Rocky Mountain Spotted Fever

Rocky Mountain spotted fever (RMSF) is an infectious disease that belongs to a group of diseases known as the spotted fever group rickettsioses. It is caused by infection with the bacterium Rickettsia rickettsii (R. rickettsii), which is usually transmitted by a tick bite. When introduced into the body, the bacterium spreads by the bloodstream or lymphatic vessels and multiplies within and damages certain cells lining the inside of small blood (vascular) vessels (i.e., endothelial cells) as well as vascular smooth muscle cells. Such damage leads to inflammatory changes of affected blood vessels (vasculitis), leakage of fluid from the blood vessels, an abnormal accumulation of fluid in body tissues (edema), and additional abnormalities, resulting in the symptoms and findings associated with the disease.

Rocky Mountain spotted fever (RMSF) is considered the most potentially severe form of the spotted fevers.  The onset of symptoms typically occurs approximately two to 14 days (with an average of seven days) after having been bitten by a tick carrying the R. rickettsii bacterium. Early symptoms usually include a fever that may reach 103 or 104 degrees Fahrenheit; chills; extreme exhaustion (prostration); muscle pain (myalgia); and severe headaches that are often associated with pain upon moving the eyes and increased sensitivity to light (photophobia).  Many also develop nausea, with or without vomiting, and loss of appetite (anorexia).  Additional early symptoms may include diarrhea, abdominal tenderness, and abdominal pain.  The disease may be difficult to diagnose in early stages since its early symptoms and signs are nonspecific, resembling those associated with many other infectious and non-infectious diseases.

The group of infectious diseases known as spotted fevers (i.e., spotted fever group rickettsioses), including Rocky Mountain spotted fever (RMSF), are caused by bacteria belonging to the Rickettsiae family.  RMSF is caused by a bacterium called Rickettsia rickettsii (R. rickettsii), named after its discoverer, Howard T. Ricketts. As noted above, the disease is usually transmitted to humans via a tick bite.  In many cases, the R. rickettsii bacterium is transmitted from infected ticks to their offspring; in other instances, uninfected ticks may become carriers (i.e., vectors) by feeding on infected mammals (e.g., rodents or dogs).

Rocky Mountain spotted fever (RMSF) was first described in the late 1800s in Idaho. The disease was initially recognized as existing in only the Rocky Mountain (western) area of the United States. However, beginning in the 1930s, the disease was noted in other regions of the country.  Currently, the frequency of the disease is higher in the west south-central region and the South Atlantic states than in the Rocky Mountain states.  RMSF has been reported in almost every state as well as other countries, including Canada, Mexico, Brazil, Columbia, Costa Rica, and Panama.

Symptoms of the following disorders may be similar to those of Rocky Mountain spotted fever (RMSF). Comparisons may be useful for a differential diagnosis:

Because its early symptoms and findings may be similar to those associated with many other infectious and non-infectious diseases, Rocky Mountain spotted fever (RMSF) may be difficult to diagnose in its early stages. The classic triad of the disease is fever, rash, and a history of tick bite. However, rash often is not present when affected individuals initially seek medical attention. In addition, as noted above, some do not recall recent tick exposure.


Rosai-Dorfman Disease

Rosai-Dorfman disease is a rare disorder characterized by overproduction (proliferation) and accumulation of a specific type of white blood cell (histiocyte) in the lymph nodes of the body (lymphadenopathy), most often those of the neck (cervical lymphadenopathy). In some cases, abnormal accumulation of histiocytes may occur in other areas of the body besides the lymph nodes (extranodal). These areas include the skin, central nervous system, kidney, and digestive tract. The symptoms and physical findings associated with Rosai-Dorfman disease vary depending upon the specific areas of the body that are affected. The disorder predominantly affects children, adolescents or young adults. The exact cause of Rosai-Dorfman disease is unknown.

The symptoms and physical findings associated with Rosai-Dorfman disease vary greatly from one person to another depending upon the extent of the disorder and the specific organ systems affected. Some cases may only affect the lymph nodes and may not cause any serious complications. Less often, some cases may affect various organ systems of the body and may potentially cause serious complications. Any organ system of the body may become affected.

The exact cause of Rosai-Dorfman disease is unknown (idiopathic), but it does not seem to be of neoplastic nature. Researchers have suggested that the disorder may be caused by an infectious agent, immunodeficiency, or autoimmunity.

Some studies suggest that Rosai-Dorfman disease affects males more often than females. The disorder can affected individuals of any age, but most often affects young adults under the age of 20. Cutaneous Rosai-Dorfman disease occurs more often in females in their 20s or 30s. More than 650 cases have been reported in the medical literature since the disorder’s first description in the medical literature in 1969.

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

The diagnosis of Rosai-Dorfman disease may be confirmed by a thorough clinical evaluation, a detailed patient history and a variety of specialized tests, such as surgical removal and microscopic examination of affected tissue (biopsy).


Charcot-Marie-Tooth disease type 1

Rosenberg-Chutorian syndrome is an extremely rare genetic disorder characterized by the triad of hearing loss, degeneration of the optic nerve (optic atrophy) and neurological abnormalities, specifically disease of the nerves outside of the central nervous system (peripheral neuropathy). The arms and legs are most often affected by peripheral neuropathy. Rosenberg-Chutorian syndrome is inherited as an X-linked disorder with occasional mild symptoms present in the female carrier.

The symptoms of Rosenberg-Chutorian syndrome often become apparent during infancy or early childhood. The clinical triad of hearing loss, optic atrophy, and peripheral neuropathy characterizes the disorder.

Rosenberg-Chutorian syndrome is caused by a mutation in the phosphoribosylpyrophosphate  synthetase I (PRPS1) gene located on the X chromosome.

Rosenberg-Chutorian syndrome is a rare genetic disorder that affects males more often than females. Symptoms are more severe in males. Some carrier females may exhibit symptoms of the disorder.

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

A diagnosis of Rosenberg-Chutorian syndrome is made based upon a thorough clinical evaluation, a detailed patient history and identification of characteristic findings. Molecular genetic testing for PRSP1 gene mutations is available to confirm the diagnosis. Carrier testing and prenatal diagnosis are available if a PRSP1 gene mutation has been identified in an affected family member.


Rothmund-Thomson syndrome

Rothmund-Thomson syndrome is a rare genetic disorder that manifests in early infancy. The range and severity of symptoms may vary from person to person. RTS is typically characterized by skin rash, sparse hair, malformed bones, abnormal clouding of the lenses of the eyes (juvenile cataracts), small stature and other physical abnormalities. Intelligence is usually normal, but some affected individuals have been reported to have intellectual disability.

Rothmund-Thompson syndrome is a genetic disorder that is inherited in an autosomal recessive pattern. Approximately 2/3 of individuals with RTS are found to have an abnormality (variant or mutation) in the RECQL4 gene (type 2 RTS) or the ANAPC1 gene (type 1 RTS). The RECQL4 gene is responsible for production of a protein that is involved in the replication and repair of DNA, the genetic material in the cells of the body. ANAPC1 encodes a protein, APC1, which is important for cell cycle progression and also plays a role in DNA replication and repair. Since about 1/3 of affected individuals do not have detectable variants in these genes, other as yet undiscovered genes are probably also associated with RTS.

RTS has been diagnosed in people of all races and has been described in multiple nationalities; therefore, it does not appear that there is any particular population at increased risk for developing the disease.

The following disorders share some overlapping clinical features with those of RTS. RAPADILINO and Baller-Gerold syndromes are related to RTS because they can also be caused in some cases by variants in the RECQL4 gene. Bloom and Werner syndromes are related to RTS because they are caused by variants in the BLM and WRN genes, respectively, which both belong to the same gene family as RECQL4.

Rothmund-Thompson syndrome is diagnosed based on the onset, appearance and progression of the poikilodermatous rash. A diagnosis of RTS may be suspected if the rash is present but atypical and other physical characteristics associated with RTS are present. Molecular genetic testing for the RECQL4 gene is available to confirm the diagnosis, although in one-third of cases of RTS this test can be negative. Thus, a negative test does not rule out the diagnosis of RTS, but a positive test confirms the diagnosis.

The treatment of Rothmund-Thomson syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, surgeons, physicians who specialize in the diagnosis and treatment of disorders of the skin (dermatologists), doctors who specialize in genetic disorders (geneticists), eye specialists (ophthalmologists), specialists who diagnose and treat bone disorders (orthopedists), dental specialists and/or other health care professionals may need to plan an affected child’s management systematically and comprehensively.


Roussy Lévy Syndrome

Roussy-Lévy Syndrome, also known as hereditary areflexic dystasia, is a rare genetic neuromuscular disorder that typically becomes apparent during early childhood. The disorder is characterized by incoordination, poor judgment of movements (sensory ataxia), and absence of reflexes (areflexia) of the lower legs and, eventually, the hands; weakness and degeneration (atrophy) of muscles of the lower legs; abnormally high arches of the feet with increased extension of the toes (pes cavus or clawfoot); and tremors of the hands. Many affected individuals also have an abnormal front-to-back and sideways curvature of the spine (kyphoscoliosis). In individuals with Roussy-Lévy Syndrome, there is a failed communication of certain nerve signals to muscles of the lower legs (denervation). Roussy-Levy Syndrome is inherited as an autosomal dominant genetic trait.

Symptoms of Roussy-Lévy Syndrome are similar to other hereditary motor sensory neuropathies in that there is weakness and atrophy of the leg muscles with some loss of feeling. People with this syndrome have difficulty walking and a lack of reflexes and deformity of the foot or feet (pes cavus). Roussy-Lévy differs, however, from other hereditary motor sensory neuropathies because of the very early onset of the disorder during childhood and its slowly progressive course. Roussy-Lévy also has as one of its characteristics a slight tremor in the hands.

