Sitosterolemia

Signs and symptoms of sitosterolemia vary from person to person, but any one of these symptoms alone is reason enough to be tested for it. Some patients (especially children) present with high cholesterol. While most cases of high cholesterol are not caused by sitosterolemia, if a patient’s cholesterol varies greatly with diet, but does not respond well to statins, then it could be a sign of sitosterolemia.

Sitosterolemia is an autosomal recessive genetic condition caused by mutations in the ABCG5 or ABCG8 gene.

A recent report suggests that sitosterolemia has a global prevalence of at least 1 in 2.6 million for an ABCG5 gene mutation and 1 in 360,000 for an ABCG8 gene mutation [Hooper, et al, 2016]. The routine clinical test for measuring plasma concentration of cholesterol does not measure plant sterols; therefore sitosterolemia is likely to be underdiagnosed. Men and women are equally likely to have sitosterolemia, and anyone with this condition will have had it from birth, although many are not diagnosed until later.

Symptoms of the following disorders can be similar to sitosterolemia.

The diagnosis of sitosterolemia is established in individuals who have greatly increased plant sterol concentrations (especially sitosterol, campesterol, and stigmasterol) in the blood and tissues. Shellfish sterols can also be elevated.


Sjögren-Larsson syndrome

The first sign of Sjögren-Larsson syndrome is often preterm birth. Apparent at birth, the ichthyosis associated with SLS often starts as thickened skin that is yellow-brown in color (hyperkeratosis). This thickened skin eventually progresses to full scaling, especially at the neck, lower abdomen, and underarms, groin, and back of knees (flexures).  Unique to SLS is the itchy characteristic of the skin (pruritis).

The gene that is altered in patients with Sjögren-Larsson syndrome is the aldehyde dehydrogenase 3A2 (ALDH3A2) gene. 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, or absent. Depending upon the functions of the particular protein, this can affect many organ systems of the body, including the brain.

Sjögren-Larsson syndrome affected both males and females equally and its onset is from birth. The incidence of this condition worldwide is unknown. However, the prevalence in Sweden is 1 in every 250,000 individuals.

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

A diagnosis of Sjögren-Larsson syndrome may be suspected at birth. A clinical diagnosis can be made by age 3 when the primary features of the disorder are usually apparent. The affected individual usually does not have a family history of this disease.


Small Cell Lung Cancer

The signs and symptoms of small cell lung cancer can vary from one person to another. Specific findings depend on numerous factors including the exact location and size of the tumor, the extent of invasion of the tumor into nearby tissue or organs and whether the disease has remained localized or spread to other areas of the body (metastasized). Early in the course of the disease, there may be no symptoms (asymptomatic) or only a few, mild symptoms. As the tumor grows, more signs and symptoms develop.

SCLC is primarily caused by cancer causing chemicals (carcinogens) that are found in tobacco smoke. These carcinogens cause damage to the DNA (deoxyribonucleic acid; genes) in cells which leads to cancer formation. However, the exact reason normal cells become cancerous is not known. Most likely, multiple factors including genetic and environmental ones play a role in the development of SCLC in certain people. Current research suggests that abnormalities of DNA, which is the carrier of the body’s genetic code, are the underlying basis of normal cells transforming into cancer cells.

The incidence of small cell lung cancer in the United States has been declining over the last two decades, which most researchers attribute to the decline in smoking in the country. Lung cancer, as a group, is the second most common form of cancer in the United States. SCLC accounts for about 10%-15% of people who have lung cancer. There are about 30,000 to 35,000 new patients diagnosed with SCLC each year in the United States. Almost everyone who develops SCLC has a history of smoking. It is extremely rare in individuals who have never smoked.

A diagnosis of small cell lung cancer is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. SCLC is an aggressive cancer and in many affected individuals the cancer has already spread when the diagnosis is made.


Smith-Magenis syndrome

chromosome 17, interstitial deletion 17p

Smith-Magenis syndrome is a highly variable disorder. The specific symptoms present and the overall severity of the disorder can vary from one person to another. It is important to understand that affected individuals will not have all of the symptoms discussed below and that every individual case is unique. Parents should talk to the physician and medical team about their child’s specific case, associated symptoms and overall prognosis.

In approximately 90% of affected individuals, a portion of the short arm (p) of chromosome 17 (17q11.2) is missing, which is referred to as deleted or monosomic. Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated p and a long arm designated q. Chromosomes are further sub-divided into many bands that are numbered. For example, chromosome 17p11.2 refers to band 11.2 on the short arm of chromosome 17. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Smith-Magenis syndrome affects males and females in equal numbers. The incidence is estimated to be 1 in 15,000-25,000 people in the general population in the United States. However, cases may go undiagnosed or misdiagnosed, making it difficult to determine the true frequency of SMS in the general population. SMS has been reported throughout the world and in all ethnic groups.

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

A diagnosis of Smith-Magenis syndrome is based upon identification of characteristic symptoms, a detailed patient and family history, a thorough clinical evaluation and a variety of specialized genetic tests. The diagnosis of SMS is confirmed when deletion 17p11.2 (cytogenetic analysis or microarray) or RAI1 gene mutation is identified.


巨颅畸形-智力发育迟缓-神经发育迟缓-小胸廓-综合征

Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome

Many symptoms and features are thought to be part of SKS. Some of these characteristics occur more frequently than others. Since there is great variability, not every person with SKS will have all these features. As research progresses, the formal description of SKS will likely change.

SKS is usually an autosomal dominant condition, which means that one copy of the altered MTOR gene in each cell is sufficient to cause the disorder.

MTOR-related disorders are extremely rare. The total patient population is still unknown, but it is estimated that there are about 10 people with MTOR gene disorders (with some MTOR mutations causing SKS) in every 10,000 individuals. However, SKS may go undiagnosed or misdiagnosed, making it extremely difficult to determine the true frequency in the general population. Based on the current understanding of this condition, SKS occurs worldwide in people of all ethnic groups.

SKS is a rare condition that many physicians are not familiar with. A diagnosis of SKS is suspected based upon the identification of characteristic features, a detailed patient and family history and a thorough clinical evaluation.

Currently, there is no cure for SKS, and no treatments approved by the U.S. Food and Drug Administrations (FDA). Treatment is based on a child’s specific symptoms. Patients and their families typically visit one or more of the following medical specialists:


Smith-Lemli-Opitz syndrome

The features of SLOS are not the same in every patient. Common findings are slowed growth before and after birth, a small head (microcephaly) and a spilt in the roof of the mouth (cleft palate). Most babies have differences in their fingers and/or toes. This includes fused toes (2-3 syndactyly) and extra fingers or toes (polydactyly). Males with SLOS can have underdeveloped genitals that may resemble female genitals. People with SLOS often experience behavioral problems, sleep problems and mild to severe intellectual disability.

The chromosomes in our cells carry our genes which occur in pairs and are instructions to make proteins. One copy of each gene is inherited from the mother, and the other from the father. SLOS is caused by having a harmful change (mutation) in both copies of the DHCR7 gene. This causes lack of an enzyme (7-dehydrocholesterol reductase) which is needed to make cholesterol. Cholesterol is a waxy substance that is important for making cell structures. Cholesterol is necessary for development before and after birth. Mistakes in DHCR7 also leads to a buildup of 7-dehydrocholesterol (7-DHC) which is toxic to the body. Buildup of 7-DHC along with low cholesterol cause the features of SLOS.

About 1 in 20,000 to 1 in 60,000 people in the US have SLOS. This condition affects males and females equally. However, females are less likely to be diagnosed because they do not have genital differences. SLOS occurs more often in people of European ancestry.

Meckel syndrome is also an autosomal recessive condition. There are 13 genes known to cause Meckel syndrome. It occurs in 1 in 13,250 to 1 in 140,000 people. Like SLOS, babies with Meckel syndrome may have extra fingers or toes (polydactyly). They often have large cyst-filled (polycystic) kidneys. Incorrect development of the brain and spinal cord (neural tube defects) can occur. Meckel syndrome can also affect the eyes, facial features, heart, bones, urinary system and genitals. Like SLOS, Meckel syndrome varies between people. (For more information on this condition, choose Meckel syndrome as your search term in the Rare Disease Database.)

The diagnosis of SLOS is based on physical findings and either biochemical or genetic testing. Biochemical testing looks for protein levels in the blood. In patients with SLOS, the protein 7-dehydrocholesterol is elevated. Genetic testing looks for changes in a patient’s genes. SLOS is diagnosed if there are harmful changes in both copies of the DHCR7 gene.


Sneddon syndrome

livedo reticularis racemosa and cerebrovascular accidents

Sneddon syndrome is a rare progressive disorder affecting small- and medium-sized blood vessels. The disorder is characterized by the association of a skin condition and neurological abnormalities. Characteristic findings include multiple episodes of reduced blood flow to the brain (cerebral ischemia) causing mini-strokes or stroke and bluish net-like patterns of discoloration on the skin surrounding normal-appearing skin (livedo reticularis). Additional symptoms may include headache, dizziness, abnormally high blood pressure (hypertension), and heart disease. Lesions may develop within the central nervous system as a result of reduced blood flow to the brain, which can cause reduced intellectual ability, memory loss, personality changes, and/or other neurological symptoms. The combination of stroke symptoms and livedo reticularis differentiates this syndrome from other disorders. The exact cause of Sneddon syndrome is not fully understood.

