Gamborg Nielsen syndrome
* Greither disease
* Haber syndrome
* Hereditary punctate palmoplantar keratoderma
* Jadassohn–Lewandowsky syndrome
* Keratosis follicularis spinulosa decalvans
* Keratosis linearis with ichthyosis congenital and sclerosing keratoderma syndrome
* Meleda disease
* Mucosa hyperkeratosis syndrome
* Naegeli–Franceschetti–Jadassohn syndrome
* Naxos disease
* Olmsted syndrome
* Palmoplantar keratoderma and leukokeratosis anogenitalis
* Pandysautonomia
* Papillomatosis of Gougerot and Carteaud
* Papillon–Lefèvre syndrome
* Punctate porokeratotic keratoderma
* Richner–Hanhart syndrome
* Schöpf–Schulz–Passarge syndrome
* Unna Thost disease
* Vohwinkel syndrome
* Wong's dermatomyositis
## Treatment[edit]
Systemic retinoids are the drugs used for tylosis.
## Terminology[edit]
The condition is also referred to by several other names, including "familial keratoderma with carcinoma of the esophagus," "focal non-epidermolytic palmoplantar keratoderma with carcinoma of the esophagus,"[29] "Palmoplantar ectodermal dysplasia type III," "palmoplantar keratoderma associated with esophageal cancer," "tylosis"[30]:213[31]:511 and "tylosis–esophageal cancer"[29]
## See also[edit]
* Palmoplantar keratoderma
* List of cutaneous conditions
## References[edit]
1. ^ "Tylosis with esophageal cancer". rarediseases.info.nih.gov. Genetic and Rare Diseases Information Center (GARD) – NIH. 18 January 2013. Retrieved 16 August 2014.
2. ^ Howel-Evans, W; McConnell, RB; Clarke, CA; Sheppard, PM (July 1958). "Carcinoma of the oesophagus with keratosis palmaris et plantaris (tylosis): a study of two families". Q. J. Med. 27 (107): 413–29. PMID 13579162.
3. ^ Marger RS, Marger D (1993) Carcinoma of the esophagus and tylosis. A lethal genetic combination. Cancer 72(1):17–19
4. ^ Baykal C, Savci N, Kavak A, Kurul S (2002) Palmoplantar keratoderma and oral leucoplakia with cutaneous horn of the lips. Br J Dermatol 146(4):680–683
5. ^ Maillefer RH, Greydanus MP (1999) To B or not to B: is tylosis B truly benign? Two North American genealogies. Am J Gastroenterol 94(3):829–834
6. ^ McRonald FE, Liloglou T, Xinarianos G, Hill L, Rowbottom L, Langan JE, Ellis A, Shaw JM, Field JK, Risk JM (2006) Down-regulation of the cytoglobin gene, located on 17q25, in tylosis with oesophageal cancer (TOC): evidence for trans-allele repression. Hum Mol Genet 15(8):1271–1277
7. ^ Saarinen S, Vahteristo P, Lehtonen R, Aittomäki K, Launonen V, Kiviluoto T, Aaltonen LA (2012) Analysis of a Finnish family confirms RHBDF2 mutations as the underlying factor in tylosis with esophageal cancer. Fam Cancer
8. ^ Freeman M (2009) Rhomboids: 7 years of a new protease family. Semin Cell Dev Biol 20(2):231–239
9. ^ Mayer U, Nüsslein-Volhard C (1988) A group of genes required for pattern formation in the ventral ectoderm of the Drosophila embryo. Genes Dev. 1988 Nov;2(11):1496–511
10. ^ Bier E, Jan LY, Jan YN (1990) Rhomboid, a gene required for dorsoventral axis establishment and peripheral nervous system development in Drosophila melanogaster. Genes Dev 4(2):190–203
11. ^ Koonin EV, Makarova KS, Rogozin IB, Davidovic L, Letellier MC, Pellegrini L (2003) The rhomboids: a nearly ubiquitous family of intramembrane serine proteases that probably evolved by multiple ancient horizontal gene transfers. Genome Biol. 2003; 4(3):R19
12. ^ Wojnarowicz PM, Provencher DM, Mes-Masson A-M, Tonin PN (2012) Chromosome 17q25 genes, RHBDF2 and CYGB, in ovarian cancer. Int J Oncol 40 (6) 1865-1880 Doi: 10.3892/ijo.2012.1371
13. ^ Wagle PK, Shetty TS, Darbari A, Tapia AA, Katrak MP, Joshi RM (2002) Carcinoma of stomach in a patient with familial tylosis. Indian J Gastroenterol 21(6):227
14. ^ Murata I, Ogami Y, Nagai Y, Furumi K, Yoshikawa I, Otsuki M (1998) Carcinoma of the stomach with hyperkeratosis palmaris et plantaris and acanthosis of the esophagus. Am J Gastroenterol 93(3):449–451
15. ^ Grundmann JU, Weisshaar E, Franke I, Bonnekoh B, Gollnick H (2003) Lung carcinoma with congenital plantar keratoderma as a variant of Clarke-Howel-Evans syndrome. Int J Dermatol 42(6):461–463
16. ^ Nomori H, Horio H, Iga R, Fuyuno G, Kobayashi R, Morinaga S (1996) Squamous cell carcinoma of the lung associated with palmo-plantar hyperkeratosis. Nihon Kyobu Shikkan Gakkai Zasshi 34(1):76–79
17. ^ Khanna SK, Agnone FA, Leibowitz AI, Raschke RA, Trehan M (1993) Nonfamilial diffuse palmoplantar keratoderma associated with bronchial carcinoma. J Am Acad Dermatol 28(2 Pt 2):295–297
18. ^ Murata Y, Kumano K, Tani M, Saito N, Kagotani K (1988) Acquired diffuse keratoderma of the palms and soles with bronchial carcinoma: report of a case and review of the literature. Arch Dermatol 124(4):497–498
19. ^ Wong ML, Tay JS (1991) Congenital heart disease in tylosis: case report. J Singapore Paediatr Soc 33(1–2):45–48
20. ^ Hoeger PH, Yates RW, Harper JI (1998) Palmoplantar keratoderma associated with congenital heart disease. Br J Dermatol 138(3):506–509
21. ^ Fitzgerald DA, Verbov JL (1996) Hereditary palmoplantar keratoderma with deafness. Br J Dermatol 134(5):939–942
22. ^ Dimsdale H (1949) Hereditary optic atrophy in family with keratodermia palmaris et plantaris (tylosis). Proc R Soc Med 42(10):796
23. ^ Abba MC, Lacunza E, Nunez MI, Colussi A, Isla-Larrain M, Segal-Eiras A, Croce MV, Aldaz CM (2009) Rhomboid domain containing 2 (RHBDD2): a novel cancer-related gene over-expressed in breast cancer. Biochim Biophys Acta 1792(10):988–997
24. ^ Zou H, Thomas SM, Yan ZW, Grandis JR, Vogt A, Li LY (2009) Human rhomboid family-1 gene RHBDF1 participates in GPCR-mediated transactivation of EGFR growth signals in head and neck squamous cancer cells. FASEB J 23(2):425–432
25. ^ Wang Y, Guan X, Fok KL, Li S, Zhang X, Miao S, Zong S, Koide SS, Chan HC, Wang L (2008) A novel member of the Rhomboid family, RHBDD1, regulates BIK-mediated apoptosis. Cell Mol Life Sci 65(23):3822–3829
26. ^ Walder K, Kerr-Bayles L, Civitarese A, Jowett J, Curran J, Elliott K, Trevaskis J, Bishara N, Zimmet P, Mandarino L, Ravussin E, Blangero J, Kissebah A, Collier GR (2005) The mitochondrial rhomboid protease PSARL is a new candidate gene for type 2 diabetes. Diabetologia 48(3):459–468
27. ^ Itin PH, Fistarol SK (2005) Palmoplantar keratodermas. Clin Dermatol 23(1):15–22
28. ^ Ratnavel RC, Griffiths WA (1997) The inherited palmoplantar keratodermas. Br J Dermatol 137(4):485–490
29. ^ a b Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.
30. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
31. ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0.
## External links[edit]
Classification
D
* ICD-10: Q82.8
* OMIM: 148500
* MeSH: C536164
* DiseasesDB: 33404
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Howel–Evans syndrome | c1835664 | 4,064 | wikipedia | https://en.wikipedia.org/wiki/Howel%E2%80%93Evans_syndrome | 2021-01-18T18:31:22 | {"gard": ["3102"], "mesh": ["C536164"], "umls": ["C1835664"], "orphanet": ["2198"], "wikidata": ["Q5921848"]} |
Clear-cell adenocarcinoma
Micrograph of an ovarian clear-cell adenocarcinoma. H&E stain.
SpecialtyOncology
Clear-cell adenocarcinoma is a type of adenocarcinoma that shows clear cells.[1]
Types include:
* Clear-cell adenocarcinoma of the vagina
* Clear-cell ovarian carcinoma
* Uterine clear-cell carcinoma
* Clear-cell adenocarcinoma of the lung (which is a type of Clear-cell carcinoma of the lung)
## See also[edit]
* Clear-cell sarcoma
## References[edit]
1. ^ "NCI Dictionary of Cancer Terms". National Cancer Institute. 2 February 2011. Retrieved 10 July 2019.
## External links[edit]
Classification
D
* MeSH: D018262
* DiseasesDB: 2786
* v
* t
* e
Glandular and epithelial cancer
Epithelium
Papilloma/carcinoma
* Small-cell carcinoma
* Combined small-cell carcinoma
* Verrucous carcinoma
* Squamous cell carcinoma
* Basal-cell carcinoma
* Transitional cell carcinoma
* Inverted papilloma
Complex epithelial
* Warthin's tumor
* Thymoma
* Bartholin gland carcinoma
Glands
Adenomas/
adenocarcinomas
Gastrointestinal
* tract: Linitis plastica
* Familial adenomatous polyposis
* pancreas
* Insulinoma
* Glucagonoma
* Gastrinoma
* VIPoma
* Somatostatinoma
* Cholangiocarcinoma
* Klatskin tumor
* Hepatocellular adenoma/Hepatocellular carcinoma
Urogenital
* Renal cell carcinoma
* Endometrioid tumor
* Renal oncocytoma
Endocrine
* Prolactinoma
* Multiple endocrine neoplasia
* Adrenocortical adenoma/Adrenocortical carcinoma
* Hürthle cell
Other/multiple
* Neuroendocrine tumor
* Carcinoid
* Adenoid cystic carcinoma
* Oncocytoma
* Clear-cell adenocarcinoma
* Apudoma
* Cylindroma
* Papillary hidradenoma
Adnexal and
skin appendage
* sweat gland
* Hidrocystoma
* Syringoma
* Syringocystadenoma papilliferum
Cystic, mucinous,
and serous
Cystic general
* Cystadenoma/Cystadenocarcinoma
Mucinous
* Signet ring cell carcinoma
* Krukenberg tumor
* Mucinous cystadenoma / Mucinous cystadenocarcinoma
* Pseudomyxoma peritonei
* Mucoepidermoid carcinoma
Serous
* Ovarian serous cystadenoma / Pancreatic serous cystadenoma / Serous cystadenocarcinoma / Papillary serous cystadenocarcinoma
Ductal, lobular,
and medullary
Ductal carcinoma
* Mammary ductal carcinoma
* Pancreatic ductal carcinoma
* Comedocarcinoma
* Paget's disease of the breast / Extramammary Paget's disease
Lobular carcinoma
* Lobular carcinoma in situ
* Invasive lobular carcinoma
Medullary carcinoma
* Medullary carcinoma of the breast
* Medullary thyroid cancer
Acinar cell
* Acinic cell carcinoma
This oncology article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Clear-cell adenocarcinoma | c0206681 | 4,065 | wikipedia | https://en.wikipedia.org/wiki/Clear-cell_adenocarcinoma | 2021-01-18T18:50:36 | {"mesh": ["D018262"], "umls": ["C0206681"], "wikidata": ["Q5130800"]} |
Acrodysostosis syndrome
Other namesArkless-Graham syndrome,[1] Maroteaux-Malamut syndrome[2][3]
Acrodysostosis is a rare congenital malformation syndrome which involves shortening of the interphalangeal joints of the hands and feet, intellectual disability in approximately 90% of affected children, and peculiar facies. Other common abnormalities include short head (as measured front to back), small broad upturned nose with flat nasal bridge, protruding jaw, increased bone age, intrauterine growth retardation, juvenile arthritis and short stature. Further abnormalities of the skin, genitals, teeth, and skeleton may occur.[citation needed]
## Contents
* 1 Cause
* 2 Diagnosis
* 3 Treatment
* 4 Epidemiology
* 5 References
* 6 External links
## Cause[edit]
Most reported cases have been sporadic, but it has been suggested that the condition might be genetically related i.e. in an autosomal dominant mode of transmission. Both males and females are affected. The disorder has been associated with the older age of parents at the time of conception.
A PRKAR1A mutation has been identified in acrodysostosis with hormone resistance.[4]
## Diagnosis[edit]
This section is empty. You can help by adding to it. (February 2018)
## Treatment[edit]
This section is empty. You can help by adding to it. (February 2018)
## Epidemiology[edit]
This disorder is present at birth, however, it may not be understood until several years after birth. Acrodysostosis affects males and females in almost similar numbers. It is difficult to determine the frequency of acrodysostosis in the population as many cases of this disorder cannot be diagnosed properly.[5]
## References[edit]
1. ^ Arkless R, Graham CB (1967). "An unusual case of brachydactyly. Peripheral dysostosis? Pseudo-pseudo-hypoparathyroidism? Cone epiphyses?". Am J Roentgenol Radium Ther Nucl Med. 99 (3): 724–35. doi:10.2214/ajr.99.3.724. PMID 6020652.
2. ^ Maroteaux P, Malamut G (1968). "[Acrodysostosis]". Presse Med (in French). 76 (46): 2189–92. PMID 5305130.
3. ^ synd/1623 at Who Named It?
4. ^ Linglart A, Menguy C, Couvineau A, et al. (June 2011). "Recurrent PRKAR1A mutation in acrodysostosis with hormone resistance". N. Engl. J. Med. 364 (23): 2218–26. doi:10.1056/NEJMoa1012717. PMID 21651393.
5. ^ http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/613/printFullReport
## External links[edit]
* "Acrodysostosis: Disease Information from NORD". National Organization for Rare Disorders.
* Acrodysostosis at NIH's Office of Rare Diseases
Classification
D
* ICD-10: Q75.4
* OMIM: 101800
* MeSH: C538179
* DiseasesDB: 31405
External resources
* MedlinePlus: 001248
* Orphanet: 950
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Acrodysostosis | c0220659 | 4,066 | wikipedia | https://en.wikipedia.org/wiki/Acrodysostosis | 2021-01-18T18:29:28 | {"gard": ["5724", "2015"], "mesh": ["C538179"], "umls": ["C0220659"], "orphanet": ["950"], "wikidata": ["Q4357287"]} |
Benign pyruvate carboxylase (PC) deficiency (Type C) is a rare, very mild form of PC deficiency characterized by episodic metabolic acidosis and normal or mildly delayed neurological development.
## Epidemiology
Benign PC deficiency is a very rare form of PC deficiency and has been described in fewer than 10 patients to date. No ethnic predilection has been reported.
## Clinical description
Onset typically occurs during the first year of life with episodic metabolic acidosis associated with lactic acidemia and occasionally with ketoacidosis during metabolic stress. Neurological development is normal or mildly impaired. Other signs include dystonia, episodic ataxia, dysarthria, transitory hemiparesis and seizures.
## Etiology
Type C PC deficiency is caused by mutations in the PC gene (11q13.4-q13.5).
## Diagnostic methods
Blood lactic acid levels are usually between 2 and 5 mmol/l. The abnormal biochemical parameters found in severe forms of PC deficiency are absent in patients with Type C, although lysine, proline and alanine may be elevated, while citrulline is normal. PC enzyme activity assay demonstrating deficiency of the PC enzyme in fibroblasts is also diagnostic, along with mutations in the PC gene identified via molecular genetic testing.
## Genetic counseling
Pyruvate carboxylase deficiency is inherited in an autosomal recessive manner.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Pyruvate carboxylase deficiency, benign type | c0034341 | 4,067 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=353320 | 2021-01-23T16:52:45 | {"mesh": ["D015324"], "omim": ["266150"], "icd-10": ["E74.4"], "synonyms": ["Pyruvate carboxylase deficiency type C"]} |
Menstrual extractionBackground
Abortion typeSurgical
First use1971
GestationFirst trimester
Usage
Developed and used in a feminist, non-medicalized context.
Infobox references
Menstrual extraction (ME) is a type of manual vacuum aspiration technique developed by feminist activists Lorraine Rothman and Carol Downer to pass the entire menses at once. The non-medicalized technique has been used in small feminist self-help groups since 1971 and has a social role of allowing access to early abortion without needing medical assistance or legal approval.[1][2][3]:406 ME usage declined after 1973, when Roe v. Wade legalized abortion in the United States. There has been renewed interest in the technique, in the 1990s and more recently in the 2010s, due to increased restrictions on abortion. In some countries where abortion is illegal, such as Bangladesh, the terms “menstrual regulation” or “menstrual extraction” are used as euphemisms for early pregnancy terminations.
## Contents
* 1 Development within a feminist context
* 2 Legality
* 3 Usage
* 3.1 Pre-Roe v. Wade
* 3.2 After legalization of abortion
* 4 Similar techniques
* 5 Footnotes
* 6 Further reading
## Development within a feminist context[edit]
The Del Em
In 1971, Lorraine Rothman and Carol Downer, members of a feminist reproductive health self-help group, modified equipment found in an underground abortion clinic that was developed for a new non-traumatic, manually-operated-suction abortion technique.[4] They took the thin, flexible plastic Karman cannula (about the size of a soda straw), and the syringe (50 or 60ml), and added a one-way bypass valve, to fix two main problems.[2] The contraption could prevent air from being pumped into the uterus, and also suctioned uterine contents directly into the syringe, thus limiting the amount that could be removed. They added two lengths of clear plastic tubing, one from the cannula to the collection jar and another to go from the collection jar to the syringe. With this new setup, the contents of the uterus went directly into the jar, allowing for the extraction of more material, and the two-way bypass valve diverted any air that may have been inadvertently pushed back toward the body to exit harmlessly into the air; this would prevent air from entering the uterus.[2] Rothman and Downer dubbed the new invention the "Del Em". By making it possible for more than one person to operate the device, the skill level of the operators was greatly reduced. One person could concentrate on guiding the sterile cannula through the vaginal cavity into the cervical os while another could pump the syringe to develop the vacuum. The Del Em made the procedure more comfortable, with personal control of the suction.[5]
Downer considers the teaching and usage of menstrual extraction to be a key radical feminist action to ensure women's reproductive sovereignty.[6]
## Legality[edit]
ME was developed and used before the Roe v. Wade Supreme Court decision legalized abortion in 1973. In order to avoid legal issues, Downer and Rothman downplayed the device's potential use as an abortion method. They called new technique "menstrual extraction" or "ME" to highlight its harmless use in suctioning out menstrual blood and tissue. To further emphasize the innocuousness of ME, "the procedure was only performed when a woman’s period was due, and they wouldn't take a pregnancy test beforehand. That way, everyone had plausible deniability."[4]
Since 1971, groups performing menstrual extractions have had an excellent safety record, obviating any opportunity for legal action culminating in the prosecution of any individual. However, the possibility of legal troubles continues to exist, and because of that many of these self-help groups have sought legal advice and researched the laws in the states in which they perform ME. Additionally, many of these self-help groups do not publicize themselves or offer menstrual extraction to those outside of their tight-knit groups, in order to protect themselves and their techniques from legal investigations.[7]
There is one instance in which Carol Downer had legal entanglements. It is well known as the "Yogurt Defense" case, in which Downer was arrested while at her self-help group and charged with practicing medicine without a license because she inserted yogurt into the vagina of Z. Budapest, another member of the group, as treatment for a yeast condition.[8] Downer went to trial and was acquitted, as the jury did not see inserting yogurt as practicing medicine.[2][9]:57
## Usage[edit]
### Pre-Roe v. Wade[edit]
ME made its debut at the National Organization for Women conference in Santa Monica, California, in August 1971. To Rothman and Downer's dismay, the organizers of the conference were "so appalled that they refused to give the women exhibit space."[10] Instead, Downer and Rothman hung flyers around the conference, announcing a demonstration in their hotel room. The attendees were given a plastic speculum to begin their education. From the extensive mailing list collected during these demonstrations, Downer and Rothman began a national tour, going all over the country (to 23 cities on a Greyhound bus) teaching the new technique.[7][11][12] According to the National Women's Health Network, "the early self-helpers advocated that women join self-help groups and practice extracting each others' menses around the time of their expected periods."[13] The Roe v. Wade Supreme Court decision made abortion legal in 1973. After that, menstrual extraction was practiced much less, though it did not disappear.
### After legalization of abortion[edit]
It did begin to regain in popularity in the late 1980s and early 1990s, when the U.S. Supreme Court ruled on Webster v. Reproductive Health Services, which limited access to abortion by state of residence and type of medical insurance.[2] Self-helpers even reprised the 1971 tour, traveling around the U.S. sharing self-examination and menstrual extraction techniques; however it never reached the heights of the early 1970s.[13]
Menstrual extraction has regained popularity once again in the 2010s, in addition to other self-induced abortion methods.[14][15] These self-helpers are following the 1970s methods of teaching by meeting in other women's homes, performing cervix examinations on each other, and learning menstrual extraction directly from other women. One new underground network, made up of women knowledgeable on ME and other self-induced abortion methods, has performed over 2,000 abortions between 2015 and 2018.[15] The women involved in this network range from those in medical professions, such as nurses or midwives, while others are herbalists or just interested in learning the procedure. Many of the participants in these networks, and women who seek in self-induced abortions overall, are low-income, cannot travel to obtain an abortion, or dislike clinical settings.[14][16]
## Similar techniques[edit]
Although menstrual extraction is technically similar to manual vacuum aspiration (MVA) and menstrual regulation (MR), it is a unique form because it is not medicalized. It originated in the feminist self-help movement and it is performed by small groups of women where the person getting a ME has complete control over the procedure. Menstrual extraction "minimiz[es]... power differentials between providers and receivers... [which] stands in direct contrast to [MVA and MR]."[2]
Around the same time that menstrual extraction was first used in the United States, a method utilizing nearly identical technology was beginning to be used internationally. This method, another type of manual vacuum aspiration, is most often called menstrual regulation. As with ME, menstrual regulation, when desired as a method of controlling fertility, is performed very early in the menstrual cycle, earlier than a pregnancy test can be performed. One main difference between these two methods is the equipment used. While the Del Em was created such that one is able to put it together from individual pieces and it consists of three parts: the cannula with a one-way valve, a collection jar and the syringe, which are connected by plastic tubing; menstrual regulation is performed with a commercially produced kit which consists of two parts, the cannula with a one-way valve and a directly connected syringe. With this kit, the contents of the uterus are sucked directly into the syringe. ME is performed by a group; menstrual regulation is performed by an individual practitioner.[2][9]:169
According to the National Abortion Federation (NAF), "in the developing world, menstrual regulation is still a crucial strategy to circumvent anti-abortion laws." Although abortion is illegal in Bangladesh, the government has long supported a network of menstrual regulation clinics.[17][18] It is estimated that 468,000 menstrual regulations are performed each year in Bangladesh.[19] NAF also reports "some other countries allow menstrual regulation because it presumably takes place without a technical verification of pregnancy".[20] Said countries are claimed to include Korea, Singapore, Hong Kong, Thailand, and Vietnam.[21] In Cuba, where abortion is legal, menstrual regulation is widely practiced— menstrual extraction is offered to everyone whose period is two weeks late, without a pregnancy test.[22]
## Footnotes[edit]
1. ^ Sage-Femme Collective (2008). Natural Liberty: Discovering Self-Induced Abortion Methods. Las Vegas, Nevada: Sage Femme!. pp. 30, 63–77. ISBN 978-0964592001.CS1 maint: uses authors parameter (link)
2. ^ a b c d e f g Copelton, Denise A. "Menstrual Extraction, Abortion, and the Politics of Feminist Self-help". Advances in Gender Research. 8: 129–164.
3. ^ Boston Women's Health Book Collective (1992). The New Our Bodies, Ourselves (Updated and Expanded for the '90s ed.). New York: Simon and Schuster Inc. ISBN 978-0671791766.CS1 maint: uses authors parameter (link)
4. ^ a b Greenspon, Christopher (2017-04-14). "The secret home abortion movement that started in LA two years before Roe v. Wade". Off-Ramp. Southern California Public Radio. Retrieved 2018-07-23.
5. ^ Chalker, Rebecca (Spring 1993). "The Whats, Hows, and Why of Menstrual Extraction". On The Issues. Retrieved 5 January 2018.
6. ^ Downer, Carol (January 9, 2015). "Reproductive Sovereignty or Bust!". CounterPunch. Retrieved 2018-10-18.
7. ^ a b Chalker, Rebecca; Downer, Carol (1992). A Woman's Book of Choices, Abortion, Menstrual Extraction, RU-486. New York: Four Walls Eight Windows. ISBN 978-0941423861.
8. ^ Downer, Carol (May 21, 2015). "DIY Abortions Can Have Legal Complications". Women's eNews. Retrieved 2018-07-23.
9. ^ a b Ruzek, Sheryl Burt (1979). The Women's Health Movement: Feminist Alternatives to Medical Control. New York: Praeger Publishers. ISBN 978-0030414367.
10. ^ Woo, Elaine (October 3, 2007). "Lorraine Rothman, 75; feminist clinic's co-founder helped demystify gynecology". Obituaries. Los Angeles Times.
11. ^ Davis, Flora (1991). Moving the Mountain: The Women's Movement in America since 1960. New York: Simon Schuster. p. 233. ISBN 9780671792923.
12. ^ Morgen, Sandra (2002). Into Our Hands The Women's Health Movement in the United States, 1969-1990. New Brunswick, New Jersey: Rutgers University Press. p. 8. ISBN 978-0813530710.
13. ^ a b Pearson, Cindy (March–April 1996). "Self Help Clinic Celebrates 25 Years". Network News. National Women's Health Network. Retrieved 5 January 2018.
14. ^ a b Liss-Schultz, Nina (March–April 2018). "Inside the Top-Secret Abortion Underground". Mother Jones. Retrieved 2018-10-18.
15. ^ a b Presser, Lizzie (2018-03-28). ""Whatever's your darkest question, you can ask me." A secret network of women is working outside the law and the medical establishment to provide safe, cheap home abortions". The California Sunday Magazine. Retrieved 2018-10-18.
16. ^ Ojanen-Goldsmith, A; Prager, S (October 2016). "Beyond the clinic: preferences, motivations, and experiences with alternative abortion care in North America". Contraception. 94 (4): 398–399. doi:10.1016/j.contraception.2016.07.062. ISSN 0010-7824.
17. ^ Bergum, SE (1993). "Saving lives with menstrual regulation". Plan Parent Chall, International Planned Parenthood Newsletter (1): 30–1. PMID 12345324.
18. ^ Amin, R; Kamal, GM; Mariam, AG (27 October 1988). "Menstrual regulation in Bangladesh: an evaluation of training and service programs". International Journal of Gynecology & Obstetrics. 27 (2): 265–71. doi:10.1016/0020-7292(88)90018-5. PMID 2903095.
19. ^ Henshaw, Stanley K; Singh, Susheela; Haas, Taylor (19 January 1999). "Incidence of Abortion Worldwide". Guttmacher Institute. International Perspectives on Sexual and Reproductive Health. ISSN 1944-0405. Retrieved 5 January 2018.
20. ^ C Joffe (1999). "Abortion in Historical Perspective". In Paul M, Lichtenberg ES, Borgatta L, Grimes DA, Stubblefield PG (eds.). A Clinician's Guide to Medical and Surgical Abortion. Philadelphia: Churchill Livingstone. Archived from the original (Reprint by National Abortion Federation) on 2006-09-22.
21. ^ "Abortion for All: How the International Planned Parenthood Federation promotes abortion around the world - IPPF's Illegal Activities". lifeissues.net. 2000.
22. ^ Veeken, Hans (7 October 1995). "Cuba: plenty of care, few condoms, no corruption". BMJ. 311 (7010): 935–7. doi:10.1136/bmj.311.7010.935. PMC 2550926. PMID 7580557. Retrieved 5 January 2018.
## Further reading[edit]
* Rebecca Chalker and Carol Downer (1996). A Woman's Book of Choices: Abortion, Menstrual Extraction, RU-486. Seven Stories Press. ISBN 1-888363-28-2.