Roussy-Lévy is inherited through autosomal dominant genetic transmission. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother. In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed dominating the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.

Roussy-Lévy is a rare disorder that affects both sexes in equal numbers. Onset is during early childhood.

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

Charcot-Marie-Tooth Disease is an hereditary neurological disorder. It is characterized by weakness and atrophy of the legs and disappearance of the fatty shield surrounding the nerves. The most incapacitating initial symptom is foot drop. The disorder has a gradual progression usually beginning in middle childhood through age 30. Symptoms of CMT may arrest spontaneously or it may continue to progress slowly. Patients may remain active for years. (For more information on this disorder, choose Charcot-Marie-Tooth as your search term in the Rare Disease Database.)

Treatment of Roussy-Lévy Syndrome may include use of braces for the foot deformity or orthopedic surgery on the feet to correct the imbalance of the affected muscles. Genetic counseling may be of benefit to patients and their families. Other treatment is symptomatic and supportive.


Rubella, Congenital

Congenital rubella is a syndrome that occurs when a fetus has been infected with the rubella virus while in the uterus. It is primarily characterized by abnormalities of the heart and nervous system, the eyes and the ears. The fetus is most vulnerable to the virus during the first three months of pregnancy, although pregnant women are advised to avoid exposure to rubella virus at all times. Women who contract rubella during pregnancy have a high risk of having a baby with congenital rubella.

Classic congenital rubella syndrome symptoms include a combination of heart, eye and hearing defects, although infection and damage can occur in almost every organ system.  Of the abnormalities most likely to be present at birth, cardiovascular defects are most common, such as underdevelopment (hypoplasia) of the pulmonary artery and the failure of a duct connecting the pulmonary artery and aorta (patent ductus arteriosus) to close.

Congenital rubella can affect a fetus when a pregnant woman who is not immune to the virus contracts rubella (German Measles).  The baby may also be affected if the mother contracts rubella immediately before conception.  The fetus is most vulnerable during the first three months (first trimester) of a pregnancy.

Congenital rubella is found in newborns and infants of mothers who were infected with rubella immediately before or during the early months of pregnancy.  The frequency of congenital rubella thus depends upon the number of women of childbearing age who are susceptible to the virus, and the frequency of rubella infection in the community.  Before the development of rubella virus vaccine, epidemics of rubella and congenital rubella occurred about every six to nine years.  During epidemic years, congenital rubella infection was found (using serologic testing to identify nonsymptomatic cases) in as many as 2% of newborns; the rate of its presence at other times (the endemic rate) is 0.1%.  Widespread use of rubella vaccine in the United States has eliminated epidemics, but the endemic rate of congenital infection appears to be about the same.

There is no treatment for maternal rubella or congenital rubella syndrome. Therefore, prevention assumes paramount importance. It is most important to immunize all children, in an attempt to prevent epidemics. Children should receive rubella immunization at 15 months of age, along with mumps and measles in a combined vaccine. Many authorities now recommend that a repeat rubella immunization be given to 10-year-olds, because vaccine-induced immunity may not persist as long as naturally acquired immunity.


Rubella

Rubella is a viral infection characterized by fever, headache, swollen lymph nodes, aching joints, and a distinctive red rash. Although it is sometimes called German measles or three-day measles, it is not caused by the same virus that causes measles. Rubella is generally mild in children and more severe but not life-threatening in adults. However, if a pregnant woman is infected with rubella, it can cause serious problems for the unborn child. In the United States, most children receive the measles-mumps-rubella (MMR) vaccine, and therefore the disease has become uncommon. In March 2005, health officials announced that rubella has been eliminated from the United States. However, it is still important for Americans to vaccinate their children, and women who are pregnant or might get pregnant still need to be sure they are immune, because the disease exists elsewhere. According to the Centers for Disease Control and Prevention (CDC), nine rubella cases were reported in the United States in 2004, and all of them originated in other countries.

Rubella is predominantly a childhood disease, although it also occurs among adolescents and adults.  It has a 14- to 21-day incubation period and a 1- to 5-day preliminary phase in children.  The preliminary phase may be minimal or absent in adolescents and adults.  Tender swelling of the glands in the back of the head, the neck and behind the ears is characteristic.  The typical rash appears days after onset of these symptoms.

Rubella is caused by a virus and is spread by airborne droplet clusters or by close contact with an infected person.  A patient can transmit the disease from 1 week before onset of the rash until 1 week after it fades.  Congenitally infected infants are potentially infectious for a few months after birth.  Rubella is apparently less contagious than measles, and many persons are not infected during childhood.  As a result, 10% to 15% of young adult women are susceptible if they have not been vaccinated against the disorder.  Many cases are misdiagnosed or go unnoticed.

Rubella affects males and females in equal numbers.  During 1964 and 1965, according to the CDC, a rubella epidemic in the United States caused an estimated 12.5 million cases of rubella and 20,000 cases of congenital rubella syndrome, which led to more than 11,600 babies born deaf, 11,250 fetal deaths, 2,100 neonatal deaths, 3,580 babies born blind, and 1,800 babies born mentally retarded.  Since 1969, the rubella virus has been included in the measles, mumps, and rubella (MMR) vaccine routinely given to babies and young children.

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

Allergic contact dermatitis is an itchy skin condition caused by an allergic reaction to material in contact with the skin.  It arises some hours after the skin has come into contact with the responsible substance, and gradually goes away over a period of days.  Contact allergy usually is the result of the allergen on the skin rather than from internal sources or food. The first contact usually does not result in allergy; often the person has been able to touch the material for many years without adverse reaction.


Rubinstein-Taybi syndrome

Rubinstein-Taybi syndrome (RSTS) is a rare genetic disorder that affects many organ systems. RSTS is characterized by growth delays, distinctive facial features, intellectual disability (with an average IQ of 25-79), broad and often angulated thumbs and great toes (halluces) and feeding difficulties (dysphagia). Craniofacial features of RSTS include downward slanted eyes (down slanted palpebral fissures), long eyelashes, high-arched eyebrows, low-hanging nasal septum (columella), high palate and an extra cusp on the lingual side of a front tooth (talon cusps). In most affected children, RSTS occurs as the result of a new (de novo) gene variant (mutation), although rarely, the syndrome has been inherited from an affected parent in an autosomal dominant pattern. Management generally involves monitoring of growth and feeding, yearly eye and hearing evaluations, and evaluation for cardiac, dental, and renal abnormalities. Behavioral therapy and special education are also indicated.

In most affected children, RSTS occurs as the result of a new (de novo) genetic mutation that is not present in or carried by the parents. In these cases, the risk of having a second affected child is less than 1%.

RSTS is a rare disorder that affects males and females in equal numbers. The exact incidence of RSTS is unknown, although a study in the Netherlands estimates the incidence to be between 1/100,000 to 1/125,000 individuals.

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

Saethre-Chotzen syndrome: For more information on this disorder, choose Saethre Chotzen as your search term in the Rare Disease Database.


Russell-Silver Syndrome

The symptoms of RSS vary greatly from one individual to another. Some are mildly affected; others may have serious complications. The wide range of potential features can affect many different parts of the body. It is important to note that affected individuals will not have all of the symptoms discussed below. Affected individuals/ parents should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis. With appropriate medical care, most individuals with RSS will live full, productive lives.

In the last few years it has become possible to confirm the clinical diagnosis by genetic testing in approximately 60% of individuals with RSS. Two main genetic changes (involving chromosome 7 and chromosome 11) are currently known to cause RSS. These are specific to the condition and not seen in most children with IUGR and poor postnatal growth.

RSS occurs in all populations and affects males and females in equal numbers. In the past, many infants with IUGR and relatively large head circumference were incorrectly diagnosed with RSS. Because of the difficulty in diagnosis, other cases may go unrecognized and undiagnosed or misdiagnosed, making it difficult to determine the true frequency of the disorder in the general population. Recent data suggests that around 1 in 15,000 children will have RSS.

Poor growth prior to birth (IUGR) is a feature of many different congenital disorders. Although some of these disorders may have signs and symptoms that are similar to RSS, they usually have other physical features that help differentiate them. For example, relative microcephaly (head size smaller than expected for height and weight) is almost never seen in RSS. Alternative diagnoses should also be considered if there is global developmental delay or significant intellectual disability, no history of feeding difficulties, distinctive facial features (different from those described in RSS), additional congenital anomalies or other features atypical for RSS. (For more information on these disorders, choose the exact disease name in question as your search term in the Rare Disease Database.)

The diagnosis of RSS is based on clinical findings. Because many of the symptoms are nonspecific, making a diagnosis of RSS remains difficult. Consensus guidelines for investigation and diagnosis of RSS have recently been published, based on the Netchine-Harbison clinical scoring system for RSS: https://www.nature.com/nrendo/journal/v13/n2/full/nrendo.2016.138.html


Sacrococcygeal Teratoma

Sacrococcygeal teratomas are rare tumors that develop at the base of the spine by the tailbone (coccyx) known as the sacrococcygeal region. Although most of these tumors are non-cancerous (benign), they may grow quite large and once diagnosed, always require surgical removal. It is likely that all sacrococcygeal teratomas are present at birth (congenital) and most are discovered before birth by a routine prenatal ultrasound examination or an exam indicated for a uterus too large for dates. In rare cases, sacrococcygeal teratomas may be cancerous (malignant) at birth and many will become malignant if surgical resection is not performed. In extremely rare cases, sacrococcygeal tumors may be seen in adults. Most of these represent slow growing tumors that originated prenatally. In the majority of these cases, the tumor is benign, but may cause lower back pain and genitourinary and gastrointestinal symptoms. The cause of sacrococcygeal teratomas is unknown.

The symptoms that occur with sacrococcygeal teratomas vary widely depending upon the size and specific location of the tumor. Small tumors often do not cause any symptoms (asymptomatic) and can usually be removed surgically after birth without difficulty.