Sneddon syndrome is a slowly progressive disorder of small- and medium-sized arteries, which are the blood vessels that carry blood away from the heart. The disorder is characterized by blockages (occlusions) of the arteries that cause a reduction of blood flow to the brain and to the skin. Associated symptoms vary from one person to another based, in part, upon the specific arteries that are affected. An irregular, net-like pattern of bluish skin discoloration surrounding areas of normal-appearing skin (livedo reticularis) is characteristic of this disorder. The arms and legs are most often affected as well as the trunk, buttocks, and hands and feet. Livedo reticularis is worsened by cold and pregnancy. (In the European medical literature, the term livedo reticularis is used to describe the skin changes of the extremities only that disappear when the skin is warmed. Livedo racemosa is used to describe skin changes that involve also the buttocks and the trunk and do not disappear with warm temperatures. These two dermatologic conditions are separated because livedo reticularis is much more frequent, but the association with strokes exists for livedo racemosa only).

The exact cause of Sneddon syndrome is unknown. Most cases occur randomly for no apparent reason (sporadically). Possible immunological, environmental, genetic, and/or other factors are under investigation as potential causes of the disorder.

Sneddon syndrome has been reported more often in females than in males. Almost 80% of the patients are women with a median age of diagnosis at 40 years. Symptoms usually begin in early to middle adulthood, but can occur at any age including childhood. The incidence and prevalence are unknown. One estimate places the incidence at approximately one out of 250,000 individuals in the general population.

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

Lupus is a chronic, inflammatory autoimmune disorder affecting the connective tissue. In autoimmune disorders, the body’s own immune system attacks healthy cells and tissues causing inflammation and malfunction of various organ systems. In lupus, the organ systems most often involved include the skin, kidneys, blood and joints. Many different symptoms are associated with lupus, and most affected individuals do not experience all of the symptoms. In some cases, lupus may be a mild disorder affecting only a few organ systems. In other cases, it may result in serious complications. Initial symptoms may include excessive fatigue, fever, swollen glands, loss of appetite (anorexia) and weight loss, and headaches. Vascular symptoms in people with Lupus may include a permanent increase in the diameter (dilation) of very small blood vessels (capillary telangiectasis), painfully cold fingers and toes caused by spasms of small blood vessels in response to cold (Raynaud’s phenomenon), and inflammation of the blood vessels (vasculitis). There are at least three forms of lupus: the classic form, systemic lupus erythematosus; a form that only affects the skin, discoid lupus erythematosus; and drug-induced lupus erythematosus. The term lupus is most often used to denote systemic lupus erythematosus.


X连锁智力障碍，Snyder亚型

X-linked intellectual disability, Snyder type

The symptoms, progression and severity of SRS exhibit some variability across families and individual patients. Affected children have a gestalt consisting of facial dysmorphism with a prominent lower lip, an asthenic build, low muscle mass, kyphoscohosis and speech abnormalities. Males with SRS have low muscle tone (hypotonia) at birth. Symptoms appear early, especially the facial features. Developmental milestones are also not met early in life. The developmental delay progresses such that many boys with SRS have some motor disability. Osteoporosis develops which can result in numerous fractures without a causative event. Seizures have been noted in many affected males and severity varies.

All presently known cases of Snyder-Robinson syndrome are caused by changes (mutations) in the SMS gene. Thus far, 21 mutations are known although not all have been published. Since the gene resides on the X chromosome only males are affected. If the mother of a male with SRS carries the mutation, there is a 50% chance another son will have SRS and a daughter will be a carrier. The rate of new mutations appears to be low as only a single case exists in which the mother of the boy with SRS was not a carrier.

Snyder-Robinson syndrome is a rare X-linked intellectual disability disorder and as such it is difficult to estimate its prevalence. As SRS has been identified in patients located in the United States, South America and Europe, it is likely not restricted to any ethnic population geographical locale.

Many XLID disorders present with hypotonia very early in life. However, SRS is the only human disorder related to an abnormality in polyamine biosynthesis.

A diagnosis of Snyder-Robinson syndrome can be made based on the clinical presentation and confirmed by sequencing of the SMS gene. However, since SRS is a rare XLID condition, more likely the diagnosis is made after whole exome sequencing (WES) identifies a mutation in the SMS gene. Additionally, since at present only one mutation in SMS has appeared more than once, biochemical studies (SMS activity and cellular spermidine/spermine ratios) should be conducted to absolutely insure a proper diagnosis of SRS.


Soft Tissue Sarcoma

The signs and symptoms of soft tissue sarcomas can vary greatly from one person to another. Specific findings depend on numerous factors including the specific subtype, the exact location of the tumor, the extent of the tumor into nearby tissue or organs, the specific organs involved and whether the disease has remained localized or spread to other areas of the body (metastasized).

As with many forms of cancer, the exact, underlying cause of soft tissue sarcoma is not fully understood. In most affected individuals, this cancer is thought to occur randomly, for no specific reason (sporadically). Sporadic occurrence of cancer is thought to occur because of multiple factors acting together. This can include genetic and environmental factors. Current research suggests that abnormalities in DNA, which is the carrier of the body’s genetic code, are the underlying basis that causes cells to become cancerous (malignant). The specific cell that becomes cancerous differs depending upon the specific subtype of soft tissue sarcoma. In most instances, these changes in DNA are acquired during life and are not inherited, nor do soft tissue sarcomas tend to run in families, unless affected individuals also have a genetic cancer-predisposition syndrome.

Soft tissue sarcomas affect males and females and individuals of any age and every racial and ethnic group. This is a large group of tumors, but overall, they are still classified as rare disorders. Estimates of their frequency varies. The American Cancer Society estimates that soft tissue sarcomas account for about 2% of all cancers in the United States. However, because rare diseases often go misdiagnosed or undiagnosed, determining their true frequency in the general population is difficult.

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

A diagnosis of soft tissue sarcoma is based upon identification of characteristic symptoms, a detailed patient and family history, a thorough clinical evaluation and a variety of specialized tests. A physical examination can reveal a mass or growth that can be painless.


Sotos syndrome

Sotos syndrome is a genetic disorder, described in 1964, characterized by excessive growth before and after birth, a large, elongated (dolichocephalic) head, distinctive facial configuration, and a non-progressive neurological disorder with intellectual disability. Advanced bone age is present in approximately 75 to 85% of patients.

The main clinical finding is prenatal and postnatal overgrowth. The growth velocity is particularly excessive in the first 3 to 4 years of life and subsequently proceeds at the normal rate, but in the high percentiles. The mean height is usually 2 to 3 years ahead of peers during childhood. The weight is usually appropriate for the height and the bone age is advanced mean by 2 to 4 years over chronological age, during childhood. Adult height usually exceeds the average of normal men or women. Some individuals may reach excessive adult heights; males of 193 cm to 203 cm (6 ft. 4 in. to 6 ft. 8 in.) and females up to 188 cm (6 ft. 2 in.) are known.

Sotos syndrome is caused by mutations (abnormalities) in the NSD1 (nuclear receptor-binding SET domain protein 1) gene. Mutations in this gene have been identified in approximately 90% of affected patients (Sotos syndrome 1). A few years ago, mutations in the NFIX gene (nuclear factor I, X type) were identified in 5 patients with Sotos syndrome (Sotos syndrome 2). In 2015, a loss-of-function mutation in the APC2 (adenomatous polyposis coli 2) gene was reported in 2 siblings with some neural features of Sotos syndrome including intellectual disability, abnormal brain structure, and typical facial features, but no other features such as bone or heart abnormalities (Sotos syndrome 3). The parents were blood relatives (consanguineous). The APC2 gene is specifically expressed in the nervous system, and is a crucial downstream gene of NSD1. In other words, mutations in the NSD1 gene affects the APC2 gene and results in the neural abnormalities.

Sotos syndrome affects males and females in equal numbers, occurs in all ethnic groups and has been detected throughout the world. This condition occurs in about one in 14,000 live births.

Symptoms of the following disorders may be similar to those of Sotos syndrome. Comparisons may be useful for a differential diagnosis. Confirmation of any of the syndromes can be obtained by genetic testing.

There is no biochemical marker for the disease. The diagnosis is based on clinical grounds. The most characteristic manifestations are the craniofacial configuration, excessive growth, and developmental delay. The diagnosis of a patient with the typical craniofacial configuration and excessive growth can be made at the first site. The craniofacial configuration is the most distinctive, and only rarely (~ 1%), is not present. Ten percent of the children and adolescents may be below +2 SD in height and 10 or 15% of the patients may not have developmental delay. Advanced bone age may be present in 76 to 86% of the patients and is helpful but not specific. Brain abnormalities are present in 60 to 80% of patients, such as communicating hydrocephalous, and others, but are not diagnostic and are non-specific.


家族性激素抵抗性肾病综合征伴肾上腺功能不全

Familial steroid-resistant nephrotic syndrome with adrenal insufficiency

Sphingosine Phosphate Lyase Insufficiency Syndrome

primary adrenal insufficiency-steroid-resistant nephrotic syndrome due to SGPL1 deficiency

Sphingosine phosphate lyase insufficiency syndrome (SPLIS) is a very rare genetic condition that affects the kidneys, adrenal glands and nervous system.  Symptoms vary from individual to individual, but most people with SPLIS have signs of abnormal kidney and adrenal gland function, which can include a buildup of extra fluid, vomiting and diarrhea.  Some people with SPLIS have dry, scaly, cracked or darkened skin and problems with their immune system. SPLIS is caused by changes (disease-causing variants) of the sphingosine-1-phosphate lyase 1 gene (SGPL1) and is inherited in an autosomal recessive pattern. SPLIS is diagnosed based on the symptoms, clinical examination and through genetic testing. There is no specific treatment for SPLIS.  Medication and supportive care can help with some of the symptoms. The long-term outlook for people with this disorder is unknown.

The age of onset is not the same for everyone, but signs and symptoms of SPLIS usually appear in infancy or early childhood. Some people with SPLIS may be more severely affected than others, with the most severe cases of this condition resulting in early fetal death due to excess fluid accumulation. Some of the more common signs and symptoms of SPLIS include:

SPLIS is caused by variants in the spingosine-1-phosphate lyase 1 (SGPL1) gene. The protein made by this gene, sphingosine-1-phosphate lyase (SPL) is found in many different organs, including the kidneys, adrenal and other endocrine glands. It is involved in many important processes of cellular function.  SPL is a vitamin B6-dependent enzyme, i.e, it needs vitamin B6 to function.

