肉毒碱棕榈酰转移酶IA缺乏症

Carnitine palmitoyl transferase 1A deficiency

Carnitine Palmitoyltransferase 1A Deficiency

CPT1A deficiency in a developing baby can cause abnormal findings during pregnancy, including maternal fatty liver, low blood sugar (hypoglycemia), abnormal liver enzymes, high amounts of ammonia (hyperammonenmia), and increased susceptibility to bleeding due to abnormal liver function.

CPT1A deficiency is caused by harmful changes (mutations) in the CPT1A gene that codes for the carnitine palmitoyltransferase 1 enzyme. This enzyme breaks down long fatty acids. If fats cannot be properly processed, then energy production is decreased.

CPT1A deficiency has been reported in approximately 60 individuals. The incidence of this condition may be higher in the Hutterite populations in the northern United States and Canada and the Inuit populations in northern Canada, Alaska and Greenland. This condition occurs in both males and females equally.

CPT1A deficiency belongs to a category of conditions called fatty acid oxidation disorders (FODs), in which the body cannot properly break down fatty acids to create energy in the body. The fats that are not broken down cannot be used for energy, and the increased fat by-products can become toxic and cause problems in the body. Other FODs can have similar symptoms to CPT1A deficiency such as:

CPT1A deficiency can be diagnosed by using genetic testing to find two mutations in the CPT1A gene. Additionally, the level of carnitine palmitoyltransferase 1 (CPT1) enzyme can be measured from skin cells. Other laboratory findings can support this diagnosis, including low levels of ketones, elevated liver enzymes, elevated ammonia, and elevated carnitine in blood. Some state newborn screening programs perform screening for CPT1A deficiency by measuring the ratio of free to total carnitine in blood plasma or serum.


Homocarnosinosis

Carnosinemia is a very rare inherited metabolic disorder characterized by developmental delays and seizures. Symptoms can begin during infancy and may include drowsiness, seizures that may be accompanied by involuntary jerking muscle movements of the arms, legs, or head (myoclonic seizures), and intellectual disability.

The symptoms of carnosinemia include extreme drowsiness and seizures that can occur in children under the age of one year. Slow growth, low muscle tone, motor delays, and delayed intellectual development also occur in children with this disorder. Seizures may be accompanied by myoclonic seizures. By approximately 2 years of age, affected children show variable degrees of intellectual deficit leading to intellectual disabilities and developmental regression. Some affected children also have muscle weakness (congenital myopathy). Electroencephalogram (EEG), a test that detects electrical activity in the brain, may be abnormal.  A few patients reported with this condition have few or no symptoms.

The exact nature of the biochemical abnormality that causes carnosinemia is not clear, but carnosinase, the enzyme responsible for carnosine breakdown, is known to be present in the brain, as well as the blood. Studies of muscle tissue from affected individuals suggest that the metabolism of two dipeptides present in meats, carnosine and anserine, by the enzyme carnosinase, is abnormal. The role of the enzyme carnosinase is to break down carnosine into two basic elements. Affected individuals usually have abnormally high levels of carnosine in their urine (carnosinuria) and abnormally low levels of the enzyme carnosinase in their blood.

Carnosinemia is a very rare disorder that affects males and females in equal numbers. Approximately 30 individuals with carnosinemia have been reported in the medical literature world-wide.

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

Gamma-amino butyric acid (GABA) transaminase deficiency is an extremely rare autosomal recessive genetic disorder caused by mutations in the ABAT gene. Symptoms can include slow growth, motor delays, low muscle tone, hyperactive responses, lethargy, seizures, and abnormalities on an EEG.


Caroli Disease

congenital dilatation of intrahepatic bile duct

Bile needs to be able to move through the bile ducts without getting stuck. When these ducts become too wide, bile can collect easily. As bile collects over time, the build-up can cause small stones to form. These small stones usually do not cause symptoms unless they block the bile duct. When a bile duct is blocked due to stones, the bile ducts become swollen (cholangitis). This can cause pain on the right side of the body, vomiting, fever, and yellowing of the skin (jaundice). People with Caroli disease experience many episodes of cholangitis. Rarely, tumors called cholangiocarcinomas can form in the bile duct due to the build-up of bile. Usually, symptoms happen before the age of 30, but can happen at any age. Some people with Caroli disease may only have one episode of cholangitis, so it is important to understand how the disease impacts a person’s life.