The cause of sacrococcygeal teratomas is unknown. Sacrococcygeal teratomas are germ cell tumors. Germ cells are the cells that develop into the embryo and later on become the cells that make up the reproductive system of men and women. Most germ cell tumors occur in the testes or ovaries (gonads) or the lower back. When these tumors occur outside of the gonads, they are known as extragonadal tumors. Researchers do not know how extragonadal germ cell tumors form. One theory suggests that germ cells accidentally migrate during to unusual locations early during the development of the embryo (embryogenesis). Normally, such misplaced germ cells degenerate and die, but in cases of extragonadal teratomas researchers speculate that these cells continue to undergo mitosis, the process where cells divide and multiply, eventually forming a teratoma.

Sacrococcygeal teratomas occur in females more often than males by a 4:1 ratio. Malignancy is more common in males. The prevalence of these tumors is estimated to be between 1 in 30,000-70,000 live births. Sacrococcygeal teratomas are the most common solid tumor found in newborn babies (neonates). The sacrococcygeal region is the most common site for a teratoma in infants. Sacrococcygeal teratomas affecting adults is extremely rare. Adults cases often represent tumors that were present at birth (congenital), but not detected until adulthood.

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

In most cases, sacrococcygeal teratomas are diagnosed at birth when a large tumor is detected protruding from the sacral region. Many sacrococcygeal teratomas are found incidentally on routine prenatal ultrasounds or they may be detected on an ultrasound that is obtained because the uterus is too large for the stage of pregnancy due to the bulk of the tumor, or accumulation of amniotic fluid. During an ultrasound, reflected sound waves create an image of the developing fetus. Even small sacrococcygeal teratomas may be visible on an ultrasound picture.


Saethre-Chotzen syndrome

Saethre Chotzen syndrome (SCS) belongs to a group of rare genetic disorders known as acrocephalosyndactyly disorders. All of these are characterized by premature closure of the fibrous joints (cranial sutures) between certain bones of the skull (craniosynostosis), and/or webbing or fusion (syndactyly) of certain fingers or toes (digits).

SCS is primarily characterized by premature closure of the fibrous joints (cranial sutures) between certain bones in the skull (craniosynostosis), distinctive facial variations, and/or variations of the fingers and toes (digits). However, associated symptoms and findings may be extremely variable, including among affected members of the same family. For example, there have been reports in which some family members have had characteristic digital abnormalities alone, whereas others have been primarily affected by craniosynostosis.

In most individuals, SCS is caused by mutations in the TWIST1 gene. The TWIST1 gene has been mapped to the short arm (p) of chromosome 7 (7p21). Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as p and a long arm identified by the letter q. Chromosomes are further subdivided into bands that are numbered. For example, 7p21 refers to band 21 on the short arm of chromosome 7.

SCS affects males and females in equal numbers. Due to its variability including that manifestations can be mild, SCS may often go unrecognized. Therefore, it is difficult to determine the true frequency of the disorder in the general population.

The findings in the following disorders may be similar to those of Saethre-Chotzen syndrome. Comparisons may be useful for a differential diagnosis:

The diagnosis of SCS is primarily based on physical signs and symptoms. Molecular genetic testing for mutations in the TWIST1 gene can be identified in some, but not all, individuals.


GM1 gangliosidosis type 2

GM1神经节苷脂贮积病2型

Sandhoff disease is caused by harmful mutations in a gene called HEXB. These gene mutations cause decreased amounts of two important enzymes: beta-hexosaminidase A and beta-hexosaminidase B. These enzymes are found in the recycling centers (lysosomes) of the cell and their job is to break down fatty substances called GM2 gangliosides and globosides. The symptoms of Sandhoff disease happen because these fats (lipids) accumulate in harmful amounts in the brain and nerve cells. This damages the brain and spinal cord (central nervous system).

Sandhoff disease is a rare disorder that is estimated to affect 1 in 1,000,000 individuals. It affects males and females in equal numbers. Sandhoff disease occurs in multiple populations but may be most common in the Creole population of Argentina, Metis citizens of Saskatchewan, Canada and people with Lebanese ancestry.

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

Sandhoff disease is commonly diagnosed by testing the activity of the beta-hexosaminidase A and beta-hexosaminidase B enzymes (enzyme assays). People with Sandoff disease have reduced or absent activity of both enzymes. Genetic testing is used to confirm the diagnosis.

There is currently no cure for Sandhoff disease. Management is based on the symptoms and is mostly supportive. Supportive treatment includes ensuring proper nutrition and hydration, keeping the airway open, and seizure control with anticonvulsants.


Schimke immuno-osseous dysplasia

Schimke免疫性骨发育不良

Schimke immuno-osseous dysplasia (SIOD) is a multisystem disorder that is inherited in an autosomal recessive pattern. It usually manifests first with growth failure. Other features of the disease are generally noted in the ensuing evaluation of the growth failure or develop in the following years. According to the severity of the clinical features and the age of onset, SIOD has been divided into an infantile or severe early-onset form and a juvenile or milder late-onset form. Affected individuals with early-onset manifest severe symptoms and have a mean age of death at 9.2 years. These individuals have died from strokes, severe opportunistic infections, bone marrow failure, complications of kidney failure, congestive heart failure, and unspecified lung disease. On the other hand, those with milder disease have survived into the fifth decade if symptomatically treated. However, severity and age of onset of symptoms do not invariably predict survival as a few of those with early-onset disease have survived into the third and fourth decade.

The multiple symptoms of SIOD and the relative frequency of them are listed in the table. The symptoms are subsequently discussed according to the organ system affected.

SIOD is inherited in an autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits an abnormal gene from each parent. If an individual receives one normal gene and one abnormal 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 abnormal gene and, therefore, 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 is 25%. The risk is the same for males and females.

SIOD is panethnic with an unknown prevalence. As deduced from referrals and published birth rates, the incidence is approximately 1 per million live births in North America.

The diagnosis of SIOD is made on clinical findings. The most definitive diagnostic findings are skeletal dysplasia (spondyloepiphyseal dysplasia), renal dysfunction (urinary protein loss), T lymphocyte deficiency (particularly for naïve CD4 and CD8 T cells), dysmorphic facial features, and hyperpigmented macules. Anthropometry can help to distinguish SIOD from other forms of chronic kidney disease: a sitting height: leg length ratio of < 0.83 is consistent with a diagnosis of SIOD whereas a ratio of > 1.01 is indicative of non-SIOD chronic kidney disease. DNA testing for mutations in the SMARCAL1 gene is available to confirm the diagnosis.


α-N-乙酰半乳糖胺酶缺乏症

Schindler disease is a rare inherited metabolic disorder characterized by the deficient activity of the lysosomal enzyme alpha-N-acetylgalactosaminidase (alpha-NAGA or alpha-galactosidase B). The enzyme defect leads to the abnormal accumulation of certain complex compounds (glycosphingolipids, glycoproteins, and oligosaccharides), which have terminal or preterminal N-acetylgalactosaminyl residues in many tissues of the body and in urine. Two major forms of Schindler disease exist – a severe form with onset in infancy (type I) and a milder form with onset in adulthood (type II). Some researchers have proposed a type III form of Schindler disease that is less severe than type I, but more severe than type II. The specific symptoms and severity of Schindler disease can vary from one person to another. Schindler disease is caused by mutations of the NAGA gene and is inherited as an autosomal recessive trait.

Some researchers have broken Schindler disease into three distinct types. Type I is a severe form that occurs during infancy and is associated with neurological symptoms. Type II is a milder form of the disorder with onset usually in adulthood and mild, if any associated neurological symptoms. Type III is an intermediate form whose onset and severity fall in between the other two. Consequently, the severity and specific symptoms of Schindler disease can vary greatly from patients in one family to those in another.

Schindler disease is caused by mutations in the NAGA gene. These mutations are inherited as autosomal recessive traits. Genetic diseases are determined by the combination of mutations for a particular trait that are on the chromosomes received from the father and the mother. Recessive genetic disorders occur when an individual inherits an abnormal gene for the same trait 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, therefore, have an affected child is 25 percent with each pregnancy. The risk to have a child who is a carrier like the parents is 50 percent 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 percent. The risk is the same for males and females.

Schindler disease affects males and females in equal numbers. The exact incidence of Schindler disease in the general population is unknown. Because cases of Schindler disease may go unrecognized or misdiagnosed, determining the disorder’s true frequency in the general population is difficult. As a group, lysosomal storage diseases are infrequent, although certain disorders may occur in specific ethnic or demographic groups at higher frequencies, about one in every 1,000-2,000 live births for Gaucher and Fabry diseases, or very infrequently (1 in 100,000 to 200,000 live births) for most of these disorders, which may be the case for alpha-N-acetylgalactosaminidase deficiency. Schindler disease was first reported in the medical literature in the late 1980s.

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

Schindler disease may be diagnosed after birth (postnatally) by a thorough clinical evaluation, detailed patient history, and a variety of specialized tests. Urinary analysis (e.g., oligosaccharide and glycopeptide profiles) may reveal increased levels of certain complex compounds in the urine (e.g., oligosacchariduria and glycopeptiduria). Reduced activity of the alpha-NAGA enzyme may be confirmed by conducting enzyme tests (assays) on cultured white blood cells (leukocytes), blood plasma, and/or certain skin cells (fibroblasts) from affected individuals.


Schinzel-Giedion syndrome

Schinzel Giedion syndrome (SGS) is a very rare genetic disorder with characteristic facial features, skeletal abnormalities, and obstruction of the tube that carries urine from the kidney to the bladder (ureter). This obstruction may lead to enlarged and damaged kidneys (hydronephrosis). Symptoms characteristic of SGS also include excessive hair-growth (hypertrichosis), a flat midface (midface retraction), seizures, clubfeet, broad ribs, profound intellectual disability and short arms and legs. SGS is caused by a new mutation in the SETBP1 gene that is not inherited from the parents. SGS is a severe progressive syndrome and most affected individuals do not survive infancy.

