Athabaskan brainstem dysgenesis syndrome (ABDS)

Human HOXA1 syndromes are rare disorders with complex neurological and systemic symptoms. These syndromes are found among a few American Indian tribes such as the Navajo and Apaches, who are related to Athabaskan Indians of northern Canada.

Both populations studied (those related to Athabaskan Native Americans and the groups from the Middle East) presented with Duane syndrome and/or horizontal gaze palsy, both of which are characterized by restrictions in horizontal eye movements. Both populations also shared deafness, developmental delays, and a spectrum of internal carotid artery and conotruncal heart malformations. Facial asymmetries and mild external ear malformations were also sometimes present.

Human HOXA1 syndromes are inherited as autosomal recessive genetic conditions.

About the only thing known about the distribution, incidence and/or prevalence of the Human HOXA1 Syndromes is that they have only been identified among three groups in North America, Saudi Arabia, and Turkey. Each group harbors its own founder mutation, suggesting that there is no epidemiological relationship between the diseases in these different locations. Based on a study of languages among North American Indian populations, anthropologists and clinicians believe that the mutation found in the Native American population originated in a population that crossed the Bering Sea to Alaska and northern Canada about 4,000 years ago.

Duane syndrome (DS) is an eye movement disorder present at birth (congenital) characterized by a limited ability to move the eye inward toward the nose (adduction), outward toward the ear (abduction), or in both directions. In addition, when the affected eye(s) moves inward toward the nose, the eyeball retracts (pulls in) and the eye opening (palpebral fissure) narrows. In some cases, when the eye attempts to look inward, it moves upward (upshoot) or downward (downshoot). Duane syndrome falls under the larger heading of strabismus (misalignment of the eyes) under the subclassification of incomitant strabismus (misalignment of the eyes that varies with gaze directions) and subheading of extraocular fibrosis syndromes (conditions associated with fibrosis of the muscles that move the eyes).

The diagnosis of human HOXA1 syndromes may be confirmed by a thorough clinical evaluation of members of the suspect populations and a variety of specialized tests, particularly advanced imaging techniques. For example, magnetic resonance angiography (MRA) of the head and neck will reveal malformations of the carotid arteries and outflow tracts of the heart. Other magnetic resonance studies will show whether parts of the brain are lacking or underdeveloped.


Huntington disease

Huntington’s disease is a genetic, progressive, neurodegenerative disorder characterized by the gradual development of involuntary muscle movements affecting the hands, feet, face, and trunk and progressive deterioration of cognitive processes and memory (dementia). Neurologic movement abnormalities may include uncontrolled, irregular, rapid, jerky movements (chorea) and athetosis, a condition characterized by relatively slow, writhing involuntary movements. Dementia is typically associated with progressive disorientation and confusion, personality disintegration, impairment of memory control, restlessness, agitation, and other symptoms and findings. In individuals with the disorder, disease duration may range from approximately 10 years up to 25 years or more. Life-threatening complications may result from pneumonia or other infections, injuries related to falls, or other associated developments.

Huntington’s disease is characterized by rapid uncontrollable muscle movements such as tics or muscle jerks (choreiform movements or chorea). This disorder causes a loss of coordination and personality changes.  As the disease progresses, the ability to speak may be impaired, memory may fade, and the involuntary jerky muscle movements (chorea) become more severe.

Huntington’s disease is inherited as an autosomal dominant trait.  Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother.

About 30,000 people in the United States have Huntington’s disease and another 200,000 are at risk of developing the condition. Symptoms commonly develop between ages 30 and 50. The disease progresses slowly and a person may live for another 15-20 years after the onset of symptoms.

Symptoms of the following disorders can be similar to those of Huntington’s disease.  Comparisons may be useful for a differential diagnosis:

Hallervorden-Spatz disease is a rare progressive disorder that affects muscle movement.  It is associated with the degeneration of the nervous system.  Hallervorden-Spatz Disease is characterized by uncontrolled muscle movements (dystonia), muscular rigidity, and the loss of cognitive abilities (dementia).  The symptoms of this disease typically begin during childhood, although occasionally the disease begins in adulthood.  Approximately one-third of people with Hallervorden-Spatz disease experience sudden jerky muscle movements.  Other less frequent symptoms may include joint pain (dysarthria), mental retardation, facial grimacing, impaired speech (dysphasia), and impaired vision.  (For more information on this disorder, choose Hallervorden-Spatz as your search term in the Rare Disease Database.)


Hutchinson-Gilford progeria syndrome

Progeria, or Hutchinson-Gilford progeria syndrome (HGPS), is a rare, fatal, genetic condition of childhood with striking features resembling premature aging. Children with progeria usually have a normal appearance in early infancy. At approximately nine to 24 months of age, affected children begin to experience profound growth delays, resulting in short stature and low weight. They also develop a distinctive facial appearance characterized by a disproportionately small face in comparison to the head; an underdeveloped jaw (micrognathia); malformation and crowding of the teeth; abnormally prominent eyes; a small nose; and a subtle blueness around the mouth. In addition, by the second year of life, the scalp hair, eyebrows, and eyelashes are lost (alopecia), and the scalp hair may be replaced by small, downy, white or blond hairs. Additional characteristic features include generalized atherosclerosis, cardiovascular disease and stroke, hip dislocations, unusually prominent veins of the scalp, loss of the layer of fat beneath the skin (subcutaneous adipose tissue), defects of the nails, joint stiffness, skeletal defects, and/or other abnormalities. Individuals with HGPS develop premature, widespread thickening and loss of elasticity of artery walls (arteriosclerosis), which result in life-threatening complications during childhood, adolescence, or early adulthood. Children with progeria die of heart disease (atherosclerosis) at an average age of 14.5 years. As with any person suffering from heart disease, children with progeria can experience  high blood pressure, strokes, angina (chest pain due to poor blood flow to the heart itself), enlarged heart, and heart failure, all conditions associated with aging.

Newborns with HGPS may have certain suspicious findings present at birth, such as unusually taut, shiny, hardened (i.e., scleroderma-like) skin over the buttocks, upper legs, and lower abdomen; bluish discoloration of the skin and mucous membranes within the mid-portion of the face (midfacial cyanosis); and/or a sculptured nose. Profound, progressive growth delay usually becomes evident by approximately 24 months of age, resulting in short stature and weight that remains extremely low for height. Affected children who are 10 years of age typically have a height approximating that of an average three-year-old child.

HGPS is caused by a single-letter misspelling in a gene on chromosome 1 that codes for lamin A, a protein that is a key component of the membrane surrounding the cell’s nucleus. The abnormal lamin A protein produced in HGPS is called progerin.

HGPS is a rare disorder that appears to affect males and females equally, and all races equally. The disorder was originally described in the medical literature in 1886 (J. Hutchinson) and 1897 (H. Gilford). The prevalence of HGPS is approximately 1 in 20 million, so at any given time, there are approximately 400 children living with progeria worldwide. Two sets of affected identical twins have been reported in the literature. As of December 2020, the Progeria Research Foundation International Progeria Registry has identified a total of 131 children and young adults living with progeria worldwide including 20 living in the US.

Symptoms of the following disorders can be similar to those of HGPS. Comparisons may be useful for a differential diagnosis:

Hallermann-Streiff syndrome is a rare genetic disorder that is primarily characterized by distinctive malformations of the skull and facial (craniofacial) region; sparse hair (hypotrichosis); eye (ocular) abnormalities; dental defects; degenerative skin changes (atrophy), particularly in the scalp and nasal regions; and/or short stature (i.e., dwarfism). Characteristic craniofacial features include a short, broad head (brachycephaly) with an unusually prominent forehead and/or sides of the skull (frontal and/or parietal bossing); a small, underdeveloped lower jaw (hypoplastic mandible); a narrow, highly arched roof of the mouth (palate); and a thin, pinched, tapering nose. Many affected individuals also have clouding of the lenses of the eyes at birth (congenital cataracts); unusually small eyes (microphthalmia); and/or other ocular abnormalities. Dental defects may include the presence of certain teeth at birth (natal teeth) and absence (hypodontia or partial adontia), malformation, and/or improper alignment of teeth. Hallermann-Streiff syndrome appears to occur randomly for unknown reasons (sporadically) and may be the result of a new dominant genetic mutation. (For more information on this disorder, choose Hallermann-Streiff as your search term in the Rare Disease Database.)


Hydranencephaly

Hydranencephaly is a central nervous system disorder characterized by an enlarged head and neurological deficits. The exact cause of Hydranencephaly is not known. This extremely rare form of Hydrocephalus involves the absence of portions of the brain. Results of neurologic examination in newborns may be normal or abnormal. The head usually appears enlarged at birth. Vision impairment, lack of growth and intellectual deficits are symptomatic of this disorder.

Hydranencephaly can usually be detected at birth due to an enlarged head. Some infants may appear healthy at birth but may later fail to grow at a normal rate.  Irritability, poor feeding, infantile spasms or seizures,  and spasticity or rigidity of arms and legs are symptomatic of this disorder.  Some affected individuals may experience an exaggeration of muscular reflexes (hyperreflexia) and/or increased muscle tone (hypertonia).  Poor body temperature regulation, vision impairment and mental retardation may also occur.

Hydranencephaly is suspected to be an inherited disorder although the mode of transmission remains unknown.  Some researchers believe that prenatal blockage of the carotid artery where it enters the cranium may be a cause of this disorder.  However, the reason for the blockage is not known.

Hydranencephaly is a rare disorder that affects males and females in equal numbers.

Porencephaly is a disorder of the central nervous system involving cerebral cysts or cavities in cortical brain tissue.  The disorder can occur before or after birth.  Fluid which can accumulate in the head can be drained through a surgical shunt procedure.  The prognosis is variable.  Some patients with this disorder may develop only minor neurological problems and have normal intelligence, while others may be severely disabled.

The diagnosis of Hydranencephaly may be confirmed based upon a thorough clinical evaluation, the identification of characteristic physical findings, a detailed patient history, and advanced imaging techniques, such as transillumination, an x-ray of the blood vessels using dye (angiogram), or computerized tomography (CT scan). During CT scanning, a computer and x-rays are used to create a file showing cross-sectional images of internal structures such as the brain.