* "Unofficial Abortion". Time Magazine. September 11, 1972.
* Emin-Tunc, Tanfer (Summer 2004). "Into Our Own Hands: The Women's Health Movement in the United States, 1969-1990". NWSA Journal. 16 (2): 237–239. doi:10.1353/nwsa.2004.0052.
* No Going Back: A Pro-Choice Perspective (Documentary). Produced by Carol Downer, directed by Irene Schonwit, written by Regina Leeds. 1988.CS1 maint: others (link)\- Video which presents menstrual extraction as an abortion method that can be used by women in self-help health groups.
* Ninia Baehr (1990). Abortion without Apology: A Radical History for the 1990s. Boston: South End Press. p. 21.
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*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
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*[CEEs]: conjugated estrogens
| Menstrual extraction | c0362068 | 4,068 | wikipedia | https://en.wikipedia.org/wiki/Menstrual_extraction | 2021-01-18T18:41:41 | {"wikidata": ["Q2621784"]} |
Pancoast tumor
Other namesPulmonary sulcus tumor, superior sulcus tumor
Chest radiograph showing a Pancoast tumor (labeled as P, non-small cell lung carcinoma, right lung), from a 47-year-old female smoker.
SpecialtyOncology
A Pancoast tumor is a tumor of the pulmonary apex. It is a type of lung cancer defined primarily by its location situated at the top end of either the right or left lung. It typically spreads to nearby tissues such as the ribs and vertebrae. Most Pancoast tumors are non-small cell cancers.
The growing tumor can cause compression of a brachiocephalic vein, subclavian artery, phrenic nerve, recurrent laryngeal nerve, vagus nerve, or, characteristically, compression of a sympathetic ganglion (the stellate ganglion), resulting in a range of symptoms known as Horner's syndrome.
Pancoast tumors are named for Henry Pancoast, an American radiologist, who described them in 1924 and 1932.[1]
## Contents
* 1 Signs and symptoms
* 2 Diagnosis
* 3 Treatment
* 4 References
* 5 External links
## Signs and symptoms[edit]
Aside from cancer general symptoms such as malaise, fever, weight loss and fatigue, Pancoast tumor can include a complete Horner's syndrome in severe cases: miosis (constriction of the pupils), anhidrosis (lack of sweating), ptosis (drooping of the eyelid), and pseudoenophathalmos (because of the ptosis). In progressive cases, the brachial plexus is also affected, causing pain and weakness in the muscles of the arm and hand with a symptomatology typical of thoracic outlet syndrome. The tumor can also compress the recurrent laryngeal nerve and from this a hoarse voice and "bovine" (non-explosive) cough may occur.[citation needed]
In superior vena cava syndrome, obstruction of the superior vena cava by a tumor (mass effect) causes facial swelling cyanosis and dilatation of the veins of the head and neck.[citation needed]
A Pancoast tumor is an apical tumor that is typically found in conjunction with a smoking history. The clinical signs and symptoms can be confused with neurovascular compromise at the level of the superior thoracic aperture. The patient's smoking history, rapid onset of clinical signs and symptoms, and pleuritic pain can suggest an apical tumor. A Pancoast tumor can give rise to both Pancoast syndrome and Horner's syndrome. When the brachial plexus roots are involved, it will produce Pancoast syndrome; involvement of sympathetic fibers as they exit the cord at T1 and ascend to the superior cervical ganglion will produce Horner's syndrome.[citation needed]
## Diagnosis[edit]
Diagnosis of Pancoast tumor is usually made after evaluating clinical symptoms and imaging. Chest X-ray is a good screening test even though Chest CT scan can provide a better resolution and extent to which internal organs are being compressed.[citation needed]
## Treatment[edit]
The treatment of a Pancoast lung cancer may differ from that of other types of non-small cell lung cancer. Its position and close proximity to vital structures (such as nerves and spine) may make surgery difficult. As a result, and depending on the stage of the cancer, treatment may involve radiation and chemotherapy given prior to surgery (neoadjuvant treatment). Surgery may consist of the removal of the upper lobe of a lung together with its associated structures (subclavian artery, vein, branches of the brachial plexus, ribs and vertebral bodies), as well as mediastinal lymphadenectomy. Surgical access may be via thoracotomy from the back[2] or the front of the chest[3] and modifications.[4] Nonsurgical treatment may consist of radiation therapy alone or clinical trials of new combinations of treatment.[5]
* CT scan showing a Pancoast tumor (labeled as P, non-small cell lung carcinoma, right lung), from a 47-year-old female smoker
## References[edit]
1. ^ synd/2953 at Who Named It?
2. ^ Paulson DL, Shaw RR (May 1960). "Results of bronchoplastic procedures for bronchogenic carcinoma". Ann. Surg. 151 (5): 729–40. doi:10.1097/00000658-196005000-00013. PMC 1613696. PMID 14431029.
3. ^ Dartevelle PG, Chapelier AR, Macchiarini P, et al. (June 1993). "Anterior transcervical-thoracic approach for radical resection of lung tumors invading the thoracic inlet". J. Thorac. Cardiovasc. Surg. 105 (6): 1025–34. doi:10.1016/S0022-5223(19)33774-2. PMID 8080467.
4. ^ Nazari S (August 1996). "Transcervical approach (Dartevelle technique) for resection of lung tumors invading the thoracic inlet, sparing the clavicle". J. Thorac. Cardiovasc. Surg. 112 (2): 558–60. doi:10.1016/s0022-5223(96)70296-9. PMID 8751536.
Grunenwald D, Spaggiari L (February 1997). "Transmanubrial osteomuscular sparing approach for apical chest tumors". Ann. Thorac. Surg. 63 (2): 563–6. doi:10.1016/S0003-4975(96)01023-5. PMID 9033349.
Anterior Access for radical resection of Pancoast tumors on YouTube
5. ^ "Non-Small Cell Lung Cancer Treatment (PDQ®)–Patient Version - National Cancer Institute". www.cancer.gov. 2020-05-22. Retrieved 2020-06-10.
## External links[edit]
Classification
D
* ICD-10: C34.1
* ICD-9-CM: 162.3
* MeSH: D010178
* DiseasesDB: 31266
External resources
* eMedicine: med/3418
* Pancoast Tumor at eMedicine
* Pulmonary sulcus tumor entry in the public domain NCI Dictionary of Cancer Terms
This article incorporates public domain material from the U.S. National Cancer Institute document: "Dictionary of Cancer Terms".
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*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Pancoast tumor | c0549471 | 4,069 | wikipedia | https://en.wikipedia.org/wiki/Pancoast_tumor | 2021-01-18T18:34:36 | {"mesh": ["D010178"], "umls": ["C0549471"], "icd-9": ["162.3"], "icd-10": ["C34.1"], "wikidata": ["Q1750884"]} |
Alkaptonuria is an inherited condition that causes urine to turn black when exposed to air. Ochronosis, a buildup of dark pigment in connective tissues such as cartilage and skin, is also characteristic of the disorder. This blue-black pigmentation usually appears after age 30. People with alkaptonuria typically develop arthritis, particularly in the spine and large joints, beginning in early adulthood. Other features of this condition can include heart problems, kidney stones, and prostate stones.
## Frequency
This condition is rare, affecting 1 in 250,000 to 1 million people worldwide. Alkaptonuria is more common in certain areas of Slovakia (where it has an incidence of about 1 in 19,000 people) and in the Dominican Republic.
## Causes
Mutations in the HGD gene cause alkaptonuria. The HGD gene provides instructions for making an enzyme called homogentisate oxidase. This enzyme helps break down the amino acids phenylalanine and tyrosine, which are important building blocks of proteins. Mutations in the HGD gene impair the enzyme's role in this process. As a result, a substance called homogentisic acid, which is produced as phenylalanine and tyrosine are broken down, accumulates in the body. Excess homogentisic acid and related compounds are deposited in connective tissues, which causes cartilage and skin to darken. Over time, a buildup of this substance in the joints leads to arthritis. Homogentisic acid is also excreted in urine, making the urine turn dark when exposed to air.
### Learn more about the gene associated with Alkaptonuria
* HGD
## Inheritance Pattern
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Alkaptonuria | c0002066 | 4,070 | medlineplus | https://medlineplus.gov/genetics/condition/alkaptonuria/ | 2021-01-27T08:24:45 | {"gard": ["5775"], "mesh": ["D000474"], "omim": ["203500"], "synonyms": []} |
A number sign (#) is used with this entry because of evidence that intrahepatic cholestasis of pregnancy-1 (ICP1) can be caused by heterozygous mutation in the ATP8B1 gene (602397) on chromosome 18q21.
Mutation in the ATP8B1 gene can also cause progressive familial intrahepatic cholestasis-1 (PFIC1; 211600) and benign recurrent intrahepatic cholestasis-1 (BRIC1; 243300).
Description
Intrahepatic cholestasis of pregnancy is a reversible form of cholestasis that occurs most often in the third trimester of pregnancy and recurs in 45 to 70% of subsequent pregnancies. Symptoms include pruritus, jaundice, increased serum bile salts, and abnormal liver enzymes, all of which resolve rapidly after delivery. However, the condition is associated with fetal complications, including placental insufficiency, premature labor, fetal distress, and intrauterine death. Some women with ICP may also be susceptible to oral contraceptive-induced cholestasis (OCIC) (summary by Pasmant et al., 2012).
### Genetic Heterogeneity of Intrahepatic Cholestasis of Pregnancy
See also ICP3 (614972), caused by mutation in the ABCB4 gene (171060).
Clinical Features
Intrahepatic cholestasis of pregnancy was reported in sisters by Svanborg and Ohlsson (1959), Cahill (1962), and Fast and Roulston (1964).
Holzbach and Sanders (1965) reported a mother and 2 daughters with recurrent ICP characterized by generalized itching, with or without jaundice, during pregnancy. The disorder began primarily in the third trimester and disappeared shortly postpartum. There was no biliary colic, no jaundice or pruritus between pregnancies, and no chronic liver disease. Holzbach et al. (1983) updated the pedigree. In all, there were 5 affected women in 4 sibships spanning 3 generations. The authors favored female-limited autosomal dominant inheritance. A male transmitted the disorder from his mother to his daughter. During periods between pregnancies, the trait could be demonstrated by an oral steroid hormone challenge test or by use of oral contraceptives.
Somayaji et al. (1968) reported sisters who developed cholestatic jaundice following the taking of an oral contraceptive agent. One of them had had pruritus during the latter part of each of 3 pregnancies. McKusick and Clayton (1968) observed that mothers of patients with PFIC1 had severe pruritus in late pregnancy, raising the possibility that cholestasis of pregnancy may be a manifestation of the heterozygous state of the gene which in the homozygote produces a fatal form of cholestasis.
Reyes et al. (1978) and Reyes (1982) reported that ICP is frequent in the Araucanian Indians of Chile. Reyes et al. (1976) reported a large kindred from Chile in which 10 of 32 multiparous women in the last 2 generations had ICP. There were 2 probable instances of males who transmitted the disorder to a daughter.
Inheritance
Hirvioja and Kivinen (1993) reported 3 sisters with ICP, which was observed in 5 successive generations of their family. Most of the patients also had cholelithiasis. Uniform expression, complete penetrance, and direct parent-to-child transmission supported dominant inheritance.
Molecular Genetics
In 4 of 182 unrelated patients with ICP1, Mullenbach et al. (2005) identified heterozygous mutations in the ATP8B1 gene (602397.0010; 602397.0011).
Heterogeneity
### Genetic Heterogeneity
Savander et al. (2003) prospectively interviewed 69 Finnish patients with ICP for a family history of the disorder; 11 of the patients were found to have familial ICP and 58 had sporadic ICP. The pedigree structures in 16% (11 of 69) patients suggested dominant inheritance. Patients with familial ICP had higher serum amino transferase levels and a higher recurrence risk (92% vs 40%). Haplotype and multipoint linkage analysis excluded the ABCB11 (603201), ATP8B1, and the ABCB4 genes in 2 pedigrees. Savander et al. (2003) concluded that ICP is genetically heterogeneous.
In a large screening of the ATP8B1 gene in 176 familial and sporadic patients with ICP, Painter et al. (2005) concluded that ATP8B1 is probably not a major gene contributing to the disorder.
Population Genetics
ICP affects approximately 0.5 to 0.7% of all pregnancies in the UK (Mullenbach et al., 2005).
INHERITANCE \- Autosomal dominant ABDOMEN Liver \- Intrahepatic cholestasis during pregnancy, resolves postpartum \- Abnormal liver function tests during pregnancy, resolves postpartum \- Hepatic fibrosis seen on biopsy (in some patients) \- Ductal proliferation seen on biopsy (in some patients) SKIN, NAILS, & HAIR Skin \- Pruritus during pregnancy, resolves postpartum \- Jaundice (in some patients), resolved postpartum PRENATAL MANIFESTATIONS Movement \- Fetal distress Delivery \- Premature delivery \- Intrauterine fetal death LABORATORY ABNORMALITIES \- Abnormal liver function tests during pregnancy, resolves postpartum \- Increased serum bile acid concentration during pregnancy, resolves postpartum MISCELLANEOUS \- Occurs during pregnancy, most often in the third trimester \- No chronic or permanent liver damage \- Oral contraceptives may also cause symptoms MOLECULAR BASIS \- Caused by mutation in the ATPase, class I, type 8B, member 1 gene (ATP8B1, 602397.0010 ) ▲ Close
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| CHOLESTASIS, INTRAHEPATIC, OF PREGNANCY, 1 | c3549845 | 4,071 | omim | https://www.omim.org/entry/147480 | 2019-09-22T16:39:25 | {"doid": ["0070228"], "mesh": ["C535932"], "omim": ["147480"], "orphanet": ["69665"], "synonyms": ["Recurrent intrahepatic cholestasis of pregnancy", "CHOLESTASIS, PREGNANCY-RELATED, 1", "Gravidic intrahepatic cholestasis", "Pregnancy-related cholestasis", "Alternative titles"]} |
A rare malignant germ cell tumor characterized by predominant composition of embryoid bodies consisting of a central core of embryonal carcinoma cells, an amnion-like cavity, and a yolk sac tumor component. The tumor usually occurs as the dominant component of a mixed germ cell tumor, with teratoma being the most common associated element. It may manifest as an abdominal mass or with abdominal pain, menstrual irregularities, or precocious puberty in women, while men typically present with testicular enlargement. Serum alpha-fetoprotein and/or beta-human chorionic gonadotropin can be elevated.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Polyembryoma | c0334518 | 4,072 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=180229 | 2021-01-23T17:05:06 | {"gard": ["9621"], "umls": ["C0334518"]} |
Refractory anemia with ring sideroblasts
Other namesRARS
Refractory anemia with ring sideroblasts is a type of myelodysplastic syndrome. RARS is characterized by 5% or less myeloblasts in bone marrow. RARS is distinguished from refractory anemia by having 15% or more ringed sideroblasts among the erythroid precursors in the bone marrow.[1]
## References[edit]
1. ^ Fedoriw, Yuri. "Pathology of Refractory Anemia With Ring Sideroblasts". Retrieved 28 August 2013.
## External links[edit]
Classification
D
* ICD-O: M9982/3
* v
* t
* e
Myeloid-related hematological malignancy
CFU-GM/
and other granulocytes
CFU-GM
Myelocyte
AML:
* Acute myeloblastic leukemia
* M0
* M1
* M2
* APL/M3
MP
* Chronic neutrophilic leukemia
Monocyte
AML
* AMoL/M5
* Myeloid dendritic cell leukemia
CML
* Philadelphia chromosome
* Accelerated phase chronic myelogenous leukemia
Myelomonocyte
AML
* M4
MD-MP
* Juvenile myelomonocytic leukemia
* Chronic myelomonocytic leukemia
Other
* Histiocytosis
CFU-Baso
AML
* Acute basophilic
CFU-Eos
AML
* Acute eosinophilic
MP
* Chronic eosinophilic leukemia/Hypereosinophilic syndrome
MEP
CFU-Meg
MP
* Essential thrombocytosis
* Acute megakaryoblastic leukemia
CFU-E
AML
* Erythroleukemia/M6
MP
* Polycythemia vera
MD
* Refractory anemia
* Refractory anemia with excess of blasts
* Chromosome 5q deletion syndrome
* Sideroblastic anemia
* Paroxysmal nocturnal hemoglobinuria
* Refractory cytopenia with multilineage dysplasia
CFU-Mast
Mastocytoma
* Mast cell leukemia
* Mast cell sarcoma
* Systemic mastocytosis
Mastocytosis:
* Diffuse cutaneous mastocytosis
* Erythrodermic mastocytosis
* Adult type of generalized eruption of cutaneous mastocytosis
* Urticaria pigmentosa
* Mast cell sarcoma
* Solitary mastocytoma
Systemic mastocytosis
* Xanthelasmoidal mastocytosis
Multiple/unknown
AML
* Acute panmyelosis with myelofibrosis
* Myeloid sarcoma
MP
* Myelofibrosis
* Acute biphenotypic leukaemia
This oncology article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Refractory anemia with ring sideroblasts | c1264195 | 4,073 | wikipedia | https://en.wikipedia.org/wiki/Refractory_anemia_with_ring_sideroblasts | 2021-01-18T18:38:19 | {"gard": ["7644"], "umls": ["C1264195"], "icd-10": ["D46.1"], "orphanet": ["75564"], "wikidata": ["Q16938550"]} |
Brachytelephalangy - dysmorphism - Kallmann syndrome is a developmental anomaly characterized by brachytelephalangy, distinct craniofacial features (prominent square forehead, telecanthus, small nose, malar hypoplasia, smooth philtrum and thin upper lip), and relative to other family members, a short stature. These features may be associated with anosmia and hypogonadotropic hypogonadism (considered as Kallman syndrome ; see this term). Brachytelephalangy - dysmorphism - Kallmann syndrome has been described in a mother and her son and there have been no further descriptions in the literature since 1986.
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Brachytelephalangy-dysmorphism-Kallmann syndrome | c2931421 | 4,074 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1295 | 2021-01-23T18:37:41 | {"mesh": ["C537101"], "omim": ["113480"], "umls": ["C2931421"], "icd-10": ["Q87.0"]} |
Immunotactoid glomerulopathy, also known as glomerulonephritis with organized monoclonal microtubular immunoglobulin deposits (GOMMID), is a very uncommon cause of glomerular disease. It is related to a similar disease known as fibrillary glomerulopathy, which is more common. Both disorders probably result from deposits derived from immunoglobulins, but in most cases the cause is idiopathic (unknown). On electron microscopy, immunotactoid glomerulopathy is characterized by the formation of microtubules which are much larger than the fibrils observed in fibrillary glomerulonephritis (30 to 50 versus 16 to 24 nm in diameter). The signs and symptoms include blood (hematuria) and protein (proteinuria) in the urine, kidney insufficiency and high blood pressure. Both fibrillary glomerulonephritis and immunotactoid glomerulopathy have been associated with hepatitis C virus infection and with malignancy and autoimmune disease. Also, patients with immunotactoid glomerulopathy have a greater risk to have chronic lymphocytic leukemia and B cell lymphomas and should be screened for all of these conditions. Treatment is generally determined by the severity of the kidney problems.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Immunotactoid glomerulopathy | c0268749 | 4,075 | gard | https://rarediseases.info.nih.gov/diseases/12048/immunotactoid-glomerulopathy | 2021-01-18T17:59:48 | {"orphanet": ["97567"], "synonyms": ["Immunotactoid glomerulonephritis"]} |
Diffuse idiopathic skeletal hyperostosis
Other namesForestier's disease, senile ankylosing spondylosis, ankylosing hyperostosis
DISH in an 80 year old female, also with T11 fracture.
SpecialtyRheumatology
Diffuse idiopathic skeletal hyperostosis (DISH) is a condition characterized by abnormal calcification/bone formation (hyperostosis) of the soft tissues surrounding the joints of the spine, and also of the peripheral or appendicular skeleton.[1] In the spine, there is bone formation along the anterior longitudinal ligament and sometimes the posterior longitudinal ligament, which may lead to partial or complete fusion of adjacent vertebrae. The facet and sacroiliac joints tend to be uninvolved. The thoracic spine is the most common level involved.[2] In the peripheral skeleton, DISH manifests as a calcific enthesopathy, with pathologic bone formation at sites where ligaments and tendons attach to bone.
## Contents
* 1 Signs and symptoms
* 2 Cause
* 3 Diagnosis
* 4 Treatment
* 5 See also
* 6 References
* 7 External links
## Signs and symptoms[edit]
The majority of people with DISH are not symptomatic,[3] and the findings are an incidental imaging abnormality.
In some, the x-ray findings may correspond to symptoms of back stiffness with flexion/extension or with mild back pain.[2] Back pain or stiffness may be worse in the morning.[4] Rarely, large anterior cervical spine osteophytes may affect the esophagus or the larynx and cause pain, difficulty swallowing[5][6] or even dyspnea.[7] Similar calcification and ossification may be seen at peripheral entheseal sites, including the shoulder, iliac crest, ischial tuberosity, trochanters of the hip, tibial tuberosities, patellae, and bones of the hands and/or feet.[6]
## Cause[edit]
The exact cause is unknown. Mechanical, dietary factors and use of some medications (e.g. isotretinoin, etretinate, acitretin and other vitamin A derivatives)[8] may be of significance. There is a correlation between these factors but not a cause or effect. The distinctive radiological feature of DISH is the continuous linear calcification along the antero-medial aspect of the thoracic spine. DISH is usually found in people in their 60s and above, and is extremely rare in people in their 30s and 40s. The disease can spread to any joint of the body, affecting the neck, shoulders, ribs, hips, pelvis, knees, ankles, and hands. The disease is not fatal; however, some associated complications can lead to death. Complications may include paralysis, dysphagia (difficulty swallowing), and lung infections.
Although DISH manifests in a similar manner to ankylosing spondylitis, they are separate diseases. Ankylosing spondylitis is a genetic disease with identifiable marks, tends to start showing signs in adolescence or young adulthood, is more likely to affect the lumbar spine, and affects organs. DISH has no indication of a genetic link, is primarily thoracic and does not affect organs other than the lungs, and only indirectly due to the fusion of the rib cage.[9]
Long term treatment of acne with vitamin derived retinoids, such as etretinate[10] and acitretin,[11] have been associated with extraspinal hyperostosis.
## Diagnosis[edit]
DISH is diagnosed by findings on x-ray studies. Radiographs of the spine will show abnormal bone formation (ossification) along the anterior spinal ligament. The disc spaces, facet and sacroiliac joints remain unaffected. Diagnosis requires confluent ossification of at least four contiguous vertebral bodies.[2] Classically, advanced disease may have "melted candle wax" appearance along the spine on radiographic studies.[12] In some cases, DISH may be manifested as ossification, or enthesis, in other parts of the skeleton.
The calcification and ossification is most common on the right side of the spine. In people with dextrocardia and situs inversus this calcification occurs on the left side.[9]
* Examples of DISH
* Confluent ossification of multiple contiguous vertebral bodies in diffuse idiopathic skeletal hyperostosis (DISH)
* "Melted candle wax" appearance of calcification and ossification in diffuse idiopathic skeletal hyperostosis (DISH). Note the preponderance on the patient's left side (right side of image).
* Ectopic calcification and new bone formation in diffuse idiopathic skeletal hyperostosis (DISH)
* Ossification of the posterior longitudinal ligament in DISH
## Treatment[edit]
There is limited scientific evidence for the treatment for symptomatic DISH.
Symptoms of pain and stiffness may be treated with conservative measures, analgesic medications (such as non-steroidal anti-inflammatory drugs), and physical therapy.[13]
In extraordinary cases where calcification or osteophyte formation is causing severe and focal symptoms, such as difficulty swallowing or nerve impingement, surgical intervention may be pursued.[14]
## See also[edit]
* Ankylosing spondylitis
* Enthesitis
* Osteoarthritis
* Retinoids
## References[edit]
1. ^ Resnick, D.; Shaul, S. R.; Robins, J. M. (June 1975). "Diffuse idiopathic skeletal hyperostosis (DISH): Forestier's disease with extraspinal manifestations". Radiology. 115 (3): 513–524. doi:10.1148/15.3.513. ISSN 0033-8419. PMID 1129458.
2. ^ a b c Sarwark, John, ed. (2010). "Diffuse Idiopathic Skeletal Hyperostosis". Essentials of Musculoskeletal Care (4 ed.). Rosemont, IL: American Academy of Orthopaedic Surgeons. ISBN 978-0-89203-579-3.
3. ^ Mader, Reuven; Verlaan, Jorrit-Jan; Buskila, Dan (November 2013). "Diffuse idiopathic skeletal hyperostosis: clinical features and pathogenic mechanisms". Nature Reviews Rheumatology. 9 (12): 741–750. doi:10.1038/nrrheum.2013.165. ISSN 1759-4804. PMID 24189840.
4. ^ Resnick, Donald; Shapiro, Robert F.; Wiesner, Kenneth B.; Niwayama, Gen; Utsinger, Peter D.; Shaul, Stephen R. (1978). "Diffuse idiopathic skeletal hyperostosis (DISH) [ankylosing hyperostosis of forestier and Rotes-Querol]". Seminars in Arthritis and Rheumatism. 7 (3): 153–187. doi:10.1016/0049-0172(78)90036-7. PMID 341323.
5. ^ Utsinger PD (August 1985). "Diffuse idiopathic skeletal hyperostosis". Clinics in Rheumatic Diseases. 11 (2): 325–51. PMID 3899489.
6. ^ a b Mata S, Fortin PR, Fitzcharles MA, Starr MR, Joseph L, Watts CS, Gore B, Rosenberg E, Chhem RK, Esdaile JM (March 1997). "A controlled study of diffuse idiopathic skeletal hyperostosis. Clinical features and functional status". Medicine. 76 (2): 104–17. doi:10.1097/00005792-199703000-00003. PMID 9100738.
7. ^ Psychogios, Georgios; Jering, Monika; Zenk, Johannes (2018). "Cervical Hyperostosis Leading to Dyspnea, Aspiration and Dysphagia: Strategies to Improve Patient Management". Frontiers in Surgery. 5: 33. doi:10.3389/fsurg.2018.00033. ISSN 2296-875X. PMC 5928235. PMID 29740589.
8. ^ Nascimento; et al. (2014). "Diffuse idiopathic skeletal hyperostosis: A review". Surg Neurol Int. 5 (Suppl 3): S122–S125. doi:10.4103/2152-7806.130675. PMC 4023007. PMID 24843807.
9. ^ a b Forestier J, Lagier R (January 1971). "Ankylosing hyperostosis of the spine". Clinical Orthopaedics and Related Research. 74: 65–83. doi:10.1097/00003086-197101000-00009. PMID 4993095.
10. ^ DiGiovanna JJ, Helfgott RK, Gerber LH, Peck GL (November 1986). "Extraspinal tendon and ligament calcification associated with long-term therapy with etretinate". The New England Journal of Medicine. 315 (19): 1177–82. doi:10.1056/NEJM198611063151901. PMID 3463863.
11. ^ DiGiovanna JJ (November 2001). "Isotretinoin effects on bone". Journal of the American Academy of Dermatology. 45 (5): S176–82. doi:10.1067/mjd.2001.113721. PMID 11606950.
12. ^ Waldron, T. "Paleopathology". Cambridge University Press, 2009, p. 73.
13. ^ Al-Herz A, Snip JP, Clark B, Esdaile JM (February 2008). "Exercise therapy for patients with diffuse idiopathic skeletal hyperostosis". Clinical Rheumatology. 27 (2): 207–10. doi:10.1007/s10067-007-0693-z. PMID 17885726.
14. ^ Castellano DM, Sinacori JT, Karakla DW (February 2006). "Stridor and dysphagia in diffuse idiopathic skeletal hyperostosis (DISH)". The Laryngoscope. 116 (2): 341–4. doi:10.1097/01.mlg.0000197936.48414.fa. ISSN 0023-852X. PMID 16467731.
## External links[edit]
Classification
D
* ICD-10: M48.1
* ICD-9-CM: 721.6
* OMIM: 106400
* MeSH: D004057
* DiseasesDB: 4932
External resources
* eMedicine: article/1258514 article/388973
* Patient UK: Diffuse idiopathic skeletal hyperostosis
Wikimedia Commons has media related to Diffuse idiopathic skeletal hyperostosis.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Diffuse idiopathic skeletal hyperostosis | c0020498 | 4,076 | wikipedia | https://en.wikipedia.org/wiki/Diffuse_idiopathic_skeletal_hyperostosis | 2021-01-18T18:44:43 | {"gard": ["6460"], "mesh": ["D004057"], "omim": ["106400"], "umls": ["C1862851"], "icd-9": ["721.6"], "icd-10": ["M48.1"], "orphanet": ["2206"], "synonyms": [], "wikidata": ["Q742762"]} |
A rare X-linked syndromic intellectual disability characterized by global development delay, postnatal growth retardation leading to short stature, facial dysmorphism, short hands with tapering fingers and progressive skeletal abnormalities including kyphoscoliosis and pectus carinatum/excavatum. Intellectual disability ranges from mild to severe.