Schinzel Giedion syndrome is characterized by an unusual facial appearance as well as abnormalities of the skeleton, kidney, hair and brain. Individuals with this disorder have an obstruction of the tube that carries urine from the kidney into the bladder (ureter). This causes the kidney to become swollen as urine accumulates (hydronephrosis).

Schinzel Giedion syndrome is caused by a new spontaneous mutation of the SETBP1 gene. The disorder is not inherited from the parents. The SETBP1 gene is a cancer promoting gene, and affected children who survive past three years of age are at risk for different types of cancer.

Schinzel Giedion syndrome is a very rare disorder that affects males and females in equal numbers. The birth prevalence is unknown.  There have been 50 cases reported worldwide.

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

Mucopolysaccharidosis (MPS) is a group of hereditary disorders of lysosomal storage. These diseases are characterized by an abnormal accumulation of mucopolysaccharides, especially in the cartilage and bone tissue. Symptoms of this disorder may include: abnormally slow growth and intellectual disability; vision and hearing problems; stiff joints; an excess of hair; dwarfism; and/or heart and breathing problems. (For more information on this disorder, choose Mucopolysaccharidosis as your search term in the Rare Disease Database.)

SGS is a severe progressive syndrome and most affected individuals do not survive infancy. However, one child has been reported to live until 6 years of age and another to still be living at 15 years of age.


Ulnar-mammary syndrome

Schinzel syndrome, also known as ulnar-mammary syndrome, is a rare inherited disorder characterized by abnormalities of the bones of the hands and forearms in association with underdevelopment (hypoplasia) and dysfunction of certain sweat (apocrine) glands and/or the breasts (mammary glands). Abnormalities affecting the hands and/or forearms range from underdevelopment of the bone in the tip of the fifth finger (hypoplastic terminal phalanx) to underdevelopment or complete absence of the bone on the outer aspect of the forearm (ulna).

Schinzel syndrome, also known as ulnar-mammary syndrome (UMS), is an extremely rare inherited disorder characterized by abnormalities affecting the bones of the hands and forearms and/or underdevelopment (hypoplasia) and dysfunction of certain sweat glands (apocrine) and/or the breasts (mammary glands).  The physical features and symptoms associated with Schinzel syndrome vary greatly from case to case.

Schinzel syndrome is inherited as an autosomal dominant genetic trait.  It occurs as a result of an abnormality in a gene on the long arm of chromosome 12 (12q24.1).

Schinzel syndrome is a very rare disorder that affects males and females in equal numbers.  Between 50 and 75 cases have been reported in the medical literature.  Of these, about 33 cases involve individuals within one family (kindred) from Utah.  The syndrome has been described in Asians, Africans, and Europeans.

Symptoms of the following disorder may be similar to those of Schinzel syndrome.  A comparison may be useful for differential diagnosis:

In some cases, a diagnosis of Schinzel syndrome may be made at birth based upon a thorough clinical evaluation, the identification of characteristic physical findings, and specialized imaging techniques. Such imaging studies may be conducted to confirm and/or characterize bone abnormalities affecting the fingers, hands, wrists, and/or arms; certain genital abnormalities (e.g., bicornate uterus in females, cryptorchidism in males); and/or other malformations (e.g., pyloric stenosis, inguinal hernia). Specialized tests may also be conducted to detect and verify dysfunction of certain sweat (apocrine) glands and/or the mammary glands in affected females. In addition, in some cases, additional testing may be conducted (e.g., echocardiograms, electrocardiograms, cardiac catheterization, specialized x-ray studies, etc.) to detect the presence of and/or characterize ventricular septal defects, which have been reported in one family with the disorder.


Schnitzler syndrome

Schnitzler syndrome is a rare disorder characterized by a chronic reddish rash that resembles hives (urticaria) and elevated levels of a specific protein in the blood (monoclonal IgM gammopathy). Symptoms associated with Schnitzler syndrome may include repeated bouts of fever, joint inflammation (arthritis), joint pain (arthralgia), bone pain, and other findings such as enlarged lymph nodes (lymphadenopathy). A monoclonal IgM gammopathy refers to the uncontrolled growth of a single clone (monoclonal) of plasma cells, which results in the abnormal accumulation of M-proteins (also known as immunoglobulin M or IgM) in the blood. However, the specific role these proteins play and the exact cause of Schnitzler syndrome is unknown. Schnitzler syndrome is difficult to classify and some researchers have suggested that it is an acquired autoinflammatory syndrome. Autoinflammatory syndromes are a group of disorders characterized by recurrent episodes of inflammation due to an abnormality of the innate immune system. They are not the same as autoimmune disorders, in which the adaptive immune system malfunctions and mistakenly attacks healthy tissue.

The symptoms associated with Schnitzler syndrome can vary from one person to another. The symptoms can occur all at once or, because they often come and go, the symptoms can occur at different times. The symptoms tend to persist for many years (chronic disease).

The exact cause of Schnitzler syndrome is unknown. Researchers believe that specific parts of the immune system may not function properly, eventually causing Schnitzler syndrome.

Schnitzler syndrome affects males slightly more often than females. However, only approximately 160 cases of this rare disorder have been reported in the medical literature so no definitive conclusions can be made about ethnic or gender predispositions. Because of the varied symptoms and rarity of Schnitzler syndrome, a diagnosis is usually delayed by several years and researchers believe that the disorder is underdiagnosed, making it difficult to determine its true frequency in the general population. Most individuals with Schnitzler syndrome are in their 50s when the characteristic symptoms develop.

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

A diagnosis of Schnitzler syndrome is based upon a thorough clinical evaluation, a detailed patient history, exclusion of other disorders, and identification of characteristic findings, specifically a urticarial rash, an M protein and at least two of the following findings – fever, joint pain or inflammation, bone pain, palpable lymph nodes, enlargement of the liver or spleen, elevated numbers of white blood cells (leukocytosis), elevated red blood cell (erythrocyte) sedimentation rate or abnormalities on bone morphological study, which can reveal increased bone density (osteosclerosis).


Schwartz-Jampel syndrome

Schwartz-Jampel syndrome (SJS) is a rare genetic disorder characterized by abnormalities of the skeletal muscles, including muscle weakness and stiffness (myotonic myopathy); abnormal bone development (bone dysplasia); permanent bending or extension of certain joints in a fixed position (joint contractures); and/or growth delays resulting in abnormally short stature (dwarfism). Affected individuals may also have small, fixed facial features and various abnormalities of the eyes, some of which may cause impaired vision. The range and severity of symptoms may vary from person to person. Two types of the disorder have been identified that may be differentiated by age of onset and other factors. SJS type 1, which is considered the classical form of the disorder, may become apparent during early to late infancy or childhood. SJS type 2, a more rare form of the disorder, is typically recognized at birth (congenital). Most researchers now believe that SJS type 2 is actually the same disorder as Stuve-Wiedemann syndrome and not a form of SJS. (For more information on Stuve-Wiedemann syndrome see the Related Disorders section of this report.)

SJS is primarily characterized by abnormalities of skeletal muscle, bone, and cartilage; malformations of the eyes and the face; and growth delays. In some cases, additional abnormalities may also be present. The range and severity of associated symptoms and physical findings varies from person to person, depending upon the form of the disorder present and other factors. Two forms of the disorder have been recognized, which are known as SJS types 1 and 2. SJS type 1, which is considered the classical form of the disorder, may be recognized during early to late infancy or childhood, whereas SJS type 2 is apparent at birth (congenital).

SJS types 1 and 2 are both thought to have autosomal recessive inheritance. Genetic diseases are determined by two genes, one received from the father and one from the mother.

SJS (SJS) types 1 and 2 are rare disorders that appear to affect males and females in equal numbers. More than 85 cases have been reported in the medical literature, including individuals affected by the classical (type 1) and the more severe neonatal form (type 2) of the disorder. SJS type 2 appears to be most common in individuals of United Arab Emirates descent. Depending upon the form of the disorder present, associated symptoms and findings may be recognized at birth or may become apparent during infancy or within the second year of life.

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

Stuve-Wiedemann syndrome is a rare skeletal disorder present at birth (congenital). It is characterized by short stature, bowing of the long bones of the arms and legs (campomelia), and fingers or toes that are permanently flexed (camptodactyly) outward away from the thumb (ulnar deviation). Affected infants may develop life-threatening complications such as episodes where there is a sudden rise in body temperature (hyperthermia) or respiratory distress. Stuve-Wiedemann syndrome is inherited as an autosomal recessive trait. Some researchers believe that Stuve-Wiedemann syndrome and SJS type II are the same disorder. SJS was previously believed to be the newborn (neonatal) form of SJS. However, the clinical and radiographic pictures of Stuve-Wiedemann and SJS type II are nearly identical leading many researchers to believe the two disorders are a single entity. (For more information on this disorder, choose Stuve-Wiedemann as your search term in the Rare Disease Database.)


Scleroderma

Scleroderma is a rare autoimmune connective tissue disorder characterized by abnormal thickening of the skin. Connective tissue is composed of collagen, which supports and binds other body tissues. There are several types of scleroderma. Some types affect certain, specific parts of the body, while other types can affect the whole body and internal organs (systemic). Scleroderma is also known as progressive systemic sclerosis. The exact cause of scleroderma is unknown.

The early symptoms of scleroderma vary considerably. Distinctive abnormalities on the skin (cutaneous lesions) usually appear later in the course of the disease. Common symptoms of scleroderma may include painful joints (arthralgia), morning stiffness, fatigue, and/or weight loss. The intermittent loss (triggered by cold temperatures) of blood supply to the fingers, toes, nose, and/or ears (Raynaud’s phenomenon) is an early and frequent complaint of people with scleroderma.