Less than 100 people have been reported in the medical literature with SPLIS.

The following conditions have symptoms that can be similar to SPLIS: steroid-resistant nephrotic syndrome, nephrotic syndrome, glomerulosclerosis, primary adrenal insufficiency (Addison’s disease), primary immunodeficiency, Charcot Marie Tooth disease (peripheral neuropathy) and ichthyosis.

SPLIS may be suspected based on symptoms and clinical examination. The diagnosis is confirmed by genetic testing that identifies disease-causing variants in both copies of the SGPL1 gene.


Spina Bifida

Spina bifida is characterized by incomplete closure of certain bones of the spinal column (vertebrae), leaving a portion of the spinal cord exposed. Part of the contents of the spinal canal may protrude through this opening. In the most severe form, rachischisis, the opening is extensive. Spina bifida may cause difficulties with bladder control, walking and/or other functions, depending on the severity of associated symptoms.

Patients with spina bifida have a wide variety of symptoms and physical findings, depending on the extent of the defect in the spine. The mildest form of the condition, spina bifida occulta, causes few if any symptoms, and may go undetected.  In this mild form, the lack of closure of the neural tube affects only a small area of the spine and is found on X-rays. The disorder may be suspected because of a dimple or tuft of hair on the back overlying the affected area.  Impaired bladder control is a common finding, even with relatively mild forms of the condition.

The exact cause of spina bifida is not known.  A combination of hereditary and environmental factors may be involved.  Studies have also indicated that a lack of folic acid in the mother’s diet during pregnancy heightens the risk of spina bifida and other neural tube defects.

Spina bifida is the most common neural tube defect in the United States. Between 1,500 and 2,000 babies out of about 4 million births are born with this disorder each year in the United States.

Spina bifida is usually an isolated birth defect but it can also occur as part of a syndrome with other birth defects.  It is one of a group of disorders known as neural tube defects.


常染色体隐性遗传远端型遗传运动神经病

Autosomal recessive distal hereditary motor neuropathy

Spinal Muscular Atrophy with Respiratory Distress Type 1

autosomal recessive distal spinal muscular atrophy 1s

Symptoms of SMARD1 generally begin during infancy. Early features of SMARD1 include a weak cry, feeding problems, difficult and noisy breathing- especially when inhaling (inspiratory stridor) and recurrent pneumonia. Between 6 weeks and 6 months of age, affected infants typically experience sudden onset of shortness of breath with progressive respiratory distress. This is due to paralysis of the diaphragm, (primary inspiratory muscle) and abdomen resulting in ineffective breathing with an increased respiratory rate (tachypnea) and eventual inability to breathe (respiratory failure). Diaphragmatic paralysis can result from a dysfunction of the phrenic nerve that supplies the diaphragm. This paralysis (phrenic nerve palsy) usually starts on the right side although it can affect one or both halves of the diaphragm.

SMARD1 is caused by variants (mutations) in the IGHMBP2 gene. Researchers have found more than 60 different mutations in the IGHMBP2 gene that cause SMARD1. The IGHMBP2 gene is responsible for providing instructions necessary for making the IGHMBP2 protein that is involved in DNA replication and production of RNA and proteins. However, the exact role of the IGHMBP2 protein is currently unknown.

The exact prevalence of SMARD1 is currently unknown. Studies show that diaphragmatic paralysis affects about 1% percent of individuals diagnosed with early onset spinal muscular atrophy. As of 2015, greater than 60 cases of SMARD1 have been described in scientific literature.

Symptoms of the following disorders may have characteristics like SMARD1. Comparing the clinical features of these disorders could be helpful in obtaining an accurate diagnosis.

A diagnosis of SMARD1 is based upon the presence of characteristic features. Diagnosis usually follows severe and rapidly progressive respiratory distress caused by diaphragm paralysis, which often requires mechanical ventilation. An abnormally high position of the diaphragm can be indicative of SMARD1 if this occurs with one or more of the following signs: an infant with respiratory distress; family history of sudden infant death syndrome; close familial relation (consanguinity) of parents; and foot and hand muscle weakness and/or distal articular retractions. Genetic testing can detect the presence of mutations in the IGHMBP2 gene and confirm a clinical diagnosis. Further testing- such as an x-ray, electromyogram (EMG), and nerve conduction study (NCS), or muscle biopsy- may be performed to rule out related disorders.


Proximal spinal muscular atrophy

Spinal muscular atrophy (SMA) is a group of inherited neuromuscular disorders characterized by loss of nerve cells in the spinal cord called lower motor neurons or anterior horn cells. Lower motor neurons originate in the brainstem or the spinal cord and relay nerve impulses from upper motor neurons, located in the brain, to the muscles they control. The loss of lower motor neurons leads to progressive muscle weakness, muscle wasting (atrophy) and low muscle tone (hypotonia) that is typically more pronounced in muscles closest to the trunk of the body (proximal muscles) such as the shoulders, hips and back. However, neurons controlling most voluntary muscles can be affected, including those that control muscles involved in feeding, swallowing and breathing.

The signs and symptoms of SMA are a consequence of lower motor neuron loss. The features of lower motor neuron disease include muscle weakness and atrophy, hypotonia, decreased or absent reflexes (hypo- or areflexia) and twitching of muscle fibers (fasciculations). Although SMA is a disease spectrum, the five subtypes are determined based on their age of symptom onset and maximum motor function achieved. This classification for SMA was established prior to the availability of genetic testing and prior to the availability of disease modifying treatments.

SMA is caused by deletion or variant in the SMN1 gene, which encodes a protein known as survival motor neuron (SMN). This protein plays an important role in the functioning and maintenance of motor neurons. Approximately 95-98% of affected individuals have deletions in the SMN1 gene and 2-5% have a point variant in the SMN1 gene that results in a decreased production of the SMN protein.

The incidence of SMA is approximately 1 in 10,000 livebirths. SMA affects females and males equally.

Symptoms of the following disorders can be similar to those of SMN-related SMA. Comparisons may be useful for a differential diagnosis.

The treatment of SMA requires a multidisciplinary team approach and should notably include neurologists, medical geneticists, physical therapists, speech pathologists, pulmonologists, respiratory therapists, medical social workers, nutritionists, psychologists and specialized nurses. There are two main components to SMA management: treatment that slows the progression of the disease (disease-modifying therapy) and therapy that helps manage symptoms and improves quality of life (supportive therapy).


脊髓小脑性共济失调伴轴索神经病1型

Spinocerebellar ataxia with axonal neuropathy type 1

Spinocerebellar Ataxia with Axonal Neuropathy

Spinocerebellar ataxia with axonal neuropathy (SCAN1) is a neurodegenerative disorder that is inherited in an autosomal recessive pattern. SCAN1 is characterized by late childhood-onset of a slowly progressive cerebellar ataxia, followed by areflexia and signs of peripheral neuropathy. Gaze nystagmus and cerebellar dysarthria usually develop after the onset of ataxic gait. As the disease advances, pain and touch sensation become impaired in the hands and legs; vibration sense disappears in hands and lower thigh. Individuals with advanced disease develop a steppage gait and pes cavus; and later become wheelchair dependent. Affected individuals have normal intellect and longevity.

SCAN1 is suspected in individuals with the following clinical features:

SCAN1 is inherited as an autosomal recessive disorder. Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

SCAN1 has been identified in a single Saudi Arabian family. It has not been identified in other ataxic individuals.

Partial symptomatic overlap with SCAN1 can be seen in several spinocerebellar ataxias including ataxia oculomotor apraxia 1 (AOA1), ataxia oculomotor apraxia 2 (AOA2), Friedreich ataxia (FRDA) and ataxia with vitamin E deficiency (AVED). AOA1 is characterized by early onset cerebellar ataxia, axonal neuropathy, oculomotor apraxia and chorea or dystonia. Serum concentration of albumin is decreased and total cholesterol is increased. The presence of oculomotor apraxia (80% of individuals with AOA1) differentiates AOA1 from SCAN1; however, this sign is not obvious in the early stages of the disease. AOA1 is caused by mutations of APTX.

The diagnosis of SCAN1 is made on history and clinical signs as listed above. DNA testing for mutations in TDP1 is only available on a research basis.


Isolated split hand-split foot malformation

Split hand/foot malformation (SHFM) is a limb abnormality that is present at birth. It is characterized by absence of certain fingers and toes (ectrodactyly) that suggest a claw-like appearance and webbing of fingers and toes may also be present. SHFM can be inherited as a single abnormality or as a part of syndrome that includes other characteristics. There is a wide variety of symptoms and genetic causes of SHFM, and there can be varying levels of severity in people who are affected. Severity can vary even among members of the same family.

Symptom presentation varies from person to person. Most people with SHFM have fewer than five fingers or toes on a hand or foot (oligodactyly). A smaller proportion of individuals affected by SFHM have finger fusing (syndactyly) of multiple fingers on the hands. This is often referred to as the lobster claw variety where the third digit is absent and replaced with a cone-shaped cleft that tapers in toward the wrist and divides the hand into two parts resembling a lobster claw. The remaining fingers or parts of fingers on each side of the cleft are often joined or webbed together. A cleft, or the absence of bones in the hands before the fingers, usually occurs in both hands. A similar deformity commonly occurs in the feet.

There are multiple genetic causes (genetic heterogeneity) of split hand/foot malformation which makes it difficult to pinpoint a single causative mutation that leads to the condition.