Hydrocephalus

Hydrocephalus is a condition in which abnormally widened (dilated) cerebral spaces in the brain (ventricles) inhibit the normal flow of cerebrospinal fluid (CSF). The cerebrospinal fluid accumulates in the skull and puts pressure on the brain tissue. An enlarged head in infants and increased cerebrospinal fluid pressure are frequent findings but are not necessary for the diagnosis of Hydrocephalus. There are several different forms of Hydrocephalus: communicating hydrocephalus, non-communicating hydrocephalus or obstructive hydrocephalus, internal hydrocephalus, normal pressure hydrocephalus, and benign hydrocephalus.

Hydrocephalus is characterized in children by an unusually large head (cephalomegaly); a thin, transparent scalp; a bulging forehead with prominent spaces between the bones of the skull (fontanelles); and a downward gaze.  Other symptoms may include convulsions, abnormal reflexes, a slowed heartbeat and respiratory rate, headache, vomiting, irritability, weakness, and problems with vision.  Blindness and continuing mental deterioration may occur if treatment is not administered.

The cause of hydrocephalus is not known.  Very few cases are caused by a birth defect; others can follow hemorrhage, viral infection, or meningitis.  A genetic predisposition has been proposed, with transmission through autosomal recessive or X-linked genes.

Most cases of Hydrocephalus are diagnosed in the first 2 years of life, but onset may occur at any age, depending on the cause.  Most types of Hydrocephalus (with the exception of those caused by an X-linked genetic trait) seem to affect males and females equally.

The following disorders can occur in conjunction with Hydrocephalus. Comparisons may be useful for differential diagnosis.

The diagnosis of hydrocephalus may be confirmed based upon a thorough clinical evaluation, the identification of characteristic physical findings, a detailed patient history, and advanced imaging techniques, such as transillumination, an x-ray of the blood vessels using dye (angiogram), computerized tomography (CT scan), or magnetic resonance imaging (MRI). During CT scanning, a computer and x-rays are used to create a file showing cross-sectional images of internal structures such as the brain. During MRI, a magnetic field and radio waves are used to create cross-sectional images of certain structures.


Hyper IgM Syndromes

The signs and symptoms of hyper IgM syndromes can vary from one person to another. This is true even among members of the same family. Affected individuals are more susceptible to developing various infections and cannot fight off infections well once they occur. Without treatment, these disorders can become life-threatening during childhood or adolescence. The initial symptoms of hyper IgM syndrome usually develop in the first or second year of life.

Hyper IgM syndromes are caused by variations (mutations) in specific genes. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, absent, or overproduced. Depending upon the functions of the particular protein, this can affect many organ systems of the body. X-linked hyper IgM syndrome is caused by a variation in the CD40LG gene. Hyper IgM syndrome type 2 is caused by a variation in the AICDA (also called AID) gene. Hyper IgM syndrome type 3 is caused by a variation in the CD40 gene. The genetic cause of hyper IgM syndrome type 4 is unknown. Hyper IgM syndrome type 5 is caused by a variation in the UNG gene.

X-liked hyper IgM syndrome is estimated to affect about 2 in 1,000,000 newborn boys. The autosomal recessive forms of hyper IgM syndrome are extremely rare. Hyper IgM syndrome type 2 is estimated to affect fewer than 1 in 1,000,000 people in the general population. The other forms of hyper IgM syndrome have only been described in the medical literature in a very small number of people. Because rare disorders often go undiagnosed, determining their true frequency in the general population is difficult. The X-linked form predominately affects males; the autosomal recessive forms affect both males and females. X-linked hyper IgM syndrome accounts for about 70% of people with this disorder.

Symptoms of the following disorders can be similar to those of hyper IgM syndromes. Comparisons may be useful for a differential diagnosis.

A diagnosis of hyper IgM syndrome is based upon identification of characteristic symptoms, a detailed patient and family history, a thorough clinical evaluation, a variety of specialized tests, including laboratory testing that can detect a pattern of immune system defects.


Hyperekplexia

There are major and minor forms of hyperekplexia. In the major form, hyperekplexia is characterized by an unusually extreme startle reaction to sudden unexpected noise, movement, or touch. Arching of the head (exaggerated head-retraction reflex or HRR), spastic jerking movements (myoclonic jerks) or falling stiffly to the ground (without losing consciousness) tend to occur when the individual is startled.  The frequency and severity of the startle response can be increased by emotional tension, stress, or fatigue.

In most cases, hyperekplexia is inherited as an autosomal dominant trait, but can also follow autosomal recessive or X-linked inheritance.  Mutations in the following genes are associated with the condition: GLRA1, SLC6A5, GLRB, GPHN, and ARHGEF9 (X-linked).  Most affected individuals have a mutation in either the GLRA1, SLC6A5 gene and have an affected parent.

Hyperekplexia is a rare genetic disorder that is most often present at birth and affects both males and females. In some individuals, onset of the disorder may be delayed until adolescence or adulthood. Hyperekplexia affects approximately one in 40,000 people in the United States.

Symptoms of the following disorders can be similar to those of Hyperekplexia. Comparisons may be useful for a differential diagnosis:

Hyperekplexia is one thing that should be considered when an infant has seizures. A family history is an important part of the diagnosis, because of the usual genetic linkage. The major features of hyperekplexia are an excessive startle reflex/response, stiffness at birth, and brief impaired voluntary movement following the startle response


遗传性高铁蛋白血症-白内障综合征

hereditary hyperferritinemia cataract syndrome

Hyperferritinemia-cataract syndrome is an extremely rare genetic disorder characterized by the early onset of cataracts associated with persistently elevated levels of ferritin in the blood plasma. Ferritin is a protein that binds to iron and is used as an indicator of the body’s iron stores. Cataracts are the only known complication associated with this disorder. Hyperferritinemia-cataract syndrome is caused by mutations to ferritin light chain (FTL) gene. This mutation is inherited as an autosomal dominant trait.

The only known symptom of hyperferritinemia-cataract syndrome is the early onset of cataracts, usually between the second and fourth decades of life. However, onset of the disorder has been reported in children as young as five and adults more than 40. The overall prognosis of the disorder is very good. The severity of the hyperferritinemia-cataract syndrome can vary greatly from one person to another even among members of the same family. Some individuals with characteristic mutations of the FLT gene have not developed any symptoms (asymptomatic).

Hyperferritinemia-cataract syndrome is caused by mutations of the ferritin light chain (FTL) gene and is inherited as an autosomal dominant trait.

Hyperferritinemia-cataract syndrome is an extremely rare disorder that affects males and females in equal numbers. More than 100 families with the disorder have been described in the medical literature. The prevalence of hyperferritinemia-cataract syndrome has been estimated at 1 in 200,000 people in the general population. Because the disorder is so rare, it often goes unrecognized or undiagnosed, making it difficult to determine the disorder’s true frequency in the general population. Hyperferritinemia-cataract syndrome was first described in the medical literature in 1995.

Symptoms of the following disorders can be similar to those of hyperferritinemia-cataract syndrome. Comparisons may be useful for a differential diagnosis.

A diagnosis of hyperferritinemia-cataract syndrome is made based upon identification of characteristic symptoms (e.g., cataracts), a detailed patient history, a thorough clinical evaluation and a variety of specialized tests such as blood tests, which can reveal elevated levels of ferritin in the blood plasma.


Hyperlipoproteinemia Type III

Hyperlipoproteinemia type III is a genetic disorder that causes the body to breakdown (metabolize) fats (lipids) incorrectly. This results in the buildup of lipids in the body (hyperlipidemia) and can lead to the development of multiple small, yellow skin growths (xanthomas). Affected individuals may also develop the buildup of fatty materials in the blood vessels (atherosclerosis) blocking blood flow and potentially leading to heart attack or stroke. Hyperlipoproteinemia type III affects 1-5,000 to 1 in 10,000 people in the general population. Without treatment, affected individuals are 5-10 times more likely to develop cardiovascular disease.

The symptoms of hyperlipoproteinemia type III may vary from person to person. Some individuals may not show any symptoms (asymptomatic). Symptoms of hyperlipoproteinemia type III often do not appear unless additional conditions are present such as diabetes, obesity, or hypothyroidism.

Hypolipoproteinemia type III is a genetic condition caused by changes in the APOE gene. The APOE gene provides instructions for making a protein called apolipoprotein E. This protein combines with fats (lipids) in the body to form molecules called lipoproteins. Lipoproteins are responsible for packaging cholesterol and other fats, carrying them through the bloodstream, and helping clear them from the bloodstream.

Hyperlipoproteinemia type III affects males more often than females. Of the 10-15% of people who develop symptoms, this most often happens in early adulthood. Most people begin to experience symptoms in early adulthood, although some individuals have symptoms begining in childhood or late adulthood. Women are rarely affected until after menopause.

Symptoms of the following disorders can be similar to those of hyperlipoproteinemia type III:

A diagnosis of hyperlipoproteinemia type III can be made based upon a thorough clinical evaluation, a detailed patient and family history and identification of characteristic findings such as xanthoma striata palmaris. Arterial imaging and a cardiac stress test can identify signs of silent atherosclerosis in young adults.


Morgagni-Stewart-Morel syndrome

Hyperostosis Frontalis Interna is characterized by the thickening of the frontal bone of the skull. It is not clear that this disorder is actually rare. Some clinicians believe that it may be a common abnormality found in as many as 12 percent of the female population. The disorder may be found associated with a variety of conditions such as seizures, headaches, obesity, diabetes insipidus, excessive hair growth and sex gland disturbances. Increased serum alkaline phosphatase and elevated serum calcium may occur.

The major feature of Hyperostosis Frontalis Interna is excessive growth or thickening of the frontal bone of the head.  This excess growth can only be seen in an x-ray.  As a result, scientists feel that this condition may be much more prevalent than suspected, but often goes undetected.  Many people have no apparent symptoms.

Hyperostosis Frontalis Interna has been found in multiple generations suggesting that the disorder may be inherited as a dominant trait.  It is not known if the disorder is autosomal dominant or X-linked.  There are no known cases of male-to-male (father to son) transmission.