The exact cause of scleroderma is unknown. The immune system and vascular system as well as connective tissue metabolism are known to play some role in the disease process. Researchers believe that several factors interact to produce scleroderma. These include abnormal immune activity, potential environmental triggers, and genetic makeup. Scleroderma is not thought to be passed on from parent to child, but it is believed that the presence of certain genes may make it more likely that a person will develop the disease (genetic predisposition).

The systemic form of scleroderma is thought to affect from 40,000 to 165,000 people in the United States. The disease is three to four times more common in females than in males. Scleroderma may occur at any age but the symptoms most frequently begin during midlife.

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

Mixed connective tissue disease (MCTD) is a rare inflammatory disorder of the connective tissue.  The symptoms of this disorder overlap with those of lupus (systemic lupus erythematosus), scleroderma, and polymyositis/dermatomyositis.  Early symptoms may include a fever of unknown origin, painfully cold fingers in response to cold (Raynaud’s phenomenon), swollen hands, fatigue, and/or non-deforming arthritis.  Arthritis occurs in almost every case of mixed connective tissue disease, but rarely results in deformities similar to those seen in rheumatoid arthritis.  People with mixed connective tissue disease commonly experience muscle pain and skin rashes. (For more information on this disorder, choose Mixed Connective Tissue Disease as your search term in the Rare Disease Database.)

Treatment of scleroderma is symptomatic and supportive. Medications used to control the hardening of the skin and internal organs (fibrosis) are D- penicillamine and cholchicine. Other skin care may include lubricating creams or antibiotic ointments for infected ulcerations.


Craniodigital Syndrome-Mental Retardation, Scott Type

Scott craniodigital syndrome is a condition that has only been found in two families. The manifestations include unusual head shape, growth and developmental delay, and mild webbing between the fingers and toes (syndactyly)

Individuals with Scott craniodigital syndrome have a combination of mental and growth retardation, minor craniofacial anomalies, and mild webbing between the fingers and toes.  Birth weight and length are typically within normal limits, but subsequent growth retardation occurs.

Scott craniodigital syndrome is believed to be inherited as an X-linked recessive genetic trait, based on the presence of the condition in males only.  Carrier females have very mild manifestations.  Only two families have been described with the condition, so the true gene frequency is unknown.

Scott Craniodigital Syndrome With Mental Retardation is an extremely rare inherited disorder that is fully expressed in males only.  However, females who carry a single copy of the disease gene (heterozygotes) may exhibit some of the symptoms associated with the disorder.  The disorder has been reported in two separate families (kindreds) in the medical literature.  Most of the symptoms are apparent at birth.

Chitayat syndrome refers to a birth defect that combines unusual facial features in association with a malformation of the intestine.  The head may broad and short with a high forehead and heavy bones over the eyes, which are abnormally widely spaced (telecanthus).

Scott Craniodigital Syndrome With Mental Retardation may be diagnosed at birth, based upon a thorough clinical evaluation and identification of characteristic physical findings.


Seckel Syndrome

Seckel syndrome is rare genetic condition with slow growth before birth (intrauterine growth restriction) resulting in low birth weight. Slow growth continues after birth (postnatal), causing short height (dwarfism). Some features of Seckel syndrome are a small head (microcephaly) and intellectual disability. Possible facial features are a sloping forehead and beak-like nose. Other features may include large eyes, a narrow face, ears of a different shape and/or a small jaw (micrognathia). In addition, some affected infants may have curving of the pinkie finger (clinodactyly) or unusual development of the hips (hip dysplasia). They may also have dislocation of a bone in the forearm (radial dislocation) and/or other physical features.

Seckel syndrome presents with slow growth during fetal development (intrauterine growth restriction). This results in low birth weight. Slow growth (growth retardation and delayed bone maturation) continues after birth (postnatal). This can lead to short height (dwarfism) with arms and legs that are proportionate to height. (This is different than short height with small arms and legs). Moderate to severe intellectual disability may

Seckel syndrome is rare genetic disorder that is inherited in an autosomal recessive pattern. There are multiple types of Seckel syndrome caused by harmful changes in genes (mutations) on multiple chromosomes. The types and gene names are:

Seckel syndrome is a rare genetic disorder that affects males and females in equal numbers. About 1 in 10,000 individuals have Seckel syndrome.

Symptoms of the following conditions can be similar to those of Seckel syndrome. Comparisons may be useful to make the correct diagnosis:

Seckel syndrome is one of six disorders in the class of dwarfism known as the primordial dwarfism. These disorders share similar features. They include skeletal differences (dysplasia) and slow growth before birth (intrauterine growth retardation) and after. This results in varying levels of short height. This group of conditions currently includes five major subtypes: Seckel syndrome, ear-patella-short stature (Meier-Gorlin) syndrome; Russell-Silver syndrome; osteodysplastic primordial dwarfism type I/III; osteodysplastic primordial dwarfism type II.


常染色体显性遗传多巴反应性肌张力障碍

Autosomal dominant dopa-responsive dystonia

autosomal dominant dopa-responsive dystonia (DRD

Segawa syndrome is a rare genetic disorder characterized by an uncoordinated or clumsy manner of walking (abnormal gait) and dystonia. Dystonia is a general term for a group of muscle disorders generally characterized by involuntary muscle contractions that force the body into abnormal, sometimes painful, movements and positions (postures). Dystonia in Segawa syndrome usually affects the legs, but some children may first develop dystonia in the arms. In some cases, usually in adolescents and adults, the symptoms of Segawa syndrome may become noticeably worse or more pronounced in the afternoon and evening than in the morning (marked diurnal fluctuation). The symptoms of Segawa syndrome usually become apparent by around six years of age. Intelligence is not affected. Children with Segawa syndrome usually show a dramatic and sustained improvement when treated with levodopa. Levodopa is an amino acid that is converted to dopamine, a brain chemical that serves as a neurotransmitter. Dopamine is deficient in children with Segawa syndrome. The disorder is caused by mutations of the GCH-1 gene. The GCH-1 gene mutation is inherited as an autosomal dominant trait.

The symptoms and severity of Segawa syndrome can vary greatly from one person to another, even among members of the same family. Symptoms usually become apparent by around six years of age. In some cases, symptoms may not become apparent until later in childhood or even as late as adulthood.

Segawa syndrome is caused by mutations of the guanosine triphosphate cyclohydrolase I (GCH-1) gene. The GCH-1 gene mutation is inherited as an autosomal dominant trait or occurs as a spontaneous genetic change (i.e., new mutation) that occurs sporadically for no apparent reason.

Segawa syndrome affects girls and women more often than boys and men. In sporadic cases (i.e., new mutations), women are affected four times more often than men. Women are also more likely to have severe symptoms than men are. The exact incidence of Segawa syndrome in the general population is unknown. Researchers believe that the disorder is often misdiagnosed or goes undiagnosed, making it difficult to determine its true frequency in the general population. Segawa syndrome and tyrosine hydroxylase deficiency, which is also known as autosomal recessive dopa-responsive dystonia, account for approximately 5-10 percent of all cases of primary dystonia in childhood. Segawa syndrome was first described in the medical literature in 1971. It was originally called hereditary progressive dystonia with marked diurnal fluctuation.

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

A diagnosis of Segawa syndrome is made based upon a thorough clinical evaluation, a detailed patient history, identification of characteristic findings, and a response to therapy with low doses of levodopa. An examination of cerebrospinal fluid (CSF) can detect certain substances that are byproducts of metabolism (metabolites) specifically pterins. Identification of reduced levels of pterins in CSF can help to confirm a diagnosis of Segawa syndrome and distinguish the disorder from related neurotransmitter disorders. A sample of CSF is obtained through a procedure called a spinal tap (lumbar puncture), in which a needle is inserted into the spinal canal in the lower back.


Senior-Løken Syndrome

juvenile nephronophthisis with leber amaurosis

Senior-Løken syndrome (SLS) is a rare disorder belonging to the general group of rare diseases called ciliopathies that result in nephronophthisis and Leber congenital amaurosis. Nephronophthisis is the progressive wasting of the filtering unit of the kidney; it is characterized by cysts that develop in the kidneys during infancy or early childhood. Individuals will also develop symptoms of early-onset retinal dystrophy, a progressive retina disease that damages vision, within the first few years of life. Eventually the individual may experience renal failure and vision loss.

Senior-Løken syndrome is a rare inherited disorder characterized by progressive kidney and eye problems.

Senior-Løken syndrome is currently known to be caused by changes (pathogenic variants or mutations) in at least 10 genes: NPHP1, INVS /NPHP2, NPHP3, NPHP4, IQCB1/NPHP5, CEP290/NPHP6, SDCCAG8/NPHP10, WDR19/NPHP13, CEP164 and TRAF3IP1.

Senio-Løken syndrome is a very rare disorder affects males and females in equal numbers. It is estimated that the prevalence is 1/1 million people worldwide. Only a few families with the condition have been described in the medical literature.

Early onset retinal dystrophy is part of Senior-Løken syndrome, so symptoms can be similar to other non-syndromic retinal dystrophies.

Juvenile nephronophthisis-medullary cystic disease is a diffuse kidney disease, either genetic or congenital in origin, which usually appears in children or young adults (juvenile nephronophthisis). It is characterized by a gradual increase of urea and other by-products of protein breakdown in the blood (uremia) due to progressive failure of kidney function. (For more information on this disorder, choose Medullary Cystic Disease as your search term in the Rare Disease Database.)

Children affected with Senior-Løken syndrome should be monitored regularly by a pediatric nephrologist. The child’s weight and height, kidney function, urinary concentration and blood pressure should be monitored. An early diagnosis of nephronophthisis can be managed and delay the progression of kidney failure; however, once end-stage kidney disease develops patients will require dialysis or a kidney transplant.