Split hand/foot malformation affects males and females at similar rates, due to the nature of SHFM being inherited in an autosomal dominant, autosomal recessive or X-linked manner. The X-linked SHFM cases typically manifest in males. The total frequency of all SHFM cases is approximately 1 out of every 90,000-100,000 live births, worldwide.

This disorder falls under the category of ectodermal dysplasia. Related disorders in this category are characterized by ectrodactyly; the absence of tear ducts; cleft lip and/or palate; and sparse scalp hair, lashes and eyebrows.

SHFM is usually diagnosed by physical features present at birth. The presence of abnormal number of toes and finger dysplasia is usually obvious during initial evaluations. Genetic testing for the genes previously discussed is available to further support the initial diagnosis.


Spondylocostal Dysplasia

常染色体显性遗传脊椎肋骨发育不全

The signs and symptoms of spondylocostal dysplasia can vary greatly from one person to another, even among members of the same family. Affected individuals have abnormalities in the development of the spine and ribs.

Spondylocostal dysplasia is caused by a change (mutation) in one of at least five different genes, specifically the DLL3, MESP2, LFNG, HES7, and TBX6 genes. An altered DLL3 gene is the most common cause. Many people do not have a mutation in any of these genes, suggesting that as-yet-unidentified genes also cause spondylocostal dysplasia. 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, or absent. Depending upon the functions of the protein, this can affect many organ systems of the body.

Spondylocostal dysplasia is a rare disorder. The exact prevalence or incidence of the disorder is unknown. Because it is a rare disorder, some people may go undiagnosed or misdiagnosed, making it difficult to determine the true frequency in the general population. Spondylocostal dysplasia affects both men and women, and is seen in all ethnic groups (panethnic).

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

A diagnosis of spondylocostal dysplasia is based upon identification of characteristic symptoms, a detailed patient and family history, a thorough clinical evaluation and a variety of specialized tests.


Spondyloepiphyseal Dysplasia Tarda

Young boys with SEDT do not typically show signs of the condition and have otherwise normal height and body proportions until the age of 6 to 8 years old. Around this time, symptoms of the disorder begin to develop, hence the word tarda in SEDT which refers to the later onset of this condition.

SEDT is caused by changes (mutations) in a gene on the short arm of the X chromosome at Xp22.2-p22.1. The gene, known as SEDL or TRAPPC2, is widely expressed in tissues throughout the body, but mutations in this gene appear to only affect cartilage. Mutations have been found to be distributed throughout the gene [Gedeon et al., 2001]. The TRAPPC2 gene encodes the instructions for a protein product called sedlin, which is thought to help transport proteins within the cell. There are no other disorders linked to TRAPPC2.

SEDT affects individuals of many different ancestral groups. Individuals with SEDT have been reported in European, American, Asian and Australian populations (but not in populations of African ancestry to date). SEDT is estimated to occur in 2 persons per million.

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

A diagnosis of SEDT is usually made through radiological findings (X-ray), but a diagnosis can also be made through molecular genetic testing.


Spondyloepiphyseal dysplasia congenita

The specific symptoms and severity of spondyloepiphyseal dysplasia congenita can vary greatly from one person to another. Affected individuals may not have all of the symptoms discussed below. In most cases, certain symptoms are noticeable at birth (congenital).

Spondyloepiphyseal dysplasia congenital is caused by a mutation in the COL2A1 gene. 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, or absent. Depending upon the functions of the particular protein, this can affect many organ systems of the body.

Males and females are affected in equal numbers. The exact incidence or prevalence is unknown, but spondyloepiphyseal dysplasia congenita is estimated to occur in approximately 1 in 100,000 live births. Collectively, the skeletal dysplasias are estimated to occur in approximately 1 in 5,000 individuals in the general population.

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

A diagnosis of spondyloepiphyseal dysplasia congenita is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. A diagnosis may be suspected at birth because of characteristic findings.


Spontaneous intracranial hypotension

spontaneous spinal cerebrospinal fluid leak

The onset of symptoms and signs may be relatively abrupt or more gradual. Patients may be minimally affected or profoundly disabled with limited ability to function while upright. Quality of life measures in this population are very poor. The hallmark of intracranial hypotension is a positional headache. This headache is worse when upright and improves when lying down. It usually occurs within 15 minutes of assuming the upright position and is relieved after lying down within 15-30 minutes, however it may take hours to worsen or improve with change of position. Over time, the positional aspect of the headache tends to lessen and may even disappear. Headache is not universally positional and may be absent. The location of the headache is most often in the back of the head or base of the skull, but can also occur in the front, sides or all over the head. The headache is rarely on just one side of the head. The quality of the headache is often described as a pulling sensation from the back of the head to the neck although many other qualities are reported. The severity of the headache can range from mild to very severe and disabling.

The underlying cause of spontaneous intracranial hypotension is a loss of cerebrospinal fluid (CSF) volume through a hole or tear in the spinal dura. The dura is the tough outermost layer of the meninges (connective tissues that surround the brain and spinal cord) that holds in the CSF. When this fluid volume is reduced, there is less fluid available to cushion the brain inside the skull. This loss of CSF volume is thought to cause headache and other neurological signs and symptoms and may result in a range of complications. With upright posture, the loss of CSF volume has a greater effect on the brain.

Males and females of any age may develop spontaneous intracranial hypotension, but it is diagnosed more often in females. The peak age of diagnosis is age 40.

In addition to spontaneous cases, intracranial hypotension may also occur as a result of medical procedures such as a lumbar puncture, epidural injection, over-drainage of CSF shunts or spinal or other surgery. It may also occur as a result of an injury, such as a motor vehicle accident, sports injury or penetrating trauma. Cases related to medical procedures and injuries are usually more readily identified than cases of spontaneous intracranial hypotension.

The diagnosis of spontaneous intracranial hypotension is initially suspected based on presenting signs and symptoms. Many physician specialties may be involved in the care of patients, including primary care physicians, emergency medicine physicians, neurologists, neuroradiologists, pain management physicians, anesthesiologists, neurosurgeons and geneticists.


Inclusion body myositis

Sporadic inclusion body myositis (sIBM) is an acquired progressive muscle disorder that becomes apparent during adulthood. The symptoms and progression of sIBM vary from one person to another. In most cases, sIBM is characterized by progressive weakness and degeneration (atrophy) of the muscles especially those of the arms and the legs. sIBM can progress to cause severe disability. sIBM is an autoimmune disease mediated by cytotoxic T cells, but the exact cause of the disorder is unknown. sIBM, like all autoimmune diseases, is a complex disorder and, most likely, multiple factors including genetic, immunological and environmental ones in combination all play a role in its development.

The distribution, severity and progression of muscle weakness vary from one person to another. In some patients, sIBM may affect one arm or leg more than the other. In most cases, the progression is very slow. The muscles of the anterior thighs (quadriceps) and wrist and finger flexors are usually affected more severely than other muscles. Many individuals with sIBM first present with a tendency to trip or fall or with difficulty with handgrip, or with difficulty swallowing.

The cause of sIBM is unknown and complex. Researchers believe multiple immunological, genetic and environmental factors and factors related to aging all play a role in the development of the disorder. Researchers have identified two distinct processes – one autoimmune and one degenerative – that occur in individuals with sIBM. It appears likely that autoimmunity drives the disease and accounts for the minor degenerative pathological changes seen in sIBM skeletal muscle.

sIBM affects males slightly more often than females. Its prevalence is estimated to be between 10-112 people per 1,000,000 in the general population. It occurs with greater frequency in individuals more than 50 years of age. The prevalence is estimated to be 51-139 per 1,000,000 individuals in the general population over 50, making sIBM the most common acquired muscle disorder (myopathy) in that age group. Despite growing awareness of this disorder, many researchers believe it remains underdiagnosed.

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

The diagnosis of sIBM is made based upon a thorough clinical evaluation, a careful patient history, and a variety of specialized tests, such as a muscle biopsy. A muscle biopsy is a procedure in which a tiny amount of muscle tissue is surgically removed and studied under a microscope to detect characteristic changes that indicate sIBM. Additional tests that can be used to aid in a diagnosis include electromyography and blood tests that measure the amount of certain enzymes in muscle tissue. A blood test specifically for IBM was developed in 2013 and is now commercially available for diagnostic use.


Sprengel deformity

Sprengel deformity is a rare congenital disorder in which the shoulder blade (scapula) is too high on one side of the body. The affected abnormal shoulder blade is also abnormally connected to the spine, often restricting movement of the shoulder. The affected shoulder blade may also be underdeveloped and smaller than normal and rotated toward the middle of the body. In some cases, the shoulder blade may be irregularly-shaped (dysplastic). In addition, a lump may develop at the base of the neck. Sprengel deformity can occur as an isolated, single defect or in association with other abnormalities. The disorder is typically present at birth (congenital), although it may not become apparent until an affected individual grows older. The exact, underlying cause of Sprengel deformity is unknown. The disorder appears to occur randomly, for no apparent reason (sporadically), although some rare cases have run in families.

Often, only one shoulder blade (i.e. one side of the body) is affected. However, in some cases both shoulder blades can be affected. Generally, these abnormalities tend to be painless. The degree of elevation and displacement in Sprengel deformity can vary greatly from one person to another and can range from very mild, in which the abnormality cannot be seen when wearing clothes, to severe cases in which the shoulder is noticeably elevated. Milder cases can go undiagnosed until adolescence. The reported range of displacement of the shoulder blade is 2-10 centimeters, or approximately a half an inch to 4 inches.

The exact underlying cause is unknown. Most cases occur randomly, for no apparent reason (sporadically).

Most reports in the medical literature state that Sprengel deformity affects females more often than males by a ratio of 3-1. However, other reports state that the disorder affects males and females in equal numbers.