## Epidemiology
The exact prevalence is not known but is estimated to be 1/50,000 to 1/100,000. Male patients are generally moderately to severely affected while most female carriers have mild features.
## Clinical description
Severe clinical presentation was reported in the first male patients described. Following the wide application of molecular genetic testing, the phenotype is now recognized as very variable. Affected newborn males often show hypotonia and hyperlaxity of joints with normal growth parameters. Growth retardation and global developmental delay become visible in the first years of life. The facial dysmorphism visible in late childhood and adulthood include prominent forehead, hypertelorism, down-slanting palpebral fissures, epicanthic folds, prominent ears, wide mouth, thick lips with everted lower vermilion, thick nasal alae, and septum. Oral findings include a high narrow palate, a midline lingual furrow, hypodontia, and peg-shaped incisors. Microcephaly is common. Hands are short, soft, and fleshy with skin/joint laxity and tapering fingers. Full and fleshy forearms can be present in childhood. Skeletal abnormalities appear gradually and may include spinal kyphoscoliosis (often progressive) and pectus carinatum/excavatum. Cognitive impairment is variable in severity. Other neurological findings may include epilepsy, progressive paraplegia and stimulus-induced drop attacks (SIDAs). Brain abnormalities have been reported but without a consistent pattern. A happy personality is common although behavioral abnormalities can be present. Other less frequent manifestations are sensorineural hearing loss and heart anomalies. Final stature is usually below the third percentile.
## Etiology
Coffin-Lowry syndrome (CLS) is caused by pathogenic variations in the RPS6KA3 gene (Xp22.2-p22.1), which encodes ribosomal protein S6 kinase alpha-3, a growth-factor-regulated protein kinase.
## Diagnostic methods
Diagnosis is suspected on clinical presentation and confirmed by the following genetic tests: sequencing of RPS6KA3 or Intellectual Disability-related Next Generation Sequencing panel that includes this gene. If sequencing results are negative, multiplex ligation-dependent probe amplification analysis should be performed in order to assess deletions or duplications.
## Differential diagnosis
Differential diagnosis includes Alpha-thalassemia-X-linked intellectual disability (ATRX) syndrome, Borjeson-Forssman-Lehmann syndrome, FG syndrome type 1, Williams syndrome and Pitt-Hopkins syndrome.
## Antenatal diagnosis
Prenatal genetic counseling should be offered to parents of patients who are hemizygotes for the pathogenic variant to discuss genetic risk and reproductive options.
## Genetic counseling
Coffin-Lowry syndrome is an X-linked dominant disorder. About two-thirds of cases occur de novo. The risk of recurrence for the sibs of a proband depend on the mother's genotype. If the mother is a carrier of the pathogenic variation, the risk of transmitting the variant in subsequent pregnancies is 50%. Male offspring inheriting the mutation are affected, and female carriers can be unaffected or show milder phenotypes (Symptomatic form of Coffin-Lowry syndrome in female carriers). If the mother is not a carrier, the risk of recurrence is very low and linked to the possibility of germinal mosaicism.
## Management and treatment
Management requires an early multidisciplinary approach. Kyphoscoliosis/spinal stenosis and SIDAs should be recognized and treated to avoid secondary complications.
## Prognosis
Prognosis is poor and depends on the severity of the disease. Life span is reported to be reduced.
* European Reference Network
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Coffin-Lowry syndrome | c0265252 | 4,077 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=192 | 2021-01-23T17:30:28 | {"gard": ["6123"], "mesh": ["D038921"], "omim": ["303600"], "umls": ["C0265252"], "icd-10": ["Q87.0"], "synonyms": ["CLS"]} |
A number sign (#) is used with this entry because progressive microcephaly with seizures and cerebral and cerebellar atrophy (MSCCA) is caused by compound heterozygous mutation in the QARS gene (QARS1; 603727) on chromosome 3p21.
Description
Progressive microcephaly with seizures and cerebral and cerebellar atrophy is a severe autosomal recessive neurodevelopmental and neurodegenerative disorder with onset in the first days or months of life. Patients are born with microcephaly and soon develop intractable seizures, resulting in profoundly delayed development and hypotonia (summary by Zhang et al., 2014).
Clinical Features
Zhang et al. (2014) reported 4 children from 2 unrelated families who presented at birth with sloping forehead and microcephaly. All showed profound developmental delay and progressive microcephaly (in 1 patient, -10 SD) in the first years of life. Three patients developed severe intractable seizures in the first days of life, including status epilepticus in 1 patient and migrating partial seizures in another. The fourth patient developed recurrent intractable seizures at age 1 month. In 1 family, 2 brothers had episodes of agitation associated with pneumonia and rhabdomyolysis. Other more variable features included cortical visual impairment, lack of visual contact, loss of visual contact after onset of seizures, hypotonia, and hyperreflexia. Dysmorphic features were also variable and included bitemporal narrowing, epicanthal folds, broad flat nasal bridge, hypotelorism, and low-set, posteriorly rotated ears. Brain imaging showed apparent neurodegeneration, hypomyelination or delayed myelination, thin corpus callosum, enlarged cerebral ventricles, and small cerebellar vermis. Two brothers, who had more severe microcephaly, also had a simplified gyral pattern on brain imaging.
Inheritance
The transmission pattern of MSCCA in the family reported by Zhang et al. (2014) was consistent with autosomal recessive inheritance.
Molecular Genetics
In 4 patients from 2 unrelated families with MSCCA, Zhang et al. (2014) identified compound heterozygous mutations in the QARS gene (603727.0001-603727.0004). The mutations were found by whole-exome sequencing. Studies in patient cells and expression of recombinant variants in E. coli showed that all 4 mutations caused a severe loss of QARS catalytic activity, consistent with a loss-of-function effect. Homozygous loss of qars in zebrafish caused decreased brain and eye size and extensive cell death in the brain. The results suggested that QARS is essential for normal brain development.
INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Microcephaly, progressive (-3 to -10 SD) \- Sloping forehead \- Bitemporal narrowing Ears \- Low-set ears \- Posteriorly rotated ears Eyes \- Hypotelorism \- Epicanthal folds \- Lack of visual contact Nose \- Broad, flat nasal bridge MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Delayed psychomotor development, profound \- Seizures, severe, intractable \- Status epilepticus \- Partial migrating seizures seen on EEG (in some patients) \- Hypotonia \- Hyperreflexia (in some patients) \- Enlarged ventricles \- Cerebral atrophy \- Thin corpus callosum \- Atrophy of the cerebellar vermis \- Hypomyelination \- Simplified gyral pattern (in some patients) MISCELLANEOUS \- Onset at birth or early infancy \- Progressive disorder \- Dysmorphic features are variable \- Two unrelated families have been reported (last curated April 2014) MOLECULAR BASIS \- Caused by mutation in the glutaminyl-tRNA synthetase gene (QARS, 603727.0001 ) ▲ Close
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*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| MICROCEPHALY, PROGRESSIVE, WITH SEIZURES AND CEREBRAL AND CEREBELLAR ATROPHY | c4014239 | 4,078 | omim | https://www.omim.org/entry/615760 | 2019-09-22T15:51:04 | {"omim": ["615760"], "orphanet": ["404437"], "synonyms": []} |
For a general phenotypic description and a discussion of genetic heterogeneity of vesicoureteral reflux, see VUR1 (193000).
Clinical Features
Briggs et al. (2010) ascertained a large sample of children with vesicoureteral reflux, including 151 girls and 70 boys from 98 Caucasian families. Among the 98 probands, urinary tract infection was the most common presentation (75%), occurring predominantly in girls (90%). Prenatal hydronephrosis was the mode of presentation in 13% of probands, occurring more commonly in boys (69%). Four percent of patients presented with voiding problems or abdominal pain, and 8% had a parental history of the disorder. Most were younger than 5 years of age.
Mapping
By genomewide linkage analysis of 98 Caucasian families with 2 or more children with vesicoureteral reflux, including 150 affected sib pairs, Briggs et al. (2010) found significant linkage to chromosome 5, with a multipoint lod score of 4.46 at 98.58 cM from pter (nearest marker, SNP rs1501656).
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| VESICOURETERAL REFLUX 4 | c3280439 | 4,079 | omim | https://www.omim.org/entry/614317 | 2019-09-22T15:55:42 | {"doid": ["9620"], "omim": ["614317"], "orphanet": ["289365"], "synonyms": ["Familial VUR"]} |
A number sign (#) is used with this entry because of evidence that Ehlers-Danlos syndrome dermatosparaxis type (EDSDERMS) is caused by mutation in the gene encoding the procollagen protease ADAMTS2 (604539) on chromosome 5q35.
Description
Dermatosparaxis (meaning 'tearing of skin') is an autosomal recessive disorder of connective tissue resulting from deficiency of procollagen peptidase, an enzyme that aids in the processing of type I procollagen. The disorder and the responsible biochemical defect was first observed in cattle (Lapiere et al., 1971). Lapiere and Nusgens (1993) reviewed the discovery of dermatosparaxis in cattle, the elucidation of the disorder, its occurrence in other animals, and the delayed recognition of the disorder in the human.
Clinical Features
Lichtenstein et al. (1973) reported 2 patients with severe joint hyperextensibility and mild stretchability and bruisability of the skin similar to that seen in dermatosparaxis in cattle. Other clinical features in the patients included short stature, epicanthal folds, depressed nasal bridge, and micrognathia. Cultured fibroblasts showed decreased activity of procollagen peptidase. Lichtenstein et al. (1973) concluded that the clinical manifestations were related to impaired enzymatic conversion of procollagen to collagen due to an enzyme defect.
Nusgens et al. (1992) reported an affected 2-year-old girl with dysmorphic facial features and soft skin. She had large-appearing eyes and thickened eyelids, small stature, and lack of ossification of cranial bones. Easy bruising was noted at the end of the first year, and she developed a left occipital fracture with massive hematoma following a minor fall. EDS was suspected on the basis of blue sclerae and soft, velvety, hyperextensible skin. She also had marked bruising and open wounds following minor trauma, and suturing was not possible due to the extreme fragility of the skin. Surgical removal of a large umbilical hernia was performed at the age of 20 months; the excised skin could be torn by hand. The parents were unrelated and phenotypically normal. Electron microscopy of skin samples demonstrated altered polymers seen as hieroglyphic pictures, accumulation of type I p-N-alpha-1 and p-N-alpha-2 polypeptides in the dermis, and absence of processing of these polypeptides in fibroblast cultures, similar to that observed in animal models of dermatosparaxis. The authors postulated a deficiency of procollagen I N-proteinase. Nusgens et al. (1992) noted that the clinical manifestations of EDS VIIC were different from those of EDS VIIA (130060) and VIIB, in which the clinical picture is dominated by joint laxity and subluxations. The skin fragility EDS VIIC can be as severe as that observed in the dermatosparactic calves. Thus, the clinical picture is that of dermatosparaxis and not that of arthrochalasis multiplex congenita.
Wertelecki et al. (1992) provided clinical details of the 2 patients reported by Smith et al. (1992). The authors emphasized the large fontanels and wide sagittal and metopic sutures, blue sclerae, micrognathia, and umbilical hernia. Electron microscopic examination of the skin showed collagen sheets rather than fibrils, and characteristic distortions resembling hieroglyphics.
Petty et al. (1993) reported a patient with dermatosparaxis, emphasizing marked skin fragility and laxity, blue sclerae, increased bruisability, micrognathia, umbilical hernia, and growth retardation. The patient was a male infant born at 35 weeks' gestation after premature rupture of the membranes. He presented at birth with large full-thickness groin fissures, large fontanels, umbilical hernia, and dental laminal cysts. The diagnosis of dermatosparaxis was made by electron microscopic findings consisting of characteristic small, irregular, and circular collagen fibers in the skin.
Reardon et al. (1995) described a case of dermatosparaxis in a 15-year-old girl and noted that 3 previously reported patients with this disorder died before the age of 3 years. Easy bruising, severe skin laxity and fragility, extensive scar formation, and joint laxity were the main clinical manifestations in their patient. Her soft, doughy skin was easily stretchable, but did not recoil. Electron microscopy showed typical hieroglyphic figures upon cross-section of collagen fibrils.
Malfait et al. (2004) reported a 5-year-old boy with dermatosparaxis-type EDS and provided follow-up of 2 previously reported patients at the ages of 7 and 12 years. All had characteristic facial features, including large fontanels in infancy, puffy eyelids, epicanthal folds, downslanting palpebral fissures, and micrognathia. Skin was soft, doughy, and redundant. They had short limbs, hands, feet, fingers, and toes. Two patients had spontaneous bladder rupture and 1 had rupture of the diaphragm following vomiting. Orofacial features included gingival hyperplasia, hypodontia, microdontia, and tooth discoloration. Deciduous dentition showed abnormal morphology of the molars and enamel attrition. Skin bruising, skin tearing, and joint hypermobility increased with age.
Colige et al. (2004) reported a boy with EDS dermatosparaxis type confirmed by genetic analysis (604539.0003). At birth, there was rupture of the umbilical cord and generalized edema with swollen eyelids. Craniofacial features included short forehead, flat supraorbital ridges, broad nasal root, wide nares, large mouth, micrognathia, hypodontia, gingival hyperplasia, and hypertrichosis. He had short hands, arms, and legs. Other features included joint hypermobility, easy bruising, fragile skin, and blue sclera. In vitro studies showed impaired aminocollagen processing.
Bar-Yosef et al. (2008) reported an infant of Ashkenazi Jewish origin with EDS dermatosparaxis type confirmed by genetic analysis (604539.0001). He was delivered preterm by cesarean due to fetal heart decelerations and with multiple congenital nontraumatic skull fractures and intracranial hemorrhage. Eight days prior to delivery the mother was admitted to the hospital with premature rupture of the membranes. He died at age 145 days due to sepsis. Family history indicated that the paternal and maternal grandparents originated in Belarus.
Van Damme et al. (2016) reported 5 new patients from 4 unrelated families with the dermatosparaxis type of EDS, bringing the total of molecularly characterized patients to 15. Three of these patients displayed a phenotype that was milder than previously reported. Among the 5 newly reported patients, only 1 had preterm birth, and none exhibited severe neonatal complications. All had a large fontanel and blue sclerae, but only 1 had eyelid edema and blepharochalasis, which was a common feature in previously reported cases. Umbilical hernia was present in all 5 of the newly reported patients and in 14 of 15 patients overall. Van Damme et al. (2016) suggested updated diagnostic criteria, including major diagnostic criteria of severe skin fragility; sagging, redundant skin; easy bruising; and a typical facial gestalt that is congenital and/or postnatal and progressive, with swelling of the periorbital soft tissue, blue sclerae, downslanting palpebral fissures, epicanthal folds, micrognathia, delayed fontanel closure, and dental anomalies. Suggested minor diagnostic criteria included postnatal growth restriction, short limbs with short hands and feet, joint hypermobility, umbilical hernia, and congenital or postnatal visceral and vascular fragility. The authors noted that arterial rupture and aortic dilatation had not been reported.
Pathogenesis
Minor et al. (1986) examined cell lines from 3 new Ehlers-Danlos syndrome variants showing decreased processing of procollagen. In 1, a structural defect in the alpha-2(I) chain was demonstrated, consistent with EDS VIIB. In the other 2, the collagen chains appeared to be normal, and procollagen N-proteinase activity appeared to be decreased.
Smith et al. (1992) identified possible humans case of procollagen protease deficiency on the basis of electron microscopic changes showing a 'hieroglyphic' appearance of the collagen identical to that seen in cattle with dermatosparaxis (Lapiere et al., 1971).
Smith et al. (1992) identified 2 children with soft, lax, and fragile skin which on transmission electron microscopy was found to contain twisted, ribbon-like collagen fibrils characteristic of dermatosparaxis. The skin from 1 child was shown to contain collagen precursors with amino-terminal extensions. Cultured fibroblasts from both children failed to cleave the amino-terminal propeptides from both alpha chains of type I procollagen. Extracts of normal cells cleaved normally the type I procollagen synthesized by cells from both children, demonstrating that the enzyme, not the substrate, was defective.
Molecular Genetics
Colige et al. (1999) identified mutations in the ADAMTS2 gene causing EDS type VIIC in the 6 known affected individuals and also in 1 strain of dermatosparactic calf. Five of the individuals with EDS type VIIC were homozygous for a gln225-to-ter substitution (604539.0001). Four of these 5 patients were homozygous at 3 downstream polymorphic sites. The sixth patient was homozygous for a trp795-to-ter substitution (604539.0002). In the dermatosparactic calf, the mutation was a 17-bp deletion that changed the reading frame of the message.
In 2 unrelated patients with EDS type VIIC, Colige et al. (2004) identified homozygosity or compound heterozygosity for mutations in the ADAMTS2 gene (see, e.g., 604539.0003).
Van Damme et al. (2016) identified 3 novel homozygous loss-of-function mutations and 1 compound heterozygous mutation in ADAMTS2 in 5 patients from 4 unrelated families with dermatosparaxis-type EDS.
Nomenclature
Nusgens et al. (1992) referred to this disorder as Ehlers-Danlos syndrome type VIIC, reserving EDS VIIA and EDS VIIB for the disorders resulting from defects in the procollagen alpha-1 and alpha-2 polypeptides, respectively. McKusick (1979) had previously used the designations VII-A1 and VII-A2 for VII-A and VII-B, and VII-B instead of VII-C for deficiency of procollagen peptidase.
Animal Model
EDS type VIIC has been demonstrated in cattle (Lapiere et al., 1971), sheep (Fjolstad and Helle, 1974), and the Himalayan cat (Counts et al., 1980; Holbrook et al., 1980).
INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature HEAD & NECK Head \- Large anterior fontanel \- Delayed closure anterior fontanel Face \- Micrognathia \- Recurrent mandibular subluxations Eyes \- Blue sclerae \- Epicanthal folds \- Blepharochalasis \- Downslanting palpebral fissures \- Puffy eyelids \- Myopia Mouth \- Frontal open bite \- Gingival hyperplasia \- Gingival hyperkeratosis \- Gingival bleeding \- Excessive buccal mucosa \- Prominent lips Teeth \- Hypodontia \- Tooth discoloration \- Deciduous molars show abnormal morphology \- Deciduous dentition shows enamel attrition RESPIRATORY Lung \- Neonatal pneumothorax ABDOMEN External Features \- Umbilical hernia GENITOURINARY External Genitalia (Male) \- Inguinal hernia SKELETAL \- Joint laxity, marked \- Osteopenia Limbs \- Short limbs Hands \- Short fingers Feet \- Short toes SKIN, NAILS, & HAIR Skin \- Skin fragility \- Easy bruisability \- Soft, doughy skin \- Sagging, redundant skin \- Normal wound healing Electron Microscopy \- Collagen fibrils show hieroglyphic pattern Hair \- Hirsutism, mild NEUROLOGIC Central Nervous System \- Delayed motor milestones PRENATAL MANIFESTATIONS Delivery \- Premature rupture of membranes \- Premature delivery MISCELLANEOUS \- Internal organ rupture may occur MOLECULAR BASIS \- Caused by mutations in the procollagen I N-proteinase gene (ADAMTS2, 604539.0001 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| EHLERS-DANLOS SYNDROME, DERMATOSPARAXIS TYPE | c2700425 | 4,080 | omim | https://www.omim.org/entry/225410 | 2019-09-22T16:28:22 | {"mesh": ["C567527"], "omim": ["225410"], "orphanet": ["1901"], "synonyms": ["Alternative titles", "DERMATOSPARAXIS", "EHLERS-DANLOS SYNDROME, TYPE VII, AUTOSOMAL RECESSIVE", "EDS VIIC", "EDS7C"]} |
Xeroderma pigmentosum/Cockayne syndrome complex (XP/CS complex) is characterized by the cutaneous features of xeroderma pigmentosum (XP) (see this term) together with the systemic and neurological features of Cockayne syndrome (CS; see this term).
## Epidemiology
Less than 30 cases have been described to date.
## Clinical description
The disease manifests during infancy. Patients present with cutaneous UV-sensitive lesions that generally develop into skin cancer, and also develop characteristic CS manifestations such as microcephaly, hydrocephalus, cachexia, premature aging, dwarfism, skin atrophy, arteriosclerosis, progressive hearing loss, cognitive deficit, spasticity, ataxia, pigmentary retinopathy and optic atrophy. In contrast to the neurological abnormalities of XP which are predominantly secondary to neuronal degeneration, in XP/CS complex, dysmyelination typical of CS is observed.
## Etiology
Affected individuals have mutations in one of three XP genes: ERCC3 (2q21), ERCC2 (19q13.3), or ERCC5 (13q22-q34). Recently, one patient with XP/CS complex and additional features of Fanconi anemia (see this term) was reported with a mutation in the ERCC4 gene (16p13.3).
## Genetic counseling
Transmission is autosomal recessive and genetic counseling is possible.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Xeroderma pigmentosum-Cockayne syndrome complex | c0268138 | 4,081 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=220295 | 2021-01-23T19:12:06 | {"mesh": ["C562591"], "omim": ["278730", "278760", "278780", "610651"], "icd-10": ["Q82.1", "Q87.1"], "synonyms": ["XP/CS complex"]} |
Cultured cells of many species infected with RNA or DNA viruses have been shown to produce not only standard reference virions but also defective virus particles which interfere with the replication of their parental infectious viruses. This phenomenon is known as homologous viral interference and the substances produced are referred to as defective interfering (DI) particles. It has been postulated that these are involved in overcoming viral infections. Kang et al. (1981) studied the role of the host cell in the induction of DI particles. In human-mouse somatic cell hybrids, they found that generation of DI particles was correlated with the absence or presence of chromosome 16. The human parental cell line did not synthesize DI particles when infected with vesicular stomatitis virus and the hybrid cells also did not, when chromosome 16 was present.
Immunology \- Homologous viral interference Lab \- Defective virus particles produced Inheritance \- Autosomal dominant ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| DEFECTIVE INTERFERING PARTICLE INDUCTION, CONTROL OF | c1852265 | 4,082 | omim | https://www.omim.org/entry/125260 | 2019-09-22T16:42:31 | {"omim": ["125260"], "synonyms": ["Alternative titles", "DIPI, CONTROL OF", "HOMOLOGOUS VIRAL INTERFERENCE", "VESICULAR STOMATITIS VIRUS DEFECTIVE INTERFERING PARTICLE REPRESSOR"]} |
Familial osteodysplasia, Anderson type is a rare, genetic dysostosis disorder characterized by craniofacial bone abnormalities (i.e. midface hypoplasia, broad, flat nasal bridge, narrow, thin prognathic mandible with pointed chin, malocclusion, partial dental agenesis) associated with additional osseous anomalies, including scoliosis, calvarial thinning, pointed spinous processes, clinodactyly and abnormal phalanges. Elevated erythrocyte sedimentation rate, hyperuricemia and hypertension have also been reported. There have been no further descriptions in the literature since 1982.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Familial osteodysplasia, Anderson type | c1850186 | 4,083 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2769 | 2021-01-23T18:45:32 | {"gard": ["4136"], "mesh": ["C564923"], "omim": ["259250"], "umls": ["C1850186"]} |
This syndrome is characterised by the association of acanthosis nigricans, insulin resistance, severe muscle cramps and acral hypertrophy.
## Epidemiology
At least five cases have been described in the literature so far.
## Clinical description
Enlargement of the kidneys was also reported in some cases.
## Genetic counseling
Transmission is autosomal recessive.
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Acanthosis nigricans-insulin resistance-muscle cramps-acral enlargement syndrome | c1860215 | 4,084 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=90301 | 2021-01-23T18:55:54 | {"gard": ["453"], "mesh": ["C536000"], "omim": ["200170"]} |
Opitz G/BBB syndrome is a genetic condition that causes several abnormalities along the midline of the body. "G/BBB" represents the first letters of the last names of the families first diagnosed with this disorder and "Opitz" is the last name of the doctor who first described the signs and symptoms. There are two forms of Opitz G/BBB syndrome, X-linked Opitz G/BBB syndrome and autosomal dominant Opitz G/BBB syndrome. The two forms are distinguished by their genetic causes and patterns of inheritance. The signs and symptoms of the two forms are generally the same.
Nearly everyone with Opitz G/BBB syndrome has wide-spaced eyes (ocular hypertelorism). Affected individuals commonly have defects of the voice box (larynx), windpipe (trachea), or esophagus. These throat abnormalities can cause difficulty swallowing or breathing, in some cases resulting in recurrent pneumonia or life-threatening breathing problems. A common defect is a gap between the trachea and esophagus (laryngeal cleft) that allows food or fluids to enter the airway. The cleft can vary in size, and infants may struggle to breathe when feeding. Most males with Opitz G/BBB syndrome have genital abnormalities such as the urethra opening on the underside of the penis (hypospadias), undescended testes (cryptorchidism), an underdeveloped scrotum, or a scrotum divided into two lobes (bifid scrotum). These genital abnormalities can lead to problems in the urinary tract.
Mild intellectual disability and developmental delay occur in about 50 percent of people with Opitz G/BBB syndrome. Affected individuals have delayed motor skills, such as walking, speech delay, and learning difficulties. Some people with Opitz G/BBB syndrome have features of autistic spectrum disorders, which are characterized by impaired communication and socialization skills. About half of affected individuals also have an opening in the lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate). Some have cleft palate without cleft lip. Less common features of Opitz G/BBB syndrome, affecting less than half of people with this disorder, include minor heart defects, an obstruction of the anal opening (imperforate anus), and brain defects such as a small or absent connection between the left and right halves of the brain (corpus callosum). Distinct facial features that may be seen in this disorder include a prominent forehead, widow's peak hairline, flat nasal bridge, thin upper lip, and low-set ears. These features vary among affected individuals, even within the same family.
## Frequency
X-linked Opitz G/BBB syndrome is thought to affect 1 in 10,000 to 50,000 males, although it is likely that this condition is underdiagnosed.
The incidence of autosomal dominant Opitz G/BBB syndrome is unknown. It is part of a larger condition known as 22q11.2 deletion syndrome, which is estimated to affect 1 in 4,000 people.
## Causes
X-linked Opitz G/BBB syndrome is caused by mutations in the MID1 gene. The MID1 gene provides instructions for making a protein called midline-1. This protein attaches (binds) to microtubules, which are rigid, hollow fibers that make up the cell's structural framework (the cytoskeleton). Microtubules help cells maintain their shape, assist in the process of cell division, and are essential for the movement of cells (cell migration). Midline-1 assists in recycling certain proteins that need to be reused instead of broken down. MID1 gene mutations lead to a decrease in midline-1 function, which prevents protein recycling. The resulting accumulation of proteins impairs microtubule function, leading to problems with cell division and migration. It is unclear how these changes disrupt normal development and cause the signs and symptoms of Opitz G/BBB syndrome.
Autosomal dominant Opitz G/BBB syndrome is caused by changes in chromosome 22. Some affected individuals have a deletion of a small piece of chromosome 22, specifically at an area of the chromosome designated 22q11.2. Because this same region is deleted in another condition called 22q11.2 deletion syndrome, researchers often consider Opitz/GBBB syndrome caused by this genetic change to be a form of 22q11.2 deletion syndrome. It is not known which of the deleted genes contribute to the signs and symptoms of Opitz G/BBB syndrome.
In other people, autosomal dominant Opitz/GBBB syndrome is caused by a mutation in the SPECC1L gene, which is near the 22q11.2 region but is not in the area that is typically deleted in other individuals with autosomal dominant Opitz G/BBB syndrome or 22q11.2 deletion syndrome. The SPECC1L gene provides instructions for making a protein called cytospin-A. This protein interacts with components of the cytoskeleton and stabilizes microtubules, which is necessary for these fibers to regulate various cell processes including the movement of cells to their proper location (cell migration). Cytospin-A is particularly involved in the migration of cells that will form the facial features. Mutations in the SPECC1L gene result in the production of a protein with a decreased ability to interact with components of the cytoskeleton. As a result, microtubules are disorganized and cells have trouble migrating to their proper location. Because the SPECC1L gene plays a role in facial development, mutations in this gene likely account for the cleft lip and palate seen in some individuals with Opitz G/BBB syndrome, but it is unclear how SPECC1L gene mutations cause the other features of this disorder.
Some people with Opitz G/BBB syndrome do not have any of the genetic changes described above. The cause of the condition in these individuals is unknown.