墨喋呤还原酶缺乏所致多巴反应性肌张力障碍

Dopa-responsive dystonia due to sepiapterin reductase deficiency

Although researchers have been able to establish a clear syndrome with characteristic or core symptoms, much about sepiapterin reductase deficiency is not fully understood. Several factors including the small number of identified cases, the lack of large clinical studies, and the possibility of other genes influencing the disorder prevent physicians from developing an accurate picture of associated symptoms and prognosis. Therefore, it is important to note that affected individuals may not have all of the symptoms discussed below. Parents should talk to their children’s physician and medical team about their specific case, associated symptoms and overall prognosis.

Sepiapterin reductase deficiency is caused by mutations in the SPR 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.

Sepiapterin reductase deficiency is an extremely rare disorder that affects males and females in equal numbers. More than 40 cases have been described in the medical literature. The exact incidence or prevalence is unknown. Because cases can go undiagnosed or misdiagnosed, determining the true frequency of the disorder in the general population is difficult.

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

A diagnosis of sepiapterin reductase deficiency is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. Unlike other disorders of tetrahydrobiopterin deficiency, sepiapterin reductase deficiency is not associated with elevated phenylalanine levels and, consequently, will not be detected upon newborn screening.


Focal facial dermal dysplasia type III

局灶性面部皮肤发育不良III型

Setleis syndrome is an extremely rare inherited disorder that belongs to a group of diseases known as ectodermal dysplasias. Ectodermal dysplasias typically affect the hair, teeth, nails, and/or skin. Setleis syndrome is characterized by distinctive abnormalities of the facial area that may be apparent at birth (congenital). Most affected infants have multiple, scar-like, circular depressions on both temples (bitemporal). These marks closely resemble those made when forceps are used to assist delivery. In addition, affected infants may have puffy, wrinkled skin around the eyes (periorbital) and/or abnormalities of the eyelashes, eyebrows, and eyelids. Infants with Setleis syndrome may be missing eyelashes on both the upper and lower lids, or they may have multiple rows of lashes on the upper lids but none on the lower lids. In addition, in some cases, the bridge of the nose may appear flat, while the tip may appear unusually rounded (bulbous). Affected infants often have loose, excessive (redundant) skin, particularly in the area of the nose and the chin. Due to such facial abnormalities, infants with Setleis syndrome may have an aged and/or leonine (lion-like) appearance. The range and severity of symptoms may vary from case to case. Most cases of Setleis syndrome are thought to be inherited as an autosomal recessive genetic trait.

Setleis syndrome, an extremely rare inherited disorder, belongs to a group of diseases known as ectodermal dysplasias that typically affect the hair, teeth, nails, and/or skin.  Setleis syndrome is characterized by distinctive abnormalities of the facial area.  The range and severity of symptoms may vary from case to case.

In most cases, Setleis syndrome is thought to be inherited as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother.

Setleis syndrome is an extremely rare inherited disorder that, in theory, affects males and females in equal numbers. Approximately 20 cases have been reported in the medical literature. The majority of these cases have occurred in individuals from Puerto Rico.

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

Setleis syndrome is usually diagnosed shortly after birth based upon a thorough clinical evaluation and identification of characteristic features, such as distinctive scar-like, circular depressions on both temples; an aged and/or leonine facial appearance; and characteristic abnormalities of the eyelashes, eyebrows, and eyelids. It is possible that microscopic examination of small samples of skin tissue (biopsy) from the temples may reveal abnormal thinning of the outer layer of the skin (epidermis) and absence of certain specialized structures normally located within the inner layer of the skin (e.g., sweat glands, sebaceous glands, hair follicles).


Severe Chronic Neutropenia

重型先天性中性白细胞减少症

Severe chronic neutropenia (SCN) is a rare blood disorder characterized by abnormally low levels of certain white blood cells (neutrophils) in the bloodstream (neutropenia) not explained by medication use, infections or another underlying health condition like blood cancers or systemic autoimmune diseases associated with neutropenia. Neutrophils play an essential role in fighting bacterial infections by surrounding and destroying invading bacteria (phagocytosis). Symptoms associated with severe chronic neutropenia include recurring fevers, mouth sores (ulcers), inflammation of the tissues that surround and support the teeth (periodontitis) and inflammation of the sinuses (sinusitis), throat (pharyngitis) and/or ear (otitis). Due to low levels of neutrophils, affected individuals may be more susceptible to recurring bacterial infections that, in some patients, may result in life-threatening complications. SCN may last for months or years and can affect both children and adults. Clinicians recognize three forms of the disorder: congenital, autoimmune and idiopathic neutropenia. The term idiopathic neutropenia is used when severe chronic neutropenia occurs for unknown reasons.

Symptoms and physical findings associated with severe chronic neutropenia vary greatly depending on how low the level of neutrophils in the blood falls. As earlier noted, the three main subdivisions of severe chronic neutropenia are congenital, autoimmune and idiopathic.

Severe chronic neutropenia is a rare blood disorder that appears to affect females more than males in its idiopathic and autoimmune forms, with less discrepancy between the sexes in congenital forms. Both children and adults may be affected. Severe congenital neutropenia is estimated to affect approximately 1-4 people per million population in the United States.

Symptoms of the following disorders may be similar to those of severe chronic neutropenia. Comparisons may be useful for a differential diagnosis.

Severe chronic neutropenia can be diagnosed with a bone marrow aspirate, blood counts and genetic testing. The aspirate is collected after a detailed patient history, thorough clinical evaluation and blood tests (i.e., white blood cell count) that measure the various types of blood cells in the circulation. In individuals with severe chronic neutropenia, such blood counts demonstrate abnormally low levels of neutrophils. Normal counts of neutrophils range between 1.5 and 7 billion cells per liter of blood. If the neutrophil count falls below 0.5, then severe neutropenia is suggested.


Severe combined immunodeficiency

Severe combined immunodeficiency (SCID) is a group of rare congenital syndromes with little or no immune responses.  This results in frequent recurring infections with bacteria, fungi, and viruses. Infections that are minor in most people can be life‑threatening in people with SCID.

All newborn babies receive antibodies from their mothers during pregnancy that protect them from infections during the first few months of their lives. In the absence of family history of SCID and prior to newborn screening, babies with SCID often presented to medical attention between three and six months with severe infections as their maternal antibodies naturally decreased.  Symptoms included rashes, diarrhea, recurrent infections, difficulty gaining weight, weakness and/or growth delay.

All types of SCID are very rare disorders that occur in approximately 1 or fewer births in 100,000 in the United States. SCID may be more common in people with Navajo, Apache, or Turkish ancestry.

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


Sheehan Syndrome

Excessive blood loss during or after delivery of a baby may affect the function of the pituitary gland, leading to a form of maternal hypopituitarism known as Sheehan syndrome (SS). Such extensive bleeding may reduce the blood flow to the pituitary gland causing the pituitary cells to be damaged or die (necrosis). Thus, the production of the usual pituitary hormones will be reduced, perhaps by a significant amount. During pregnancy the pituitary gland will enlarge and may double in size. At this time the gland is especially vulnerable to a severe drop in blood pressure (sometimes called shock) and excessive maternal bleeding may induce the shock and the damage to the cells of the gland. At that time the amount of hormones produced by the pituitary may be decreased giving rise to the symptoms associated with hypopituitarism. There appear to be two forms of the disorder: a chronic form and an acute form, depending on the amount of damage to the gland’s cells. The acute form reflects considerable damage so that symptoms become apparent soon after delivery. In chronic cases, the volume of damage is much less, and symptoms may not appear for months or years after delivery.

The clinical features of Sheehan syndrome are highly variable and depend on the degree of failure of secretion of pituitary hormones including:

In most instances, a precipitous drop in blood pressure and consequent shock, due to obstetrical bleeding, precede the onset of symptoms. According to many physicians the amount of damage that must be done to the anterior pituitary before Sheehan syndrome occurs varies from 75 to 90 percent. The enlarged pituitary requires more than normal volumes of oxygen, and any disruption of blood flow is a threat to the gland.

Sheehan syndrome affects women with excessive blood loss and circulatory collapse following childbirth. The incidence of Sheehan syndrome is not known.

Antiphospholipid syndrome (APLS) is a rare autoimmune disorder characterized by recurring blood clots that usually appear before 45 years of age. It may also be associated with repeated spontaneous abortions for no apparent reason in young women. There may be a family history of blood clotting disorders in some cases. APLS may occur in individuals with lupus or related autoimmune diseases or as a primary syndrome in otherwise healthy individuals. (For more information on this condition, search for APLS in the Rare Disease Database.)

In patients with severe hemorrhaging on delivery accompanied by long-lasting low blood pressure, treatment is started as soon as possible. Women believed to have the chronic form usually have blood drawn and the levels for several hormones are determined.  Often, a head computed tomography (CT) or magnetic resonance imaging (MRI) scan is done; acutely this will usually show hemorrhage in the pituitary but chronically, as the blood resolves, this will show just a diminished size of the pituitary.


Short Bowel Syndrome

The symptoms and severity of short bowel syndrome can vary greatly depending upon the length and function of the remaining or undamaged portion of the small intestine. Because short bowel syndrome can vary so greatly, it is important to note that affected individuals may not have all of the symptoms discussed below. Affected individuals or parents of affected children or infants should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis.

Short bowel syndrome is generally broken down into individuals in whom the disorder is acquired during life and newborns in which the disorder is present at birth (congenital). Acquired short bowel syndrome is more common than the congenital form of the disorder.

Short bowel syndrome affects males and females in equal numbers. The disorder is usually acquired during life, but in rare cases may be present at birth (congenital). In adults, short bowel syndrome usually results from the surgical removal of a portion of the small intestine. Crohn’s disease is the most frequent cause of surgical removal of the small intestine in adults. In newborns, necrotizing enterocolitis is the most common cause of surgical removal of the small intestines. The exact incidence and prevalence of short bowel syndrome in the general population is unknown.