Hyperostosis Frontalis Interna affects females 9 times more often than males. This disorder presents itself most often among the middle-aged and elderly but has also been found in adolescents.

Symptoms of the following disorders can be similar to those of Hyperostosis Frontalis Interna.  Comparisons may be useful for a differential diagnosis:

Acromegaly is a slowly progressive, chronic metabolic disorder in which an excess of growth hormone causes abnormal enlargement of various tissues of the body and unusual height.  Most conspicuously affected are the extremities, jaws, and face.  The enlargement of soft tissue, especially of the heart, is a serious feature of this disorder.  High blood pressure (hypertension) may be another serious consequence of Acromegaly.  (For more information on this disorder choose Acromegaly as your search term in the Rare Disease Database.)

There is no known treatment for Hyperostosis Frontalis Interna. Seizures and headaches can be treated with standard medications.


Hyperprolinemia type 1

HPI does not usually cause symptoms, but patients with intellectual disability and/or generalized epilepsy have been reported. A relationship between adult schizophrenia or schizoaffective disorders and HPI has been discussed. Kidney (renal) symptoms have been reported in some affected people. Other symptoms include abnormal EEG readings, generalized low muscle tone (hypotonia), global developmental delay, aggressive behavior, hyperactivity and repetitive movements (stereotypy).

Hyperprolinemia has been reported in patients with a microdeletion of the POX (PRODH) gene in the chromosome 22q11 region. Various mutations have been reported. This gene is involved in the initial steps of breaking down proline. The PRODH mutations have been divided into three groups: those leading to mild (<30%); moderate (30–70%); and severe (>70%) reductions of POX enzyme activity. Serum proline level seems to correlate with the severity of POX enzyme deficiency but not to be related with clinical severity.

HPI is a very rare disorder that is present at birth. It affects males and females in equal numbers. There appears to be no differences across ethnicities. The prevalence is unknown, but current studies of different populations suggest rates of 1 in 310,000 to 1 in 700,000.

Symptoms of the following disorders are similar to those of HPI. Comparisons may be useful for a differential diagnosis.

HPI is diagnosed biochemically based on a high plasma proline level without urinary excretion of P5C. In contrast, the presence of P5C in the urine is indicative of HPII.


Hyperprolinemia Type II

Pyrroline Carboxylate Dehydrogenase Deficiency

Two types of hyperprolinemia are recognized by physicians and clinical researchers. Each represents an inherited inborn error of metabolism involving the amino acid, proline.

Hyperprolinemia Type II is characterized by an abnormally high level of the amino acid proline in the blood.  Fevers associated with seizures are common and mild mental retardation may be present.

Hyperprolinemia Type II is an autosomal recessive disorder.  The gene involved has been mapped to the short arm of chromosome 1 (1p36).  Chromosomes, which are present in the nucleus of human cells, carry the genetic characteristics of each individual.  Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males, and two X chromosomes for females.  Each chromosome has a short arm designated as p and a long arm identified by the letter q.  Chromosomes are further subdivided into many bands that are numbered.  For example, chromosome 1p36 refers to band 36 on the short arm of chromosome 1.

Hyperprolinemia Type II is a very rare disorder that is present at birth.  It affects males and females in equal numbers.

Symptoms of the following disorder are similar to those of Hyperprolinemia Type II.  Comparisons may be useful for a differential diagnosis:

Hyperprolinemia Type I is a hereditary condition characterized by an excessive level of proline in the blood.  However, the levels of proline are lower than those in Type II Hyperprolinemia.  This condition is caused by a deficiency of the enzyme proline dehydrogenase.  It may be associated with kidney disease.  (For more information, choose Hyperprolinemia Type I as your search term in the Rare Disease Database.)


Hypersensitivity pneumonitis

The clinical presentation of a patient with HP varies substantially depending on the type, duration and intensity of the inciting antigen exposure and whether they have lung fibrosis. Symptoms of early non-fibrotic HP may arise several hours after the exposure and consist of a flu-like syndrome with malaise, fever and chills. Respiratory symptoms include non-productive cough and difficulty breathing. Symptoms usually resolve within 24-48 hours but may recur upon re-exposure to the antigen. The presentation of fibrotic HP has a more gradual onset with dry cough, exertional breathlessness and fatigue as the most common symptoms.

Hundreds of antigen exposure sources have been implicated in causing HP. These causes of HP are frequently named according to the setting in which the patient was exposed (e.g., humidifier lung, farmer’s lung, mushroom picker’s disease, bird fancier lung). HP antigens can be grouped according to three main categories – microbial, animal proteins and chemical sensitizers. These exposures can take place in residential, occupational, avocational or geographic settings.

The prevalence rate for HP in the U.S. is approximately 2 to 3 cases per 100,000 persons. HP is one of the most common diagnoses encountered at interstitial lung disease referral centers worldwide.

Symptoms of the following disorders can be similar to HP. Comparisons may be useful for a differential diagnosis.

HP is classified based on the presence or absence of radiologic or lung tissue fibrosis, antigen exposure likelihood, and the confidence level of imaging and lung tissue findings by a radiologist and pathologist, respectively. Both lung fibrosis and inciting antigen exposure characterization have implications for diagnosis, prognosis and treatment. The diagnosis of HP requires the exclusion of other conditions and a thorough multidisciplinary evaluation. No single test can confidently establish or exclude a diagnosis of HP. Exposure history, clinical manifestations, and radiological and lung tissue biopsy information must be considered before a diagnosis is made.

All symptoms can usually be resolved in acute cases if they are diagnosed and treated early before permanent changes in the lungs can develop. If permanent lung changes such lung scarring are present at the time of diagnosis, it is possible that the patient may not respond well to treatment.


Hypochondroplasia

Hypochrondroplasia is a genetic disorder characterized by small stature and disproportionately short arms, legs, hands, and feet (short-limbed dwarfism). Short stature often is not recognized until early to mid childhood or, in some cases, as late as adulthood. In those with the disorder, bowing of the legs typically develops during early childhood but often improves spontaneously with age. Some affected individuals may also have an abnormally large head (macrocephaly), a relatively prominent forehead, and/or other physical abnormalities associated with the disorder. In addition, in about 10 percent of cases, mild mental retardation may be present.

Hypochondroplasia is primarily characterized by small stature, disproportionately short arms and legs (limbs), mild to moderate shortness of the fingers and toes (brachydactyly), and broad, short hands and feet (i.e., short-limbed dwarfism).  Slow growth often is not apparent at birth; as noted above, it may not be recognized until about two to three years of age, later during childhood, or as late as adulthood.

In some cases, hypochondroplasia appears to occur randomly for unknown reasons (sporadically) with no apparent family history of the disorder.  According to researchers, such cases typically represent new (sporadic) genetic changes (mutations) that may be transmitted as an autosomal dominant trait (i.e., new dominant gene mutations).  Investigators have noted increased age of the father (advanced paternal age) in some instances of apparently sporadic hypochondroplasia.

Hypochondroplasia appears to affect females and males in relatively equal numbers.  The features of the disorder were originally reported in 1913; hypochondroplasia was described as a distinct disease entity in 1924.  Over 100 cases have since been recorded in the medical literature, including isolated (sporadic) and familial cases.  Hypochondroplasia is thought to have an incidence of approximately one-twelfth that of achondroplasia.  (Incidence refers to the number of new cases of a particular disorder or condition during a specific period.)  The estimated frequency of achondroplasia has ranged from about one in 15,000 to one in 35,000 births.  (For further information on achondroplasia, please see the Related Disorders section of this report below.)

Symptoms of the following disorders may be similar to those of hypochondroplasia. Comparisons may be useful for a differential diagnosis:

Achondroplasia is a genetic disorder characterized by short-limbed dwarfism that is apparent at birth.  Although hypochondroplasia has certain similar findings, experts indicate that it may be distinguished from achondroplasia by less severe skeletal malformations of the hands and spine; absence of pelvic involvement; lack of or relatively mild associated abnormalities of the skull and facial (craniofacial) region; and/or other differences as determined by clinical and x-ray (radiographic) evaluation.


Hypohidrotic ectodermal dysplasia

Hypohidrotic ectodermal dysplasia (HED) is a rare inherited multisystem disorder that belongs to the group of diseases known as ectodermal dysplasias. Ectodermal dysplasias typically affect the hair, teeth, nails, sweat glands, and/or skin. HED is primarily characterized by partial or complete absence of certain sweat glands (eccrine glands), causing lack of or diminished sweating (anhidrosis or hypohidrosis), heat intolerance, and fever; abnormally sparse hair (hypotrichosis), and absence (hypodontia) and/or malformation of certain teeth. Many individuals with HED also have characteristic facial abnormalities including a prominent forehead, a sunken nasal bridge (so-called saddle nose), unusually thick lips, and/or a large chin. The skin on most of the body may be abnormally thin, dry, and soft with an abnormal lack of pigmentation (hypopigmentation). However, the skin around the eyes (periorbital) may be darkly pigmented (hyperpigmentation) and finely wrinkled, appearing prematurely aged. In many cases, affected infants and children may also exhibit underdevelopment (hypoplasia) or absence (aplasia) of mucous glands within the respiratory and gastrointestinal (GI) tracts and, in some cases, decreased function of certain components of the immune system (e.g., depressed lymphocyte function, and rarely cellular immune hypofunction), potentially causing an increased susceptibility to certain infections and/or allergic conditions. Many affected infants and children experience recurrent attacks of wheezing and breathlessness (asthma), respiratory infections; chronic inflammation of the nasal passages (atrophic rhinitis), scaling, itchy (pruritic) skin rashes (eczema), and/or other findings.

HED is characterized by lack of or diminished sweating (anhidrosis or hypohidrosis), abnormally sparse hair (hypotrichosis), and/or absence (hypodontia) and/or malformation of certain teeth. In addition, affected individuals often have characteristic facial abnormalities, irregularities of the skin, abnormalities of the mucous membranes lining the respiratory and gastrointestinal (GI) tracts, an increased tendency to develop certain infections and allergic conditions, and/or other abnormalities. The range and severity of the symptoms and findings associated with HED varies from case to case.