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

Scoliosis is a common condition in which the spine abnormally curves to the side instead of running straight up and down. Scoliosis can be mild, but can worsen as an affected child grows. In many cases, the exact cause of scoliosis is unknown (idiopathic). In other cases, the condition can develop as part of a large syndrome such as muscular dystrophy. Affected children may have uneven shoulders, one shoulder blade that appears to be more pronounced or prominent than the other, and uneven hips. Some children may experience backaches or lower back pain.

The mainstay of treatment for Sprengel deformity is surgery. However, many affected individuals will not require surgical intervention because they have a mild form of the disorder with minimal restriction of movement. Children between 3-8 years of age are the best candidates for surgical intervention, which is based on significant cosmetic or functional (i.e. significant restriction of movement) concerns. In some cases, shoulder blade position and/or shoulder range of motion can still be abnormal even after surgery. The presence of additional abnormalities can affect the outcome of surgery. An omovertebral bone or its fibrous equivalent must be removed during surgery.


Staphylococcal scalded skin syndrome

葡萄球菌性烫伤样皮肤综合征

Staphylococcal scalded skin syndrome (SSSS) is a disorder that develops because of a toxin produced by a staphylococcal infection. A toxin is a harmful substance that causes disease when it enters tissues of the body. In SSSS the toxin spreads to the skin through the blood stream and specifically binds to desmoglein 1, an adhesion molecule target protein very high in the epidermis (outer layer of the skin) producing total body reddening of the skin and blistering and sloughing of the skin resembling a hot water burn or scalding of the skin. The top layer of the skin may peel off and shed. Affected individuals may also experience nonspecific symptoms such as fever (usually low grade), chills and weakness. Unlike similar disorders that cause a scalded skin appearance, the mucous membranes are not affected. Infants and younger children are most susceptible, because they lack antibodies to the toxin and may be slow to clear the toxin-antibody complex in their immature kidneys, but the disorder can also occur in certain older children or adults such as people who have compromised immune systems or insufficient kidney (renal) function. Staphylococcal scalded skin syndrome is caused by toxins produced by certain strains (most commonly phage group 2 strains 55 and 71) of the bacterial germ Staphylococcus aureus.

Initial symptoms can include fever (usually low grade), generalized redness and tenderness of the skin. The onset of symptoms is usually rapid. Some individuals may experience nonspecific symptoms that develop before the skin symptoms including a sore throat and inflammation of the eyelids known as conjunctivitis.

Staphylococcal scalded skin syndrome is caused by a Staphylococcus or Staph infection. Staphylococcus is a type of bacterium of which there are more than 30 different varieties. Staphylococcus aureus is the most common form associated with disease. Staphylococcus aureus is commonly found on human skin and begins colonization immediately after birth. Usually, this bacterium resides on the skin and mucous membranes of humans but does no harm. However, it does predispose an individual to infection, especially when given the opportunity to break through the skin. Staphylococcus aureus is the underlying infection in individuals with staphylococcal scalded skin syndrome. However, in many healthy children no underlying bacterial infection can be detected clinically.

Staphylococcal scalded skin syndrome affects males and females in equal numbers. The incidence, which has doubled in the last decade (based on national hospitalization data), is estimated to be between .09 and .56 per 1,000,000 individuals in the general population. However, these estimates may reflect cases reported in the medical literature, and the disorder most likely is more common in the United States than estimated, particularly in infants and young children. Most cases are in children under the age of 6. Newborns (neonates) are at particular risk because they do not have fully developed immune systems, do not have neutralizing antibodies for the toxin, and their kidneys cannot fully clear toxins from the body yet. For similar reasons certain adults, specifically adults with a compromised immune system or poor kidney function, are at a greater risk than the general population of developing the disorder.

Symptoms of the following disorders can be similar to those of staphylococcal scalded skin syndrome and should be differentiated from SSSS. Comparisons may be useful for a differential diagnosis.

A diagnosis of staphylococcal scalded skin syndrome is based upon identification of characteristic symptoms, a thorough clinical evaluation and a detailed patient history. Although not usually necessary, in some cases, a skin biopsy, in which a tiny piece of affected skin is removed and studied under a microscope, may be performed. A biopsy can reveal non-inflammatory superficial splitting of the epidermis, which is indicative of the disorder and can differentiate it from similar disorders.


STEC Hemolytic Uremic Syndrome

志贺毒素相关性溶血性尿毒症综合征

The hemolytic uremic syndrome is defined by the sudden occurrence of acute hemolytic anemia with fragmented red blood cells, low levels of platelets in the blood (thrombocytopenia), and acute kidney injury. Hemolytic uremic syndrome is a general term that covers five main subtypes STEC (typical), atypical hemolytic uremic syndrome [complement dysregulation], Sp HUS (Streptococcal pneumonia associated HUS) and metabolic causes of HUS. This report covers STEC (typical) hemolytic uremic syndrome, which is most often associated with E. coli infection and bloody diarrhea. NORD has a separate report on the rarer atypical hemolytic uremic syndrome, which is not caused by infection with E. coli and is often the result of a genetic mutation.

The symptoms and severity of STEC HUS vary greatly from one person to another. The disorder can be mild or it can progress to cause life-threatening complications. Most children with STEC HUS recover without permanent damage; however, about a small percent recover with complications. Chronic complications include chronic kidney disease, proteinuria, hypertension, diabetes mellitus, gall stones, neurological deficits.

In most people, STEC HUS occurs in association with infection by a particular strain of (E. coli) known as O157:H7. In a recent European outbreak, the strain was O104:H4 and there were 4320 people with bloody diarrhea, 850 people with HUS and 82 deaths. The bacterium may reside in the intestinal tract of domestic animals, mainly cattle, and may be transmitted to humans through the consumption of unpasteurized milk or infected, undercooked meat or poultry. Cases have been reported in which STEC HUS occurred after the consumption of unpasteurized or otherwise untreated apple juice or cider. Epidemics have followed ingestion of contaminated lettuce, spinach or bean sprouts. It is important to note that transmission may be the result of person-to-person contact within a family or at a kindergarten or an infected wading pool.

STEC HUS affects males and females in equal numbers. Some studies have suggested that the disorder affects females more severely than males. It can affect children or adults, but is more common in children under 10, especially children between 7 months and 6 years of age. STEC HUS is the most common cause of acute renal failure in children. STEC HUS is estimated to occur in 1-3 per 100,000 people in the general population. The incidence rate of E. coli infection in North America is estimated to be 8 in 100,000 people in the general population. Fortunately, only 5 to 15 percent of individuals infected with E. coli progress to develop STEC HUS.

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

A diagnosis of STEC HUS may be suspected upon identification of characteristic findings. STEC HUS should be suspected in anyone, especially young children who develop sudden acute renal failure, anemia and thrombocytopenia after an episode of gastroenteritis with bloody diarrhea.


Stevens-Johnson syndrome/toxic epidermal necrolysis spectrum

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Most cases of SJS/TEN begin with the development of general, non-specific symptoms including flu-like symptoms, fever, burning or stinging of the eyes, body aches and discomfort or difficulty swallowing. Additional non-specific symptoms include headaches, chills, joint pain and a general feeling of poor health (malaise). A pus-producing (purulent) cough that also brings up mucous, phlegm and saliva (sputum) may also occur. These symptoms usually precede the development of skin involvement by a few days and characteristically happen one to eight weeks after exposure to the trigger.

SJS and TEN are life-threatening reactions that are predominantly drug-induced. Approximately 75% of SJS and TEN cases are caused by medications, but this percentage varies according to age, with a higher percentage in adults and a lower percentage in children. The drugs most associated with these disorders include allopurinol, a drug commonly used to treat gout or kidney stones; anti-convulsants (anti-epileptics) including phenytoin, carbamazepine, lamotrigine and phenobarbital; sulfonamide medications; antibiotics such as minocycline; nonsteroidal anti-inflammatory drugs (NSAIDs); anti-HIV medications such as nevirapine and anti-tuberculosis (TB) medications. In the last few years, multiple new anticancer treatments were developed and have also been recognized as an important trigger for adverse drug reactions. Various other drugs have been reported as triggers of SJS and TEN, and almost any medication can cause SJS/TEN, including over-the-counter medications and herbal/natural preparations.

SJS and TEN can affect individuals of any age, but the incidence is much higher in the elderly population. This may be related to increased exposures to potentially causative medications. Individuals of every race and ethnicity can develop these disorders; however, it is more common in Asian populations. The incidence in western societies is 1-2 per 1,000,000 people in the general population.

Disorders with similar symptoms include:

There are no specific blood tests yet to diagnose SJS/TEN. The diagnosis is based upon identification of characteristic signs and symptoms, a detailed history from the patient and/or relatives, a thorough physical examination and the results of blood tests and a skin biopsy. A biopsy involves taking a small sample of affected skin and examining it under a microscope. An additional skin biopsy for immunofluorescence (special staining) may also be performed to exclude other conditions such as autoimmune blistering disorders which may have similar manifestations to SJS/TEN, especially early on (please see list above).


Stickler syndrome

Stickler syndrome refers to a group of disorders of connective tissue. Connective tissue, which is distributed throughout the body, can affect multiple organ systems. The specific symptoms present in Stickler syndrome often vary greatly from one individual to another. Affected individuals may not have all of the symptoms .The eyes, ears, skeleton and joints are most often affected. Affected individuals may also have distinctive facial features and palate abnormalities.

Stickler syndrome type I (STL1) is responsible for approximately 70% of reported cases and presents with a wide variety of symptoms affecting the eye, ear, facial appearance, palate and musculoskeletal system and occurs due to mutations over the entire COL2A1 gene on chromosome 12q13.11. These mutations cause loss of function of the COL2A1 gene. The majority of these mutations are associated with normal stature and early onset osteoarthritis. Only a few non-glycine missense mutations have been reported and among these, the arginine to cysteine substitutions predominate and these mutations cause some unusual disorders which may be described as Stickler-like but have short stature and brachydactyly. The inheritance pattern for Stickler syndrome type I is autosomal dominant.