### Learn more about the genes and chromosome associated with Opitz G/BBB syndrome
* MID1
* SPECC1L
* chromosome 22
## Inheritance Pattern
When caused by mutations in the MID1 gene, Opitz G/BBB syndrome has an X-linked pattern of inheritance. It is considered X-linked because the MID1 gene is located on the X chromosome, one of the two sex chromosomes in each cell. In males, who have only one X chromosome, a mutation in the only copy of the gene in each cell is sufficient to cause the condition. In females, who have two copies of the X chromosome, one altered copy of the gene in each cell can lead to less severe features of the condition or may cause no symptoms at all. Because it is unlikely that females will have two altered copies of the MID1 gene, females with X-linked Opitz G/BBB syndrome typically have hypertelorism as the only sign of the disorder. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.
Rarely, Opitz G/BBB syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. These cases are caused by a mutation in the SPECC1L gene or by a deletion of genetic material from one copy of chromosome 22 in each cell. Males and females with autosomal dominant Opitz G/BBB syndrome usually have the same severity of symptoms.
In both types of Opitz G/BBB syndrome, some affected people inherit the genetic change from an affected parent. Other cases may result from new mutations. These cases occur in people with no history of the disorder in their family.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
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*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Opitz G/BBB syndrome | c2936904 | 4,085 | medlineplus | https://medlineplus.gov/genetics/condition/opitz-g-bbb-syndrome/ | 2021-01-27T08:24:58 | {"gard": ["10299", "193"], "mesh": ["C567932"], "omim": ["300000", "145410"], "synonyms": []} |
A number sign (#) is used with this entry because ACTN3 deficiency is caused by a homozygous nonsense polymorphism in the ACTN3 gene (102574) on chromosome 11q13.
Description
Approximately 16% of the world population is predicted to have congenital deficiency of alpha-actinin-3 based on a common nonsense polymorphism in the ACTN3 gene. Expression of alpha-actinin-3 is limited to a subset of type 2 (fast) fibers. No disease phenotype is associated with this deficiency (North et al., 1999).
Clinical Features
Although ACTN3 deficiency is not associated with a disease phenotype, there are some reports that ACTN3 genotype is associated with athletic performance, including sprinting and endurance; see MOLECULAR GENETICS.
Molecular Genetics
### ACTN3 Deficiency
North et al. (1999) identified a common nonsense mutation in ACTN3, arg577-to-ter (R577X; 102574.0001; rs1815739), in the general population in many ethnic groups. The R577X mutation had an allele frequency ranging from 0.22 +/- 0.05 to 0.52 +/- 0.04 in ethnic populations from Asia, the Americas, Australasia, Africa, and Europe. Approximately 16% of the world population is predicted to have congenital deficiency of alpha-actinin-3. No disease phenotype is associated with this deficiency. North et al. (1999) concluded that other factors likely compensate for the absence of alpha-actinin-3 at the Z lines of skeletal muscle fast fibers. These results demonstrated that ACTN3 is not an essential gene, and suggested that absence of a structural protein caused by homozygosity for a null mutation cannot be assumed to be disease-related without additional family and population data.
### Sprinting Performance
Yang et al. (2003) demonstrated highly significant associations between ACTN3 genotype and athletic performance. Both male and female elite sprint athletes had significantly higher frequencies of the 577R allele than did controls. This suggested that the presence of alpha-actinin-3 has a beneficial effect on the function of skeletal muscle in generating forceful contractions at high velocity, and provides an evolutionary advantage because of increased sprint performance. There is also a genotype effect in female sprint and endurance athletes, with higher than expected numbers of R577X heterozygotes among sprint athletes and lower than expected numbers among endurance athletes. The lack of a similar effect in males suggested that the ACTN3 genotype affects athletic performance differently in males and females. The differential effects in sprint and endurance athletes suggested that the R577X polymorphism may have been maintained in the human population by balancing natural selection. It is likely that there is a 'trade off' between sprint and endurance traits that imposes important constraints on the evolution of physical performance in humans and other vertebrates (Garland et al., 1990). This hypothesis is supported by data from world-class decathletes, which demonstrated that performance in the 100-meter sprint, shot put, long jump, and 110-meter hurdles (which rely on explosive power and fast fatigue-susceptible muscle fibers) is negatively correlated with performance in the 1,500-meter race (which requires endurance and fatigue-resistant slow fiber activity) (Van Damme et al., 2002).
Niemi and Majamaa (2005) determined the ACTN3 R577X genotype in 52 elite Finnish endurance and 89 sprint athletes and found that the frequency of the XX genotype was higher and RR lower among the endurance athletes, and that none of the top Finnish sprinters had the XX genotype.
The association of the R577X polymorphism with elite athlete status and human muscle performance suggests that ACTN3 deficiency influences the function of fast muscle fibers. MacArthur et al. (2007) showed that loss of ACTN3 expression in a knockout mouse model resulted in a shift in muscle metabolism toward the more efficient aerobic pathway and an increase in intrinsic endurance performance. In addition, they demonstrated that the genomic region surrounding the 577X null allele shows low levels of genetic variation and recombination in individuals of European and East Asian descent, consistent with strong, recent positive selection. They proposed that the 577X allele has been positively selected in some human populations owing to its effect on skeletal muscle metabolism.
In a study of 992 Greek adolescent boys and girls, Moran et al. (2007) found a significant association between the ACTN3 R577X polymorphism and 40 meter sprint times in males (p = 0.003) that accounts for 2.3% of phenotypic variance, with the 577R allele contributing to faster times in an additive fashion. The R577X polymorphism was not associated with other predominantly strength/power-related or endurance phenotypes.
Saunders et al. (2007) genotyped 457 Caucasian male triathletes who completed the 2000 and/or 2001 226 km South African Ironman Triathlons and 143 Caucasian controls for the ACTN3 R577X mutation. They found no significant differences in either the genotype (p = 0.486) or allele (p = 0.375) frequencies within the fastest, middle of the field, or slowest Caucasian male finishers and the control population.
In 52 white and 23 black elite-level bodybuilders and powerlifters from the U.S., Roth et al. (2008) found significantly lower XX genotype frequency in strength athletes (6.7%) compared to controls (16.3%; p = 0.005). The XX genotype was significantly lower in white athletes (9.7%) compared to white controls (19.9%; p = 0.018), but did not reach significance in black athletes (0%) compared to black controls (4.8%; p = 0.10). Roth et al. (2008) concluded that the 577X allele is underrepresented in elite strength athletes in addition to sprint athletes, consistent with previous reports indicating that ACTN3 deficiency appears to impair muscle performance.
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*[AA]: Adrenergic agonist
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*[HAART]: highly active antiretroviral therapy
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*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| ACTN3 DEFICIENCY | c3888204 | 4,086 | omim | https://www.omim.org/entry/617749 | 2019-09-22T15:44:58 | {"omim": ["617749"], "synonyms": ["Alternative titles", "ALPHA-ACTININ-3 DEFICIENCY"]} |
## Clinical Features
Kala-azar, also known as visceral leishmaniasis, is a life-threatening protozoal disease caused by Leishmania parasites (L. donovani, L. chagasi, and L. infantum). It is prevalent in Africa, South America, Asia, and the Mediterranean basin. Epidemics occur periodically, killing a large number of infected individuals. Bucheton et al. (2003) performed a longitudinal study in a population during an outbreak of kala-azar in a Sudanese village during 1995-2002. Sera epidemiologic surveys showed that almost all of the population had been exposed to infection and that 25% of inhabitants had been affected by kala-azar. Familial clustering of kala-azar cases and marked differences in disease prevalence between the ethnic groups in the village indicated that the population was suitable for studies aimed at identifying loci that might predispose to infection (Bucheton et al., 2002).
Mapping
Bucheton et al. (2003) performed a genomewide linkage study on 63 Sudanese families selected from the most affected ethnic group, including 169 children with kala-azar. Significant linkage was found to markers on chromosome 22q12; when the analysis included all patients, the lod score was 3.50, and when it was limited to patients who were affected early in the outbreak, the lod score was 3.90. Bucheton et al. (2003) also found modest support for the location of another kala-azar locus in the 2q35 region, which contains the NRAMP gene (SLC11A1; 600266). These results were said to provide the first evidence of a major genetic effect on the development of human kala-azar. Bucheton et al. (2003) suggested the interleukin-2 receptor beta-chain gene (IL2RB; 146710) as a candidate gene for susceptibility to kala-azar on chromosome 22q12.
By examining a northeastern Brazilian population with high rates of admixture from African, European, and native Brazilian groups and high rates of visceral leishmaniasis caused by L. chagasi, Ettinger et al. (2009) discerned no particular admixture proportion in the spectrum of clinical phenotypes. However, they detected excess European ancestry for D22S1169, a microsatellite marker on chromosome 22q12, in individuals with visceral leishmaniasis compared with asymptomatic individuals with type hypersensitivity to Leishmania antigen. Ettinger et al. (2009) noted that this region is the same as that identified by Bucheton et al. (2003) in a Sudanese population.
Heterogeneity
In addition to the KAZA1 locus on chromosome 22q12, kala-azar susceptibility loci have been identified on chromosomes 1p22 (KAZA2; 611381) and 6q27 (KAZA3; 611382).
### Associations Pending Confirmation
Bucheton et al. (2003) performed a genomewide linkage study on 63 Sudanese families selected from the most affected ethnic group, including 169 children with kala-azar. In addition to significant linkage to chromosome 22q12, they found modest support for linkage to the 2q35 region, which contains the NRAMP gene (SLC11A1; 600266).
Mohamed et al. (2004) examined polymorphisms in the SLC11A1 gene in 59 multicase families with visceral leishmaniasis from the high-incidence Masalit tribe in Sudan. Multipoint nonparametric analysis showed significant linkage across SLC11A1 (Z(lr) scores, 2.38-2.55, p between 0.008 and 0.012). Mohamed et al. (2004) suggested that polymorphisms in the SLC11A1 gene may be associated with susceptibility to visceral leishmaniasis in the Masalit tribe in Sudan.
To identify susceptibility loci for visceral leishmaniasis in Indian and Brazilian populations, the LeishGEN Consortium and Wellcome Trust Case Control Consortium 2 (2013) used genomewide association studies and variance components methodology (i.e., a mixed model) to avoid confounding due to population structure and relatedness. They found that the HLA-DRB1 (142857)-HLA-DQA1 (146880) region on chromosome 6p21 was the only region to show strong evidence of association in both discovery populations and in a second Indian replication population. The SNP most significantly associated with visceral leishmaniasis that was common to all 3 populations was rs9271858, and combined analysis across the 3 cohorts for rs9271858 showed P-combined of 2.76 x 10(-17) and an odds ratio of 1.41. The LeishGEN Consortium and Wellcome Trust Case Control Consortium 2 (2013) concluded that the HLA-DRB1-HLA-DQA1 region contributes to susceptibility to visceral leishmaniasis, regardless of geographic region and parasite species.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| KALA-AZAR, SUSCEPTIBILITY TO, 1 | c0023281 | 4,087 | omim | https://www.omim.org/entry/608207 | 2019-09-22T16:08:10 | {"doid": ["9146"], "mesh": ["D007896"], "omim": ["608207"], "orphanet": ["507"], "synonyms": ["Alternative titles", "LEISHMANIASIS, VISCERAL, SUSCEPTIBILITY TO, 1"]} |
Visual agnosia is an impairment in recognition of visually presented objects. It is not due to a deficit in vision (acuity, visual field, and scanning), language, memory, or intellect.[1] While cortical blindness results from lesions to primary visual cortex, visual agnosia is often due to damage to more anterior cortex such as the posterior occipital and/or temporal lobe(s) in the brain.[2] There are two types of visual agnosia: apperceptive agnosia and associative agnosia.
Recognition of visual objects occurs at two primary levels. At an apperceptive level, the features of the visual information from the retina are put together to form a perceptual representation of an object. At an associative level, the meaning of an object is attached to the perceptual representation and the object is identified.[2] If a person is unable to recognize objects because they cannot perceive correct forms of the objects, although their knowledge of the objects is intact (i.e. they do not have anomia), they have apperceptive agnosia. If a person correctly perceives the forms and has knowledge of the objects, but cannot identify the objects, they have associative agnosia.[3]
## Contents
* 1 Symptoms
* 2 Pathophysiology
* 3 Diagnosis
* 3.1 Classification
* 3.1.1 Categories and subtypes of visual agnosia
* 3.1.1.1 Subtypes of associative visual agnosia
* 4 Patient CK
* 4.1 Background
* 4.2 Associative visual agnosia
* 4.3 Evidence for double dissociation between face and object processing
* 5 In popular culture
* 6 See also
* 7 References
* 8 Further reading
## Symptoms[edit]
While most cases of visual agnosia are seen in older adults who have experienced extensive brain damage, there are also cases of young children with less brain damage during developmental years acquiring the symptoms.[4] Commonly, visual agnosia presents as an inability to recognize an object in the absence of other explanations, such as blindness or partial blindness, anomia, memory loss, etc.. Other common manifestations of visual agnosia that are generally tested for include difficulty identifying objects that look similar in shape, difficulty with identifying line drawings of objects, and recognizing objects that are shown from less common views, such as a horse from a top-down view.[4]
Within any given patient, a variety of symptoms can occur, and the impairment of ability is not only binary but can range in severity. For example, Patient SM is a prosopagnosic with a unilateral lesion to left extrastriate cortex due to an accident in his twenties who displays behavior similar to congenital prosopagnosia.[5] Although he can recognize facial features and emotions – indeed he sometimes uses a standout feature to recognize a face – face recognition is almost impossible purely from visual stimuli, even for faces of friends, family, and himself. The disorder also affects his memory of faces, both in storing new memories of faces and recalling stored memories.[5]
Nevertheless, it is important to note the reach of symptoms to other domains. SM’s object recognition is similarly impaired though not entirely; when given line drawings to identify, he was able to give names of objects with properties similar to the drawing, implying that he is able to see the features of the drawing. Similarly, copying a line drawing of a beach scene led to a simplified version of the drawing, though the main features were accounted for. For recognition of places, he is still impaired but familiar places are remembered and new places can be stored into memory.[5]
## Pathophysiology[edit]
Visual agnosia occurs after damage to visual association cortex or to parts of the ventral stream of vision, known as the "what pathway" of vision for its role in object recognition.[6] This occurs even when no damage has been done to the eyes or optic tract that leads visual information into the brain; in fact, visual agnosia occurs when symptoms cannot be explained by such damage. Damage to specific areas of the ventral stream impair the ability to recognize certain categories of visual information, such as the case of prospagnosia.[6] Patients with visual agnosia generally do not have damage to the dorsal stream of vision, known as the "where pathway" of vision because of its role determining object's position in space, allowing individuals with visual agnosia to show relatively normal visually guided behavior.[7][8]
For example, patient DF had lesions to the ventral surface that gave her apperceptive agnosia.[9] One of the tasks she was tested on required her to place a card through a thin slot that could be rotated into all orientations. As an apperceptive agnosic, it would be expected that since she cannot recognize the slot, she should not be able to correctly place the card into the slot. Indeed, when she was asked to give the direction of the slot, her responses were no better than chance. Yet, when she was asked to place the card into the slot, her success was almost to the level of the controls. This implies that in the event of a ventral stream deficit, the dorsal stream can help with processing of special information to aid movement regardless of object recognition.[9]
More specifically, the lateral occipital complex appears to respond to many different types of objects.[6] Prosopagnosia (inability to recognize faces) is due to damage of the fusiform face area (FFA). An area in the fusiform gyrus of the temporal lobe that has been strongly associated with a role in facial recognition.[6] However, this area is not exclusive to faces; recognition of other objects of expertise are also processed in this area. The extrastriate body cortex (EBA) was found to be activated by photographs, silhouettes, or stick drawings of human bodies.[6] The parahippocampal place area (PPA) of the limbic cortex has been found to be activated by the sight of scenes and backgrounds.[6] Cerebral achromatopsia (the inability to discriminate between different hues) is caused by damage to the V8 area of the visual association cortex.[6]
The left hemisphere seems to play a critical role in recognizing the meaning of common objects.[10]
## Diagnosis[edit]
### Classification[edit]
Broadly, visual agnosia is divided into apperceptive and associative visual agnosia.[11]
Apperceptive agnosia is failure of object recognition even when the basic visual functions (acuity, color, motion) and other mental processing, such as language and intelligence, are normal.[9] The brain must correctly integrate features such as edges, light intensity, and color from sensory information to form a complete percept of an object. If a failure occurs during this process, a percept of an object is not fully formed and thus it cannot be recognized.[12] Tasks requiring copying, matching, or drawing simple figures can distinguish the individuals with apperceptive agnosia because they cannot perform such tasks.
Associative agnosia is an inability to identify objects even with apparent perception and knowledge of them. It involves a higher level of processing than apperceptive agnosia.[9] Individuals with associative agnosia can copy or match simple figures, indicating that they can perceive objects correctly. They also display the knowledge of objects when tested with tactile or verbal information. However, when tested visually, they cannot name or describe common objects.[12] This means that there is an impairment in associating the perception of objects with the stored knowledge of them.
Although visual agnosia can be general, there exist many variants that impair recognition of specific types. These variants of visual agnosia include prosopagnosia (inability to recognize faces), pure word blindness (inability to recognize words, often called "agnosic alexia" or "pure alexia"), agnosias for colors (inability to differentiate colors), agnosias for the environment (inability to recognize landmarks or difficult with spatial layout of an environment, i.e. topographagnosia) and simultanagosia (inability to sort out multiple objects in a visual scene).[13][14]
#### Categories and subtypes of visual agnosia[edit]
The two main categories of visual agnosia are:
* Apperceptive visual agnosia, impaired object recognition. Individuals with apperceptive visual agnosia cannot form a whole percept of visual information.[15]
* Associative visual agnosia, impaired object identification. Individuals with associative agnosia cannot give a meaning to a formed percept. The percept is created, but it would have no meaning for individuals who have an associative agnosia.[15]
##### Subtypes of associative visual agnosia[edit]
* Achromatopsia, an inability to distinguish different colors.[9]
* Prosopagnosia, an inability to recognize human faces.[16] Individuals with prosopagnosia know that they are looking at faces, but cannot recognize people by the sight of their face, even people whom they know well.[6]
* Simultagnosia, an inability to recognize multiple objects in a scene, including distinct objects within a spatial layout and distinguishing between "local" objects and "global" objects, such as being able to see a tree but not the forest or vice versa.[14]
* Topographagnosia, an inability to process the spatial layout of an environment, including landmark agnosia, difficult recognizing buildings and places; difficulty building mental maps of a location or scene; and/or an inability to discern the orientation between objects in space.[14]
* Pure alexia, an inability to read.[14]
* Orientation agnosia: an inability to judge or determine orientation of objects.[17]
* Pantomime agnosia: an inability to understand pantomimes (gestures). It appears that the inferior cortical visual cortex is critical in recognizing pantomimes.[18]
## Patient CK[edit]
### Background[edit]
Patient C.K. was born in 1961 in England and emigrated to Canada in 1980. In January 1988, C.K. sustained a head injury from a motor vehicle accident while out for a jog. Following the accident, C.K. experienced many cognitive issues, mood swings, poor memory, and temper outbursts. C.K. also had motor weakness on the left side and a left homonymous hemianopia. He recovered well, retaining normal intelligence and normal visual acuity. He was able to complete a Masters in History, later working as a manager at a large corporation. Although his recovery was successful in other areas of cognition, C.K. still struggles to make sense of the visual world.[19]
### Associative visual agnosia[edit]
Magnetic resonance imaging (MRI) showed bilateral thinning of C.K.'s occipital lobe which resulted in associative visual agnosia.[19] Patients that suffer from visual agnosia are unable to identify visually presented objects. They can identify these objects through other modalities such as touch but if presented visually, they are unable to. Associative agnosic patients cannot create a detailed representation of the visual world in their brains, they can only perceive elements of whole objects.[19] They also cannot form associations between objects or assign meaning to objects.[20]
C.K. makes many mistakes when trying to identify objects. For example, he called an abacus "skewers on a kebab" and a badminton racquet a "fencer's mask". A dart was a "feather duster" and a protractor was mistaken for a "cockpit". Despite this impairment in visual object recognition, C.K. retained many abilities such as drawing, visual imagery, and internal imagery. As a native of England, he was tasked with drawing England, marking London and where he was born. His accurate drawing of England is just one example of his excellent drawing abilities.[19]
As aforementioned, C.K. is able to identify parts of objects but cannot generate a whole representation. It should not be surprising then that his visual imagery for object size, shape, and color is intact. For example, when shown a picture of an animal, he can correctly answer questions such as "are the ears up or down?" and "is the tail long or short?" He can correctly identify colors, for example that the inside of a cantaloupe is orange.[19] Finally, C.K. can generate internal images and perceive these generated objects. For example, Finke, Pinker, and Farah instructed C.K. to imagine a scenario where a 'B' is rotated 90 degrees to the left, a triangle is put below, and the line in the middle is removed. C.K. can correctly identify this object as a heart by picturing this transformation in his head.[21]
### Evidence for double dissociation between face and object processing[edit]
Patient C.K. provided evidence for a double dissociation between face processing and visual object processing. Patients with prosopagnosia have damage to the Fusiform Face Area (FFA) and are unable to recognize upright faces. C.K. has no difficulty with face processing and matches the performance of controls when tasked with identifying upright famous faces. When shown inverted faces of famous people, C.K. performs significantly worse than controls. This is because processing inverted faces involves a piecemeal strategy. C.K.'s performance is compared to patients with prosopagnosia who are impaired in face processing but perform well identifying inverted faces. This was the first evidence for a double dissociation between face and object processing suggesting a face-specific processing system.[20]
## In popular culture[edit]
* A famous report on this condition is the title essay of Oliver Sacks' book, The Man Who Mistook His Wife for a Hat.
* The murder suspect in the Picket Fences episode "Strangers" supposedly suffered from agnosia.
* The patient in the House episode "Adverse Events" suffered from agnosia.
* In the graphic novel Preacher, the character Lorie suffers from an extreme version of agnosia resulting from being born with a single eye. For example, she perceives Arseface, a man with severe facial deformities, as resembling a young James Dean.
* Val Kilmer's character suffers from visual agnosia in the film At First Sight.
* In "Folie à Deux", a fifth-season episode of the X Files, Mulder succumbs to the same belief as telemarketer Gary Lambert, that his boss Greg Pincus is a monster who disguises his true appearance by means of hypnosis. Scully, although believing this notion preposterous, suggests that what Mulder describes is analogous to an induced visual agnosia.
* The short story Liking What You See: A Documentary by Ted Chiang examines the cultural effects of a noninvasive medical procedure that induces a visual agnosia toward physical beauty.
## See also[edit]
* Agnosia
* Blindness
* Color agnosia
* Gestaltzerfall
* Prosopagnosia
* Riddoch syndrome
* Topographical disorientation
## References[edit]
1. ^ Delver, J. F., Seton, X., Colette, F., & Ross ion (2004). "Evidence for Perceptual Deficits in Associative Visual (Pro sop)agnosia: A Single-case Study". Parapsychologist. 42 (5): 597–612. doi:10.1016/j.neuropsychologia.2003.10.008. PMID 14725798.CS1 maint: multiple names: authors list (link)
2. ^ Riddoch, M. J., Humphreys, G. W. (1987). "A Case of Integrative Visual Agnosia". Brain. 110 (6): 1431–1462. doi:10.1093/brain/110.6.1431.CS1 maint: multiple names: authors list (link)
3. ^ Karnath H. O.; Rüter J.; Mandler A.; Himmelbach M. (2009). "The anatomy of object recognition—Visual form agnosia caused by medial occipitotemporal stroke". The Journal of Neuroscience. 29 (18): 5854–5862. doi:10.1523/JNEUROSCI.5192-08.2009. PMC 6665227. PMID 19420252.
4. ^ a b Funnell, Elaine; Wilding, John (2011). "Development of a vocabulary of object shapes in a child with a very-early-acquired visual agnosia: A unique case". Quarterly Journal of Experimental Psychology. 64 (2): 261–282. doi:10.1080/17470218.2010.498922. PMID 20680887.
5. ^ a b c Behrmann, Marlene; Kimchi, Ruth (2003). "What does visual agnosia tell us about perceptual organization and its relationship to object perception?". Journal of Experimental Psychology: Human Perception and Performance. 29: 19–42. doi:10.1037/0096-1523.29.1.19.
6. ^ a b c d e f g h Carlson, Neil R. (2010). Physiology of behavior. Boston, Mass: Allyn & Bacon. ISBN 978-0-205-66627-0. OCLC 263605380.[page needed]
7. ^ Goodale MA, Milner AD, Jakobson LS, Carey DP (1991). "A neurological dissociation between perceiving objects and grasping them". Nature. 349 (6305): 154–6. doi:10.1038/349154a0. PMID 1986306.
8. ^ Goodale MA, Milner AD (1992). "Separate visual pathways for perception and action". Trends Neurosci. 15 (1): 20–5. CiteSeerX 10.1.1.207.6873. doi:10.1016/0166-2236(92)90344-8. PMID 1374953.
9. ^ a b c d e Kolb, B. & Whishaw, I. Q. (2009). "Fundamentals of Human Neuropsychology 6th ed. New York, NY., Worth Publishers. ISBN 978-0-7167-9586-5.[page needed]
10. ^ McCarthy, R. A.; Warrington, E. K. (1986). "Visual associative agnosia: A clinico-anatomical study of a single case". Journal of Neurology, Neurosurgery & Psychiatry. 49 (11): 1233–40. doi:10.1136/jnnp.49.11.1233. PMC 1029070. PMID 3794729.
11. ^ Behrmann, Marlene; Nishimura, Mayu (2010). "Agnosias". Wiley Interdisciplinary Reviews: Cognitive Science. 1 (2): 203–213. doi:10.1002/wcs.42. PMID 26271235.
12. ^ a b Heilman, K. M. (2002). "Matter of Mind. New York, NY., Oxford University Press. ISBN 978-0-19-514490-1.[page needed]
13. ^ Biran, I.; Coslett, H. B. (2003). "Visual agnosia". Current Neurology and Neuroscience Reports. 3 (6): 508–512. doi:10.1007/s11910-003-0055-4. PMID 14565906.
14. ^ a b c d Barton, Jason JS (2011). "Disorder of higher visual function". Current Opinion in Neurology. 24 (1): 1–5. doi:10.1097/wco.0b013e328341a5c2. PMID 21102334.
15. ^ a b Ferreira, C. T.; Ceccaldi, M.; Giusiano, B.; Poncet, M. (1998). "Separate visual pathways for perception of actions and objects: Evidence from a case of apperceptive agnosia". Journal of Neurology, Neurosurgery & Psychiatry. 65 (3): 382–385. doi:10.1136/jnnp.65.3.382. PMC 2170224. PMID 9728957.
16. ^ Wolfe, Jeremy (2012). "Sensation & Perception" 3rd ed. pp. 507 ISBN 978-0-87893-876-6.[page needed]
17. ^ Harris, Irina M.; Harris, Justin A.; Caine, Diana (2001). "Object Orientation Agnosia: A Failure to Find the Axis?". Journal of Cognitive Neuroscience. 13 (6): 800–812. doi:10.1162/08989290152541467. PMID 11564324.
18. ^ Rothi, L. J.; Mack, L.; Heilman, K. M. (1986). "Pantomime agnosia". Journal of Neurology, Neurosurgery & Psychiatry. 49 (4): 451–4. doi:10.1136/jnnp.49.4.451. PMC 1028777. PMID 3701356.
19. ^ a b c d e Behrmann, M.; Moscovitch, M.; Winocur, G. (1994). "Intact visual imagery and impaired visual perception in a patient with visual agnosia". Journal of Experimental Psychology. Human Perception and Performance. 20 (5): 1068–87. doi:10.1037/0096-1523.20.5.1068. PMID 7964528.
20. ^ a b Moscovitch, M.; Winocur, G.; Behrmann, M. (1997). "What is Special about Face Recognition? Nineteen Experiments on a Person with Visual Object Agnosia and Dyslexia but Normal Face Recognition". Journal of Cognitive Neuroscience. 9 (5): 555–604. doi:10.1162/jocn.1997.9.5.555. PMID 23965118.
21. ^ Finks, R. (1989). "Reinterpreting visual patterns in mental imagery". Cognitive Science. 13: 51–78. doi:10.1016/0364-0213(89)90011-6.
## Further reading[edit]
* Cant JD, Goodale MA (March 2007). "Attention to form or surface properties modulates different regions of human occipitotemporal cortex". Cereb. Cortex. 17 (3): 713–31. doi:10.1093/cercor/bhk022. PMID 16648452.