In the majority of reported cases, HED is inherited as an X-linked recessive genetic trait and caused by a mutation of the EDA gene. The protein regulated (encoded) by this gene is a type II membrane protein that acts as a homotrimer (a protein with three identical units of polypeptide) and may be involved in cell-cell signaling during early embryonic development when ectodermal organs are beginning to be formed. The ectodermal germ cell layer normally forms the nervous system, tooth enamel, epidermis of the skin, lining of the mouth, anus, nose, sweat glands, hair, and nails, but a mutated EDA gene will disrupt the normal function of a number of these characteristics.

X-linked HED is a rare disorder that is fully expressed in males only. However, females who carry a single copy of the disease gene (heterozygote carriers) may exhibit milder symptoms associated with the disorder. In those rare cases when HED is inherited as an autosomal recessive genetic trait, males and females are affected in equal numbers. Because the vast majority of cases of HED are thought to be X-linked, it is suspected that approximately 90 percent of affected individuals are male.

Symptoms of the following disorders may be similar to those of hypohidrotic ectodermal dysplasia. Comparisons may be useful for a differential diagnosis:

In most cases, HED is diagnosed during early childhood when characteristic dental and hair abnormalities become apparent and prompt further testing. Such diagnosis is based upon a thorough clinical evaluation, identification of characteristic physical findings, a detailed patient and family history, and specialized laboratory testing. In some cases, during the newborn period, heat intolerance, unexplained fevers, and/or extensive skin peeling may lead to an earlier diagnosis.


Hypomelanosis of Ito

Hypomelanosis of Ito is a rare condition characterized by distinctive skin changes, in which areas of the body lack skin color (hypopigmentation). These skin changes may present as patches, streaks or spiral-shaped (whorled) areas. In many affected individuals, additional symptoms affecting areas outside of the skin also occur. There are a wide variety of symptoms potentially associated with hypomelanosis of Ito. Neurological findings such as seizures and developmental delays and musculoskeletal symptoms such as abnormal curvature of the spine (scoliosis) are commonly associated with this condition. Because of the neurological and skin symptoms, hypomelanosis of Ito may be referred to as a neurocutaneous syndrome. However, in many patients the condition arises from genetic irregularities that are present in some cells of the body, but not in others (mosaicism). Some researchers believe that hypomelanosis of Ito does not represent a distinct disorder but rather a symptom common to a group of disorders involving genetic mosaicism.

The most distinctive finding associated with hypomelanosis of Ito is characteristic skin changes. Most affected individuals develop areas that lack skin color (hypopigmentation). Any area of the body may be involved although the scalp, palms and soles are rarely affected. Skin changes may occur as patches, streaks or spiral-shaped (whorled) areas of discoloration and may affect one side of the body (unilateral) or both sides (bilateral). Affected areas of skin are usually normal otherwise. The skin lesions usually appear during the first year of life and remain unchanged through childhood, but may fade or darken in adulthood.  Skin lesions are not associated with inflammation or a premalignant (verrucous) condition.

The exact cause of hypomelanosis of Ito is unknown. Many cases are associated with genetic mosaicism and sporadic gene mutations. Genetic mosaicism is the term for individuals who have two distinct cell lines in the body that developed because of a gene mutation that occurred during embryonic development. The two cell lines have differences involving the chromosomes (chromosomal mosaicism).

In earlier reports, hypomelanosis of Ito affected women more often than men by a ratio of 2.5:1. More recent, larger studies suggest that the difference may not be as large. The incidence of hypomelanosis of Ito is estimated to be 1 in 8,000-10,000 people in the general population. The symptoms usually become apparent during the first or second year of life. Hypomelanosis of Ito was first described in the medical literature in 1952.

Symptoms of the following disorders can be similar to those of hypomelanosis of Ito. Comparisons may be useful for a differential diagnosis.

A diagnosis of hypomelanosis of Ito is made based upon a thorough clinical evaluation, a detailed patient history, identification of characteristic findings and a variety of specialized tests such as the finding of chromosomal mosaicism in fibroblasts (the major cell type of the lower layer of the skin) or keratinocytes (the major cell of the outer layer of the skin [epidermis]) obtained from an area of affected (hypopigmented) skin. Computed tomography (CT) scans or magnetic resonance imaging (MRI) may be able to detect structural abnormalities of the brain if neurological abnormalities are present.


Hypoparathyroidism

家族性孤立性甲状旁腺功能减退

Hypoparathyroidism is a rare condition in which the parathyroid glands fail to produce sufficient amounts of parathyroid hormone or the parathyroid hormone produced lacks biologic activity. The parathyroid glands are part of the endocrine system, the network of glands that secrete hormones into the bloodstream where they travel to various areas of the body. These hormones regulate the chemical processes (metabolism) that influence the function of various organs and activities within the body. Hormones are involved in numerous vital processes including regulating heart rate, body temperature and blood pressure as well as cell differentiation and growth and also in modulation of several metabolic processes. Parathyroid hormone (along with vitamin D and the hormone calcitonin, which is produced by the thyroid gland) plays a role in regulating the levels of calcium and phosphorus in the blood and in determining bone growth and bone cell activity. Due to a deficiency of parathyroid hormone, individuals may exhibit abnormally low levels of calcium in the blood (hypocalcemia) and high levels of phosphorus (hyperphosphatemia). Hypocalcemia can cause a variety of symptoms including weakness, muscle cramps, excessive nervousness, headaches, and/or uncontrollable twitching and cramping spasms of certain muscles such as those of the hands, feet, arms, legs, and/or face (tetany). Numbness and tingling around the mouth and in the fingers and toes can also occur. The most common cause of hypoparathyroidism is damage to or removal of the parathyroid glands due to surgery for another condition. Hypoparathyroidism can also be caused by an autoimmune process or can occur for unknown reasons (idiopathic) or in association with a number of different underlying disorders. In rare cases, hypoparathyroidism may occur as a genetic disorder. Such cases can include familial hypoparathyroidism, which may be inherited as an autosomal recessive, autosomal dominant or X-linked recessive trait. NORD has a separate report on familial isolated hypoparathyroidism.

The symptoms of hypoparathyroidism occur due to low levels of calcium in the blood. The severity of the condition can range from mild symptoms such as a tingling or numbness in the fingers, toes or around the lips (paresthesias) to severe muscle cramps and muscle spasms. The muscle symptoms are often called tetany, a condition characterized by uncontrollable twitching and cramping spasms of certain muscles such as those of the hands, feet, legs, and arms. In rare cases, seizures or fits can occur, or the level of consciousness can be depressed.

Hypoparathyroidism may result from removal of or damage to the parathyroid glands or their blood supply, the absence of or failure to function properly of the parathyroid glands at birth (congenital hypoparathyroidism) or due to or in association with a number of different underlying disorders.

Hypoparathyroidism affects males and females in equal numbers. The incidence and prevalence of hypoparathyroidism in the general population are unknown. There are approximately 70,000 people with hypoparathyroidism in the United States.  Hypoparathyroidism can affect individuals of any age.

Symptoms of the following disorders can be similar to those of hypoparathyroidism. Comparisons may be useful for a differential diagnosis.

A diagnosis of hypoparathyroidism is made based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. Blood tests can reveal abnormal levels of calcium, phosphorus, magnesium, creatinine and intact parathyroid hormone. Urine tests can reveal if the body is excreting too much calcium.


Hypophosphatasia

HPP has remarkably wide-ranging severity. The six major clinical forms are separated based primarily upon the age when symptoms occur and the diagnosis is made. By decreasing severity, these forms are called perinatal, infantile, childhood (severe or mild), adult, and odontohypophosphatasia.

HPP is caused by mutations in the ALPL gene. This is the only gene that causes HPP. Genes provide instructions for making proteins that have an important function in the body. When a mutation occurs, the protein may be faulty, inefficient, or absent, as in HPP. Depending upon the protein’s function, one or more organ systems of the body can be compromised.

HPP affects males and females in equal numbers. In Canada, severe HPP is estimated to occur in approximately 1 in 100,000 live births. The overall incidence and prevalence of the various forms of HPP is poorly understood or unknown. Milder cases can go undiagnosed or misdiagnosed. HPP occurs with greatest frequency in the Mennonite population in Canada, is relatively prevalent in Japan, and seems to be rare in individuals with Black ancestry.

Other disorders can resemble HPP.  Osteogenesis imperfecta (OI), also called brittle bone disease, is a group of rare disorders that together are more common than HPP. OI features bones that fracture easily from osteoporosis rather than rickets. OI may be mild or severe. As for HPP, the signs and symptoms and physical findings of OI vary greatly from affected person to person, even among individuals in the same family. Four main types of OI have been identified. OI type I is the most common and the mildest form. OI type II is the most severe. Most forms of OI are inherited as an autosomal dominant trait (For more information on this disorder, choose osteogenesis imperfecta as your search term in the Rare Disease Database.)

HPP is diagnosed by identifying its symptoms and complications beginning with a detailed patient history. HPP signs are revealed by a thorough clinical examination, and supported by routine x-rays and various laboratory tests including biochemical studies. HPP is often easy for physicians to identify for those familiar or experienced with this disorder. Understandably, however, most physicians have little or no knowledge of HPP. Consequently, affected individuals and families may face a frustrating delay in diagnosis. Now, genetic mutation analysis of the ALPL gene is available from commercial laboratories to support a diagnosis of HPP.

In 2015, the U.S. Food and Drug Administration (FDA) approved asfotase alfa (Strensiq) as the first medical treatment for perinatal, infantile and juvenile-onset HPP. In the US, patients of any age with pediatric-onset HPP are eligible for this bone-targeted TNSALP replacement therapy given by subcutaneous injection.


Hypoplastic Left Heart Syndrome

Aortic and Mitral Atresia with Hypoplasic Left Heart Syndrome

Hypoplastic left heart syndrome is a term used to describe a group of closely related rare heart defects that are present at birth (congenital). The normal heart has four chambers. The two upper chambers, known as atria, are separated from each other by a fibrous partition known as the atrial septum. The two lower chambers are known as ventricles and are separated from each other by the ventricular septum. Valves connect the atria (left and right) to their respective ventricles. The valves allow for blood to be pumped through the chambers. Blood travels from the right ventricle through the pulmonary artery to the lungs where it receives oxygen. The blood returns to the heart through pulmonary veins and enters the left ventricle. The left ventricle sends the now oxygen-filled blood into the main artery of the body (aorta). The aorta sends the blood throughout the body.