A diagnosis of short bowel syndrome is made based upon a detailed patient history, a thorough clinical evaluation and a variety of specialized tests including laboratory tests and X-ray studies.


短链酰基辅酶A脱氢酶缺乏症

Short Chain Acyl CoA Dehydrogenase Deficiency

Short chain acyl-CoA dehydrogenase deficiency (SCADD) is a rare autosomal recessive genetic defect in fatty acid catabolism belonging to a group of diseases known as fatty acid oxidation disorders (FOD). It occurs because of a deficiency of the short-chain acyl-CoA dehydrogenase (SCAD) enzyme.

Essentially all individuals identified through newborn screening have been healthy. Therefore, the variety of symptoms that have been reported in other individuals with SCAD deficiency are all likely coincidental. This situation has been accentuated by the existence of two very common variants in the SCAD gene that lead to blood and urine findings suggestive of SCADD but are not sufficiently severe to cause complete SCADD.

SCADD is an autosomal recessive condition caused by mutations in the Short Chain Acyl-Coenzyme A dehydrogenase (ACADS) gene leading to deficiency of the SCAD enzyme.

SCAD deficiency is thought to affect 1 in 40,000 to 100,000 newborns. In the US, ~10% of individuals have two copies of one of the common polymorphisms leading to potential identification of related metabolites in urine or blood.

The following disorders can have similar lab findings to those seen SCADD and therefore should be considered when symptoms are present. Comparisons may be useful for a differential diagnosis:

Mitochondrial respiratory chain disorders are a group of related disorders characterized by mutations affecting the parts of the cell that release energy (mitochondria). Mitochondrial disorders often hamper the ability of affected cells to combine food with oxygen to produce energy. In most mitochondrial disorders, abnormally high numbers of defective mitochondria are present in the cells of the body. Mitochondrial diseases often affect more than one organ system of the body. Common symptoms associated with mitochondrial disorders include muscle weakness, stroke-like episodes, and seizures. Exercise intolerance is another common symptom. Some forms are associated with disease of the heart muscle (cardiomyopathy). Mitochondrial disorders include Kearns-Sayre syndrome, MELAS syndrome, MERRF syndrome, NARP, and Leber hereditary optic neuropathy. (For more information on this disorder, choose the specific disorder name as your search term in the Rare Disease Database.) Ethylmalonic acid (EMA) is elevated in both mitochondrial respiratory chain disorders and SCADD.


Familial short QT syndrome

The extremely abbreviated QTc interval that characterizes the ECG of SQTS patients is associated with defects in cardiac electrical function including life-threatening arrhythmias that may appear at rest or during exercise with no apparent initiating cause.

While usually assumed to be inheritable, SQTS cases in which a familiar history is absent may be caused by a spontaneous mutation during embryonic development (known as a de novo mutation). Moreover, not all SQTS patients have an identifiable mutation.

Many SQTS patients likely go undiagnosed or misdiagnosed, and determinations of SQTS incidence and prevalence are difficult due to limited data. Some have estimated the SQTS prevalence at less than 1 in 10,000. Others have suggested that SQTS shows a peak of incidence during the first year of life, age at which many SCD events occur and another peak in late adulthood.

SQTS is classified among the channelopathies encompassing diseases caused by mutations in genes encoding ion channels. Opposite defects in the function of the products of one these genes may cause completely different diseases included in the same group. A case in point is the Andersen-Tawil syndrome (ATS). Loss-of-function mutations in KCNJ2 (gene encoding the potassium channel Kir2.1) provoke ATS type 1, while gain-of-function alterations in the same gene yield SQTS type 3. Similarly, loss-of-function mutations in KCNH2, which codes for HERG, result in long QT syndrome type 2, whereas gain-of-function mutations in the same gene result in SQTS type 1. The link between these channelopathies is the mutated gene causing each disease and its symptoms. However, the ECG findings that characterize each channelopathy are different and, for the most part, it is easy to differentiate among them. (For more information on these disorders (ATS, LQTSs, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia), choose the specific disorder name as your search term in the Rare Disease Database).

Around 250 cases and nearly 150 families have been reported in the literature with SQTS. These numbers may not be entirely accurate, as there are difficulties diagnosing these patients. While the disease may be obvious in symptomatic patients, doubts may arise when dealing with asymptomatic patients, especially if they have no family history. In the past, SQTS was diagnosed if the QTc interval was 0.3 seconds or less. Nowadays, SQTS is suspected when the QTc interval duration is 0.34 seconds, a threshold under which a definitive diagnosis is established, even in the absence of symptoms. Furthermore, SQTS is also considered in patients with a QTc interval between 0.34 and 0.36 seconds plus one or more of the following signs: history of documented ventricular tachycardia or ventricular fibrillation in the absence of heart disease or reversible causes, family history of SQTS, family history of unexplained SCD at age ≤ 40 or a confirmed disease-causing mutation.


SHORT syndrome

SHORT syndrome is a rare condition described by RJ Gorlin et al in 1975 based on the striking physical features of two infants born to unaffected parents. Over time, additional individuals have been described and the clinical definition of SHORT syndrome has been expanded. Each letter of SHORT syndrome represents one of the common findings in affected persons:

SHORT syndrome is a disorder that affects multiple organ systems. This condition was initially characterized by short stature, joints that stretch more than usual (hyperextensibility), a particular type of hernia in which the intestine protrudes through a weak spot in the abdominal muscles (inguinal hernia), deep set eyes (ocular depression), defective development of the anterior chamber of the eye that can lead to glaucoma (Rieger anomaly) and delayed eruption of teeth.

SHORT syndrome is caused by changes (pathogenic variations) in the PIK3R1 gene. This gene is responsible for proper function of the enzyme PI3K. Enzymes are proteins that are required for cellular reactions. Specifically, PI3K is involved in cell growth and division, transport of materials within cells, movement of cells and regulation of the hormone insulin.

SHORT syndrome is a very rare disorder with fewer than 50 reported cases in the literature to date. SHORT syndrome is not known to be more prevalent in a certain ethnic group or geographic location.

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

Rieger syndrome: a rare disorder inherited in an autosomal dominant pattern. The main characteristics are facial, dental and eye abnormalities. Facial characteristics include a small jaw, broad nasal bridge and/or a protruding lower lip. Although Rieger anomaly is a classic feature of SHORT syndrome, an individual may have Rieger syndrome alone without the other clinical features of SHORT syndrome. (For more information on this disorder choose Rieger as your search term in the Rare Disease Database.)

No specific treatment exists for SHORT syndrome. Treatment is symptomatic and supportive based on the features present in each patient. Rieger anomaly/glaucoma, dental anomalies, insulin resistance/diabetes mellitus and hearing loss can often be treated by appropriate medical specialists. Given the increased risk for insulin resistance, it is generally advisable to avoid growth hormone treatments.


Shprintzen-Goldberg syndrome

Most newborns with SGS are born full term and have normal weight, height and head circumference. Symptoms begin to appear in the newborn period. Both males and females are affected equally. Craniosynostosis is a common characteristic of SGS. This early fusion of skull bones prevents the skull from growing normally. Individuals with SGS tend to have mild to moderate intellectual and cognitive disabilities even if they do not have craniosynostosis.

SGS is one of many diseases that arise from variants in genes that affect the TGF-β signaling pathway. The TGF-β signaling pathway regulates many aspects of early development and tissue homeostasis, and thus SGS patients and people with related diseases have a variety of physical malformations.

SGS affects males and females in equal numbers and occurs worldwide with no ethnic predisposition. As of 2024, there are 44 known patients with SKI pathogenic variants relating to SGS. Because of the similar symptoms, SGS is often misdiagnosed as Loeys-Dietz or Marfan syndrome. The disorder is probably underdiagnosed, making it difficult to determine its true frequency. It is estimated that fewer than 1,000 people in the U.S. have this disease.

Shprintzen Goldberg syndrome is generally diagnosed after a thorough physical examination and the presence of certain craniofacial, skeletal, cardiovascular and neurologic features, brain anomalies and other characteristics such as minimal subcutaneous fat and defects in the abdominal wall and myopia. There is currently no test for SGS other than identification of a pathogenic variant in the SKI gene through genetic testing. To date, this is the only identified gene associated with SGS. Patients with Marfan syndrome and FBN1 gene variants rarely have craniosynostosis and other distinguishing features of SGS.


Shwachman-Diamond syndrome

Shwachman syndrome is a rare genetic disorder with multiple and varied manifestations. The disorder is typically characterized by signs of insufficient absorption (malabsorption) of fats and other nutrients due to abnormal development of the pancreas (pancreatic insufficiency) and improper functioning of the bone marrow (bone marrow dysfunction), resulting in low levels of circulating blood cells (hematologic abnormalities). Additional characteristic findings may include short stature; abnormal bone development affecting the rib cage and/or bones in the arms and/or legs (metaphyseal dysostosis); and/or liver abnormalities.

Shwachman syndrome is a rare genetic disorder characterized by insufficient absorption (malabsorption) of necessary nutrients due to abnormal development of the pancreas (pancreatic insufficiency); impaired functioning of the bone marrow, resulting in a reduced number of certain blood cells; abnormal bone changes that may affect the rib cage and/or bones in the arms and/or legs (metaphyseal dysostosis); short stature; and/or other physical and/or developmental abnormalities. The range and severity of symptoms may vary greatly from case to case.

Shwachman syndrome is most likely inherited as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother.

Shwachman syndrome is a rare genetic disorder that may be apparent at birth (congenital), during early infancy, or within the first few years of life. In rare cases, the diagnosis may be made during adolescence or adulthood. Reports indicate that the disorder affects males and females by a ratio of approximately 1.7 to 1.