* Cavina-Pratesi C, Kentridge RW, Heywood CA, Milner AD (February 2010). "Separate processing of texture and form in the ventral stream: evidence from FMRI and visual agnosia". Cereb. Cortex. 20 (2): 433–46. doi:10.1093/cercor/bhp111. PMID 19478035.
* Goodale MA; Milner AD (2004). Sight Unseen: An Exploration of Conscious and Unconscious Vision. Oxford UK: Oxford University Press. pp. 139. ISBN 978-0-19-856807-0. OCLC 54408420.
* Farah M (2004). Visual Agnosia. 2nd Edition. Cambridge MA: MIT Press: Bradford Books. p. 192. ISBN 978-0-262-56203-4. OCLC 57182718.
* v
* t
* e
Optical illusions (list)
Illusions
* Afterimage
* Ambiguous image
* Ames room
* Barberpole
* Bezold
* Café wall
* Checker shadow
* Chubb
* Cornsweet
* Delboeuf
* Ebbinghaus
* Ehrenstein
* Flash lag
* Fraser spiral
* Gravity hill
* Grid
* Hering
* Impossible trident
* Jastrow
* Lilac chaser
* Mach bands
* McCollough
* Müller-Lyer
* Necker cube
* Orbison
* Penrose stairs
* Penrose triangle
* Peripheral drift
* Poggendorff
* Ponzo
* Rubin vase
* Sander
* Schroeder stairs
* Shepard tables
* Spinning Dancer
* Ternus
* Vertical–horizontal
* White's
* Wundt
* Zöllner
Popular culture
* Op art
* Trompe-l'œil
* Spectropia (1864 book)
* Ascending and Descending (1960 drawing)
* Waterfall (1961 drawing)
* The dress (2015 photograph)
Related
* Accidental viewpoint
* Auditory illusions
* Tactile illusions
* Temporal illusion
* v
* t
* e
Sensation and perception
Processes and concepts
Sensation
* Stimulus
* Sensory receptor
* Transduction (physiology)
* Sensory processing
* Active sensory system
Perception
* Multimodal integration
* Awareness
* Consciousness
* Cognition
* Feeling
* Qualia
Human
External
Sensory organs
* Eyes
* Ears
* Inner ear
* Nose
* Mouth
* Skin
Sensory systems
* Visual system (sense of vision)
* Auditory system (sense of hearing)
* Vestibular system (sense of balance)
* Olfactory system (sense of smell)
* Gustatory system (sense of taste)
* Somatosensory system (sense of touch)
Sensory cranial and spinal nerves
* Optic (II)
* Vestibulocochlear (VIII)
* Olfactory (I)
* Facial (VII)
* Glossopharyngeal (IX)
* Trigeminal (V)
* Spinal
Cerebral cortices
* Visual cortex
* Auditory cortex
* Vestibular cortex
* Olfactory cortex
* Gustatory cortex
* Somatosensory cortex
Perceptions
* Visual perception (vision)
* Auditory perception (hearing)
* Equilibrioception (balance)
* Olfaction (smell)
* Gustation (taste or flavor)
* Touch
* mechanoreception
* nociception (pain)
* thermoception
Internal
* Proprioception
* Hunger
* Thirst
* Suffocation
* Nausea
Nonhuman
Animal
* Electroception
* Magnetoreception
* Echolocation
* Infrared sensing in vampire bats
* Infrared sensing in snakes
* Surface wave detection
* Frog hearing
* Toad vision
Plant
* Photomorphogenesis
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Artificial
* Robotic sensing
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Types of sensory receptors
Mechanoreceptor
* Baroreceptor
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* Lamellar corpuscle
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* Merkel nerve ending
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* Campaniform sensilla
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Photoreceptor
* Photoreceptor cell
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* ipRGC
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Chemoreceptor
* Taste receptor
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* Osmoreceptor
Thermoreceptor
* Cilium
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Nociceptor
* Nociceptin receptor
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Disorders
Visual
* Visual impairment
* Alice in Wonderland syndrome
* Amaurosis
* Anopsia
* Color blindness
* Diplopia
* Hemeralopia and Nyctalopia
* Optic neuropathy
* Oscillopsia
* Palinopsia
* Papilledema
* Photophobia
* Photopsia
* Polyopia
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* Stereoblindness
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Auditory
* Amblyaudia
* Auditory agnosia
* Auditory hallucination
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* Microwave auditory effect
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Vestibular
* Vertigo
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Olfactory
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Gustatory
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Tactile
* Astereognosis
* CMT disease
* Formication
* Hyperesthesia
* Hypoesthesia
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* Tactile hallucination
Nociception (pain)
* Hyperalgesia
* Hypoalgesia
* Pain dissociation
* Phantom pain
Proprioception
* Asomatognosia
* Phantom limb syndrome
* Somatoparaphrenia
* Supernumerary phantom limb
Multimodal
* Aura
* Agnosia
* Allochiria
* Derealization
* Hallucination
* HSAN
* Pareidolia
* Sensory processing disorder
* Synesthesia
* v
* t
* e
Phenomena of the visual system
Entoptic phenomena
* Blind spot
* Phosphene
* Floater
* Afterimage
* Haidinger's brush
* Prisoner's cinema
* Blue field entoptic phenomenon
* Purkinje images
Other phenomena
* Aura
* Form constant
* Scintillating scotoma
* Palinopsia
* Visual snow
* Afterimage on empty shape
* Cosmic ray visual phenomena
* Scotopic sensitivity syndrome
* Closed-eye hallucination
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Visual agnosia | c0234502 | 4,088 | wikipedia | https://en.wikipedia.org/wiki/Visual_agnosia | 2021-01-18T18:43:18 | {"mesh": ["C531604", "D000377"], "umls": ["C0234502"], "wikidata": ["Q18742"]} |
## Description
Y-linked deafness-1 (DFNY1) is characterized by male-limited postlingual progressive sensorineural hearing loss of variable severity, with onset in the first to third decades of life (Wang et al., 2009).
### Genetic Heterogeneity of Y-Linked Deafness
DFNY2 (400047) is caused by mutation in the TBL1Y gene (400033).
Clinical Features
Wang et al. (2004) reported a 7-generation Chinese family in which multiple male members had nonsyndromic hearing impairment. The family originated from Jiangxi Province in southeastern China. Age at onset ranged from 7 to 27 years, resulting in moderate to severe hearing impairment. Three patients had tinnitus.
Wang et al. (2009) provided follow-up of the family reported by Wang et al. (2004). Twenty-three patrilineal males spanning 9 generations were affected. There was 1 female with hearing loss attributable to gentamicin. In the affected lineage, 23 (92%) of 25 living patrilineal males were diagnosed or reported with hearing loss, and 2 children remained to be diagnosed. Based on audiologic examination of 21 male family members, the degree of hearing loss was mild in 3 patients, moderate in 7, and severe in 11. Audiometry revealed 10 (48%) males with sloping readings in high frequencies, 8 (38%) with flat readings in all frequencies, and 3 (14%) with the U-shaped readings. The age of onset ranged from 5 to 27 years, with an average of 11.5 years. Family history revealed that the family had been living in the same village of Jiangxi Province for over 200 years. The first hearing-impaired member was believed to have been born in 1847 and died in 1898.
Fu et al. (2011) studied a large 5-generation Chinese ethnic Tujia family in which 19 male members had nonsyndromic bilateral symmetric sensorineural hearing impairment. Age of onset ranged from 7 to 20 years. Hearing loss was classified as severe in 10 patients, moderate in 5, and mild in 1. Audiometric evaluation showed that 47% of the affected individuals had a high frequency and sloping auditory curve, whereas 41% had a flat curve, suggesting that additional genetic or environmental factors might have modified the expression of this trait. The authors stated that the audiometric configuration was consistent with hereditary Y-linked hearing loss.
Inheritance
Wang et al. (2004) showed only patrilineal inheritance with 91% penetrance and male-to-male transmission through each of 7 generations in a Chinese family. There were no affected females. No daughters of affected males showed hearing impairment, ruling out X-linked inheritance.
Mapping
A genomewide linkage analysis of the family described by Wang et al. (2004) showed no significant linkage to the autosomes. Wang et al. (2004) postulated that a locus on the Y chromosome was responsible for the disorder in this family.
Molecular Genetics
Wang et al. (2013) restudied the Chinese pedigree previously studied by Wang et al. (2009) and originally reported by Wang et al. (2004), analyzing in detail the Y chromosome of affected individuals and comparing it to that of an unaffected branch of the family. The DFNY1 chromosome was found to carry a complex rearrangement, including duplication of several noncontiguous segments of the Y chromosome and insertion of approximately 160 kb of DNA from chromosome 1, in the pericentric region of Yp. This segment of chromosome 1, encompassing 5 genes as well as the 5-prime end of a sixth gene, is derived almost entirely from within a known hearing impairment locus, DFNA49 (608372). Wang et al. (2013) suggested that a third copy of 1 or more genes from the shared segment of chromosome 1 might be responsible for the hearing loss phenotype.
INHERITANCE \- Y-linked HEAD & NECK Ears \- Hearing loss, sensorineural, postlingual progressive, moderate to severe \- Tinnitus (less common) MISCELLANEOUS \- Onset between 7 and 27 years of age ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| DEAFNESS, Y-LINKED 1 | c3888076 | 4,089 | omim | https://www.omim.org/entry/400043 | 2019-09-22T16:17:01 | {"omim": ["400043"]} |
For a phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000.
Clinical Features
Gieser et al. (1998) described a 5-generation family with X-linked retinitis pigmentosa designated RP24. Affected males (hemizygotes) had early onset of rod photoreceptor dysfunction; cone-receptor function was normal at first, but there was progressive loss. Patients at advanced stages showed little or no detectable rod or cone function and had clinical hallmarks of typical RP.
Mapping
Gieser et al. (1998) demonstrated linkage of X-linked retinitis pigmentosa in a 5-generation family to Xq26-q27. A maximum lod score of 4.21 was obtained with DXS8106. Haplotype analysis assigned RP24 within a 23-cM region between the DXS8094 (proximal) and DXS8043 (distal) markers.
Clinical Management
Grover et al. (2000) evaluated the progression of visual impairment in carriers of X-linked recessive retinitis pigmentosa (XLRP). They described the relationship between retinal findings at presentation and the extent of subsequent deterioration. They followed visual acuity, visual field, and electroretinograms in 27 carriers of XLRP and described 4 grades of fundus findings from grade 0 (normal) to grade 3 (diffuse changes). They found that carriers of XLRP with only a tapetal-like retinal reflex (grade 1) at presentation were more likely to retain visual function than those with peripheral retinal pigmentation. Grover et al. (2000) concluded that these data are useful in counseling such carriers as to their visual prognosis.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| RETINITIS PIGMENTOSA 24 | c0035334 | 4,090 | omim | https://www.omim.org/entry/300155 | 2019-09-22T16:20:51 | {"doid": ["0110416"], "mesh": ["D012174"], "omim": ["300155"], "orphanet": ["791"]} |
A number sign (#) is used with this entry because of evidence that mutations in various genes are responsible for susceptibility to endometrial cancer.
Approximately 20% of endometrial cancers demonstrate microsatellite instability (MSI) (Simpkins et al., 1999), a reflection of mutations in mismatch repair genes. The mismatch repair genes that have been identified as having a role in endometrial cancer include MSH2 (609309), MSH3 (600887), MSH6 (600678), MLH1 (120436), and MLH3 (604395).
In some families, endometrial cancer is associated with colorectal cancer in the same individual or individuals with hereditary nonpolyposis colorectal cancer type 1 (HNPCC1) or HNPCC2, also known as Lynch syndrome (120435). 'Lynch syndrome II' refers to extracolonic cancers, including endometrial cancers.
Mutation in the PTEN1 gene (601728) and somatic mutations in the CDH1 (192090) and FGFR2 (176943) genes have also been demonstrated in endometrial cancers.
Liu et al. (2003) found an association between the common 16189T-C transition within the D loop region of the mitochondrial chromosome and endometrial cancer; the mutation had previously been found to be associated with type II diabetes (125853) (Poulton et al., 1998) and dilated cardiomyopathy (Khogali et al., 2001).
Barnetson et al. (2007) reported a patient with endometrial adenocarcinoma and sebaceous carcinoma of the face who was compound heterozygous for 2 common mutations in the MUTYH gene (Y165C; 604933.0001 and G382D; 604933.0002). Colonic adenomas were not reported, but a paternal aunt reportedly had colorectal cancer in her thirties. Barnetson et al. (2007) noted that the phenotype associated with biallelic MUTYH mutations may include extracolonic manifestations, including endometrial cancer and sebaceous carcinoma, as seen in other inherited colorectal cancer syndromes such as Muir-Torre syndrome (158320) and Lynch syndrome (120435).
Pollock et al. (2007) identified 11 different somatic FGFR2 mutations (see, e.g., 176943.0010 and 176943.0015) in 3 (30%) of 10 endometrial cancer cell lines and in 19 (10%) of 187 primary endometrial carcinomas. The majority of the mutations were identical to germline activating mutations that cause skeletal dysplasias. There was no apparent correlation between FGFR2 mutation and overall survival.
Dutt et al. (2008) found somatic FGFR2 mutations in 15 (12.3%) of 122 primary endometrial carcinomas, as well as in 2 of 42 lung squamous cell carcinomas and in 2 of 46 cervical carcinomas. Many of the mutations were identical to those associated with congenital craniofacial developmental disorders. Ectopic expression of the mutations in mouse fibroblasts demonstrated constitutive activation and oncogenicity, and inhibition of FGFR2 kinase activity in endometrial cell lines bearing such FGFR2 mutations inhibited transformation and survival.
Le Gallo et al. (2012) used whole-exome sequencing to comprehensively search for somatic mutations in 13 primary serous endometrial tumors, and subsequently resequenced 18 genes that were mutated in more than 1 tumor and/or were components of an enriched functional grouping from 40 additional serous tumors. Le Gallo et al. (2012) identified high frequencies of somatic mutations in CHD4 (603277) (17%), EP300 (602700) (8%), ARID1A (603024) (6%), TSPYL2 (300564) (6%), FBXW7 (606278) (29%), SPOP (602650) (8%), MAP3K4 (602425) (6%), and ABCC9 (601439) (6%). Overall, 36.5% of serous tumors had a mutated chromatin-remodeling gene, and 35% had a mutated ubiquitin ligase complex gene, implicating frequent mutational disruption of these processes in the molecular pathogenesis of one of the deadliest forms of endometrial cancer.
The Cancer Genome Atlas Research Network (2013) performed an integrated genomic, transcriptomic, and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumors and approximately 25% of high-grade endometrioid tumors had extensive copy number alterations, few DNA methylation changes, low estrogen receptor (see 133430)/progesterone receptor (607311) levels, and frequent TP53 (191170) mutations. Most endometrioid tumors had few copy number alterations or TP53 mutations, but frequent mutations in PTEN (601728), CTNNB1 (116806), PIK3CA (171834), ARID1A, and KRAS (190070) and novel mutations in the SWI/SNF chromatin remodeling complex gene ARID5B (608538). A subset of endometrioid tumors had a markedly increased transversion mutation frequency and hotspot mutations in POLE (174762). The Cancer Genome Atlas Research Network (2013) concluded that their results classified endometrial cancers into 4 categories: POLE ultramutated, microsatellite instability hypermutated, copy number-low, and copy number-high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. The Cancer Genome Atlas Research Network (2013) demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect postsurgical adjuvant treatment for women with aggressive tumors.
INHERITANCE \- Somatic mutation \- Autosomal dominant NEOPLASIA \- Endometrial cancer MISCELLANEOUS \- Often seen in cancer predisposition syndromes such as hereditary nonpolyposis colorectal cancer (see 614350 and 604395 ) MOLECULAR BASIS \- Caused by somatic mutation in the mutS homolog 3 gene (MSH3, 600887.0001 ) \- Caused by somatic mutation in the mutS homolog 6 gene (MSH6, 600678.0005 ) \- Susceptibility conferred by mutation in the DNA mismatch repair protein MLH3 gene (MLH3, 604395.0006 ) \- Caused by somatic mutation in the cadherin 1 gene (CDH1, 192090.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| ENDOMETRIAL CANCER | c0476089 | 4,091 | omim | https://www.omim.org/entry/608089 | 2019-09-22T16:08:27 | {"doid": ["1380"], "mesh": ["D016889"], "omim": ["608089"]} |
Milwaukee shoulder syndrome
SpecialtyRheumotology
Milwaukee shoulder syndrome (apatite-associated destructive arthritis) is a rheumatological condition similar to calcium pyrophosphate dihydrate deposition disease (CPPD). It is associated with periarticular or intra-articular deposition of hydroxyapatite crystals. Crystal deposition in the joint causes the release of collagenases, serine proteases, elastases, and interleukin-1. This precipitates acute and rapid decline in joint function and degradation of joint anatomy. Subsequently disruption of the rotator cuff ensues.[1][2] Along with symptomatology, the disease typically presents with positive radiologic findings, often showing marked erosion of the humeral head, cartilage, capsule, and bursae. Though rare, it is most often seen in females beginning in their 50s or 60s. Diagnosis is made with arthrocentesis and Alizarin Red staining along with clinical symptoms.[3]
## Contents
* 1 Signs and symptoms
* 2 Diagnosis
* 3 Treatment
* 4 References
## Signs and symptoms[edit]
Signs and symptoms may include the following:
* Limited active range of motion, usually unrestricted passive range of movement (early)
* Joint pain
* Joint inflammation and tenderness
* Synovial hemorrhagic effusion/hematoma
* Radiologic positive findings[4]
* Hydroxyapatite crystals in synovial fluid
## Diagnosis[edit]
Xrays, arthrography, ultrasonography, CT imaging and MRI are helpful in diagnosing this condition[citation needed]
## Treatment[edit]
Treatment may include the prescription of one or more of the following:
* Non-steroidal anti-inflammatory drugs (NSAIDs)
* Intra-articular steroids
* Physical therapy
* Partial or complete arthroplasty
## References[edit]
1. ^ Milwaukee Shoulder Syndrome, Medcyclopedia (with image), via archive.org. Accessed 2013-1-27.
2. ^ Genta, Marcia S., Gambay, Cem. Milwaukee Shoulder. New England Journal of Medicine. 354;2. January 12, 2006
3. ^ Epis O, Viola E, Bruschi E, Benazzo F, Montecucco C.Reumatismo. 2005 Apr-Jun;57(2):69-77
4. ^ "Milwaukee Shoulder Syndrome". Archived from the original on 21 January 2016. Retrieved 9 Jan 2016.
* v
* t
* e
Soft tissue disorders
Capsular joint
Synoviopathy
* Synovitis/Tenosynovitis
* Calcific tendinitis
* Stenosing tenosynovitis
* Trigger finger
* De Quervain syndrome
* Transient synovitis
* Ganglion cyst
* osteochondromatosis
* Synovial osteochondromatosis
* Plica syndrome
* villonodular synovitis
* Giant-cell tumor of the tendon sheath
Bursopathy
* Bursitis
* Olecranon
* Prepatellar
* Trochanteric
* Subacromial
* Achilles
* Retrocalcaneal
* Ischial
* Iliopsoas
* Synovial cyst
* Baker's cyst
* Calcific bursitis
Noncapsular joint
Symptoms
* Ligamentous laxity
* Hypermobility
Enthesopathy/Enthesitis/Tendinopathy
upper limb
* Adhesive capsulitis of shoulder
* Impingement syndrome
* Rotator cuff tear
* Golfer's elbow
* Tennis elbow
lower limb
* Iliotibial band syndrome
* Patellar tendinitis
* Achilles tendinitis
* Calcaneal spur
* Metatarsalgia
* Bone spur
other/general:
* Tendinitis/Tendinosis
Nonjoint
Fasciopathy
* Fasciitis: Plantar
* Nodular
* Necrotizing
* Eosinophilic
Fibromatosis/contracture
* Dupuytren's contracture
* Plantar fibromatosis
* Aggressive fibromatosis
* Knuckle pads
* v
* t
* e
Diseases of joints
General
* Arthritis
* Monoarthritis
* Oligoarthritis
* Polyarthritis
Symptoms
* Joint pain
* Joint stiffness
Inflammatory
Infectious
* Septic arthritis
* Tuberculosis arthritis
Crystal
* Chondrocalcinosis
* CPPD (Psudogout)
* Gout
Seronegative
* Reactive arthritis
* Psoriatic arthritis
* Ankylosing spondylitis
Other
* Juvenile idiopathic arthritis
* Rheumatoid arthritis
* Felty's syndrome
* Palindromic rheumatism
* Adult-onset Still's disease
Noninflammatory
* Hemarthrosis
* Osteoarthritis
* Heberden's node
* Bouchard's nodes
* Osteophyte
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Milwaukee shoulder syndrome | c0409860 | 4,092 | wikipedia | https://en.wikipedia.org/wiki/Milwaukee_shoulder_syndrome | 2021-01-18T18:32:03 | {"mesh": ["D000070656"], "umls": ["C0409860"], "wikidata": ["Q3961663"]} |
## Clinical Features
Johnson et al. (1983) described a 'new' autosomal dominant neuroectodermal syndrome in which anosmia and hypogonadotropic hypogonadism were combined with conductive deafness, alopecia, and other anomalies. In 3 generations, 16 persons were affected. Deafness was associated with protruding ears, microtia, and/or atresia of the external auditory canal. There was an increased tendency to dental caries. Variable features included congenital heart defect, cleft palate, mild facial asymmetry, and mental retardation. The manifestations were explained on the basis of involvement of the ectoderm and neuroectoderm of the first 2 branchial arches, the Rathke pouch, and the diencephalon. There were several instances of male-to-male transmission. Johnston et al. (1987) reported a single patient in whom hypohidrosis was a conspicuous feature.
Hennekam and Holtus (1993) reported mother and son with facial nerve palsy, multiple truncal cafe-au-lait spots, and mild developmental delay. The mother also had hyposmia, increased tendency to caries and growth retardation; the son had hypotrichosis, hearing loss, and microtia. Bankier and Rose (1994) questioned the appropriateness of the diagnosis of the Johnson-McMillin syndrome in the family reported by Hennekam and Holtus (1993). They suggested that the manifestations in the mother and child fitted more in the oculoauriculovertebral spectrum (164210).
Schweitzer et al. (2003) described a female patient with features resembling those of previously reported cases of Johnson-McMillin syndrome. She was noted at birth to have multiple congenital anomalies including tetralogy of Fallot, microcephaly, total alopecia, cleft palate, micrognathia, bilateral microtia with canal atresia, preaxial polydactyly of the right hand, and a 2-vessel umbilical cord. The patient's mother had a history choanal stenosis and hyposmia, with total alopecia as an infant.
Inheritance
Male-to-male transmission in the family reported by Johnson et al. (1983) supports autosomal dominant inheritance.
INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature Other \- Growth retardation HEAD & NECK Head \- Alopecia, total (in some patients) \- Sparse hair (in some patients) \- Microcephaly (rare) Face \- Mild facial asymmetry (in some patients) \- Retrognathia (rare) Ears \- Protruding ears \- Microtia \- External auditory canal atresia \- Conductive deafness Eyes \- Absent eyebrows \- Absent eyelashes Nose \- Anosmia or hyposmia (in some patients) \- Choanal stenosis (rare) Mouth \- Cleft palate (rare) Teeth \- Tendency to dental caries CARDIOVASCULAR Heart \- Ventricular septal defect (rare) \- Tetralogy of Fallot (rare) Coarctation of the aorta (rare) \- Right aortic arch (rare) \- Atrial septal defect, ostium secundum (rare) \- Small left ventricle (rare) \- Small left atrium (rare) \- Endocardial fibroelastosis of the left ventricle (rare) Vascular \- Patent ductus arteriosus (rare) GENITOURINARY External Genitalia (Male) \- Small penis (rare) Internal Genitalia (Male) \- Small testes (rare) SKELETAL Skull \- Microcephaly (rare) SKIN, NAILS, & HAIR Skin \- Hypohidrosis \- Multiple truncal cafe-au-lait spots (rare) Hair \- Alopecia, total or partial NEUROLOGIC Central Nervous System \- Mental retardation (in some patients) Peripheral Nervous System \- Facial nerve palsy (in some patients) ENDOCRINE FEATURES \- Hypogonadotropic hypogonadism (rare) ▲ Close
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*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| JOHNSON NEUROECTODERMAL SYNDROME | c0796002 | 4,093 | omim | https://www.omim.org/entry/147770 | 2019-09-22T16:39:23 | {"mesh": ["C535882"], "omim": ["147770"], "orphanet": ["2316"], "synonyms": ["Alternative titles", "JOHNSON-MCMILLIN SYNDROME", "ALOPECIA-ANOSMIA-DEAFNESS-HYPOGONADISM SYNDROME", "AADH SYNDROME"]} |
A rare neurodegenerative disease usually presenting before the age of 30 and which is characterized by dystonia, L-dopa-responsive parkinsonism, pyramidal signs and rapid cognitive decline.
## Epidemiology
Prevalence is unknown. Only 14 cases have been reported to date.
## Clinical description
Disease onset occurs in late adolescence or early adulthood (usually before the age of 30) and usually presents with parkinsonism (tremor, rigidity, bradykinesia), dystonia and rapid cognitive decline. Eye movement abnormalities (supranuclear vertical gaze palsy, eyelid opening apraxia), pyramidal tract signs, and psychiatric features such as depression and personality changes have also been reported in some patients. Dopaminergic treatment is initially successful with regard to parkinsonism, but the development of prominent dyskinesias often follows.
## Etiology
Adult-onset dystonia-parkinsonism is caused by mutations in the phospholipase A2, group VI (PLA2G6) gene located on chromosome 22q13.1.
## Genetic counseling
Adult-onset dystonia-parkinsonism is inherited in an autosomal recessive manner, and genetic counseling is possible and recommended.
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Adult-onset dystonia-parkinsonism | c2751842 | 4,094 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=199351 | 2021-01-23T18:11:58 | {"gard": ["12568"], "mesh": ["C567844"], "omim": ["612953"], "umls": ["C2751842"], "icd-10": ["G24.1"], "synonyms": ["Dystonia-parkinsonism, Paisan-Ruiz type", "PARK14", "PLA2G6-related dystonia-parkinsonism"]} |
A number sign (#) is used with this entry because of evidence that cone-rod dystrophy-12 (CORD12) is caused by homozygous or heterozygous mutation in the PROM1 gene (604365) on chromosome 4p15.
For a general phenotypic description and a discussion of genetic heterogeneity of cone-rod dystrophy, see 120970.
Clinical Features
Eidinger et al. (2015) reported 3 sibs, born to consanguineous Jewish parents of Kurdish Iraqi descent, with autosomal recessive cone-rod dystrophy. The sibs had progressive visual loss, central scotomas, photosensitivity, deficient color saturation, and slowly decreasing night vision. Cone and rod ERG responses were reduced, with cones more severely affected.
Mapping
Yang et al. (2008) performed linkage analysis in a 4-generation family segregating autosomal dominant cone-rod dystrophy characterized by both cone and rod photoreceptor degeneration and obtained a lod score of 4.4 on chromosome 4p.
Molecular Genetics
In a 4-generation family segregating autosomal dominant cone-rod dystrophy mapping to chromosome 4p, Yang et al. (2008) identified heterozygosity for a missense mutation in the PROM1 gene (604365.0003). The authors identified the same mutation in a family with Stargardt disease (STGD4; 603786) and a family with retinal macular dystrophy (MCDR2; 608051); the mutation was not found in 400 matched controls.
In 2 sibs with CORD12 from a consanguineous Arab Christian family (MOL0256), Beryozkin et al. (2014) identified homozygosity for a nonsense mutation (L386X; 604365.0004) in the PROM1 gene.
In 3 sibs with CORD12 from a consanguineous Jewish family (TB126) of Kurdish Iraqi descent, Eidinger et al. (2015) identified homozygosity for a 10-bp deletion (604365.0005) in intron 1 of the PROM1 gene. The deletion segregated with the disease in the family and was not detected in public databases or in 101 ethnically-matched control individuals.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| CONE-ROD DYSTROPHY 12 | c3489532 | 4,095 | omim | https://www.omim.org/entry/612657 | 2019-09-22T16:00:53 | {"doid": ["0111019"], "mesh": ["D000071700"], "omim": ["120970", "612657"], "orphanet": ["1872"], "synonyms": []} |
A rare genetic cerebral small vessel disease characterized by leukoencephalopathy and cerebral calcification and cysts due to diffuse cerebral microangiopathy resulting in microcystic and macrocystic parenchymal degeneration. The condition can present at any age from early childhood to late adulthood and manifests as a progressive cerebral degeneration. Symptoms are variable, but restricted to the central nervous systems, and include, among others, slowing of cognitive performance, seizures, and movement disorder with a combination of pyramidal, extrapyramidal, and cerebellar features.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Leukoencephalopathy with calcifications and cysts | c3281200 | 4,096 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=542310 | 2021-01-23T18:24:49 | {"mesh": ["C000598644"], "omim": ["614561"], "synonyms": ["LCC", "Labrune syndrome"]} |
A number sign (#) is used with this entry because the serum level of interleukin-6 (IL6; 147620) is associated with a polymorphism in the gene encoding interleukin-6 receptor (147880) on chromosome 1q21.3.