Most cases of Stickler syndrome occur in families with other members that also have Stickler syndrome, due to a familial mutation of a gene inherited as an autosomal dominant trait. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent. The risk of passing the abnormal gene from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.

Stickler syndrome affects males as well as females. Prevalence rates have been estimated at 1-3 per 10,000 births and at 1 per 7,500 births. Most investigators believe that the disorder is highly under-diagnosed, making it difficult to determine the true prevalence of Stickler syndrome in the general population. Stickler syndrome is one of the most common connective tissue disorders in the United States.

Symptoms of the following disorders can be similar to those of Stickler syndrome.

A diagnosis of Stickler syndrome is made based upon a thorough clinical evaluation, a detailed patient history and identification of characteristic findings. As yet, no universally agreed upon criteria for the diagnosis of Stickler syndrome exists. A variety of tests such as x-ray studies and eye examinations may be used to detect the presence or evaluate the severity of certain abnormalities potentially associated with Stickler syndrome.


Stiff person spectrum disorder

Stiff person syndrome (SPS) is a rare acquired neurological disorder that most often causes progressive muscle stiffness (rigidity) and repeated episodes of painful muscle spasms. Muscular rigidity often fluctuates (i.e., grows worse and then improves) and usually occurs along with the muscle spasms. Spasms may occur randomly or can be triggered by a variety of different events or circumstances including a sudden noise, light physical contact or when exposed to cold. The severity and progression of SPS varies from one person to another. If left untreated, SPS can potentially progress to cause difficulty walking and significantly impact a person’s ability to perform routine, daily tasks. Although the exact cause of SPS is unknown, it is thought to be an autoimmune disorder and sometimes occurs along with other autoimmune disorders (e.g., thyroid disease, diabetes, pernicious anemia [b12 deficiency], and vitiligo).

The characteristic symptoms associated with SPS are progressive, fluctuating muscular rigidity that occurs along with muscle spasms. The severity and progression of SPS can vary from one person to another. The symptoms usually develop over a period of months to years and may remain stable for many years or slowly worsen. In some people, symptoms can be stabilized or improved through medication and non-medication interventions. Affected individuals should talk to their physician and medical team about their specific case, associated symptoms and overall treatment plan.

The exact cause of SPS is not known. Some studies in the medical literature indicate that it is likely an autoimmune disorder. Autoimmune disorders occur when the body’s natural defenses (e.g., antibodies) against foreign or invading organisms begin to attack healthy tissue for unknown reasons.

SPS is an extremely rare disorder. The exact incidence and prevalence of SPS is unknown, although one estimate places the incidence at approximately 1 in 1,000,000 individuals in the general population. However, this estimate likely does not account for the expanding clinical spectrum. The distribution of SPS between males and females indicates a female predominance. SPS usually becomes apparent sometime between 30-60 years of age. However, SPS has been reported to occur in children and older adults (>60 years old) as well. It appears that SPS can also affect any race and ethnicity.

Symptoms of the following disorders (not complete list) can be similar to those of SPS. Comparisons may be useful for a differential diagnosis.

A diagnosis of SPS is made based upon identification of characteristic symptoms, a detailed patient history, and a thorough clinical examination. Diagnostic tests are used to help support a clinical diagnosis and very importantly, to help rule out other conditions. Such tests include lab work (blood and spinal fluid) to detect the presence of antibodies against GAD-65, amphiphysin (which is most often associated with paraneoplastic SPS) and glycine receptor. Electromyography (EMG) can be helpful in individuals who have musculoskeletal involvement. This test records electrical activity in skeletal (voluntary) muscles at rest and during muscle contraction. An EMG can demonstrate continuous muscle activity in stiff muscles along with co-contraction of agonist and antagonist muscles. Muscle relaxers like diazepam will suppress the characteristic findings on EMG.


Stomach Cancer

Stomach cancer is a general term for cancer affecting the stomach. Generally, it refers to cancer that arises from the cells lining the stomach. These cells, like all cancerous cells, exhibit abnormal and rapid growth. Early in the course of the disease there are usually no symptoms (asymptomatic). As the disease progresses, symptoms like indigestion, nausea, vomiting, and feeling full earlier than normal (early satiety) may develop. The cause of stomach cancer is multifactorial, which means that multiple factors that occur together are necessary for the cancer to develop. These factors can include genetic, immunologic, infectious, and environmental factors. Stomach cancer usually develops randomly for unknown reasons (sporadically), and there is usually no family history.

The signs and symptoms can vary greatly from one person to another. Specific findings depend on numerous factors including the exact location of the tumor, the extent of the tumor into nearby tissue or organs, the specific organs involved, and whether the disease has remained localized or spread to other areas of the body (metastasized). Stomach cancer is a slow-growing cancer that usually develops over a year or longer.

The exact, underlying cause of stomach cancer is not fully understood. The reason why cancer develops is a complex question and researchers speculate that multiple factors are involved in the development of gastric cancer. These factors can include genetic, environmental, infectious, and immunologic factors.

There are about 28,000 people diagnosed with stomach cancer in the United States each year. It affects men more often than it does women, and about 75% of people are over the age of 50. Most people are diagnosed between 60-80 years of age. By some estimates, stomach cancer is the second most common cancer worldwide. Stomach cancer can affect people of all races and ethnic groups but occurs with greater frequency in individuals of African or Hispanic heritage and Native Americans. Worldwide, stomach cancer is more common in East Asia, Eastern Europe, and South America.

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

A diagnosis of stomach cancer is based upon identification of characteristic symptoms, a detailed patient and family history, a thorough clinical evaluation and a variety of specialized tests. Because stomach cancer does not usually cause symptoms in the early stages of the disease, it is often not diagnosed until the disease is advanced. There is no screening program for stomach cancer in the United States or Europe, although there are programs in other countries including Japan and Korea.


Sturge Weber Syndrome

SWS is a highly variable disorder. Some individuals may develop characteristic skin abnormalities, but no neurological abnormalities. Less often, individuals develop neurological abnormalities without the characteristic skin issues. Therefore, it is important to note that affected individuals may not have all of the symptoms discussed below and that every individual patient is unique. Parents should talk to their child’s physician and medical team about their specific case, associated symptoms and overall prognosis.

SWS is usually caused by a somatic mutation in the GNAQ gene. This genetic mutation is a somatic mutation because it occurs after fertilization of the embryo; in the case of SWS, mutation most likely occurs at an early stage of embryonic development. By definition, a somatic mutation can occur in any cell of the body except the sex cells (sperm and egg). Affected individuals will have some cells with a normal copy of the gene and some cells with the abnormal gene (mosaic pattern). This may be referred to as having two distinct cells lines in the body. The variability of symptoms associated with SWS is due, in part, to the ratio of healthy cells to abnormal cells in the body and the types of cells that are affected. Somatic mutations are not inherited and are not passed on to children. Researchers think that somatic mutations of the GNAQ gene occur randomly for no apparent reason (sporadically).

SWS affects males and females in equal numbers. The exact incidence and prevalence is unknown. One estimate places the incidence at 1 in 20,000-50,000 live births. Approximately 3 in 1,000 babies are born with a port-wine birthmark, but only approximately 6% of individuals with a port-wine birthmark on the face develop the neurological abnormalities associated with SWS. The risk increases to 20-50% when the port-wine birthmark is on the forehead, temple region or upper part of the face. SWS can affect individuals of any race or ethnicity.

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

A diagnosis of SWS is based upon identification of characteristic symptoms (e.g. port-wine birthmark), a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. A diagnosis may be straightforward in an infant with a port-wine birthmark, glaucoma, evidence of cerebral involvement and neuroimaging findings consistent with a diagnosis of SWS. Diagnosis can be more difficult in infants who have a port-wine birthmark, but no neurological symptoms. Early imaging in infants has low sensitivity and needs to be repeated after a year to exclude SWS brain involvement.


Stüve-Wiedemann syndrome

The symptoms of STWS vary from person to person. Most infants develop characteristic skeletal abnormalities including permanent flexion of fingers or toes (camptodactyly) outward away from the thumb (ulnar deviation) and bowing of the long bones of the arms and legs (camptomelia), which results in short stature. Affected infants may also have underdeveloped muscle tone (hypotonia) and/or an elbow that is permanently fixed in a bent or flexed position (elbow contracture). Some children with STWS have distinctive facial features, including a small chin (micrognathia), pursed mouth, and underdeveloped upper jaw, cheekbones, and eye sockets (midface hypoplasia) that sometimes results in protruding eyes.

STWS is caused by changes (variants or mutations) in the leukemia inhibitory factor receptor (LIFR) gene. Variants in this gene may cause the complete absence of the LIFR protein or the production of a non-functional LIFR protein. LIFR gene variants ultimately affect the JAK/STAT 3 signaling pathway. This pathway is one of the many signaling pathways involved in human development, involving many different cytokines and growth factors. Of note, not all reported individuals have a LIFR gene variant, indicating that not all of the STWS-causing genes have been identified.

STWS has a very low prevalence of <1 out of 1,000,000. However, the disease is relatively common in the United Arab Emirates with a prevalence of 1 out of 20,000 births. STWS affects males and females in equal numbers. Patients with STWS often go unrecognized, making it difficult to determine the true frequency of the disorder in the general population. STWS was first described in the medical literature in 1971.

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

Crisponi syndrome is a rare autosomal recessive genetic disorder  and is characterized by muscular contractions, episodic or continuous hyperthermia, abnormal facial features and camptodactyly. Facial differences include large, round faces with a broad nose and long philtrum. Patients also have hypotonia. Children affected with this syndrome start to exhibit symptoms at birth. Infants have shortness of breath, periods of no breathing (apnea), decreased oxygen causing the babies to turn blue-ish (cyanosis) and continuous hyperthermia, which differs from a fever in that there is no infection. These factors can lead to sudden death. Crisponi syndrome has only been documented in 30 patients, all from Italian families.