The symptoms of hypoplastic left heart syndrome are directly related to the underdevelopment of the left side of the heart and associated structures.  In all cases, infants have impaired blood flow from the lungs, through the heart, and on to other parts of the body (systemic circulation).  Symptoms may include difficulty breathing (dyspnea), a high-pitched noise while inhaling (rales), and grayish-blue discoloration of the skin (cyanosis) during the first 48 hours of life, which occurs because of low levels of circulating oxygen in the blood.  Impaired blood flow characteristic of hypoplastic left heart syndrome results in fluid buildup in the heart, lung and various body tissues (congestive heart failure).

The exact cause of most cases of hypoplastic left heart syndrome is not known. It occurs for no apparent reason (sporadically) in the majority of cases. Research suggests that the interaction of many genes and other environmental factors (multifactorial inheritance) may be responsible for hypoplastic left heart syndrome. In some cases, autosomal dominant and recessive inheritance has been suggested.

Hypoplastic left heart syndrome is a rare disorder that affects males (67 percent) more often than females. The estimated prevalence of the disorder is 1 in 100,000 live births. Hypoplastic left heart syndrome accounts for 7-9 percent of all congenital heart defects. The symptoms of this disorder are present at birth (congenital).

Symptoms of the following disorders can be similar to those of Hypoplastic Left Heart Syndrome.  Comparisons may be useful for a differential diagnosis:

Atrioventricular Septal Defect is a rare heart defect that is present at birth (congenital) and is characterized by the improper development of the septa and valves (atrial and ventricular septa and atrioventricular valves). Infants with the complete form of Atrioventricular Septal Defect usually develop congestive heart failure.  Excessive fluid also accumulates in other areas of the body, especially the lungs.  Pulmonary congestion may lead to difficulty breathing (dyspnea).  Other symptoms may include a bluish discoloration of the skin and mucous membranes (cyanosis), poor feeding, abnormally rapid breathing (tachypnea), excessive sweating, and/or an abnormally rapid heartbeat (tachycardia).  (For more information on this disorder, choose Atrioventricular Septal Defect as your search term in the Rare Disease Database.)


Hobnail hemangioma

Hypothalamic hamartomas (HH) are rare, tumor-like malformations that occur during fetal development and are present at birth. They are non-progressive lesions and do not expand, spread or metastasize to other locations. They grow in proportion to normal brain growth, and consequently their relative size to the rest of the brain is the same for the lifetime of the patient. There is tremendous diversity in the type and severity of symptoms from patient to patient. However, symptoms are apparent during childhood in the overwhelming majority of patients. Two clinical phenotypes of HH are recognized: 1) central precocious puberty and 2) epilepsy and related neurobehavioral symptoms.

Central precocious puberty (CPP) is one of the hallmark clinical syndromes associated with HH. Puberty is abnormally early if it occurs prior to the age of 8 years in girls or 9 years in boys. Central indicates that the disease process responsible for triggering puberty at an abnormally early age involves the brain, with premature pulsatile release of gonadotropin-releasing hormone (GnRH) which in turn signals the ovaries or testes to begin production of sex hormones (estrogen and progesterone in females and testosterone in males).

The underlying cause for hypothalamic hamartomas remains unknown. Over 95% of cases are sporadic (that is, there is no prior family history and the identified patient remains the only affected individual in the family). A defect in factors that regulate fetal development of the hypothalamus is most likely.

Hypothalamic hamartomas are relatively rare. Population-based research has shown that HH with epilepsy occurs in 1 of 200,000 children and adolescents. The prevalence of HH with only precocious puberty is unknown. At least for HH with epilepsy, males appear to have a slightly higher risk than females (approximately 1.3 to 1 ratio). HH occurs worldwide, without any obvious geographical concentration of cases. It is currently felt that all ethnic groups are at equal risk. There are no identified maternal risk factors or fetal exposures that increase the risk of HH.

As malformations of the ventral (inferior) hypothalamus, hypothalamic hamartomas are rather distinct from other conditions. It is important to note that tumors that occur in the same region (such as craniopharyngiomas, astrocytomas, optic nerve gliomas, etc) usually do not cause gelastic seizures. These tumors can, however, be associated with endocrine dysfunction, which includes precocious puberty under rare circumstances.

Brain imaging with magnetic resonance (MR) techniques is the single most important diagnostic test. MR imaging is sufficient to establish (or exclude) the diagnosis of HH. However, there are important considerations to imaging for HH. Imaging must be technically adequate to permit detailed visualization of the hypothalamus. Movement artifact resulting from restlessness of the patient within the scanner can obscure small HH lesions. Accordingly, for children or other patients with limited cooperation, a sedated study is recommended. Additionally, the choice of specific MR imaging sequences is also important. A coronal T2 fast spin echo (FSE) sequence is recommended, with thin slices and no gap or space between slices. Lastly, the radiologist should be informed that HH is one of the clinical conditions under consideration, so as to include careful inspection of that region of the brain. Most patients (over 90%) have normal brain findings on MR imaging aside from the HH. A small number of patients may have additional abnormalities, such as malformations of cortical development.


I Cell Disease

I-cell disease (mucolipidosis II) is a rare inherited metabolic disorder characterized by coarse facial features, skeletal abnormalities and mental retardation. The symptoms of I-cell disease are similar to but more severe than those of Hurler syndrome. The symptoms associated with this disorder typically become obvious during infancy and may include multiple abnormalities of the skull and face and growth delays.

Some of the physical features associated with I-cell disease (ML II) may be apparent at birth (congenital), whereas other features may become apparent between the ages of 6 to 10 months. Craniofacial abnormalities may include coarse facial features, a depressed nasal bridge, a long and narrow head, an unusually high and narrow forehead, and/or skin folds on the inner corners of the eyes (epicanthal folds). The skin may appear to be unusually thick and tight in certain areas of the body (e.g., face, arms, and legs).  The corneas of the eyes may appear cloudy.

I-cell disease (Mucolipidosis II) is caused by a mutation in the GNPTA gene that is located on the long arm of chromosome 4 (4q21-q23).

I-Cell Disease is a rare disorder that affects males and females in equal numbers.  Siblings of affected infants have a 1 in 4 chance of being affected by this disorder.  Approximately 30 cases of I-Cell Disease have been reported in the medical literature.  This disease appears to be more common in Japan than in other countries.

Symptoms of the following disorders can be similar to those I-cell disease. Comparisons may be useful for a differential diagnosis:

The mucopolysaccharidoses are a group of inherited lysosomal storage disorders characterized by the accumulation of certain complex carbohydrates (mucopolysaccharides) in many tissues and organs of the body (e.g., eyes, skeleton, arteries, joints, ears, skin, and/or teeth). In general, the symptoms of these disorders are progressive and vary greatly depending on the specific enzyme deficiencies. Symptoms of the mucopolysaccharidoses, which generally affect many systems of the body, may include abnormal enlargement of different organs (e.g., liver and spleen), multiple bone deformities (dysostosis multiplex) and/or unusual facial features. (For more information on these disorders, choose mucopolysaccharidoses as your search term in the Rare Disease Database.)


Ichthyosis hystrix of Curth-Macklin

Disorder of Cornification 8, Curth-Macklin Type

Ichthyosis hystrix, Curth-Macklin type is a rare inherited skin disorder. It is characterized by scaling skin (ichthyosis) ranging from mild to severe. The patches of scaly, thickened skin range from spotty to severe, and may appear on almost any part of the body.

Ichthyosis hystrix, Curth-Macklin type is characterized by patches of abnormally thick, hard skin that may appear almost anywhere on the body.  Some clinicians describe the skin as horn-like. With treatment, the patches may be considerably reduced.  Under examination by electron microscopy, numerous cells (keratinocytes) with two nuclei are found. Frequently, the nuclei are surrounded by shells of a primitive, precursor protein of the skin.

The cause of ichthyosis hystrix, Curth Macklin type is a defect in the development of the precursor, structural protein (tonofilaments).  The defect occurs as a result of a change (mutation) in the gene that produces (codes for) these proteins.  The faulty gene has been mapped to chromosome 12q13.

Ichthyosis hystrix, Curth Macklin type is a rare disorder present at birth.  It affects males and females in equal numbers.

Symptoms of the following disorders may be similar to those of Ichthyosis hystrix, Curth Macklin type.  Comparisons can be useful for a differential diagnosis:

Ichthyoses or Disorders of Cornification are general terms describing a group of scaly skin disorders.  They are characterized by an abnormal accumulation of large amounts of dead skin cells (squames) in the top layer of the skin.  The conversion of an abnormally large number of epidermal cells into squamous cells is thought to be caused by a defect in the metabolism of the skin cells known as corneocytes or of the fat-rich matrix around these cells.  The cells can be thought of as bricks, while the matrix would be the mortar holding these cells together.  (See Ichthyosis in the Rare Disease Database.)

Ichthyosis hystrix, Curth-Macklin type is treated by applying skin softening (emollient) ointments, preferably plain petroleum jelly. This can be especially effective after bathing while the skin is still moist. Salicylic acid gel is another particularly effective ointment. The skin should be covered at night with an airtight, waterproof dressing when this ointment is used. Lactate lotion can also be an effective treatment for this disorder.


Ichthyosis, CHILD Syndrome

CHILD syndrome (an acronym for congenital hemidysplasia with ichthyosiform erythroderma and limb defects) is an inherited disorder, affecting primarily women, that is characterized by ichthyosis-like skin abnormalities and limb defects on one side of the body. Other abnormalities may be present, as well.

CHILD syndrome is usually present at birth.  It may first become apparent at some point during the first month of life.

CHILD syndrome is a hereditary disorder transmitted as an X-linked dominant trait.  The faulty gene is on the long arm of the X chromosome (Xq28).  The protein/enzyme product coded by the gene has been identified as NSDHL and governs an essential step in the biosynthesis of cholesterol.