Some of the symptoms of the following disorders may be similar to those seen in Shwachman syndrome. Comparisons may be useful for a differential diagnosis:

Shwachman syndrome is usually diagnosed at birth or during early childhood based upon a thorough clinical evaluation, characteristic physical findings, and specialized tests. In rare cases, the diagnosis may be made during adolescence or adulthood.


Sialidosis

Sialidosis, also known as mucolipidosis type I, is a rare inherited metabolic disorder characterized by a deficiency of the enzyme neuraminidase (sometimes referred to as sialidase). Deficiency of neuraminidase results in the abnormal accumulation of toxic materials in the body. Sialidosis is divided into two types (i.e., type I and type II). Sialidosis type I usually becomes apparent during the second decade of life with the development of sudden involuntary muscle contractions (myoclonus), distinctive red spots (cherry-red macules) in the eyes, and sometimes additional neurological findings. Sialidosis type II is usually more severe than sialidosis type I. Type II often begins during infancy or later during childhood and is characterized by cherry-red macules, mildly coarse facial features, skeletal malformations and mild cognitive impairment. Sialidosis is inherited as an autosomal recessive trait.

The age of onset, symptoms, progression and severity of sialidosis vary greatly from one person to another. Sialidosis type I is a milder form of the disorder than sialidosis type II and has later onset. It is important to note that affected individuals may not have all of the symptoms discussed below. Affected individuals should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis.

Sialidosis is caused by mutations of the NEU1 gene. This gene mutation is inherited as an autosomal recessive trait. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

Sialidosis affects males and females in equal numbers. The exact incidence of sialidosis in the general population is unknown. One estimate places the incidence at 1 in 4.2 million individuals in the Australian population. Another estimate placed the incidence at 1-4 individuals per 200,000 of the general population. Because rare disorders like sialidosis often go unrecognized or misdiagnosed, determining the true frequency of sialidosis in the general population is difficult.

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

A diagnosis of sialidosis is made based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. An examination of urine may reveal increased levels of oligosaccharides. A urine test is usually followed up by blood tests and a skin biopsy (surgical removal and microscopic study of skin tissue). These tests can reveal low levels of the enzyme alpha-neuraminidase in blood and skin tissue.


Schnyder corneal dystrophy

Hemoglobin is an iron-rich protein contained in red blood cells and is responsible for carrying oxygen from the lungs to the rest of the body. In SCD, the symptoms stem from the abnormal hemoglobin in the red blood cells. The abnormal hemoglobin causes the red blood cells to be sickle-shaped which triggers a series of events leading to fragile red blood cells and blocking blood flow.

Sickle cell disease is caused by changes (variants) in both copies of the hemoglobin beta (HBB) gene.

The frequency of SCD varies from country to country. SCD affects 0.6 percent of the African American population in the United States (approximately 100,000 cases in the United States). It is also common in people of Hispanic descent, from India, Central America and the Arabian Peninsula, but can occur in people of any background. SCD affects approximately one in every 300 – 500 African American newborns. The sickle cell trait is present in approximately 40 percent of the general population in some areas of Africa. The incidence of sickle cell trait in Americans of African descent is 9 percent.

It has become easier to distinguish SCD from other disorders because all children born in the U.S. are screened for SCD at birth. In older patients and immigrants, SCD should be considered in people with anemia and/or recurrent pain, especially if they have family from the regions where SCD is most common (for example Africa and regions listed above).

Newborn babies in the U.S. (all 50 states and the District of Columbia) are screened for sickle cell status (SCD or SCT) 24-48 hours after birth as part of the newborn screening program. The screening test is done using electrophoresis and/or high-pressure liquid chromatography. A positive newborn screening test means that a baby is likely to have SCD or SCT, but additional testing is needed to confirm the diagnosis. Molecular genetic testing for variants in the HBB gene is also available.


Simpson-Golabi-Behmel syndrome

SGBS type 1 is caused by harmful changes (mutations) in the genes GPC3 and GPC4, located on the X chromosome. SGBS type 2 is caused by mutations in the genes OFD1 and PIGA, also located on the X chromosome. They are genetic disorders that are inherited in a recessive X-linked pattern.

SGBS is present from birth (congenital) and can be diagnosed in a baby, even though some of the features might not appear until a child is older. All males who have a mutation in one of the genes for SGBS will have the condition. It is not known what percentage of carrier females have symptoms. As of 2014, there were 250 known cases of SGBS type 1. As of 2019, there have been 8 symptomatic female carriers reported.

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

Diagnosis of SGBS type 1 is made based on physical features of the patient, family history and genetic testing. There are no official criteria that are used to diagnose the condition. The main physical features are the different types of overgrowth (large body, large head, large fetus, large baby), the specific facial features, abnormalities that happen in the middle of the body (midline defects), and risk for tumors. The other physical features that are considered are organs larger than expected (organomegaly), issues with the skeleton, and problems with the heart, central nervous system, kidney, and gastrointestinal tract that are present from birth. A family history showing an X-linked pattern of inheritance can help with diagnosis. Genetic testing can involve sequencing and deletion/duplication analysis of the GPC3 gene, a chromosomal microarray, or a multigene panel that includes GPC3, GPC4, and other genes related to differential diagnoses.


Singleton-Merten dysplasia

Singleton-Merten syndrome is an extremely rare, multisystem disorder the major characteristics of which are tooth abnormalities (dental dysplasia), calcifications in the aorta, the major artery of the body, and certain valves of the heart (i.e., aortic and mitral valves), as well as progressive thinning and loss of protein of the bones (osteoporosis), especially in the hands and feet. Other physical findings usually associated with Singleton-Merten syndrome may include generalized muscle weakness; progressive loss or wasting away of muscle tissue (atrophy); delayed growth, possibly resulting in short stature; delays in motor development; a skin condition characterized by thickened patches of red, scaly skin, particularly on the fingers; vision problems (glaucoma); abnormal ligaments of the joints and muscle; and/or malformation of the hips and/or feet. It appears that, in some cases, Singleton-Merten syndrome is present as a result of a random (sporadic) mutation that occurs for no apparent reason. In other cases, an autosomal dominant pattern of inheritance has been suggested.

Singleton-Merten syndrome, an extremely rare disorder, is characterized by abnormalities of the teeth (dental dysplasia), abnormal accumulation of calcium deposits (calcifications) in the major artery of the body (aorta) and certain valves of the heart (i.e., aortic and mitral valves), and/or progressive thinning and loss of protein of the bones (osteoporosis). Between the ages of four to 24 months, most affected infants experience generalized muscle weakness and loss or wasting away (atrophy) of muscle tissue. Affected infants may also exhibit delays in general physical (somatic) development, possibly resulting in short stature, and/or delays in the ability to coordinate muscles and perform certain tasks (motor development).

Singleton-Merten syndrome is an extremely rare disorder that is likely an autosomal dominant condition with highly variable expression. Individuals with a mild form of Singleton-Merten syndrome may show only one symptom, such as a skin rash (psoriasis). Individuals with a severe form may exhibit all the main features of Singleton-Merten syndrome including calcifications in the heart and aorta as well as skeletal and dental abnormalities.

Singleton-Merten syndrome is an extremely rare inherited disorder that, in theory, affects males and females in equal numbers. However, in reported cases, females have been affected more frequently than males (3:1). Fewer than 10 individual cases and three families (kindred) with multiple affected members have been reported in the medical literature.

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

The ectodermal dysplasias (ED) are a group of diseases typically characterized by abnormalities of the head and face (craniofacial) area, the hair, teeth, nails, and/or skin. In some cases, the abnormalities associated with some of the ectodermal dysplasias may be similar to findings associated with Singleton-Merten syndrome. Some of the ectodermal dysplasias may also be characterized by abnormalities of the heart and vascular system similar to those associated with Singleton-Merten syndrome. (For more information on these disorders, choose ectodermal dysplasia or the exact disease name in question as your search term in the Rare Disease Database).


Sirenomelia

Sirenomelia, which is also known as mermaid syndrome, is an extremely rare congenital developmental disorder characterized by anomalies of the lower spine and the lower limbs. Affected infants are born with partial or complete fusion of the legs. Additional malformations may also occur including genitourinary abnormalities, gastrointestinal abnormalities, anomalies of the lumbarsacral spine and pelvis and absence or underdevelopment (agenesis) of one or both kidneys. Affected infants may have one foot, no feet or both feet, which may be rotated externally. The tailbone is usually absent and the sacrum is partially or completely absent as well. Additional conditions may occur with sirenomelia including imperforate anus, spina bifida, and heart (cardiac) malformations. Sirenomelia is often fatal during the newborn period. The exact cause of sirenomelia is unknown, most cases occur randomly for no apparent reason (sporadically).

There are a wide range of physical malformations that can potentially occur with sirenomelia and the specific findings can vary greatly from one individual to another. Sirenomelia is associated with severe life-threatening complications and is often fatal in the first years of life. However, survival beyond infancy into later childhood or young adulthood has been reported in a handful of cases.

The exact cause of sirenomelia is unknown. Researchers believe that both environmental and genetic factors may play a role in the development of the disorder. Most cases appear to occur randomly for no apparent reason (sporadically), which suggests environmental factors or a new mutation. Most likely, sirenomelia is multifactorial, which means that several different factors may play a causative role. In addition, different genetic factors may contribute to the disorder in different people (genetic heterogeneity).

Sirenomelia affects males more often than females by a ratio of 2.7-1. The exact incidence is unknown, but sirenomelia is estimated to occur in approximately 1 in 60,000 to 100,000 births. Sirenomelia occurs with greater frequency in one twin of identical (monozygotic) twins than it does in fraternal (dizygotic) twins or individuals.

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

A diagnosis of sirenomelia can be made prenatally, most often during the second trimester, by fetal ultrasound. An ultrasound is an exam that uses high-frequency sound waves to produce an image of the developing fetus. A fetal ultrasound can detect some of the defects associated with sirenomelia.