Paraneoplastic cerebellar degeneration

Paraneoplastic cerebellar degeneration may potentially be an autoimmune disorder. Autoimmune disorders are caused when the body’s natural defenses against invading organisms mistakenly attack healthy tissue for unknown reasons. It may also be an abnormal response to cancer. In cases where there is an underlying cancer, the individual’s immune system may react to the cancer by stimulating the body’s natural defense mechanisms. These natural defense mechanisms include producing antibodies, which are proteins that help the immune system detect harmful substances, and increase the number of T-cells, which are white blood cells that destroy infected cells and tumors. These antibodies and T-cells normally target only the cancerous tumors; however, in paraneoplastic cerebellar degeneration, these antibodies bind to and attack normal cells in the nervous systems, such as Purkinje cells in the cerebellum, leading to their death and loss of function. Purkinje cells are cells specifically found in the cerebellum that gather multiple signals throughout the brain to control motor movements.

In paraneoplastic cerebellar degeneration, the average age of onset is 50 years, with females affected more often than males. This form of cerebellar degeneration may precede cancer, however <1% of patients with cancer have paraneoplastic cerebellar degeneration. Alcoholic or nutritional cerebellar degeneration affects alcoholics and people with thiamine deficiency. In alcoholic cerebellar degeneration, symptoms usually occur in middle aged individuals who have a history of chronic alcohol abuse.

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

Paraneoplastic neurologic syndromes (PNS) are a group of conditions that affect the nervous system (brain, spinal cord, nerves and/or muscles) in patients with cancer. The term paraneoplastic means that the neurological syndrome is not caused by the tumor itself, but by the immunological reactions that the tumor produces. PNS are categorized by the area of the nervous system that is principally affected, the type of symptoms or the type of immunological response. (For more information on these disorders, choose paraneoplastic neurologic syndromes as your search term in the Rare Disease Database.)

Standard therapeutic options for paraneoplastic cerebellar degeneration include diagnosing and treating the underlying cancer. Prompt tumor removal, chemotherapy and/or radiation may be beneficial and help reduce symptoms in patients. Adjuvant therapy with glucocorticoids such as methylprednisolone and immunotherapy with potent T cell inhibition, such as rituximab and tacrolimus may be elusive. However, small cases have shown both rituximab and tacrolimus may help to stabilize symptom progression in patients with paraneoplastic cerebellar degeneration only. For alcoholic/nutritional cerebellar degeneration, thiamine is given along with other B vitamins, usually relieving the condition if the patient stops drinking alcohol and resumes a normal diet. Physical therapy with focus areas on strengthening, balance and gait balance can help to restore function and prevent long term disability in patients with progressive symptoms. Occupational therapy may focus mainly on activities of daily living and dysphagia rehabilitation.


Subacute sclerosing leukoencephalitis

Subacute sclerosing panencephalitis (SSPE) is a progressive neurological disorder characterized by inflammation of the brain (encephalitis). The disease may develop due to reactivation of the measles virus or an inappropriate immune response to the measles virus. SSPE usually develops 2 to 10 years after the original viral attack. Initial symptoms may include memory loss, irritability, seizures, involuntary muscle movements, and/or behavioral changes, leading to neurological deterioration.

Subacute sclerosing panencephalitis is a rare neurological disease of childhood or young adulthood.  The first signs are usually behavioral changes such as failing schoolwork, memory loss, and/or irritability.  Involuntary muscle movements (myoclonic jerks) and generalized seizures follow.  Subacute sclerosing panencephalitis is a progressive disease which results in personality changes, outbursts of temper, sleeplessness, disorientation, stupor, spasticity, loss of previously acquired intellectual skills, poor memory and judgment (dementia), and general neurological deterioration. Blindness may develop because of a lesion in the vision center of the brain (cortical blindness) and the nerves of the eyes may waste away (optic atrophy).  The late symptoms of subacute sclerosing panencephalitis may include muscle rigidity, elevated body temperature (hyperthermia) and/or abnormalities of respiration, heartbeat, and blood pressure.  These disturbances of normal bodily functions (homeostasis) indicate that the hypothalamus gland, which is located deep inside the brain, may be affected.

Subacute sclerosing panencephalitis is thought to be caused by a slow measles virus (paramyxovirus).  Slow viruses may stay dormant in humans for extended periods of time, then for reasons yet unknown may become reactivated.  The role of heredity which may make a person susceptible to slow viruses is not well understood.

With widespread uss of the measles vaccine in the United States, the incidence of subacute sclerosing panencephalitis has been reduced dramatically, although about 10 cases per year are reported. However, in less developed parts of the world, this disorder is much more common.  In India, for example, the incidence is estimated at about 20 cases per year per million of population.  Subacute sclerosing panencephalitis seems to affect males more often than females and occurs far more often in children and adolescents than in adults.

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

Progressive rubella panencephalitis is a rare slowly progressive neurological disorder that closely resembles subacute sclerosing panencephalitis.  It is caused by the rubella virus and develops because of congenital rubella syndrome or childhood rubella infection (German measles). Symptoms usually include behavioral changes, the loss of previously acquired intellectual skills, inability to coordinate movement (ataxia), involuntary muscle movements (spasticity), and/or seizures.  There is no known treatment for this disorder.  Fewer than 20 cases have been reported in the medical literature.

The diagnosis of subacute sclerosing panencephalitis may be confirmed by clinical evaluation and blood testing that reveals abnormally high levels of the measles antibody. Examination of the electrical activity of the brain (EEG) usually shows a characteristic pattern. The fluid surrounding the brain and spinal cord (cerebrospinal fluid) typically has elevated levels of gammaglobulin and measles antibody.


Succinic semialdehyde dehydrogenase deficiency

Succinic Semialdehyde Dehydrogenase Deficiency

In individuals with SSADH deficiency, the range, severity, and presentation of certain symptoms and findings may be variable, including among affected family members. In addition, such neurological and neuromuscular symptoms are often considered nonspecific, meaning that they may be associated with any number of underlying disorders, potentially leading to difficulties with diagnosis. (For further information, please see the Standard Therapies: Diagnosis section of this report below.) However, during childhood, most affected individuals appear to have some degree of delays in the development of certain physical, mental, and behavioral skills that are typically acquired at particular stages (i.e., developmental milestones).

SSADH deficiency is a rare inborn error of metabolism that is inherited in an autosomal recessive pattern. Metabolism refers to all the chemical processes in the body, including the breakdown of complex substances into simpler ones (catabolism), usually with the release of energy, and processes in which complex substances are built up from simpler ones (anabolism), usually resulting in energy consumption. Inborn errors of metabolism result from abnormal functioning of a specific protein or enzyme that accelerates particular chemical activities in the body.

SSADH deficiency appears to affect males and females relatively equally. Since the disorder was originally described in 1981 (C. Jakobs), over 400 cases of SSADH deficiency have been identified. According to one review published in 1997 reporting 23 affected individuals (from 20 families), the age at diagnosis ranged from three months to 25 years. Most affected individuals were of Turkish, American Caucasian, Indian, and Northern European descent. Additional nationalities were also noted, including Korean, Palestinian, Syrian, Pakistani, Saudi, Chinese, and Inuit descent. A recent review of adult cases included one with long-standing intellectual disability diagnosed with SSADH deficiency at 63 years old when he had a progressive decline of function and increased seizures.

Symptoms of the following conditions may be similar to those of SSADH deficiency. Comparisons may be useful for a differential diagnosis:

The diagnosis of SSADH deficiency is usually made after birth (postnatally) during infancy or childhood (or, in some cases, adulthood), based upon a thorough clinical evaluation, identification of characteristic physical findings, and a variety of specialized tests. Due to the nonspecific nature and variability of associated symptoms, experts suggest that SSADH deficiency should be considered in any individuals with two or more features of intellectual, language, and motor delay and abnormally diminished muscle tone (hypotonia) of unknown cause (idiopathic). Specialized testing to confirm a diagnosis of SSADH deficiency typically includes studies (i.e., quantitative organic acid analysis in an appropriate specialist laboratory) that may detect increased concentrations of 4-hydroxybutyric acid (4-HBA) in urine (i.e., 4-hydroxybutyric aciduria) and testing to confirm deficient activity of the SSADH enzyme in white blood cells (leukocytes) isolated from whole blood. (Note: As mentioned above, increased concentrations of 4-HBA may also be detected in plasma and cerebrospinal fluid. In addition, deficient SSADH activity has also been demonstrated in certain cells other than leukocytes.)


Sudden Infant Death Syndrome

婴儿猝死伴睾丸发育不良综合征

Sudden infant death syndrome (SIDS) is the sudden death of an infant under the age of 1 year that remains unexplained after careful review of the history, death scene investigation, and thorough autopsy. In 2008, the most recent published data from the National Vital Statistics System indicated that SIDS was listed as the third leading cause of death in infants in the United States. Causes of SIDS are considered to be multifactorial. The triple risk hypothesis describes the presence of three risk factors that, when overlapping, predispose a baby to SIDS. These include an environmental trigger/stress, a critical developmental period, and an underlying vulnerability. Physician-scientists and scientists are studying neuropathological tissue and genetic material from SIDS victims to ascertain factors that might be responsible for heightening an infant’s vulnerability to SIDS. Others are performing physiologic studies on infants known to have an increased risk for SIDS. Basic scientists are studying animal models that might provide insight into mechanisms responsible for SIDS. Current clinical management targets improving education for families and caregivers regarding known modifiable environmental stressors (risk factors) (see below).