Only about 30 cases have been reported in the United States and of these 29 involved infant girls and only 1 involved a boy.   Of these 30 cases, only 6 cases involved organs or systems on the left side of the body.

Symptoms of the following disorders may resemble those of CHILD Syndrome. Comparisons may be useful for a differential diagnosis:

Conradi-Hunermann Syndrome is a form of Chondrodysplasia Punctata.  It is a rare inherited disorder affecting infants and young children.  This disorder is characterized by mild to moderate growth deficiencies including a shortened neck and slowed growth of arms or legs.  Unusual facial characteristics, large skin pores and sparse hair that tends to be coarse may also occur.  (For more information, choose Conradi-Hunermann Syndrome as your search term in the Rare Disease Database.)


Netherton syndrome

Netherton syndrome is a rare hereditary disorder characterized by scaling skin, hair anomalies, increased susceptibility to atopic eczema (a skin condition that can result in dry, red and flaky skin), elevated IgE levels, and other related symptoms. Netherton syndrome is inherited as an autosomal recessive trait.

Newborns with Netherton syndrome have reddened skin (erythroderma) and sometimes a thick parchment-like covering of skin (collodion membrane). The skin is red and scaly all over. Hair shafts are fragile and break easily due to trichorrhexis or bamboo hair, resulting in short sparse hair. In older children and adults the scaling may have a distinctive circular pattern (ichthyosis linearis circumflexa). Another characteristic of Netherton syndrome is a predisposition to allergies, asthma, and eczema.

The mutation that causes Netherton syndrome has been pinpointed to the gene SPINK5 located on the long arm (q) of chromosome 5 (5q32). This mutation is transmitted by autosomal recessive inheritance. Individuals must inherit two recessive genes in order to show the disorder, with each parent donating one mutated gene. The parents (carriers) show no evidence of Netherton syndrome.

Netherton syndrome is a rare hereditary disorder.  There are approximately 150 cases reported in the medical literature, but the true number of affected individuals may be much higher due to diagnostic difficulties and overlapping symptoms with common atopic dermatitis and other congenital ichthyoses.

Symptoms of the following disorders may be similar to those of Netherton syndrome.  Comparisons can be useful for a differential diagnosis.

The treatment of Netherton syndrome is symptomatic, often difficult, and should be tailored to the patient's specific needs. Recommendations include the regular use of emollients and moisturizing creams and lotions. Other topical agents should be used with caution because the skin in Netherton syndrome may allow ingredients from some topically applied medications to be absorbed into the blood, which may pose a danger to the child. Topical keratolytic agents such as urea or lactic acid derivatives may be limited by skin irritation and should generally be reserved for older children. The base line treatment also includes oral antihistamines, which can help to control the itchy, eczematous component, and topical or systemic antibiotics as needed. To treat the scaling of the scalp, mild dandruff shampoos and topical steroids might be helpful. Oral and topical steroids are beneficial in reducing inflammation and the eczematous component of the disease. However, the well-documented side effects of long-term steroid use need to be considered. Oral retinoids have been used with varying success, leading to dramatic improvement in some patients and severe worsening of the disease in others.


Ichthyosis, X Linked

Placental Steroid Sulfatase Deficiency; STS

X-linked ichthyosis is a genetic skin disorder that affects males. It is an inborn error of metabolism characterized by a deficiency of the enzyme steroid sulfatase. Under normal conditions, this enzyme breaks down (metabolizes) cholesterol sulfate, a member of the chemical family of steroids. Cholesterol sulfate plays a role in maintaining the integrity of the skin. If steroid metabolism is interrupted and cholesterol sulfate accumulates in the skin cells, the skin cells stick together more strongly than usual. The normal shedding of dead skin cells is inhibited and the skin cells build up and clump into scales.

Boys with X-linked ichthyosis appear normal at birth.  The skin symptoms generally appear within the first year of life.  Brownish scales that adhere to the skin are among the first signs of the disorder.  The back and legs are most frequently involved early.  The face, scalp, palms and soles, and hollows of the elbows and knees are usually spared.

X-linked recessive disorders are conditions that are coded on the X chromosome.  Females have two X chromosomes; males have one X chromosome and one Y chromosome.  Therefore, in females, the normal gene on one X chromosome can mask disease traits on the other X chromosome.  Since males have only one X chromosome, if they inherit the gene for a disease present on the X they will express the disease.  Men with X-linked disorders transmit the gene to all their daughters, who are carriers, but never to their sons.  Women who are carriers of an X-linked disorder have a 50 percent chance of transmitting the carrier condition to their daughters and a 50 percent risk of transmitting the disease to their sons.

X-linked ichthyosis is a rare disorder affecting one in 6,000 males.

Symptoms of the following disorders may be similar to those of X-linked ichthyosis.  Comparisons can be useful for a differential diagnosis.

X-linked ichthyosis can be diagnosed before birth by amniocentesis or chorionic villus sampling. Low maternal estriol levels can suggest the presence of X-linked ichthyosis.


Ichthyosis

Ichthyosis is a general term for a family of rare genetic skin diseases characterized by dry, thickened, scaling skin. The various forms are distinguished from one another by: 1) extent of the scaling and how widely and where the scaling is scattered over the body; 2) the presence or absence and intensity of reddening of the skin (erythroderma); 3) the mode of inheritance; and 4) the character of associated abnormalities.

Ichthyosis is characterized by scaly and dry skin usually over large areas of the body.  The skin may also itch (pruritis) and be red (erythroderma).  Babies born with some forms of the disorder may be born covered in a parchment-like membrane called a collodion membrane.

Most known forms of ichthyosis are hereditary disorders.  Some forms are caused by dominant genes; some are caused by recessive genes.

All the ichthyoses are rare disorders.  Incidences vary according to disease type.  The ichthyoses occur in all populations.  Most forms are not bounded by gender, race or ethnicity.

Ichthyosis congenita (collodion baby; congenital ichthyosiform erythroderma; xeroderma; desquamation of the newborn) is an inherited skin disorder.  It is characterized by generalized, abnormally red, dry, and rough skin with large coarse and fine white scales.  Itchiness (pruritus) usually also develops.  Skin on the palms of the hands and soles of the feet can be abnormally thick.  (For more information, choose Ichthyosis Congenita as your search term in the Rare Disease Database.)

The dry skin of ichthyosis is treating by applying skin softening emollients. This can be particularly effective after bathing while the skin is still moist. Lotions containing alpha-hydroxy acids, urea, or propylene glycol can also be effective. Skin barrier repair formulas containing ceramides or cholesterol may also improve scaling.


Idiopathic intracranial hypertension

Intracranial Hypertension (IH) is characterized by increased pressure inside the skull. Intracranial means inside the skull and hypertension means high fluid pressure. Intracranial hypertension means that the pressure of the fluid that surrounds the brain (cerebrospinal fluid or CSF) is too high. Elevated CSF pressure can cause two problems, severe headache and visual loss. If the elevated CSF pressure remains untreated, permanent visual loss or blindness may result. Pseudotumor cerebri and benign intracranial hypertension are both former names for IH, which are now considered inaccurate. These names do not adequately describe the disorder and downplay the seriousness of IH.

The most common symptom is often an unbearably painful or frequent headache, sometimes associated with nausea and vomiting that is not relieved by medication. The headache often awakens the patient from sleep. Some patients are treated in the emergency room where a lumbar puncture (spinal tap) is done as a last resort, to temporarily ease the headache. Measurement of the opening pressure is encouraged during these procedures in order to assess for intracranial hypertension.

In the idiopathic or primary type (IIH), obesity is considered a factor in young women. However, only a small fraction of obese individuals develop IH, so other unknown causes are yet to be determined.

The incidence of IIH in the general population is thought to be about 1 per 100,000. In obese young females the incidence of IIH is about 20 per 100,000. IIH occurs in men and children as well, but with substantially lower frequency. Weight is not usually a factor in men and in children under 10 years of age.

Symptoms of the following disorders can be similar to those of IIH. Comparisons may be useful for a differential diagnosis:

Arachnoiditis is a progressive inflammatory disorder affecting the middle membrane surrounding the spinal cord and brain (arachnoid membrane). It may affect both the brain and the spinal cord and may be caused by foreign solutions (such as dye) being injected into the spine or arachnoid membrane. Symptoms may include severe headaches, vision disturbances, dizziness, nausea and/or vomiting. If the spine is involved, pain, unusual sensations, weakness and paralysis can develop.

Treatment should first and foremost involve lifestyle and dietary modifications in order to promote weight loss for those patients who are overweight or obese. This may even include consultation with a nutritionist or dietician.


Nodular non-suppurative panniculitis

Idiopathic nodular panniculitis usually begins gradually. Abnormal bumps or masses (nodules) appear in the fatty layer under the skin (subcutaneous fat) of the legs, thighs and buttocks. In some patients, the arms, abdomen, and/or face may be involved. These nodules are usually 1-2 centimeters wide and may be either painful and tender or painless. In some patients, the affected area may become blue and red (erythema), ulcerated (open sore with yellow discharge) and waste away (atrophic), eventually healing and leaving a slight depression after a few weeks.

The exact cause of idiopathic nodular panniculitis is unknown. There are numerous different causes that may be associated with the development of panniculitis including Sjogren’s syndrome, inflammatory bowel disease, gout, diabetes mellitus, systemic lupus erythematosus, subacute bacterial endocarditis, tuberculosis, iodide or bromide therapy, withdrawal from large doses of corticosteroids or pancreatitis. Sometimes the cause may be identified as an allergy or possibly a predisposition of fatty tissue to inflammation following cell injury due to an infection or toxin (granulomatous reaction). One hypothesis of the cause of disease is that fat is the trigger of an autoimmune reaction, causing white blood cells to invade the area and cause pathological damage to the subcutaneous fat resulting in the nodules.

Idiopathic nodular panniculitis is a rare disorder that may affect males and females of any age group but rarely affects young children. Most cases are young adult females.