Mapping
Circulating levels of inflammatory markers can predict cardiovascular disease risk. To identify genes influencing the levels of these markers, Reich et al. (2007) genotyped 1,343 SNPs in 1,184 African Americans from the Health, Aging and Body Composition (Health ABC) Study. Using admixture mapping, they found a significant association of interleukin-6 soluble receptor (IL6SR; see 614689) with European ancestry on chromosome 1 (lod 4.59), in a region (1q21.3) that includes the IL6R gene. Genotyping 19 SNPs showed that the effect was largely explained by an allele of a nonsynonymous SNP in IL6R, rs8192284 (147880.0001), at 4% frequency in West Africans and at 35% frequency in European Americans, first described as associated with IL6SR in a Japanese cohort (Galicia et al., 2004). Reich et al. (2007) replicated this association (P much less than 1.0 x 10(-12)) and also demonstrated a new association with circulating levels of a different molecule, IL6 (P less than 3.4 x 10(-5)). After replication in 1,674 European Americans from Health ABC, the combined result was even more significant: P much less than 1.0 x 10(-12) for IL6SR, and P less than 2.0 x 10(-9) for IL6. After correction for covariates, there was a 1.09- to 1.13-fold increase in IL6SR levels with 1 copy of the C allele of rs8192284 and a 1.24- to 1.43-fold increase with 2 copies, and there was a 1.06- to 1.15-fold increase in IL6 levels with 1 copy of the C allele and a 1.22- to 1.43-fold increase with 2 copies. Surveying cell lines from several different ethnic groups showed no evidence of an association of surface IL6R with rs8192284. This finding supported the hypothesis of Galicia et al. (2004) that the mechanism of action of rs8192284 is to affect cleavage efficiency, because the SNP occurs at the proteolytic cleavage site of IL6R.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| INTERLEUKIN 6, SERUM LEVEL OF, QUANTITATIVE TRAIT LOCUS | c3540094 | 4,097 | omim | https://www.omim.org/entry/614752 | 2019-09-22T15:54:17 | {"omim": ["614752"], "synonyms": ["Alternative titles", "IL6, SERUM LEVEL OF, QUANTITATIVE TRAIT LOCUS"]} |
For other uses, see Diarrhea (disambiguation).
Loose or liquid bowel movements
Diarrhea
Other namesDiarrhoea
An electron micrograph of rotavirus, the cause of nearly 40% of hospitalizations from diarrhea in children under five[1]
SpecialtyInfectious disease, gastroenterology
SymptomsLoose frequent bowel movements, dehydration[2]
CausesUsually infection (viral, bacterial, parasitic)[2]
Risk factorsContaminated food or water[2]
PreventionHandwashing, rotavirus vaccination, breastfeeding[2]
TreatmentOral rehydration solution, zinc supplementation[2]
Frequency≈2.4 billion (2015)[3]
Deaths1.3 million (2015)[4]
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day.[2] It often lasts for a few days and can result in dehydration due to fluid loss.[2] Signs of dehydration often begin with loss of the normal stretchiness of the skin and irritable behaviour.[2] This can progress to decreased urination, loss of skin color, a fast heart rate, and a decrease in responsiveness as it becomes more severe.[2] Loose but non-watery stools in babies who are exclusively breastfed, however, are normal.[2]
The most common cause is an infection of the intestines due to either a virus, bacterium, or parasite—a condition also known as gastroenteritis.[2] These infections are often acquired from food or water that has been contaminated by feces, or directly from another person who is infected.[2] The three types of diarrhea are: short duration watery diarrhea, short duration bloody diarrhea, and persistent diarrhea (lasting more than two weeks, which can be either watery or bloody).[2] The short duration watery diarrhea may be due to cholera, although this is rare in the developed world.[2] If blood is present, it is also known as dysentery.[2] A number of non-infectious causes can result in diarrhea.[5] These include lactose intolerance, irritable bowel syndrome, non-celiac gluten sensitivity, celiac disease, inflammatory bowel disease such as ulcerative colitis, hyperthyroidism, bile acid diarrhea, and a number of medications.[5][6][7] In most cases, stool cultures to confirm the exact cause are not required.[8]
Diarrhea can be prevented by improved sanitation, clean drinking water, and hand washing with soap.[2] Breastfeeding for at least six months and vaccination against rotavirus is also recommended.[2] Oral rehydration solution (ORS)—clean water with modest amounts of salts and sugar—is the treatment of choice.[2] Zinc tablets are also recommended.[2] These treatments have been estimated to have saved 50 million children in the past 25 years.[1] When people have diarrhea it is recommended that they continue to eat healthy food and babies continue to be breastfed.[2] If commercial ORS is not available, homemade solutions may be used.[9] In those with severe dehydration, intravenous fluids may be required.[2] Most cases; however, can be managed well with fluids by mouth.[10] Antibiotics, while rarely used, may be recommended in a few cases such as those who have bloody diarrhea and a high fever, those with severe diarrhea following travelling, and those who grow specific bacteria or parasites in their stool.[8] Loperamide may help decrease the number of bowel movements but is not recommended in those with severe disease.[8]
About 1.7 to 5 billion cases of diarrhea occur per year.[2][5][11] It is most common in developing countries, where young children get diarrhea on average three times a year.[2] Total deaths from diarrhea are estimated at 1.26 million in 2013—down from 2.58 million in 1990.[12] In 2012, it was the second most common cause of deaths in children younger than five (0.76 million or 11%).[2][13] Frequent episodes of diarrhea are also a common cause of malnutrition and the most common cause in those younger than five years of age.[2] Other long term problems that can result include stunted growth and poor intellectual development.[13]
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Video explanation (script)
## Contents
* 1 Definition
* 1.1 Secretory
* 1.2 Osmotic
* 1.3 Exudative
* 1.4 Inflammatory
* 1.5 Dysentery
* 2 Health effects
* 3 Causes
* 3.1 Infections
* 3.1.1 Sanitation
* 3.1.2 Nutrition
* 3.2 Malabsorption
* 3.3 Inflammatory bowel disease
* 3.4 Irritable bowel syndrome
* 3.5 Other diseases
* 3.6 Medications
* 4 Pathophysiology
* 4.1 Evolution
* 5 Diagnostic approach
* 5.1 Chronic diarrhea
* 6 Prevention
* 6.1 Sanitation
* 6.1.1 Hand washing
* 6.1.2 Water
* 6.2 Vaccination
* 6.3 Nutrition
* 6.3.1 Breastfeeding
* 6.4 Others
* 7 Management
* 7.1 Fluids
* 7.2 Eating
* 7.3 Medications
* 7.4 Alternative therapies
* 8 Epidemiology
* 9 Terminology
* 10 See also
* 11 References
* 12 External links
## Definition
Bristol stool chart
Diarrhea is defined by the World Health Organization as having three or more loose or liquid stools per day, or as having more stools than is normal for that person.[2]
Acute diarrhea is defined as an abnormally frequent discharge of semisolid or fluid fecal matter from the bowel, lasting less than 14 days, by World Gastroenterology Organization.[14]
### Secretory
Secretory diarrhea means that there is an increase in the active secretion, or there is an inhibition of absorption. There is little to no structural damage. The most common cause of this type of diarrhea is a cholera toxin that stimulates the secretion of anions, especially chloride ions (Cl–). Therefore, to maintain a charge balance in the gastrointestinal tract, sodium (Na+) is carried with it, along with water. In this type of diarrhea intestinal fluid secretion is isotonic with plasma even during fasting.[15][16] It continues even when there is no oral food intake.
### Osmotic
Osmotic diarrhea occurs when too much water is drawn into the bowels. If a person drinks solutions with excessive sugar or excessive salt, these can draw water from the body into the bowel and cause osmotic diarrhea.[17][16] Osmotic diarrhea can also result from maldigestion, e.g. pancreatic disease or coeliac disease in which the nutrients are left in the lumen to pull in water. Or it can be caused by osmotic laxatives (which work to alleviate constipation by drawing water into the bowels). In healthy individuals, too much magnesium or vitamin C or undigested lactose can produce osmotic diarrhea and distention of the bowel. A person who has lactose intolerance can have difficulty absorbing lactose after an extraordinarily high intake of dairy products. In persons who have fructose malabsorption, excess fructose intake can also cause diarrhea. High-fructose foods that also have a high glucose content are more absorbable and less likely to cause diarrhea. Sugar alcohols such as sorbitol (often found in sugar-free foods) are difficult for the body to absorb and, in large amounts, may lead to osmotic diarrhea.[15] In most of these cases, osmotic diarrhea stops when the offending agent, e.g. milk or sorbitol, is stopped.
### Exudative
Exudative diarrhea occurs with the presence of blood and pus in the stool. This occurs with inflammatory bowel diseases, such as Crohn's disease or ulcerative colitis, and other severe infections such as E. coli or other forms of food poisoning.[16][15]
### Inflammatory
Inflammatory diarrhea occurs when there is damage to the mucosal lining or brush border, which leads to a passive loss of protein-rich fluids and a decreased ability to absorb these lost fluids. Features of all three of the other types of diarrhea can be found in this type of diarrhea.[18] It can be caused by bacterial infections, viral infections, parasitic infections, or autoimmune problems such as inflammatory bowel diseases. It can also be caused by tuberculosis, colon cancer, and enteritis.[16]
### Dysentery
If there is blood visible in the stools, it is also known as dysentery. The blood is a trace of an invasion of bowel tissue. Dysentery is a symptom of, among others, Shigella, Entamoeba histolytica, and Salmonella.[16]
## Health effects
Diarrheal disease may have a negative impact on both physical fitness and mental development. "Early childhood malnutrition resulting from any cause reduces physical fitness and work productivity in adults,"[19] and diarrhea is a primary cause of childhood malnutrition.[20] Further, evidence suggests that diarrheal disease has significant impacts on mental development and health; it has been shown that, even when controlling for helminth infection and early breastfeeding, children who had experienced severe diarrhea had significantly lower scores on a series of tests of intelligence.[19][21]
Diarrhea can cause electrolyte imbalances, kidney impairment, dehydration, and defective immune system responses. When oral drugs are administered, the efficiency of the drug is to produce a therapeutic effect and the lack of this effect may be due to the medication travelling too quickly through the digestive system, limiting the time that it can be absorbed. Clinicians try to treat the diarrheas by reducing the dosage of medication, changing the dosing schedule, discontinuation of the drug, and rehydration. The interventions to control the diarrhea are not often effective. Diarrhea can have a profound effect on the quality of life because fecal incontinence is one of the leading factors for placing older adults in long term care facilities (nursing homes).[16]
## Causes
Diagram of the human gastrointestinal tract
Acute diarrhea is most commonly due to viral gastroenteritis with rotavirus, which accounts for 40% of cases in children under five.[1] In travelers, however, bacterial infections predominate.[22] Various toxins such as mushroom poisoning and drugs can also cause acute diarrhea.
Chronic diarrhea can be the part of the presentations of a number of chronic medical conditions affecting the intestine. Common causes include ulcerative colitis, Crohn disease, microscopic colitis, celiac disease, irritable bowel syndrome, and bile acid malabsorption.
### Infections
Main article: Infectious diarrhea
There are many causes of infectious diarrhea, which include viruses, bacteria and parasites.[23] Infectious diarrhea is frequently referred to as gastroenteritis.[24] Norovirus is the most common cause of viral diarrhea in adults,[25] but rotavirus is the most common cause in children under five years old.[26] Adenovirus types 40 and 41,[27] and astroviruses cause a significant number of infections.[28] Shiga-toxin producing Escherichia coli, such as E coli o157:h7, are the most common cause of infectious bloody diarrhea in the United States.
Campylobacter spp. are a common cause of bacterial diarrhea, but infections by Salmonella spp., Shigella spp. and some strains of Escherichia coli are also a frequent cause.[29]
In the elderly, particularly those who have been treated with antibiotics for unrelated infections, a toxin produced by Clostridioides difficile often causes severe diarrhea.[30]
Parasites, particularly protozoa e.g., Cryptosporidium spp., Giardia spp., Entamoeba histolytica, Blastocystis spp., Cyclospora cayetanensis, are frequently the cause of diarrhea that involves chronic infection. The broad-spectrum antiparasitic agent nitazoxanide has shown efficacy against many diarrhea-causing parasites.[31]
Other infectious agents, such as parasites or bacterial toxins, may exacerbate symptoms.[22] In sanitary living conditions where there is ample food and a supply of clean water, an otherwise healthy person usually recovers from viral infections in a few days. However, for ill or malnourished individuals, diarrhea can lead to severe dehydration and can become life-threatening.[32]
#### Sanitation
Poverty often leads to unhygienic living conditions, as in this community in the Indian Himalayas. Such conditions promote contraction of diarrheal diseases, as a result of poor sanitation and hygiene.
Open defecation is a leading cause of infectious diarrhea leading to death.[33]
Poverty is a good indicator of the rate of infectious diarrhea in a population. This association does not stem from poverty itself, but rather from the conditions under which impoverished people live. The absence of certain resources compromises the ability of the poor to defend themselves against infectious diarrhea. "Poverty is associated with poor housing, crowding, dirt floors, lack of access to clean water or to sanitary disposal of fecal waste (sanitation), cohabitation with domestic animals that may carry human pathogens, and a lack of refrigerated storage for food, all of which increase the frequency of diarrhea ... Poverty also restricts the ability to provide age-appropriate, nutritionally balanced diets or to modify diets when diarrhea develops so as to mitigate and repair nutrient losses. The impact is exacerbated by the lack of adequate, available, and affordable medical care."[34]
One of the most common causes of infectious diarrhea is a lack of clean water. Often, improper fecal disposal leads to contamination of groundwater. This can lead to widespread infection among a population, especially in the absence of water filtration or purification. Human feces contains a variety of potentially harmful human pathogens.[35]
#### Nutrition
Proper nutrition is important for health and functioning, including the prevention of infectious diarrhea. It is especially important to young children who do not have a fully developed immune system. Zinc deficiency, a condition often found in children in developing countries can, even in mild cases, have a significant impact on the development and proper functioning of the human immune system.[36][37] Indeed, this relationship between zinc deficiency and reduced immune functioning corresponds with an increased severity of infectious diarrhea. Children who have lowered levels of zinc have a greater number of instances of diarrhea, severe diarrhea, and diarrhea associated with fever.[38] Similarly, vitamin A deficiency can cause an increase in the severity of diarrheal episodes. However, there is some discrepancy when it comes to the impact of vitamin A deficiency on the rate of disease. While some argue that a relationship does not exist between the rate of disease and vitamin A status,[39] Others suggest an increase in the rate associated with deficiency.[40] Given that estimates suggest 127 million preschool children worldwide are vitamin A deficient, this population has the potential for increased risk of disease contraction.[41]
### Malabsorption
Main article: Malabsorption
Malabsorption is the inability to absorb food fully, mostly from disorders in the small bowel, but also due to maldigestion from diseases of the pancreas.
Causes include:
* enzyme deficiencies or mucosal abnormality, as in food allergy and food intolerance, e.g. celiac disease (gluten intolerance), lactose intolerance (intolerance to milk sugar, common in non-Europeans), and fructose malabsorption.
* pernicious anemia, or impaired bowel function due to the inability to absorb vitamin B12,
* loss of pancreatic secretions, which may be due to cystic fibrosis or pancreatitis,
* structural defects, like short bowel syndrome (surgically removed bowel) and radiation fibrosis, such as usually follows cancer treatment and other drugs, including agents used in chemotherapy; and
* certain drugs, like orlistat, which inhibits the absorption of fat.
### Inflammatory bowel disease
Main article: Inflammatory bowel disease
The two overlapping types here are of unknown origin:
* Ulcerative colitis is marked by chronic bloody diarrhea and inflammation mostly affects the distal colon near the rectum.
* Crohn's disease typically affects fairly well demarcated segments of bowel in the colon and often affects the end of the small bowel.
### Irritable bowel syndrome
Main article: Irritable bowel syndrome
Another possible cause of diarrhea is irritable bowel syndrome (IBS), which usually presents with abdominal discomfort relieved by defecation and unusual stool (diarrhea or constipation) for at least three days a week over the previous three months.[42] Symptoms of diarrhea-predominant IBS can be managed through a combination of dietary changes, soluble fiber supplements and medications such as loperamide or codeine. About 30% of patients with diarrhea-predominant IBS have bile acid malabsorption diagnosed with an abnormal SeHCAT test.[43]
### Other diseases
Diarrhea can be caused by other diseases and conditions, namely:
* Chronic ethanol ingestion[44]
* Hyperthyroidism[45]
* Certain medications[45]
* Bile acid malabsorption[45]
* Ischemic bowel disease: This usually affects older people and can be due to blocked arteries.
* Microscopic colitis, a type of inflammatory bowel disease where changes are seen only on histological examination of colonic biopsies.
* Bile salt malabsorption (primary bile acid diarrhea) where excessive bile acids in the colon produce a secretory diarrhea.
* Hormone-secreting tumors: some hormones, e.g. serotonin), can cause diarrhea if excreted in excess (usually from a tumor).
* Chronic mild diarrhea in infants and toddlers may occur with no obvious cause and with no other ill effects; this condition is called toddler's diarrhea.
* Environmental enteropathy
* Radiation enteropathy following treatment for pelvic and abdominal cancers.
### Medications
Some medications, such as the penicillum can cause diarrhea.[46][47] Over 700 medications are known to cause diarrhea. The classes of medications that are known to cause diarrhea are laxatives, antacids, heartburn medications, antibiotics, anti-neoplastic drugs, anti-inflammatories as well as many dietary supplements.[16]
## Pathophysiology
Ion transporters targeted by enteric infections [48] Function Transporter
Absorption NHE, SGLT1, ENaC, DRA
Secretion CaCC, NKCC1, CFTR
Absorption and secretion Sodium potassium ATPase
### Evolution
According to two researchers, Nesse and Williams, diarrhea may function as an evolved expulsion defense mechanism. As a result, if it is stopped, there might be a delay in recovery.[49] They cite in support of this argument research published in 1973 that found that treating Shigella with the anti-diarrhea drug (Co-phenotrope, Lomotil) caused people to stay feverish twice as long as those not so treated. The researchers indeed themselves observed that: "Lomotil may be contraindicated in shigellosis. Diarrhea may represent a defense mechanism".[50]
## Diagnostic approach
The following types of diarrhea may indicate further investigation is needed:
* In infants
* Moderate or severe diarrhea in young children
* Associated with blood
* Continues for more than two days
* Associated non-cramping abdominal pain, fever, weight loss, etc.
* In travelers
* In food handlers, because of the potential to infect others;
* In institutions such as hospitals, child care centers, or geriatric and convalescent homes.
A severity score is used to aid diagnosis in children.[51]
### Chronic diarrhea
When diarrhea lasts for more than four weeks a number of further tests may be recommended including:[52]
* Complete blood count and a ferritin if anemia is present
* Thyroid stimulating hormone
* Tissue transglutaminase for celiac disease
* Fecal calprotectin to exclude inflammatory bowel disease
* Stool tests for ova and parasites as well as for Clostridioides difficile
* A colonoscopy or fecal immunochemical testing for cancer, including biopsies to detect microscopic colitis
* Testing for bile acid diarrhea with SeHCAT, 7α-hydroxy-4-cholesten-3-one or fecal bile acids depending on availability
* Hydrogen breath test looking for lactose intolerance
* Further tests if immunodeficiency, pelvic radiation disease or small intestinal bacterial overgrowth suspected.
A 2019 guideline recommended that testing for ova and parasites was only needed in people who are at high risk though they recommend routine testing for giardia.[53] Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were not recommended.[53]
## Prevention
### Sanitation
Numerous studies have shown that improvements in drinking water and sanitation (WASH) lead to decreased risks of diarrhoea.[54] Such improvements might include for example use of water filters, provision of high-quality piped water and sewer connections.[54]
In institutions, communities, and households, interventions that promote hand washing with soap lead to significant reductions in the incidence of diarrhea.[55] The same applies to preventing open defecation at a community-wide level and providing access to improved sanitation.[56][57] This includes use of toilets and implementation of the entire sanitation chain connected to the toilets (collection, transport, disposal or reuse of human excreta).
There is limited evidence that safe disposal of child or adult feces can prevent diarrheal disease.[58][59]
#### Hand washing
Basic sanitation techniques can have a profound effect on the transmission of diarrheal disease. The implementation of hand washing using soap and water, for example, has been experimentally shown to reduce the incidence of disease by approximately 42–48%.[60][61] Hand washing in developing countries, however, is compromised by poverty as acknowledged by the CDC: "Handwashing is integral to disease prevention in all parts of the world; however, access to soap and water is limited in a number of less developed countries. This lack of access is one of many challenges to proper hygiene in less developed countries." Solutions to this barrier require the implementation of educational programs that encourage sanitary behaviours.[62]
#### Water
Given that water contamination is a major means of transmitting diarrheal disease, efforts to provide clean water supply and improved sanitation have the potential to dramatically cut the rate of disease incidence. In fact, it has been proposed that we might expect an 88% reduction in child mortality resulting from diarrheal disease as a result of improved water sanitation and hygiene.[35][63] Similarly, a meta-analysis of numerous studies on improving water supply and sanitation shows a 22–27% reduction in disease incidence, and a 21–30% reduction in mortality rate associated with diarrheal disease.[64]
Chlorine treatment of water, for example, has been shown to reduce both the risk of diarrheal disease, and of contamination of stored water with diarrheal pathogens.[65]
### Vaccination
Immunization against the pathogens that cause diarrheal disease is a viable prevention strategy, however it does require targeting certain pathogens for vaccination. In the case of Rotavirus, which was responsible for around 6% of diarrheal episodes and 20% of diarrheal disease deaths in the children of developing countries, use of a Rotavirus vaccine in trials in 1985 yielded a slight (2–3%) decrease in total diarrheal disease incidence, while reducing overall mortality by 6–10%. Similarly, a Cholera vaccine showed a strong reduction in morbidity and mortality, though the overall impact of vaccination was minimal as Cholera is not one of the major causative pathogens of diarrheal disease.[66] Since this time, more effective vaccines have been developed that have the potential to save many thousands of lives in developing nations, while reducing the overall cost of treatment, and the costs to society.[67][68]
Rotavirus vaccine decrease the rates of diarrhea in a population.[1][69] New vaccines against rotavirus, Shigella, Enterotoxigenic Escherichia coli (ETEC), and cholera are under development, as well as other causes of infectious diarrhea.[medical citation needed]
### Nutrition
Dietary deficiencies in developing countries can be combated by promoting better eating practices. Zinc supplementation proved successful showing a significant decrease in the incidence of diarrheal disease compared to a control group.[70][71] The majority of the literature suggests that vitamin A supplementation is advantageous in reducing disease incidence.[72] Development of a supplementation strategy should take into consideration the fact that vitamin A supplementation was less effective in reducing diarrhea incidence when compared to vitamin A and zinc supplementation, and that the latter strategy was estimated to be significantly more cost effective.[73]
#### Breastfeeding
Breastfeeding practices have been shown to have a dramatic effect on the incidence of diarrheal disease in poor populations. Studies across a number of developing nations have shown that those who receive exclusive breastfeeding during their first 6 months of life are better protected against infection with diarrheal diseases.[74] One study in Brazil found that non-breastfed infants were 14 times more likely to die from diarrhea than exclusively breastfed infants.[75] Exclusive breastfeeding is currently recommended for the first six months of an infant's life by the WHO,[76][77] with continued breastfeeding until at least two years of age.[77]
### Others
Probiotics decrease the risk of diarrhea in those taking antibiotics.[78] Insecticide spraying may reduce fly numbers and the risk of diarrhea in children in a setting where there is seasonal variations in fly numbers throughout the year.[79]
## Management
In many cases of diarrhea, replacing lost fluid and salts is the only treatment needed. This is usually by mouth – oral rehydration therapy – or, in severe cases, intravenously.[1] Diet restrictions such as the BRAT diet are no longer recommended.[80] Research does not support the limiting of milk to children as doing so has no effect on duration of diarrhea.[81] To the contrary, WHO recommends that children with diarrhea continue to eat as sufficient nutrients are usually still absorbed to support continued growth and weight gain, and that continuing to eat also speeds up recovery of normal intestinal functioning.[17] CDC recommends that children and adults with cholera also continue to eat.[82] There is no evidence that early refeeding in children can cause an increase in inappropriate use of intravenous fluid, episodes of vomiting, and risk of having persistent diarrhea.[83]
Medications such as loperamide (Imodium) and bismuth subsalicylate may be beneficial; however they may be contraindicated in certain situations.[84]
### Fluids
See also: Management of dehydration
A person consuming oral rehydration solution
Oral rehydration solution (ORS) (a slightly sweetened and salty water) can be used to prevent dehydration. Standard home solutions such as salted rice water, salted yogurt drinks, vegetable and chicken soups with salt can be given. Home solutions such as water in which cereal has been cooked, unsalted soup, green coconut water, weak tea (unsweetened), and unsweetened fresh fruit juices can have from half a teaspoon to full teaspoon of salt (from one-and-a-half to three grams) added per liter. Clean plain water can also be one of several fluids given.[17] There are commercial solutions such as Pedialyte, and relief agencies such as UNICEF widely distribute packets of salts and sugar. A WHO publication for physicians recommends a homemade ORS consisting of one liter water with one teaspoon salt (3 grams) and two tablespoons sugar (18 grams) added[17] (approximately the "taste of tears"[85]). Rehydration Project recommends adding the same amount of sugar but only one-half a teaspoon of salt, stating that this more dilute approach is less risky with very little loss of effectiveness.[86] Both agree that drinks with too much sugar or salt can make dehydration worse.[17][86]
Appropriate amounts of supplemental zinc and potassium should be added if available. But the availability of these should not delay rehydration. As WHO points out, the most important thing is to begin preventing dehydration as early as possible.[17] In another example of prompt ORS hopefully preventing dehydration, CDC recommends for the treatment of cholera continuing to give Oral Rehydration Solution during travel to medical treatment.[82]
Vomiting often occurs during the first hour or two of treatment with ORS, especially if a child drinks the solution too quickly, but this seldom prevents successful rehydration since most of the fluid is still absorbed. WHO recommends that if a child vomits, to wait five or ten minutes and then start to give the solution again more slowly.[17]
Drinks especially high in simple sugars, such as soft drinks and fruit juices, are not recommended in children under five as they may increase dehydration. A too rich solution in the gut draws water from the rest of the body, just as if the person were to drink sea water.[17][87] Plain water may be used if more specific and effective ORT preparations are unavailable or are not palatable.[87] Additionally, a mix of both plain water and drinks perhaps too rich in sugar and salt can alternatively be given to the same person, with the goal of providing a medium amount of sodium overall.[17] A nasogastric tube can be used in young children to administer fluids if warranted.[88]
### Eating
The WHO recommends a child with diarrhea continue to be fed. Continued feeding speeds the recovery of normal intestinal function. In contrast, children whose food is restricted have diarrhea of longer duration and recover intestinal function more slowly. The WHO states "Food should never be withheld and the child's usual foods should not be diluted. Breastfeeding should always be continued."[17] And in the specific example of cholera, CDC also makes the same recommendation.[82] Breastfed infants with diarrhea often choose to breastfeed more, and should be encouraged to do so.[17] In young children who are not breast-fed and live in the developed world, a lactose-free diet may be useful to speed recovery.[89] Eating food containing fibers may help.[90]
### Medications
Main article: Antidiarrhoeal
Antidiarrheal agents can be classified into four different groups: antimotility, antisecretory, adsorbent, and anti-infectious.[91] While antibiotics are beneficial in certain types of acute diarrhea, they are usually not used except in specific situations.[92][93] There are concerns that antibiotics may increase the risk of hemolytic uremic syndrome in people infected with Escherichia coli O157:H7.[94] In resource-poor countries, treatment with antibiotics may be beneficial.[93] However, some bacteria are developing antibiotic resistance, particularly Shigella.[95] Antibiotics can also cause diarrhea, and antibiotic-associated diarrhea is the most common adverse effect of treatment with general antibiotics.