There are typically no symptoms prior to a SIDS death. Though SIDS occurs during sleep, the deaths may occur during day or night time sleep. Existing literature does not indicate any evidence for suffering by the infant in the moments preceding the sudden death.

By definition, the cause of SIDS is unknown. Therefore, the existing research addresses modifiable environmental risk factors, neuropathological and genetic factors that may predispose to SIDS, potential physiologic markers in at-risk infants, and animal modeling.

SIDS can affect all infants under 1 year of age. Most deaths occur less than 6 months of age with the peak affected age between 2 and 4 months. Gender, ethnic and racial differences also exist. For example, boys are at greater risk for SIDS than girls. Also, the SIDS rate in African American infants is 2.7 times greater than the Caucasian rate in the US. Likewise, SIDS rates are increased in the American Indians and Alaskan natives as compared to Caucasians. These differences may reflect both cultural practices and genetic variations.

There is not necessarily a definitive relationship between the following disorders and SIDS. They are often considered in the same context because of the similarity in terms of life threatening events and/or sudden death.

SIDS is a diagnosis of exclusion which means that it is only determined as the cause of death after thorough investigation of clinical history, scene of death, and autopsy reveal no other cause.


Superficial siderosis

superficial siderosis of the central nervous system

hearing loss, movement abnormalities (ataxia) and motor difficulties due to suspected spinal cord injury (myelopathy) with pyramidal signs. Proper recognition and timely early diagnosis of superficial siderosis allow for early care planning.

Superficial siderosis is an acquired disorder caused by chronic long-term subarachnoid bleeding. A large percentage of the identifiable bleed sources are abnormalities resulting from recurring brain bleeds (chronic suboccipital hematomas), sacs protruding from the spinal column (meningoceles) or spinal surgery tears resulting in pseudomeningoceles. Other causes include root avulsions or epidural cyst removal, intradural cranial surgery, brain tumors, vascular abnormalities, fragile capillary regrowth after brain surgery, nerve damage (brachial plexus injury), head injury or bone marrow exposed to the spinal (intrathecal) space.

Superficial siderosis affects all races and age groups, with males affected three times more often than females. The prevalence of superficial siderosis is estimated to be 1 in one million individuals. As of 2024, there are an estimated 300 diagnosed cases in the U.S. Diagnoses are increasing due to improved MRI techniques and neuro-radiologist awareness. The actual incidence of superficial siderosis is suspected to affect a larger population than is currently diagnosed.

Due to overlapping similarities, superficial siderosis is most often misdiagnosed as multiple sclerosis, Parkinson’s disease or multiple system atrophy.

The average time from the clinical manifestation of early symptoms such as ringing of the ears (tinnitus), complaints of dizziness, or reports of phantom odors to the diagnosis of superficial siderosis may be as long as 17 years, partly due to the slow progression of the disease. Clinical investigation of patient complaints should be reviewed against the long-term medical history focusing on previous surgical procedures, aneurysm, traumatic contusions or accidents occurring as long as thirty to forty years in the past with older patients.

The first step after a diagnosis is determining if a bleed source is present. A cause is not identified for a large percentage of patients. A CT myelogram is the preferred method to determine the location of a suspected bleed due to dural defect. The three suggested approaches for stopping a bleed are injection of fibrin glue into the dural tear site; for small leaks, an epidural blood patch may pull the dura from surrounding bone and immobilize the spinal cord long enough for healing to take place. Surgical closure of dural defects or other active bleed sites offers the best opportunity to stop additional hemosiderin deposition.


Superior mesenteric artery syndrome

The signs and symptoms can vary greatly from one person to another. Sometimes the symptoms are mild and build slowly over time. Without treatment, in some people, symptoms can be severely disabling. Generally, the initial symptoms are nonspecific, which means that symptoms are common ones that can be associated with many different conditions. Sometimes symptoms can come and go (intermittent).

SMA syndrome occurs when the duodenum is compressed by the SMA against the AA to cause blockage and prevent progression of food or fluids into the rest of the small intestine. The small intestine is a long, winding tube that connects the stomach to the large intestine ending in the anus. The small intestine is divided into three sections – duodenum, jejunum and ileum. Each section has a role in digestion and absorption of nutrients that were previously digested in the stomach.

The prevalence (the number of people with a disease or disorder in a given population at a given time) is unknown. The most frequently quoted estimate is that 0.13 to 0.3% of people in the United States general population have this disorder. SMA syndrome has been reported in greater frequency among teenagers and young adults but can occur at any age including infants and the elderly.  It seems to affect more women than men by 3:2 ratio. SMA syndrome can affect individuals of any racial or ethnic heritage hence it is worldwide. It is likely that some people with SMA syndrome have not been diagnosed so the true prevalence may be higher than reported.

There are many conditions that can cause signs and symptoms similar to SMA syndrome like peptic ulcer disease, gall bladder disease (gallstone disease or dysfunction known as biliary dyskinesia) irritable bowel disease, inflammation of the duodenum (duodenitis), visceral neuropathy, cyclic vomiting syndrome and inflammation of the pancreas (pancreatitis). Disorders that cause duodenal dysmotility including diabetes, vascular collagen disorder and chronic mesenteric ischemia can also resemble SMA syndrome. Median arcuate ligament syndrome (MALS) or celiac steal syndrome can mimic SMA syndrome.

A diagnosis of SMA syndrome is based on the identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. A team approach to diagnosis is essential and may include a primary care physician (pediatrician, internist or general practitioner), gastroenterologist, surgeon (pediatric or general), radiologist, nutritionist or dietician, pain specialist, and psychologist or psychiatrist. It is a diagnosis of exclusion hence a period of observation and trial of therapy may be required before a definitive diagnosis is made. Delay in the diagnosis and treatment worsens the condition and can lead to a fatal outcome.


Superior Semicircular Canal Dehiscence

superior semicircular canal dehiscence syndrome (SCDS)

Superior semicircular canal dehiscence (SSCD) has been defined as the absence of bone overlying the superior semicircular canal facing toward the dura of the middle cranial fossa. SSCD has been implicated as the cause of a variety of inner ear symptoms including Tullio’s phenomenon, pressure induced vertigo, aural fullness, autophony, conductive hearing loss and fluctuating or progressive sensorineural hearing loss. SSCD has also been reported to be asymptomatic in some people. In the past, many patients with SSCD were misdiagnosed as having otosclerosis, patulous eustachian tubes, middle ear perilymphatic fistulas or Ménière’s disease. Identification of this condition requires a high degree of suspicion, appropriate findings on physical exam, lab testing and confirmation on high-resolution CT scan. Surgical repair of the SSCD or occlusion of the superior canal has been reported with a high degree of symptom resolution.

SSCD has been labelled the great otologic mimicker because it can simulate the symptoms of so many other ear disorders. However, the most common symptoms are vertigo/dizziness elicited by pressure altering activity, Tullio’s phenomenon (sound-induced vertigo), fullness/pressure in the ear and autophony. Autophony is hearing internal noises louder than would be expected, such as hearing your eyes move/blink, heartbeat or joint movements. Hearing loss and fluctuating hearing loss can occur, mimicking otosclerosis or Meniere’s disease. Fullness in the ear and hearing your breathing loudly in the ear are symptoms of patulous eustachian tube but can also be found with SSCD. Finally, most patients with the anatomic defect of superior semicircular canal dehiscence have no symptoms at all for some time prior to developing symptoms.

The anatomic defect of SSCD is believed to be a developmental anomaly of the temporal bone in the vast majority of cases. At birth, the bone over the top of the inner ear, which is the floor of the middle cranial fossa, is very thin or absent. Over the first three years of life, this bone thickens considerably. However, this is variable and approximately 20% of the population is left with holes in the middle fossa floor that extend into the middle ear or mastoid. These are typically free of any symptoms unless intracranial pressure causes the brain to prolapse through one of these holes – an event typically not seen until the latter decades of life. Approximately 1-2% of the population will be left with a defect of the bone over the superior semicircular canal resulting in SSCD. However, this usually does not cause symptoms until later in life.

SSCD can affect all age groups. There are no studies looking at the demographics of SSCD, however, the vast majority of patients diagnosed with SSCD are adults. Although the incidence of finding SSCD on a scan is the same for adults and children, the incidence of symptomatic SSCD in children is much lower.

Dehiscence of bone in other parts of the otic capsule can produce similar syndromes, although they are much less common. Other locations include the posterior semicircular canal, the horizontal semicircular canal and cochlea. Posterior semicircular canal dehiscence is often due to a high riding jugular bulb but can also been seen with anomalies of the vestibular aqueduct, such as enlarged vestibular aqueduct syndrome (EVAS). EVAS, by itself can also produce symptoms similar to SSCD. Horizontal semicircular canal dehiscence is most frequently the result of an eroding process such as cholesteatoma. The cochlea can have bony dehiscence where it abuts the carotid artery and at the labyrinthine segment of the facial nerve. Lastly, the bony opening where the hearing nerve enters the cochlea (at the internal auditory canal) can be abnormally wide, resulting in symptoms similar to SSCD.

There are three essential elements to make the diagnosis of SSCD:

Because the condition of SSCD is still fairly new (identified in 1998), it could be argued that all treatments are considered experimental or investigational. However, the most frequently employed are surgical. Surgery for SSCD has included resurfacing the defect with a variety of materials, plugging the superior semicircular canal and a combination of resurfacing and plugging. These techniques can be done through a transmastoid or a middle fossa craniotomy approach. These techniques have found great success in reducing or eliminating the vestibular symptoms of SSCD. These techniques are also effective in reducing or eliminating autophony but they have not been effective in improving hearing. A lesser approach that seems to give similar benefits is reinforcement of the middle ear windows. This surgery has the advantage of being a more minimally invasive procedure, but the success rate seems to be much lower with a higher recurrence rate in the long term.