Symptoms of the following disease may be similar to those of idiopathic nodular panniculitis. Comparisons may be useful for a differential diagnosis:

Cytophagic histiocytic panniculitis is a rare disorder affecting the skin and the layers of fatty (adipose) tissue directly under the skin (subcutaneous). The first symptom of this disease is typically the appearance of reddened and tender nodules (lesions) under the skin. In addition, a fever may be present. Most affected individuals have a chronic form of the disease. As the disease progresses, the lesions may increase in size and number and the deeper layers of the skin and other organs of the body (e.g., bone marrow, lymphatic system, etc.) may also be affected. In severely affected patients, blood clotting (coagulation) abnormalities and liver malfunction may also be present. The exact cause of cytophagic histiocytic panniculitis is not known.


Idiopathic pulmonary fibrosis

In the early stages of IPF no symptoms may be present (asymptomatic). As stated above, the progression of the disorder is highly variable. Some individuals may experience ‘exacerbations’ in which symptoms worsen for a period of time, before improving somewhat. The initial, characteristic symptom is shortness of breath that is particularly noticeable during exertion such as exercise. This is known as breathlessness or dyspnea. Affected individuals may also exhibit a mild, dry cough that produces little to no sputum (nonproductive cough). Sputum is material that is coughed up from the respiratory tract and can include saliva, mucus and phlegm. This persistent, nonproductive cough lasts for more than 30 days.

The exact, underlying cause of IPF is not fully understood. The disorder is occurs in families and also sporadically. Different factors, including immunologic, environmental, and genetic ones, are thought to play a role in the development of the disorder.  The strongest risk factor, accounting for 30% of risk of developing IPF, is a variation in the MUC5B gene that results in more mucus production in the smallest airways in the lung (respiratory bronchioles).

The exact prevalence and incidence of IPF is unknown. Estimates have ranged from 2-29 people per 100,000 in the general population. This variation may be partially due to the lack of a uniform definition when attempting to identify the disorder. Additionally, many cases of IPF go undiagnosed or misdiagnosed, making it difficult to determine the true frequency in the general population. Familial IPF accounts for approximately 5-10% of all cases of IPF. IPF primarily affects older adults. Males tend to be affected more often than females.

Symptoms of the following disorders can be similar to those of idiopathic pulmonary fibrosis. Comparisons may be useful for a differential diagnosis.

A diagnosis of idiopathic pulmonary fibrosis may be suspected based upon identification of characteristic symptoms, a detailed patient history, and a thorough clinical evaluation. A diagnosis may be confirmed based upon a variety of specialized tests including traditional chest x-rays (radiography), computer tomography (CT) scans, pulmonary function tests, blood tests, and the surgical removal and microscopic examination of lung tissue (lung biopsy).


Idiopathic Pulmonary Hemosiderosis

Some patients may not show any symptoms early in the disease, but the most common symptoms include:

The cause of IPH is still not known but it is considered to be an autoimmune disease. Many patients also have celiac disease, another autoimmune disease, and the combination of celiac disease and IPH is known as Lane-Hamilton syndrome. In most patients with Lane-Hamilton syndrome, eliminating gluten from the diet also improved the symptoms of IPH. The autoimmune hypothesis theorizes that the cells responsible for providing immunity are somehow responsible for causing bleeding into the lungs and irreversible scarring over time. Although the exact mechanism is unknown, scientists have hypothesized that the offending agents could be bioactive proteins (such as histamine, ECP or VEGF). When triggered by a yet to be discovered antigen(s), the immune cells are inappropriately activated, causing the release of these factors and prompting bleeding in the lungs.

Approximately 80% of cases occur in children, mostly under 10 years old and 20% of cases occur in adults (majority under 30 years old). IPH may affect more girls than boys and more adult men than women, according to some studies.

The following conditions have signs and symptoms that are similar to IPH: Goodpasture syndrome, acute respiratory distress syndrome (ARDS), lung infections, systemic lupus erythematous, Henoch-Schoenlein purpura, ANCA vasculitis, and mixed connective tissue disease.

Since it is a rare disease, diagnosing IPH involves ruling out all other possible causes of bleeding or scarring in the lungs. This may include various blood tests (iron studies, blood cell counts and antibody levels), sputum tests, imaging (x-rays, CT scans), bronchoscopy and biopsies. A multidisciplinary team is often involved and may include pulmonologists, hospitalists, rheumatologists, respiratory therapists, intensivists and thoracic surgeons. Early recognition and treatment can help avoid serious complications and disease progression. IPH is typically diagnosed using a camera (bronchoscope) that takes samples of the fluid in the lungs, known as a bronchoalveolar lavage. The pulmonologist will also take biopsies of the lungs to confirm the diagnosis under the microscope.


Idiopathic subglottic stenosis

idiopathic subglottic and tracheal stenosis

Stridor and dyspnea are the most common symptoms. The noisy breathing that characterizes stridor can resemble (and is often mistaken for) wheezing. These symptoms often lead affected individuals to be misdiagnosed with asthma and can result in a delay in diagnosis. Stridor can become progressively worse over time. Shortness of breath upon exertion can also be slowly progressive, worsening over a period of years so that affected individuals are gasping for breath after simple activities or even at rest.

By definition, the exact, underlying cause of idiopathic subglottic stenosis is unknown. Inflammation and scarring of the affected area is usually present.

Idiopathic subglottic stenosis is a rare disorder that affects women almost exclusively. The disorder most often occurs in women between the ages of 30 and 50, but has been reported in younger women, and elderly adults as well. Idiopathic subglottic stenosis only accounts for approximately 15% of all cases of subglottic stenosis. However, the exact incidence and prevalence is unknown. Because people may go undiagnosed or misdiagnosed, determining the true frequency of idiopathic subglottic stenosis in the general population is difficult.

There are a variety of known causes of subglottic stenosis. Most often, this results from prolonged intubation (i.e. having a breathing tube in place for several days), but can result from intubation for only a short period of time as well. Subglottic stenosis also occurs as part of autoimmune disorders such as Wegener’s granulomatosis or relapsing polychondritis. Rarely, some infants are born with the disorder (congenital subglottic stenosis).

Diagnosis of idiopathic subglottic stenosis is basically one of exclusion, in which the known causes of subglottic scarring are ruled out. A diagnosis is obtained through identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests.


Immunoglobulin A nephropathy

欧洲非罕见病：贝格尔疾病

Patients with IgA nephropathy often present with:

As mentioned above, the kidneys serve as filters for the blood. Each kidney consists of about 1 million mini-filters called nephrons.

In North America and Europe, males are two times more likely to get the disease, while in Asia, females are just as likely as males to be affected. In terms of ethnicity, Asians are much more likely than Caucasians who are, in turn, much more likely than black population to get IgA nephropathy. This disease most often presents between teenage years to late 30’s but can present at any age.

Symptoms of the following disorders can be similar to those of IgA nephropathy. Comparisons may be useful for a differential diagnosis:

•	Henoch-Schönlein purpura (now considered a type of IgA that predominantly affects the small blood vessels of the body including the kidney) – For more information on this disorder choose Henoch-Schönlein Purpura as your search term in the Rare Disease Database.


Imagawa-Matsumoto syndrome

IMMAS is characterized by rapid growth in childhood and early bone maturation, leading to features such as increased height (tall stature), enlarged head circumference and hands and feet that are large for age. Children with IMMAS may have bent fingers or toes  (camptodactyly/clinodactyly) that do not completely straighten. It may also be difficult for affected individuals to extend their knees and elbows. Some patients have very flexible limbs (hypermobility of joints) and some may also develop a curved spine (scoliosis).

IMMAS is caused by changes (variants) in the SUZ12 gene. These changes can result in the production of a SUZ12 protein that does not function normally.

IMMAS is an extremely rare disorder. As of 2024, there are between 15 and 17 patients reported in the medical literature with IMMAS.

Imagawa-Matsumoto syndrome is categorized with diseases known as Weaver-like syndromes. These syndromes are clinically similar to Weaver syndrome. It is also sometimes termed an overgrowth-intellectual disability (OGID) syndrome.

IMMAS may be suspected based on a combination of the characteristic clinical features outlined above (e.g., general overgrowth, macrocephaly, increased height, developmental delay, intellectual disability, etc.).

There is currently no cure for IMMAS. Treatment for IMMAS is focused on the individual signs and symptoms in each patient.


Immune thrombocytopenia

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by abnormally low levels of blood cells called platelets, a situation referred to as thrombocytopenia. Platelets are specialized blood cells that help maintain the integrity of the walls of blood vessels and help prevent and stop bleeding by accelerating clotting where it is needed. A normal platelet count ranges from approximately 150,000 to 400,000 per microliter (µL) of blood depending on the laboratory. However substantial bleeding does not usually occur until the platelet count is less than 50,000 or even 30,000/µl.

A child or adult may display no symptoms (be asymptomatic) when a low platelet count is first discovered, or bleeding symptoms may appear first and then the platelet count is discovered to be low. Such symptoms may include:

The fundamental abnormality in ITP is that the patient’s immune system tags their own platelets as foreign, leading their B-lymphocytes and plasma cells to produce self-reactive anti-platelet antibodies that attach to platelet surfaces. A type of white blood cells in the spleen and in other organs, called macrophages, normally recognize antibody-coated particles. In ITP, antibody-coated platelets are ingested and subsequently destroyed within the macrophages. The bone marrow attempts to compensate but is often unable to keep up with the destruction, especially in severe cases. Platelet production may also be impaired when anti-platelet antibodies bind to the cells in the bone marrow called megakaryocytes that produce platelets. However, ITP is heterogeneous with respect to pathophysiology, clinical symptoms such as risk of bleeding and thrombosis or of fatigue, coincident autoimmune disease, and responses to treatments.

ITP occurs in people of all races and ethnicities. ITP can occur at any age from 3 months to over 100 years of age. About 40% of all patients diagnosed with ITP are children younger than 10 years of age. The incidence is highest between 2 to 4 years of age, and males and females are affected equally until adolescence. Between adolescence and the age of 60, ITP is more common in females. The highest prevalence is among males and females over the age of 60.