While bismuth compounds (Pepto-Bismol) decreased the number of bowel movements in those with travelers' diarrhea, they do not decrease the length of illness.[96] Anti-motility agents like loperamide are also effective at reducing the number of stools but not the duration of disease.[8] These agents should be used only if bloody diarrhea is not present.[97]
Diosmectite, a natural aluminomagnesium silicate clay, is effective in alleviating symptoms of acute diarrhea in children,[98] and also has some effects in chronic functional diarrhea, radiation-induced diarrhea, and chemotherapy-induced diarrhea.[45] Another absorbent agent used for the treatment of mild diarrhea is kaopectate.
Racecadotril an antisecretory medication may be used to treat diarrhea in children and adults.[91] It has better tolerability than loperamide, as it causes less constipation and flatulence.[99] However, it has little benefit in improving acute diarrhea in children.[100]
Bile acid sequestrants such as cholestyramine can be effective in chronic diarrhea due to bile acid malabsorption. Therapeutic trials of these drugs are indicated in chronic diarrhea if bile acid malabsorption cannot be diagnosed with a specific test, such as SeHCAT retention.[101]
### Alternative therapies
Zinc supplementation may benefit children over six months old with diarrhea in areas with high rates of malnourishment or zinc deficiency.[102] This supports the World Health Organization guidelines for zinc, but not in the very young.
Probiotics (such as Lactobacillus GG and Saccharomyces boulardii[91]) reduce the duration of symptoms by one day and reduced the chances of symptoms lasting longer than four days by 60%.[103] The probiotic lactobacillus can help prevent antibiotic-associated diarrhea in adults but possibly not children.[104] For those with lactose intolerance, taking digestive enzymes containing lactase when consuming dairy products often improves symptoms.
## Epidemiology
Deaths due to diarrhoeal diseases per million persons in 2012
0–2
3–10
11–18
19–30
31–46
47–80
81–221
222–450
451–606
607–1799
Disability-adjusted life year for diarrhea per 100,000 inhabitants in 2004[105]
no data
< 500
500–1000
1000–1500
1500–2000
2000–2500
2500–3000
3000–3500
3500–4000
4000–4500
4500–5000
5000–6000
> 6000
Worldwide in 2004, approximately 2.5 billion cases of diarrhea occurred, which resulted in 1.5 million deaths among children under the age of five.[1] Greater than half of these were in Africa and South Asia.[1] This is down from a death rate of 4.5 million in 1980 for gastroenteritis.[106] Diarrhea remains the second leading cause of infant mortality (16%) after pneumonia (17%) in this age group.[1]
The majority of such cases occur in the developing world, with over half of the recorded cases of childhood diarrhea occurring in Africa and Asia, with 696 million and 1.2 billion cases, respectively, compared to only 480 million in the rest of the world.[107]
Infectious diarrhea resulted in about 0.7 million deaths in children under five years old in 2011 and 250 million lost school days.[56][108] In the Americas, diarrheal disease accounts for a total of 10% of deaths among children aged 1–59 months while in South East Asia, it accounts for 31.3% of deaths.[109] It is estimated that around 21% of child mortalities in developing countries are due to diarrheal disease.[110]
## Terminology
The word diarrhea is from the Ancient Greek διάρροια from διά dia "through" and ῥέω rheo "flow".
Diarrhea is the spelling in American English, whereas diarrhoea is the spelling in British English.
Slang terms for the condition include "the runs", "the squirts" (or "squits" in Britain[111]) and "the trots".[112][113]
## See also
* Dysentery
* Travelers' diarrhea
## References
1. ^ a b c d e f g h "whqlibdoc.who.int" (PDF). World Health Organization. Archived (PDF) from the original on 8 November 2010.
2. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z "Diarrhoeal disease Factsheet". World Health Organization. 2 May 2017. Retrieved 29 October 2020.
3. ^ GBD 2015 Disease and Injury Incidence and Prevalence Collaborators (October 2016). "Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1545–1602. doi:10.1016/S0140-6736(16)31678-6. PMC 5055577. PMID 27733282.
4. ^ GBD 2015 Mortality and Causes of Death Collaborators (October 2016). "Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1459–1544. doi:10.1016/s0140-6736(16)31012-1. PMC 5388903. PMID 27733281.
5. ^ a b c Abdelmalak B, Doyle J, eds. (2013). Anesthesia for otolaryngologic surgery. Cambridge University Press. pp. 282–287. ISBN 978-1-107-01867-9.
6. ^ Sapone A, Bai JC, Ciacci C, Dolinsek J, Green PH, Hadjivassiliou M, et al. (February 2012). "Spectrum of gluten-related disorders: consensus on new nomenclature and classification". BMC Medicine (Review). 10: 13. doi:10.1186/1741-7015-10-13. PMC 3292448. PMID 22313950.
7. ^ Slattery SA, Niaz O, Aziz Q, Ford AC, Farmer AD (July 2015). "Systematic review with meta-analysis: the prevalence of bile acid malabsorption in the irritable bowel syndrome with diarrhoea" (PDF). Alimentary Pharmacology & Therapeutics. 42 (1): 3–11. doi:10.1111/apt.13227. PMID 25913530. S2CID 34603226.
8. ^ a b c d DuPont HL (April 2014). "Acute infectious diarrhea in immunocompetent adults". The New England Journal of Medicine. 370 (16): 1532–40. doi:10.1056/nejmra1301069. PMID 24738670.
9. ^ Crockett ME, Keystone JS (2012). "Protection of Travelers". In Fischer M, Long SS, Prober CG (eds.). Principles and practice of pediatric infectious diseases (4th ed.). Edinburgh: Elsevier Saunders. p. 82. ISBN 978-1-4557-3985-1.
10. ^ ACEP. "Nation's Emergency Physicians Announce List of Test and Procedures to Question as Part of Choosing Wisely Campaign". Choosing Wisely. Archived from the original on 17 May 2014. Retrieved 18 June 2014.
11. ^ Global Burden of Disease Study 2013 Collaborators (August 2015). "Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013". Lancet. 386 (9995): 743–800. doi:10.1016/s0140-6736(15)60692-4. PMC 4561509. PMID 26063472.
12. ^ GBD 2013 Mortality and Causes of Death Collaborators (January 2015). "Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013". Lancet. 385 (9963): 117–71. doi:10.1016/S0140-6736(14)61682-2. PMC 4340604. PMID 25530442.
13. ^ a b "Global Diarrhea Burden". CDC. 24 January 2013. Archived from the original on 7 July 2014. Retrieved 18 June 2014.
14. ^ "WGO Practice Guideline – Acute diarrhea". Archived from the original on 22 February 2011. Retrieved 9 March 2011.
15. ^ a b c "The Basics of Diarrhea". Webmd.com. 17 February 2011. Archived from the original on 11 March 2011. Retrieved 9 March 2011.
16. ^ a b c d e f g Moon C, Zhang W, Sundaram N, Yarlagadda S, Reddy VS, Arora K, Helmrath MA, Naren AP (December 2015). "Drug-induced secretory diarrhea: A role for CFTR". Pharmacological Research. 102: 107–112. doi:10.1016/j.phrs.2015.08.024. PMC 4684461. PMID 26429773.
17. ^ a b c d e f g h i j k "The Treatment Of Diarrhea, A manual for physicians and other senior health workers" (PDF). Sometimes needs to be downloaded twice. See "4.2 Treatment Plan A: home therapy to prevent dehydration and malnutrition," "4.3 Treatment Plan B: oral rehydration therapy for children with some dehydration," and "4.4 Treatment Plan C: for patients with severe dehydration" on pages 8 to 16 (12–20 in PDF). See also "8. Management of Diarrhoea with Severe Malnutrition" on pages 22–24 (26–30 in PDF) and "Annex 2: Oral and Intravenous Rehydration Solutions" on pages 33–37 (37–41 in PDF). World Health Organization. 2005. Archived (PDF) from the original on 19 October 2011.
18. ^ Sweetser S (June 2012). "Evaluating the patient with diarrhea: a case-based approach". Mayo Clinic Proceedings. 87 (6): 596–602. doi:10.1016/j.mayocp.2012.02.015. PMC 3538472. PMID 22677080.
19. ^ a b Disease Control Priorities Project. "Public Health Significance of Diarrheal Illnesses". The World Bank Group. Archived from the original on 25 January 2014. Retrieved 12 October 2013.
20. ^ Guerrant RL, Schorling JB, McAuliffe JF, de Souza MA (July 1992). "Diarrhea as a cause and an effect of malnutrition: diarrhea prevents catch-up growth and malnutrition increases diarrhea frequency and duration". The American Journal of Tropical Medicine and Hygiene. 47 (1 Pt 2): 28–35. doi:10.4269/ajtmh.1992.47.28. PMID 1632474.
21. ^ Grantham-McGregor SM, Walker SP, Chang S (February 2000). "Nutritional deficiencies and later behavioural development". The Proceedings of the Nutrition Society. 59 (1): 47–54. doi:10.1017/S0029665100000069. PMID 10828173.
22. ^ a b Wilson ME (December 2005). "Diarrhea in nontravelers: risk and etiology". Clinical Infectious Diseases. 41. 41 Suppl 8 (Suppl 8): S541-6. doi:10.1086/432949. PMID 16267716.
23. ^ Navaneethan U, Giannella RA (November 2008). "Mechanisms of infectious diarrhea". Nature Clinical Practice. Gastroenterology & Hepatology. 5 (11): 637–47. doi:10.1038/ncpgasthep1264. PMID 18813221. S2CID 34096072.
24. ^ Schlossberg D (2008). Clinical Infectious Disease. Cambridge University Press. p. 349. ISBN 978-1-139-57665-9.
25. ^ Patel MM, Hall AJ, Vinjé J, Parashar UD (January 2009). "Noroviruses: a comprehensive review". Journal of Clinical Virology. 44 (1): 1–8. doi:10.1016/j.jcv.2008.10.009. PMID 19084472.
26. ^ Greenberg HB, Estes MK (May 2009). "Rotaviruses: from pathogenesis to vaccination". Gastroenterology. 136 (6): 1939–51. doi:10.1053/j.gastro.2009.02.076. PMC 3690811. PMID 19457420.
27. ^ Uhnoo I, Svensson L, Wadell G (September 1990). "Enteric adenoviruses". Baillière's Clinical Gastroenterology. 4 (3): 627–42. doi:10.1016/0950-3528(90)90053-J. PMID 1962727.
28. ^ Mitchell DK (November 2002). "Astrovirus gastroenteritis". The Pediatric Infectious Disease Journal. 21 (11): 1067–9. doi:10.1097/00006454-200211000-00018. PMID 12442031.
29. ^ Viswanathan VK, Hodges K, Hecht G (February 2009). "Enteric infection meets intestinal function: how bacterial pathogens cause diarrhoea". Nature Reviews. Microbiology. 7 (2): 110–9. doi:10.1038/nrmicro2053. PMC 3326399. PMID 19116615.
30. ^ Rupnik M, Wilcox MH, Gerding DN (July 2009). "Clostridium difficile infection: new developments in epidemiology and pathogenesis". Nature Reviews. Microbiology. 7 (7): 526–36. doi:10.1038/nrmicro2164. PMID 19528959. S2CID 23376891.
31. ^ Rossignol JF, Lopez-Chegne N, Julcamoro LM, Carrion ME, Bardin MC (March 2012). "Nitazoxanide for the empiric treatment of pediatric infectious diarrhea". Transactions of the Royal Society of Tropical Medicine and Hygiene. 106 (3): 167–73. doi:10.1016/j.trstmh.2011.11.007. PMID 22301075.
32. ^ Alam NH, Ashraf H (2003). "Treatment of infectious diarrhea in children". Paediatric Drugs. 5 (3): 151–65. doi:10.2165/00128072-200305030-00002. PMID 12608880. S2CID 26076784.
33. ^ "WHO | Diarrhoeal disease". Who.int. Archived from the original on 1 April 2014. Retrieved 10 March 2014.
34. ^ Jamison, Dean T. (2006). Disease control priorities in developing countries (2nd ed.). New York: Oxford Univ. Press. ISBN 978-0-8213-6179-5.
35. ^ a b Brown J, Cairncross S, Ensink JH (August 2013). "Water, sanitation, hygiene and enteric infections in children". Archives of Disease in Childhood. 98 (8): 629–34. doi:10.1136/archdischild-2011-301528. PMC 3717778. PMID 23761692.
36. ^ Black RE, Sazawal S (May 2001). "Zinc and childhood infectious disease morbidity and mortality". The British Journal of Nutrition. 85 Suppl 2: S125-9. doi:10.1079/bjn2000304. PMID 11509100.
37. ^ Shankar AH, Prasad AS (August 1998). "Zinc and immune function: the biological basis of altered resistance to infection". The American Journal of Clinical Nutrition. 68 (2 Suppl): 447S–463S. doi:10.1093/ajcn/68.2.447S. PMID 9701160.
38. ^ Bahl R, Bhandari N, Hambidge KM, Bhan MK (August 1998). "Plasma zinc as a predictor of diarrheal and respiratory morbidity in children in an urban slum setting". The American Journal of Clinical Nutrition. 68 (2 Suppl): 414S–417S. doi:10.1093/ajcn/68.2.414S. PMID 9701154.
39. ^ Rice AL, West KP, Black RE (2004). "Vitamin A deficiency" (PDF). In Ezzati M, Lopez AD, Rodgers A, Murray CJ (eds.). Comparative quantification of health risks: global and regional burden of disease attributes to selected major risk factors. 1. Geneva: World Health Organization. pp. 211–56, especially 238–240.
40. ^ Sommer A, Katz J, Tarwotjo I (November 1984). "Increased risk of respiratory disease and diarrhea in children with preexisting mild vitamin A deficiency". The American Journal of Clinical Nutrition. 40 (5): 1090–5. doi:10.1093/ajcn/40.5.1090. PMID 6496388.
41. ^ West KP (September 2002). "Extent of vitamin A deficiency among preschool children and women of reproductive age". The Journal of Nutrition. 132 (9 Suppl): 2857S–2866S. doi:10.1093/jn/132.9.2857S. PMID 12221262.
42. ^ Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC (April 2006). "Functional bowel disorders". Gastroenterology. 130 (5): 1480–91. doi:10.1053/j.gastro.2005.11.061. PMID 16678561.
43. ^ Wedlake L, A'Hern R, Russell D, Thomas K, Walters JR, Andreyev HJ (October 2009). "Systematic review: the prevalence of idiopathic bile acid malabsorption as diagnosed by SeHCAT scanning in patients with diarrhoea-predominant irritable bowel syndrome". Alimentary Pharmacology & Therapeutics. 30 (7): 707–17. doi:10.1111/j.1365-2036.2009.04081.x. PMID 19570102. S2CID 11327665.
44. ^ Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL (2005). Harrison's Principles of Internal Medicine. New York: McGraw-Hill. ISBN 978-0-07-139140-5.
45. ^ a b c d Lee KJ (October 2015). "Pharmacologic Agents for Chronic Diarrhea". Intestinal Research. 13 (4): 306–12. doi:10.5217/ir.2015.13.4.306. PMC 4641856. PMID 26576135.
46. ^ Vallerand A (2017). Davis's drug guide for nurses. Philadelphia: F.A. Davis Company. pp. 989–994. ISBN 978-0-8036-5705-2.
47. ^ Dekel R, Sperber AD. "Diarrhea & Incontinence Caused by Medication". International Foundation for Gastrointestinal Disorders (IFFGD). Archived from the original on 24 February 2017. Retrieved 18 May 2017.
48. ^ Das S, Jayaratne R, Barrett KE (2018). "The Role of Ion Transporters in the Pathophysiology of Infectious Diarrhea". Cellular and Molecular Gastroenterology and Hepatology. 6 (1): 33–45. doi:10.1016/j.jcmgh.2018.02.009. PMC 6007821. PMID 29928670.
49. ^ Williams G, Nesse RM (1996). Why we get sick: the new science of Darwinian medicine. New York: Vintage Books. pp. 36–38. ISBN 978-0-679-74674-4.
50. ^ DuPont HL, Hornick RB (December 1973). "Adverse effect of lomotil therapy in shigellosis". JAMA. 226 (13): 1525–8. doi:10.1001/jama.226.13.1525. PMID 4587313.
51. ^ Ruuska T, Vesikari T (1990). "Rotavirus disease in Finnish children: use of numerical scores for clinical severity of diarrhoeal episodes". Scandinavian Journal of Infectious Diseases. 22 (3): 259–67. doi:10.3109/00365549009027046. PMID 2371542.
52. ^ Arasaradnam RP, Brown S, Forbes A, Fox MR, Hungin P, Kelman L, et al. (August 2018). "Guidelines for the investigation of chronic diarrhoea in adults: British Society of Gastroenterology, 3rd edition". Gut. 67 (8): 1380–1399. doi:10.1136/gutjnl-2017-315909. PMC 6204957. PMID 29653941.
53. ^ a b Smalley W, Falck-Ytter C, Carrasco-Labra A, Wani S, Lytvyn L, Falck-Ytter Y (September 2019). "AGA Clinical Practice Guidelines on the Laboratory Evaluation of Functional Diarrhea and Diarrhea-Predominant Irritable Bowel Syndrome in Adults (IBS-D)". Gastroenterology. 157 (3): 851–854. doi:10.1053/j.gastro.2019.07.004. PMID 31302098.
54. ^ a b Wolf J, Prüss-Ustün A, Cumming O, Bartram J, Bonjour S, Cairncross S, et al. (August 2014). "Assessing the impact of drinking water and sanitation on diarrhoeal disease in low- and middle-income settings: systematic review and meta-regression" (PDF). Tropical Medicine & International Health. 19 (8): 928–42. doi:10.1111/tmi.12331. PMID 24811732. S2CID 22903164.
55. ^ Ejemot-Nwadiaro RI, Ehiri JE, Arikpo D, Meremikwu MM, Critchley JA (September 2015). "Hand washing promotion for preventing diarrhoea". The Cochrane Database of Systematic Reviews (9): CD004265. doi:10.1002/14651858.CD004265.pub3. PMC 4563982. PMID 26346329.
56. ^ a b "Call to action on sanitation" (PDF). United Nations. Archived from the original (PDF) on 19 August 2014. Retrieved 15 August 2014.
57. ^ Spears D, Ghosh A, Cumming O (2013). "Open defecation and childhood stunting in India: an ecological analysis of new data from 112 districts". PLOS ONE. 8 (9): e73784. Bibcode:2013PLoSO...873784S. doi:10.1371/journal.pone.0073784. PMC 3774764. PMID 24066070.
58. ^ Majorin F, Torondel B, Ka Seen Chan G, Clasen T, et al. (Cochrane Infectious Diseases Group) (September 2019). "Interventions to improve disposal of child faeces for preventing diarrhoea and soil-transmitted helminth infection". The Cochrane Database of Systematic Reviews. 9: CD011055. doi:10.1002/14651858.CD011055.pub2. PMC 6757260. PMID 31549742.
59. ^ Clasen TF, Bostoen K, Schmidt WP, Boisson S, Fung IC, Jenkins MW, et al. (Cochrane Infectious Diseases Group) (June 2010). "Interventions to improve disposal of human excreta for preventing diarrhoea". The Cochrane Database of Systematic Reviews (6): CD007180. doi:10.1002/14651858.CD007180.pub2. PMC 6532559. PMID 20556776.
60. ^ Curtis V, Cairncross S (May 2003). "Effect of washing hands with soap on diarrhoea risk in the community: a systematic review". The Lancet. Infectious Diseases. 3 (5): 275–81. doi:10.1016/S1473-3099(03)00606-6. PMID 12726975.
61. ^ Cairncross S, Hunt C, Boisson S, Bostoen K, Curtis V, Fung IC, Schmidt WP (April 2010). "Water, sanitation and hygiene for the prevention of diarrhoea". International Journal of Epidemiology. 39 Suppl 1 (Suppl 1): i193-205. doi:10.1093/ije/dyq035. PMC 2845874. PMID 20348121.
62. ^ "Diarrheal Diseases in Less Developed Countries". CDC. Archived from the original on 4 November 2013. Retrieved 28 October 2013.
63. ^ Black RE, Morris SS, Bryce J (June 2003). "Where and why are 10 million children dying every year?". Lancet. 361 (9376): 2226–34. doi:10.1016/S0140-6736(03)13779-8. PMID 12842379. S2CID 14509705.
64. ^ Esrey SA, Feachem RG, Hughes JM (1985). "Interventions for the control of diarrhoeal diseases among young children: improving water supplies and excreta disposal facilities". Bulletin of the World Health Organization. 63 (4): 757–72. PMC 2536385. PMID 3878742.
65. ^ Arnold BF, Colford JM (February 2007). "Treating water with chlorine at point-of-use to improve water quality and reduce child diarrhea in developing countries: a systematic review and meta-analysis". The American Journal of Tropical Medicine and Hygiene. 76 (2): 354–64. doi:10.4269/ajtmh.2007.76.354. PMID 17297049.
66. ^ de Zoysa I, Feachem RG (1985). "Interventions for the control of diarrhoeal diseases among young children: rotavirus and cholera immunization". Bulletin of the World Health Organization. 63 (3): 569–83. PMC 2536413. PMID 3876173.
67. ^ Rheingans RD, Antil L, Dreibelbis R, Podewils LJ, Bresee JS, Parashar UD (November 2009). "Economic costs of rotavirus gastroenteritis and cost-effectiveness of vaccination in developing countries". The Journal of Infectious Diseases. 200 Suppl 1: S16-27. doi:10.1086/605026. PMID 19817595.
68. ^ Oral cholera vaccines in mass immunization campaigns (PDF). WHO. 2010. pp. 6–8. ISBN 978-92-4-150043-2. Archived (PDF) from the original on 3 September 2014.
69. ^ Soares-Weiser K, Goldberg E, Tamimi G, Pitan OC, Leibovici L, et al. (Cochrane Infectious Diseases Group) (26 January 2004). "Rotavirus vaccine for preventing diarrhoea". The Cochrane Database of Systematic Reviews (1): CD002848. doi:10.1002/14651858.CD002848.pub2. PMC 6532746. PMID 14973994.
70. ^ Black RE (May 2003). "Zinc deficiency, infectious disease and mortality in the developing world". The Journal of Nutrition. 133 (5 Suppl 1): 1485S–9S. doi:10.1093/jn/133.5.1485S. PMID 12730449.
71. ^ Bhutta ZA, Black RE, Brown KH, Gardner JM, Gore S, Hidayat A, et al. (December 1999). "Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: pooled analysis of randomized controlled trials. Zinc Investigators' Collaborative Group". The Journal of Pediatrics. 135 (6): 689–97. doi:10.1016/S0022-3476(99)70086-7. PMID 10586170.
72. ^ Mayo-Wilson E, Imdad A, Herzer K, Yakoob MY, Bhutta ZA (August 2011). "Vitamin A supplements for preventing mortality, illness, and blindness in children aged under 5: systematic review and meta-analysis". BMJ. 343: d5094. doi:10.1136/bmj.d5094. PMC 3162042. PMID 21868478.
73. ^ Chhagan MK, Van den Broeck J, Luabeya KK, Mpontshane N, Bennish ML (September 2014). "Cost of childhood diarrhoea in rural South Africa: exploring cost-effectiveness of universal zinc supplementation". Public Health Nutrition. 17 (9): 2138–45. doi:10.1017/S1368980013002152. PMID 23930984.
74. ^ "Effect of breastfeeding on infant and child mortality due to infectious diseases in less developed countries: a pooled analysis. WHO Collaborative Study Team on the Role of Breastfeeding on the Prevention of Infant Mortality". Lancet. 355 (9202): 451–5. February 2000. doi:10.1016/S0140-6736(00)82011-5. PMID 10841125. S2CID 30952224.
75. ^ Lawrence R (2016). Breastfeeding : a guide for the medical profession, 8th edition. Philadelphia, PA: Elsevier. p. 28. ISBN 978-0-323-35776-0.
76. ^ Sguassero Y. "Optimal duration of exclusive breastfeeding: RHL commentary". WHO. Archived from the original on 3 November 2013. Retrieved 14 October 2013.
77. ^ a b "Infant and young child feeding". World Health Organization. 3 October 2017. Retrieved 5 January 2018.
78. ^ Hempel S, Newberry SJ, Maher AR, Wang Z, Miles JN, Shanman R, Johnsen B, Shekelle PG (May 2012). "Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis". JAMA: The Journal of the American Medical Association. 307 (18): 1959–69. doi:10.1001/jama.2012.3507. PMID 22570464.
79. ^ Das JK, Hadi YB, Salam RA, Hoda M, Lassi ZS, Bhutta ZA, et al. (Cochrane Infectious Diseases Group) (December 2018). "Fly control to prevent diarrhoea in children". The Cochrane Database of Systematic Reviews. 12: CD011654. doi:10.1002/14651858.CD011654.pub2. PMC 6302900. PMID 30556598.
80. ^ King CK, Glass R, Bresee JS, Duggan C (November 2003). "Managing acute gastroenteritis among children: oral rehydration, maintenance, and nutritional therapy". MMWR. Recommendations and Reports. 52 (RR-16): 1–16. PMID 14627948. Archived from the original on 28 October 2014.
81. ^ "BestBets: Does Withholding milk feeds reduce the duration of diarrhoea in children with acute gastroenteritis?". Archived from the original on 4 May 2009.
82. ^ a b c Community Health Worker Training Materials for Cholera Prevention and Control Archived 20 October 2011 at the Wayback Machine, CDC, slides at back are dated 17 November 2010. Page 7 states "... Continue to breastfeed your baby if the baby has watery diarrhea, even when traveling to get treatment. Adults and older children should continue to eat frequently."
83. ^ Gregorio GV, Dans LF, Silvestre MA, et al. (Cochrane Infectious Diseases Group) (July 2011). "Early versus Delayed Refeeding for Children with Acute Diarrhoea". The Cochrane Database of Systematic Reviews (7): CD007296. doi:10.1002/14651858.CD007296.pub2. PMC 6532715. PMID 21735409.
84. ^ Schiller LR (2007). "Management of diarrhea in clinical practice: strategies for primary care physicians". Reviews in Gastroenterological Disorders. 7 Suppl 3 (Suppl 3): S27-38. PMID 18192963.
85. ^ A Guide on Safe Food for Travellers Archived 9 July 2012 at the Wayback Machine, Welcome to South Africa, Host to the 2010 FIFA World Cup (bottom left of page 1).
86. ^ a b Rehydration Project, "Diarrhoea, Diarrhea, Dehydration, Oral Rehydration, Mother and Child Nutrition, Water, Sanitation, Hygiene – Rehydration Project". Archived from the original on 8 June 2015. Retrieved 22 June 2015. Homemade Oral Rehydration Solution Recipe.
87. ^ a b "Management of acute diarrhoea and vomiting due to gastroenteritis in children under 5". National Institute of Clinical Excellence. April 2009. Archived from the original on 2 August 2009.
88. ^ Webb A, Starr M (April 2005). "Acute gastroenteritis in children". Australian Family Physician. 34 (4): 227–31. PMID 15861741.
89. ^ MacGillivray S, Fahey T, McGuire W (October 2013). "Lactose avoidance for young children with acute diarrhoea". The Cochrane Database of Systematic Reviews. 10 (10): CD005433. doi:10.1002/14651858.CD005433.pub2. PMC 4276385. PMID 24173771.
90. ^ "The Facts About Fiber".
91. ^ a b c Guarino A, Lo Vecchio A, Pirozzi MR. (2009). "Clinical role of diosmectite in the management of diarrhea". Expert Opin Drug Metab Toxicol. 5 (4): 433–440. doi:10.1517/17425250902865594. PMID 19379128. S2CID 56519371.CS1 maint: uses authors parameter (link)
92. ^ Dryden MS, Gabb RJ, Wright SK (June 1996). "Empirical treatment of severe acute community-acquired gastroenteritis with ciprofloxacin". Clinical Infectious Diseases. 22 (6): 1019–25. doi:10.1093/clinids/22.6.1019. PMID 8783703.
93. ^ a b de Bruyn G (March 2008). "Diarrhoea in adults (acute)". BMJ Clinical Evidence. 2008: 0901. PMC 2907942. PMID 19450323.
94. ^ Wong CS, Jelacic S, Habeeb RL, Watkins SL, Tarr PI (June 2000). "The risk of the hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infections". The New England Journal of Medicine. 342 (26): 1930–6. doi:10.1056/NEJM200006293422601. PMC 3659814. PMID 10874060.
95. ^ "Diarrhoeal Diseases". World Health Organization. February 2009. Archived from the original on 15 December 2008.