Thrombocytopenia can also be due several other disorders that can resemble ITP in addition to inherited and secondary thrombocytopenia. It is important that physicians develop a differential diagnosis for other possible causes of thrombocytopenia, to consider the full spectrum of what could be underlying the thrombocytopenia. The most likely underlying conditions depend on patient age, sex and many other features of the presentation. Clinical judgment is important since it is not possible to do testing for every other cause of thrombocytopenia.

Most patients with ITP present with some form of bleeding, typically in the skin. On occasion, a low platelet count may be detected incidentally by a complete blood count (CBC) ordered for other purposes such as for infection, before surgery or on a routine checkup in an individual without apparent symptoms (asymptomatic). Most ITP patients have isolated thrombocytopenia with normal appearing red cells and white cells, but anemia can result from bleeding and iron deficiency and changes in the white blood cell count can occur with recent infection. If there are lower or higher than normal WBC or RBC counts, the chance this is NOT ITP increases substantially.  Secondary forms of ITP are suspected when an individual has a history of recurrent infections, fever or weight loss, enlarged lymph nodes, joint pains, is post vaccination, etc.


Immunotactoid glomerulopathy

glomerulonephritis with organized monoclonal microtubular immunoglobulin deposits (GIMMD)

The most common symptoms of immunotactoid glomerulopathy include:

The causes of immunotactoid glomerulopathy are still unknown and are being researched. Microtubules build up in the glomerulus, often in patients with an underlying disease such as cancer (particularly leukemia, lymphoma and multiple myeloma) or a previous hepatitis C viral infection.

Adults with a history of leukemia, lymphoma, multiple myeloma or another monoclonal gammopathy are most at risk for immunotactoid glomerulopathy. Some evidence also shows an association between a previous hepatitis C viral infection and immunotactoid glomerulopathy. However, many cases have no identifiable underlying disease and the cause is unknown.

Fibrillary glomerulonephritis– a similar disease in which fibril proteins affect the glomerulus rather than microtubules and antibodies.

A diagnosis is made from a kidney biopsy to look at the microtubules under an electron microscope and immunofluorescence microscope. Routine lab tests may detect the blood and protein in the urine, but a biopsy is the only way to determine which proteins are affecting the glomerulus.


Incontinentia pigmenti

Bloch-Siemens incontinentia pigmenti melanoblastosis cutis linearis

IP is an X-linked dominant genetic disorder caused by changes (variants or mutations) in the IKBKG gene (formerly called NEMO). IKBKG codes for a protein that helps regulate other proteins that help protect cells from self-destruction in response to specific triggers.

IP affects all racial and ethnic groups.  As of 2014 there were more than 2000 female with IP reported in the scientific literature and this number, along with reports of affected males, continues to rise. Current estimates from public health and analytical systems put the birth prevalence at 0.6-2.1/1,000,000.  Orphanet reports an estimated birth prevalence of 1.2/100,000 in the European Union which is likely more accurate. The female:male ratio is 20:1.

Mutations in IKBKG can also cause ectodermal dysplasia and Immunodeficiency 1 (OLEDAID). This is an X-linked recessive disorder with variable ectodermal and immunologic features. There is most often reduced sweating (hypohydrosis) or lack of sweating (anhidrosis). There can be abnormal teeth and nails. The infection patterns are of differing severity.

Interleukin 1 receptor antagonist deficiency (DIRA) has blistering skin lesions that can be present at birth but does not follow a linear or swirled pattern. The nails can be abnormal, and biopsy of the skin shares some features with the first stage of IP. Patients with DIRA have bone abnormalities, particularly periosteal elevation. Both sexes are equally affected. DIRA has a medical treatment.


Infantile Myofibromatosis

More than 90% of cases of juvenile myofibromatosis have onset in infancy, although the disorder can first present later in childhood or less often in adults. The tumors can continue to develop throughout an individual’s life.

Most cases of infantile myofibromatosis are believed to occur spontaneously and without a known family history of the disorder. In these cases, the underlying cause of the disorder is unknown. Rare cases of myofibromatosis have been identified that run in families, and mutations in two genes have been identified as causing the disorder in some cases. These genes are the platelet-derived growth factor receptor beta (PDGFRB) gene and the neurogenic locus notch homolog protein 3 (NOTCH3) gene.

Infantile myofibromatosis affects males and females in equal numbers. Some reports have noted that males are affected more often by the solitary form and females are affected more often by multicentric forms. The exact incidence is unknown, but is estimated to be between 1 in 150,000 to 400,000 live births, reported in different ethnic and geographical groups. Because cases of this rare condition can go undiagnosed or misdiagnosed, determining the true frequency in the general population is difficult. Although rare, infantile myofibromatosis is the most common fibrous tissue tumor in infancy and early childhood.

Symptoms of the following disorders can be similar to those of infantile myofibromatosis. Comparisons may be useful for a differential diagnosis.

A diagnosis of infantile myofibromatosis is based on the microscopic examination of the tissue in a patient with characteristic symptoms and physical examination. Imaging studies including ultrasound and MRI are most often used to visualize the extent of the growths. Imaging techniques may be used to assess the extent of the growths, the progression of the growths, and to diagnose recurrence of a growth. Imaging may be used to help evaluate the size, placement, and extension of lesions and to aid surgical procedures.


Infective endocarditis

Infective endocarditis is an infection of the valves and/or lining of the heart. The presenting symptoms are a low-grade persistent fever without an obvious cause and fatigue and shortness of breath on exertion. Patients also may have joint pain (arthralgia) and muscle pain (myalgia) and their health care provider may hear a new or changing murmur. In addition, the following signs and symptoms occur:

Bacteria that cause infective endocarditis reach the heart through the bloodstream. Normally, heart valves are highly resistant to the attachment of bacteria and resulting infection. Damage to the heart valves and inner lining of the heart is the main risk factor for infective endocarditis because it leaves the tissue susceptible to bacterial overgrowth. As the microorganisms quickly move past the damaged valve lining, those strains that can most strongly adhere to the surface are bacteria that have the best chance of producing infective endocarditis. Clumps of bacteria and cells called vegetations form on the heart valves affecting proper function of the heart. If left untreated, this vegetation may cause the valve to leak or may result in an abscess next to the valve or in the heart muscles leading to tissue damage and blockage of the normal electrical conduction pathways. In addition, the vegetation may break loose and cause damage to the brain (stroke), kidneys or lungs.

Infective endocarditis appears to be approximately twice as common in men as women. In the past, disease onset occurred at an average age of 35 years of age. However, with more patients having artificial heart valves and pacemakers, the average age at onset has increased to over 50 years. Infective endocarditis has an incidence rate of 3-10 cases in every 100,000 people. No race or ethnicity is more affected than others. Prognosis of infective endocarditis remains poor despite advances in diagnosis and therapies. Mortality rates are approximately 25% even with the best therapies available.

The key step in the diagnosis of endocarditis is obtaining blood cultures before antibiotics are started. People with risk factors for endocarditis, particularly those with prosthetic valves and pacemakers, should know the symptoms of endocarditis and should insist on blood culture when they have an unexplained fever. Diagnosis of infective endocarditis can be done based on pathology or by meeting certain clinical diagnostic criteria. These criteria are known as the Duke Clinical Criteria and a patient must show either: 2 major, 1 major and 3 minor, or 5 minor criteria to be diagnosed with infective endocarditis. These include


IQSEC2-Related Disorder

重度智力障碍-进行性产后小头畸形-中线刻板手部动作综合征

Patients with IQSEC2-related disorder have a range of intellectual disabilities. Some patients can live independently with minimal support, and others require 24-hour care and in-depth support for daily activities. Many are unable to walk independently and have minimal ability to talk or respond to commands.  Most children also have some level of cognitive impairment, such as an inability to name body parts and common objects. Children with ISEC2-related disorder often have autistic features such as difficulty with communication, restricted interests, repetitive behaviors and lack of interest in other children. Associated mental health disorders may develop including anxiety, depression and schizophrenia.

IQSEC2-related disorder is a genetic condition caused by variants in the IQSEC2 gene that are not inherited. The variant occurs spontaneously in the affected person (de novo variant). The gene change is not known to be caused by environmental exposures or events during pregnancy.

It is estimated that fewer than 1,000 people in the U.S. have this disorder. There have been no studies to identify ethnic groups, regions or environmental factors that influence this disorder. Since IQSEC2-related disorder is an X-linked genetic disorder, more males are affected than females.

Rett syndrome is a progressive neurodevelopmental disorder that almost exclusively affects females. Only in rare cases are males affected. Patients with Rett syndrome have developmental regression, distinctive hand movements, small head circumference, intellectual disability and seizures. Rett syndrome is caused by variants in the MECP2 gene.

Physical examination and developmental assessments are not enough to make a diagnosis of IQSEC2-related disorder. If a child has intellectual disability and seizures, consultation with a genetic counselor and DNA testing is warranted. Identification of a pathogenic variant in the IQSEC2 gene confirms the diagnosis.

Patients should see a neurologist and start antiepileptic medication if they have frequent recurrent seizures. It is recommended to continue care with a neurologist to monitor dosage and maintain seizure control, as specific dosage can change over time. Unfortunately, most male children with IQSEC2 gene variants have drug resistant seizures.


Isolated Aniridia

Aniridia is the partial or complete absence of the iris of the eye. Vision is preserved in some patients with mild cases of aniridia. This condition occurs when the iris fails to develop normally before birth in one or both eyes. Typically, aniridia can be diagnosed at birth. Aniridia can be isolated, i.e., occur as a single abnormality or can be one of many symptoms in an underlying condition.

Most forms of isolated aniridia are caused by variants in the PAX6 gene. The PAX6 gene belongs to a family of genes that are important for the correct formation of tissues and organs during embryonic development and for maintaining the normal function of certain cells after birth.

All types of aniridia affect males and females in equal numbers. This disorder is thought to occur in approximately 1 in 40,000 to 96,000 livebirths in the United States.

Symptoms of the following disorders can be similar to those of aniridia. Comparisons may be useful in helping a doctor make a diagnosis:

Irido goniodysgenesis is a genetic eye structure disorder. People with this disorder are born with underdevelopment of the foundation substance (stroma) of the iris. Glaucoma may also occur, followed by the iris changing to a lighter color. It may result in varying degrees of pain.