96. ^ DuPont HL, Ericsson CD, Farthing MJ, Gorbach S, Pickering LK, Rombo L, Steffen R, Weinke T (2009). "Expert review of the evidence base for self-therapy of travelers' diarrhea". Journal of Travel Medicine. 16 (3): 161–71. doi:10.1111/j.1708-8305.2009.00300.x. PMID 19538576.
97. ^ Pawlowski SW, Warren CA, Guerrant R (May 2009). "Diagnosis and treatment of acute or persistent diarrhea". Gastroenterology. 136 (6): 1874–86. doi:10.1053/j.gastro.2009.02.072. PMC 2723735. PMID 19457416.
98. ^ Dupont C, Vernisse B (2009). "Anti-diarrheal effects of diosmectite in the treatment of acute diarrhea in children: a review". Paediatric Drugs. 11 (2): 89–99. doi:10.2165/00148581-200911020-00001. PMC 7100234. PMID 19301931.
99. ^ Dinnendahl V, Fricke U (eds.). Arzneistoff-Profile (in German). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3.
100. ^ Liang Y, Zhang L, Zeng L, Gordon M, Wen J, et al. (Cochrane Infectious Diseases Group) (December 2019). "Racecadotril for acute diarrhoea in children". The Cochrane Database of Systematic Reviews. 12: CD009359. doi:10.1002/14651858.CD009359.pub2. PMC 6923519. PMID 31858591.
101. ^ Wilcox C, Turner J, Green J (May 2014). "Systematic review: the management of chronic diarrhoea due to bile acid malabsorption". Alimentary Pharmacology & Therapeutics. 39 (9): 923–39. doi:10.1111/apt.12684. PMID 24602022. S2CID 12016216.
102. ^ Lazzerini M, Wanzira H (December 2016). "Oral zinc for treating diarrhoea in children". The Cochrane Database of Systematic Reviews. 12 (12): CD005436. doi:10.1002/14651858.CD005436.pub5. PMC 5450879. PMID 27996088.
103. ^ Allen SJ, Martinez EG, Gregorio GV, Dans LF (November 2010). "Probiotics for treating acute infectious diarrhoea". The Cochrane Database of Systematic Reviews. 2010 (11): CD003048. doi:10.1002/14651858.CD003048.pub3. PMC 6532699. PMID 21069673.
104. ^ Kale-Pradhan PB, Jassal HK, Wilhelm SM (February 2010). "Role of Lactobacillus in the prevention of antibiotic-associated diarrhea: a meta-analysis". Pharmacotherapy. 30 (2): 119–26. doi:10.1592/phco.30.2.119. PMID 20099986. S2CID 21836205.
105. ^ "Mortality and Burden of Disease Estimates for WHO Member States in 2004" (xls). World Health Organization.
106. ^ Mandell GL, Bennett JE, Dolin R (2004). Mandell's Principles and Practices of Infection Diseases (6th ed.). Churchill Livingstone. ISBN 978-0-443-06643-6. Archived from the original on 18 October 2013.
107. ^ "Diarrhoea: why children are still dying and what can be done" (PDF). World Health Organization. Archived (PDF) from the original on 19 October 2013. Retrieved 12 October 2013.
108. ^ Walker CL, Rudan I, Liu L, Nair H, Theodoratou E, Bhutta ZA, O'Brien KL, Campbell H, Black RE (April 2013). "Global burden of childhood pneumonia and diarrhoea". Lancet. 381 (9875): 1405–1416. doi:10.1016/S0140-6736(13)60222-6. PMC 7159282. PMID 23582727.
109. ^ Walker CL, Aryee MJ, Boschi-Pinto C, Black RE (2012). "Estimating diarrhea mortality among young children in low and middle income countries". PLOS ONE. 7 (1): e29151. Bibcode:2012PLoSO...729151F. doi:10.1371/journal.pone.0029151. PMC 3250411. PMID 22235266.
110. ^ Kosek M, Bern C, Guerrant RL (2003). "The global burden of diarrhoeal disease, as estimated from studies published between 1992 and 2000". Bulletin of the World Health Organization. 81 (3): 197–204. PMC 2572419. PMID 12764516.
111. ^ The dictionary definition of squits at Wiktionary
112. ^ The dictionary definition of runs at Wiktionary
113. ^ "Definition of Diarrhea by Merriam-Webster". Merriam Webster. Retrieved 11 December 2018.
## External links
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Classification
D
* ICD-10: A09, K59.1
* ICD-9-CM: 787.91
* MeSH: D003967
* DiseasesDB: 3742
External resources
* MedlinePlus: 003126
* eMedicine: ped/583
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* t
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Diseases of the digestive system
Upper GI tract
Esophagus
* Esophagitis
* Candidal
* Eosinophilic
* Herpetiform
* Rupture
* Boerhaave syndrome
* Mallory–Weiss syndrome
* UES
* Zenker's diverticulum
* LES
* Barrett's esophagus
* Esophageal motility disorder
* Nutcracker esophagus
* Achalasia
* Diffuse esophageal spasm
* Gastroesophageal reflux disease (GERD)
* Laryngopharyngeal reflux (LPR)
* Esophageal stricture
* Megaesophagus
* Esophageal intramural pseudodiverticulosis
Stomach
* Gastritis
* Atrophic
* Ménétrier's disease
* Gastroenteritis
* Peptic (gastric) ulcer
* Cushing ulcer
* Dieulafoy's lesion
* Dyspepsia
* Pyloric stenosis
* Achlorhydria
* Gastroparesis
* Gastroptosis
* Portal hypertensive gastropathy
* Gastric antral vascular ectasia
* Gastric dumping syndrome
* Gastric volvulus
* Buried bumper syndrome
* Gastrinoma
* Zollinger–Ellison syndrome
Lower GI tract
Enteropathy
Small intestine
(Duodenum/Jejunum/Ileum)
* Enteritis
* Duodenitis
* Jejunitis
* Ileitis
* Peptic (duodenal) ulcer
* Curling's ulcer
* Malabsorption: Coeliac
* Tropical sprue
* Blind loop syndrome
* Small bowel bacterial overgrowth syndrome
* Whipple's
* Short bowel syndrome
* Steatorrhea
* Milroy disease
* Bile acid malabsorption
Large intestine
(Appendix/Colon)
* Appendicitis
* Colitis
* Pseudomembranous
* Ulcerative
* Ischemic
* Microscopic
* Collagenous
* Lymphocytic
* Functional colonic disease
* IBS
* Intestinal pseudoobstruction / Ogilvie syndrome
* Megacolon / Toxic megacolon
* Diverticulitis/Diverticulosis/SCAD
Large and/or small
* Enterocolitis
* Necrotizing
* Gastroenterocolitis
* IBD
* Crohn's disease
* Vascular: Abdominal angina
* Mesenteric ischemia
* Angiodysplasia
* Bowel obstruction: Ileus
* Intussusception
* Volvulus
* Fecal impaction
* Constipation
* Diarrhea
* Infectious
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Rectum
* Proctitis
* Radiation proctitis
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Anal canal
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GI bleeding
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* Upper
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Accessory
Liver
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Gallbladder
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Bile duct/
Other biliary tree
* Cholangitis
* Primary sclerosing cholangitis
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* Ascending
* Cholestasis/Mirizzi's syndrome
* Biliary fistula
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* Sphincter of Oddi dysfunction
Pancreatic
* Pancreatitis
* Acute
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Other
Hernia
* Diaphragmatic
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Peritoneal
* Peritonitis
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* v
* t
* e
Symptoms and signs relating to the human digestive system or abdomen
Gastrointestinal
tract
* Nausea
* Vomiting
* Heartburn
* Aerophagia
* Pagophagia
* Dysphagia
* oropharyngeal
* esophageal
* Odynophagia
* Bad breath
* Xerostomia
* Hypersalivation
* Burping
* Wet burp
* Goodsall's rule
* Chilaiditi syndrome
* Dance's sign
* Aaron's sign
* Arapov's sign
* Markle sign
* McBurney's point
* Sherren's triangle
* Radiologic signs: Hampton's line
* Klemm's sign
Accessory
* liver: Councilman body
* Mallory body
* biliary: Boas' sign
* Courvoisier's law
* Charcot's cholangitis triad/Reynolds' pentad
* cholecystitis (Murphy's sign
* Lépine's sign
* Mirizzi's syndrome)
* Nardi test
Defecation
* Flatulence
* Fecal incontinence
* Encopresis
* Fecal occult blood
* Rectal tenesmus
* Constipation
* Obstructed defecation
* Diarrhea
* Rectal discharge
* Psoas sign
* Obturator sign
* Rovsing's sign
* Hamburger sign
* Heel tap sign
* Aure-Rozanova's sign
* Dunphy sign
* Alder's sign
* Lockwood's sign
* Rosenstein's sign
Abdomen
Pain
* Abdominal pain
* Acute abdomen
* Colic
* Baby colic
* Abdominal guarding
* Blumberg sign
Distension
* Abdominal distension
* Bloating
* Ascites
* Tympanites
* Shifting dullness
* Ascites
* Fluid wave test
Masses
* Abdominal mass
* Hepatosplenomegaly
* Hepatomegaly
* Splenomegaly
Other
* Jaundice
* Mallet-Guy sign
* Puddle sign
* Ballance's sign
* Aortic insufficiency
* Castell's sign
* Kehr's sign
* Cullen's sign
* Grey Turner's sign
Hernia
* Howship–Romberg sign
* Hannington-Kiff sign
Other
* Cupola sign
* Fothergill's sign
* Carnett's sign
* Sister Mary Joseph nodule
Authority control
* GND: 4070636-9
* NDL: 00562417
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Diarrhea | c0013369 | 4,098 | wikipedia | https://en.wikipedia.org/wiki/Diarrhea | 2021-01-18T19:01:56 | {"mesh": ["D004403", "D003967"], "umls": ["C0013369"], "icd-10": ["K59.1", "A09"], "wikidata": ["Q40878"]} |
A number sign (#) is used with this entry because autosomal dominant adult-onset demyelinating leukodystrophy (ADLD) is caused by a heterozygous tandem genomic duplication resulting in an extra copy of the lamin B1 gene (LMNB1; 150340) on chromosome 5q.
One family with a complex deletion upstream of the LMNB1 gene has also been reported (Giorgio et al., 2015).
Description
Autosomal dominant adult-onset demyelinating leukodystrophy is a slowly progressive and fatal disorder that presents in the fourth or fifth decade of life and is characterized clinically by early autonomic abnormalities, pyramidal and cerebellar dysfunction, and symmetric demyelination of the CNS. ADLD differs from multiple sclerosis and other demyelinating disorders in that neuropathology shows preservation of oligodendroglia in the presence of subtotal demyelination and lack of astrogliosis (summary by Padiath et al., 2006). Characteristic MRI findings include T2-weighted hyperintense changes in the upper corticospinal tract and cerebellar peduncles, with later development of confluent white matter changes in the frontoparietal area with relative sparing of the periventricular white matter (summary by Schuster et al., 2011).
Clinical Features
Zerbin-Rudin and Peiffer (1964) described a familial disorder similar to Pelizaeus-Merzbacher disease (PMD; 312080) except that it showed later onset and autosomal dominant inheritance rather than X-linked inheritance typical of PMD. The disease was noted to be similar to multiple sclerosis (MS; 126200) in some respects. It may be the same disorder as that reported by Camp and Lowenberg (1941).
Eldridge et al. (1984) described a large American-Irish kindred with a chronic progressive neurologic disorder affecting at least 10 men and 11 women in 4 generations in an autosomal dominant pattern. Multiple sclerosis was diagnosed in 20 of the patients evaluated before the availability of CT imaging and without regard to the family history. Neurologic symptoms began in the 4th and 5th decades and included cerebellar, pyramidal, and autonomic abnormalities. The autonomic dysfunction involved bowel and bladder regulation and orthostatic hypotension; these were often the earliest changes but were frequently disregarded. Survival for 20 years after onset was common. CT imaging showed symmetrical decreases in white-matter density, beginning in the frontal lobes and extending to all of the centrum ovale and cerebellar white matter. In patients from this family, Brown et al. (1987) demonstrated findings consistent with denervation supersensitivity, suggesting a distal lesion of sympathetic noradrenergic neurons. Absence of the epinephrine response to insulin-induced hypoglycemia indicated that autonomic neuropathy was attended by severe adrenal medullary dysfunction.
Laxova et al. (1985) described a Scottish-Irish family with a similar, possibly identical disorder. Onset in the late 30s was marked by autonomic symptoms, including postural hypotension, neurogenic bladder, and rectal incontinence. Progressive spasticity followed, with death in 10 to 15 years. Orientation and affect remained intact. CT scans and magnetic resonance imaging showed symmetric atrophy of white matter. Some clinically unaffected offspring showed the same change. The condition was often misdiagnosed as multiple sclerosis.
Schwankhaus et al. (1994) reported autopsy findings from a 64-year-old affected woman of the kindred reported by Eldridge et al. (1984). Her symptoms began at age 44 years. The most striking finding was leukoencephalopathy preferentially affecting the frontal and parietal lobes, including the lateral margins of the corpus callosum, and diminishing in severity toward the occipital lobes. Subcortical U fibers were spared. There was no inflammation or metachromasia. No lipid accumulation was seen by oil red O or with Sudan black. No histologic abnormality was seen in the peripheral nervous system or in the adrenal glands, despite clinical evidence of autonomic dysfunction which is typically a presenting feature of adult-onset leukodystrophy. Although there were vacuolar changes in the white matter reminiscent of a classic spongiform encephalopathy, Schwankhaus et al. (1994) thought that the large size of the vacuoles, the absence of any changes in the gray matter, and the clinical course argued against this. No prion studies were done. The authors suggested that the early autonomic insufficiency seen in their patient was a feature that distinguished autosomal dominant, adult-onset leukodystrophy from adult-onset Pelizaeus-Merzbacher disease, which they referred to as Lowenberg-Hill disease (Rodriguez et al., 1983).
Labauge et al. (2005) reported a mother and son with an adult-onset disorder similar to vanishing white matter disease (VWM; 603896) except for apparent autosomal dominant inheritance. At age 35, the son had an acute episode of brain dysfunction after a viral illness. Features included excessive somnolence and mental confusion, apathy, vomiting, and left-sided hemiparesis requiring mechanical ventilation. Brain CT scan showed extensive hypodensity of the cerebral white matter. Similar episodes occurred following viral infections at ages 36, 39, and 40 years. After the fourth episode, progressive neurologic deterioration was observed, including cerebellar ataxia, spastic quadriparesis, and pseudobulbar syndrome. MRI showed progressive cortical and subcortical diffuse white matter abnormalities suggesting cavitating white matter degeneration. The patient's mother developed progressive ataxia at age 38, suffered a fall with head trauma, and subsequently died. Neuropathologic examination showed grayish, gelatinous, and precavitary changes in the white matter; U fibers and part of the optic radiations were unaffected. Myelin stains showed a severe depletion of myelin sheaths with spongiform changes and precavitary appearance in the most affected areas. There was a preservation of oligodendrocytes with abundant foamy cytoplasm and decreased numbers of astrocytes, although those that remained showed highly reactive features. Although Labauge et al. (2005) concluded that the phenotype was consistent with VWM disease, genetic analysis of the proband excluded mutations in the EIF2B genes (see, e.g., EIF2B1; 606686).
Ptacek et al. (2006) suggested that the mother and son reported by Labauge et al. (2005) had ADLD. They suggested that the acute episodes of brain dysfunction after mild insults may represent uncovering of compromised nervous system function. In a response to Ptacek et al. (2006), Labauge et al. (2006) stated that their patients lacked early autonomic features characteristic of ADLD and that acute neurologic deterioration observed in their patients had not been described in ADLD, but noted that overlap exists among various leukodystrophies.
Brussino et al. (2009) reported a 3-generation Italian family with ADLD that was confirmed genetically in 2 affected individuals. These 2 patients presented as adults with autonomic dysfunction, including micturition defects and impotence. The disorder progressed to involve walking difficulties; 1 patient became wheelchair-bound. Brain MRI of both patients showed diffuse subcortical infra- and supratentorial white matter abnormalities with sparing of the U-fibers and optic radiations. Genetic analysis identified a heterozygous 140- to 190-kb duplication of a region including the LMNB1 gene as well as neighboring sequences. There was a positive family history of a similar neurodegenerative disorder.
Sundblom et al. (2009) reported 2 unrelated Swedish families with ADLD. Twelve individuals examined, including 11 patients and 1 asymptomatic individual, were found to have a thin spinal cord on MRI. There was also a slight general white matter signal intensity increase in the whole spinal cord, mainly visible in T2-weighted transverse images. Postmortem examination of 1 patient showed discrete demyelination in the spinal cord.
Schuster et al. (2011) reported 4 unrelated families with ADLD. Two families were of Swedish origin and had previously been reported (Sundblom et al., 2009). The other 2 families were of German and Israeli-Arab descent, respectively. One of the Swedish families had 31 affected individuals spanning at least 4 generations. Disease onset occurred in the fifth or sixth decade. Autonomic symptoms included urinary bladder symptoms, constipation, postural hypotension, erectile dysfunction, and heat intolerance. Affected individuals later developed ataxia and pyramidal signs. Some patients showed cognitive decline. Brain MRI showed signs characteristic of this type of leukodystrophy.
Dos Santos et al. (2012) reported a 3-generation family in Germany with ADLD. The proband presented at age 47 with a 2-year history of urinary difficulties, personality changes, and depression. He was found to have gait and limb ataxia, spastic paraparesis, hyperreflexia, and extensor plantar responses. Brain MRI showed extensive T2-weighted hyperintense lesions in the subcortical and deep cerebral white matter with relative sparing of the periventricular rim and corpus callosum. Other affected brain regions included the middle cerebellar peduncles, the pyramidal tracts, medial lemniscus in the midbrain, pons, medulla, and the decussation of the superior cerebellar peduncles. Family history revealed numerous affected members in an autosomal dominant pattern. The patient's 44-year-old sister was clinically asymptomatic, but her cerebral MRI showed extensive bilateral signal hyperintensities in the subcortical and deep cerebral white matter and in the middle cerebellar peduncles.
Flanagan et al. (2013) reported a 63-year-old man with genetically confirmed ADLD who presented with REM sleep behavior disorder (RBD) characterized by dream enactment behavior up to 3 times per week for the previous 4 years. During the episodes, he would scream, shout, flail his arms, and kick his legs. Polysomnography showed markedly increased muscle tone during REM sleep. Additional neurologic features included left-sided spasticity and cerebellar signs, hyperreflexia, and rare bowel incontinence. Brain MRI showed cervical spinal cord atrophy and T2-weighted hyperintense lesions in the brainstem, cerebellar peduncles, and subcortical white matter. Flanagan et al. (2013) postulated that damage to the myelinated axons from the subceruleus nucleus and adjacent areas to alpha-motor neurons may have impaired normal motor inhibition during REM sleep.
### Clinical Variability
Quattrocolo et al. (1997) reported a large multigenerational family from northern Italy with adult-onset leukoencephalopathy. Patients presented in the fifth decade with insidious and variable symptoms, including gait impairment, pyramidal signs, lower limb weakness/paraplegia, action tremor, dysarthria, and dysphagia. The full clinical picture included spastic quadriparesis, pseudobulbar dysfunction, and urinary incontinence. Cognition was mostly spared. Brain imaging showed marked atrophy of the cerebral cortex and white matter signal abnormalities in the cortex and brainstem, with sparing of the cerebellum. Brussino et al. (2010) reported follow-up of the Italian family (ADLD-1-TO) reported by Quattrocolo et al. (1997), noting that the disorder had some distinguishing features from classic ADLD in that the Italian family lacked autonomic involvement and had sparing of the cerebellar white matter on brain imaging. Linkage analysis showed significant linkage to a region on chromosome 5q23 that included the LMNB1 gene (Zmax of 6.83 at marker D5S2955), but no point mutations or copy number defects were detected in LMNB1. Patient-derived lymphoblasts showed increased LMNB1 expression, consistent with a diagnosis of ADLD. Giorgio et al. (2015) reported follow-up of family ADLD-1-TO. Postmortem examination of an affected individual showed overexpression of LMNB1 in the cortical frontal lobe. Patient fibroblasts showed accumulation of LMNB1 within the nuclear lamina, abnormal nuclear morphology, and a 44% increase in nuclear rigidity compared to controls. Genetic analysis identified a deletion upstream of the LMNB1 gene that affected gene expression via an enhancer adoption mechanism (see CYTOGENETICS).
Inheritance
The transmission pattern of ADLD in the 4 unrelated families reported by Schuster et al. (2011) was consistent with autosomal dominant inheritance.
Diagnosis
Schuster et al. (2011) found about a 2-fold increased level of LMNB1 protein in white blood cells from 5 patients with genetically confirmed ADLD. LMNB1 mRNA was also increased compared to controls. Schuster et al. (2011) concluded that an accurate molecular diagnosis of the disorder could be made by direct analysis of LMNB1 in peripheral leukocytes.
Mapping
Coffeen et al. (2000) reported additional clinical, neuroradiologic, and neuropathologic data from the family with autosomal dominant leukodystrophy originally reported by Eldridge et al. (1984). Furthermore, they localized the ADLD gene to a 4-cM region on chromosome 5q31. Linkage analysis of this family yielded a lod score of 5.72 at theta = 0.0 with the microsatellite marker D5S804.
Molecular Genetics
Padiath et al. (2006) found duplication of the LMNB1 gene (150340.0001) as the cause of ADLD in affected members of 4 families. One of these was the family described by Eldridge et al. (1984); haplotype analysis suggested that this family and a second Irish-American family shared a common founder. Lamin B1 was found to be overexpressed in brain tissue from affected individuals. Antibodies to lamin B are found in individuals with autoimmune diseases, and it is also an antigen recognized by a monoclonal antibody raised against plaques from brains of individuals with multiple sclerosis. The clinical similarity of ADLD to multiple sclerosis and the identification of autoantibodies to lamin B suggested to Padiath et al. (2006) that a closer examination of the involvement of lamin B in multiple sclerosis is warranted.
Brussino et al. (2009) found a 140- to 190-kb duplication of 5q including the entire LMNB1 gene, the AX748201 transcript, and the 3-prime end of the MARCH3 gene (613333) in 1 of 8 Italian probands with adult-onset leukoencephalopathy. The patient's affected cousin also carried the duplication, and there was a family history of a similar disorder. Lamin B1 expression was increased in lymphoblasts from one of the patients with the duplication.
In affected members of 4 unrelated families with ADLD, Schuster et al. (2011) found duplication of the LMNB1 gene. All 4 duplications were of different sizes, ranging from 107 to 218 kb, supporting independent events. Each duplication extended over part of the MARCH3 gene, but MARCH3 mRNA was not increased in patient leukocytes.
In a symptomatic man with ADLD and his asymptomatic sister who had leukodystrophy on brain imaging, Dos Santos et al. (2012) identified a 148-kb duplication on chromosome 5q23.2 including the LMNB1 gene, but not the MARCH3 gene. The findings confirmed the central role of the LMNB1 gene in ADLD.
Using a custom array, Giorgio et al. (2013) performed detailed breakpoint junction sequence analysis of the duplicated 5q23 region containing the LMNB1 gene in 20 independent families with ADLD in whom genomic LMNB1 duplication was initially identified by aCGH, QT-PCR, or MLPA. Seven families had previously been reported (Brussino et al., 2009; Schuster et al., 2011; Dos Santos et al., 2012). There were a total of 16 unique rearrangements. Three of the duplications were shared by more than 1 family: 1 was found in 3 families and the other 2 duplications were found in 2 families each. Individuals with identical junctions shared the same haplotype, consistent with a founder effect. Duplication sizes ranged from about 128 kb to 475 kb. The largest duplication also included the PHAX (604924), ALDH7A1 (107323), and GRAMD3 genes. Comparison of all the samples identified a 72-kb minimal critical duplicated region required for ADLD that contained only the LMNB1 gene. All but 1 of the duplications were in the direct tandem orientation; the remaining duplication was inverted. Characterization of the junction sequences showed that most (11 of 15) showed short stretches of microhomology overlap ranging from 1 to 6 nucleotides, whereas the others showed small insertions at the breakpoints. All duplications resulted from intrachromosomal rearrangements. Analysis of the genomic architecture suggested several potential mechanisms for the duplications, including nonhomologous end joining (NHEJ) or fork stalling and template switching/microhomology-mediated break-induced repair (FoSTeS/MMBIR). The enrichment of Alu repetitive elements at the centromeric breakpoints (found in 4 cases), higher GC content, and high frequency of repetitive sequences at breakpoints likely also played a role in mediating ADLD duplications. RT-PCR of patients fibroblasts or blood showed increased LMNB1 expression (2.1- to 4.8-fold compared to controls), as well as increased protein levels (1.6- to 3.2-fold compared to controls). There was no apparent difference in phenotype according to duplication size, with the exception of the 1 family with a large inverted duplication affecting multiple genes.
Cytogenetics
Using custom array CGH to analyze affected members of the Italian family (ADLD-1-TO) with a variant form of ADLD described by Brussino et al. (2010), Giorgio et al. (2015) identified a heterozygous 660-kb deletion on chromosome 5q23 that included 3 genes: PHAX (604924), ALDH7A1 (107323), and GRAMD3, with the closest deletion boundary located 66 kb upstream of the LMNB1 gene. The deletion was not present in the Database of Genomic Variants or in 100 Italian control individuals. Analysis of the breakpoint regions suggested that the deletion was mediated by Alu elements. In vitro studies showed that single-copy loss of the PHAX, ALDH7A1, and GRAMD3 genes did not affect LMNB1 expression, and deletion of these genes was considered unlikely to contribute to disease pathogenesis. A circular chromosome conformation capture (4C) analysis and expression studies in patient fibroblasts showed that the deletion resulted in repositioning of a forebrain-specific enhancer element closer to the LMNB1 promoter ('enhancer adoption'). The findings were consistent with the mainly cerebral localization of LMNB1 overexpression and myelin degeneration in affected members of this family.
INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Nystagmus CARDIOVASCULAR Vascular \- Orthostatic hypotension due to autonomic dysfunction ABDOMEN Gastrointestinal \- Abnormal bowel regulation due to autonomic dysfunction GENITOURINARY External Genitalia (Male) \- Impotence due to autonomic dysfunction Bladder \- Abnormal bladder regulation due to autonomic dysfunction SKIN, NAILS, & HAIR Skin \- Decreased sweating due to autonomic dysfunction NEUROLOGIC Central Nervous System \- Cerebellar signs \- Cerebellar ataxia \- Loss of fine motor skills \- Pyramidal signs \- Spasticity \- Hyperreflexia \- Extensor plantar responses \- Pseudobulbar syndrome \- Autonomic dysfunction \- Cognitive impairment (in some patients) \- Leukodystrophy, demyelinating \- Leukoencephalopathy, diffuse \- Demyelination, symmetric \- Decreased white matter density \- Cavitating white matter degeneration \- Atrophy of the corpus callosum \- Hypotrophic brainstem \- White matter lesions in the brainstem may occur \- Neuropathologic findings include leukoencephalopathy, predominantly in the upper corticospinal tract and cerebellar peduncles (initially) \- Leukoencephalopathy in the frontal and parietal lobes (later) \- Atrophic spinal cord \- Oligodendrocytes with foamy cytoplasm \- Decreased numbers of astrocytes \- Astrocytes show reactive changes \- Lack of inflammatory infiltrate \- Preservation of U fibers \- Sparing of optic tracts Behavioral Psychiatric Manifestations \- Personality changes \- Depression LABORATORY ABNORMALITIES \- Patient cells have increased levels of LMNB1 mRNA and protein MISCELLANEOUS \- Onset in the fourth to sixth decades (mean 40 years) \- Autonomic dysfunction usually precedes obvious neurologic deterioration \- Progressive disorder \- Acute neurologic deterioration after viral illness has been reported \- Duplication of LMNB1 is sufficient for the disorder, although patients may also have larger duplications \- One family with a deletion upstream of the LMNB1 gene did not have autonomic symptoms or cerebellar involvement MOLECULAR BASIS \- Caused by duplication of 72 kb of 5q23.2 including at a minimum the lamin B1 gene (LMNB1, 150340.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| LEUKODYSTROPHY, DEMYELINATING, ADULT-ONSET, AUTOSOMAL DOMINANT | c3164344 | 4,099 | omim | https://www.omim.org/entry/169500 | 2019-09-22T16:36:30 | {"doid": ["0060785"], "omim": ["169500"], "orphanet": ["99027"], "synonyms": ["Alternative titles", "PELIZAEUS-MERZBACHER DISEASE, AUTOSOMAL DOMINANT OR LATE-ONSET TYPE, FORMERLY"], "genereviews": ["NBK338165"]} |
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