Caroli disease and Caroli syndrome are thought to be genetic conditions. Caroli disease usually occurs sporadically, but has been reported to follow autosomal dominant inheritance in some families.

Caroli disease and Caroli syndrome can affect people of all ethnic and ancestral backgrounds. Symptoms typically start in adulthood, but can sometimes start in childhood. Caroli disease is rarer than Caroli syndrome, but it is estimated that 1 out of 1,000,000 individuals are affected by Caroli disease. Caroli syndrome has been estimated to affect 1 out of 100,000 individuals, but it is difficult to identify people with Caroli syndrome since features can overlap with other conditions.

Many conditions have similar symptoms to both Caroli disease and Caroli syndrome. It is important to know the conditions that could be confused for the two types of Caroli disease:

Based on symptoms, imaging may be done to see if there are any problems with the liver or bile ducts.


Carpenter syndrome

Carpenter syndrome belongs to a group of rare genetic disorders known as acrocephalopolysyndactyly (ACPS) disorders. All forms of ACPS are characterized by premature closure of the fibrous joints (cranial sutures) between certain bones of the skull (craniosynostosis), causing the top of the head to appear pointed (acrocephaly); webbing or fusion (syndactyly) of certain fingers or toes (digits); and/or more than the normal number of digits (polydactyly). Carpenter syndrome is also known as ACPS type II.

Primary findings associated with Carpenter syndrome include premature closure of the fibrous joints (cranial sutures) between particular bones in the skull (craniosynostosis), characteristic facial abnormalities, and/or malformations of the fingers and toes (digits). However, associated features may vary in range and severity from one person to another, even among affected members of the same family.

In most instances Carpenter syndrome are caused by a mutation in the RAB23 gene. In a small subset of people, Carpenter syndrome is caused by a mutation in the MEGF8 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.

Carpenter syndrome appears to affect males and females in relatively equal numbers. More than 70 cases of the disorder have been recorded. In 10 patients that had sequence analysis for the disease causing gene, homozygosity (two copies) for the same nonsense mutation, (a change in the DNA that causes a change in the protein) was found. This is indicative of a founder effect in patients of northern European descent, which means that a high prevalence of a genetic disorder in an isolated or inbred population is due to the fact that many members of the population are derived from a common ancestor who had the disease causing mutation.

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

Pfeiffer syndrome is a rare genetic disorder characterized by abnormalities of the skull and facial (craniofacial) region and distinctive malformations of the fingers and toes (digits). Also known as acrocephalosyndactyly (ACS) type V, Pfeiffer syndrome is generally accepted to be the same disease entity as Noack syndrome (acrocephalopolysyndactyly [ACPS] type I). Researchers have described three major subtypes of Pfeiffer syndrome: i.e., Pfeiffer syndrome types I, II, and III. Findings that may be associated with all subtypes include premature closure of the fibrous joints between particular bones of the skull (craniosynostosis); unusually broad, deviating thumbs and great toes; and webbing or fusion (syndactyly) of certain fingers and toes. Pfeiffer syndrome may result from new (sporadic) genetic changes (mutations) or be inherited as an autosomal dominant trait. Evidence suggests that the disorder may be caused by specific mutations in a gene known as fibroblast growth factor receptor-2 (FGFR2) or another gene called fibroblast growth factor receptor-1 (FGFR1). Individuals with FGFR1 mutations usually have milder craniofacial features compared to those with FGFR2 mutations.


Castleman disease

Castleman disease describes a group of rare disorders with a wide range of symptoms. People with these conditions have enlarged lymph nodes that have a similar appearance when reviewed under the microscope. Castleman disease is first classified based on the number of regions of enlarged lymph nodes that have these abnormal features. Unicentric Castleman disease (UCD) involves a single enlarged lymph node or single region of enlarged lymph nodes whereas multicentric Castleman disease (MCD) involves multiple regions of enlarged lymph nodes. There are two subtypes of MCD. One subtype is caused by human herpesvirus-8 (HHV-8; also known as Kaposi sarcoma–associated herpesvirus). These cases are called HHV-8-associated MCD. The other subtype includes MCD patients who are negative for the HHV-8 virus, and the cause is unknown. These cases are called HHV-8 negative or idiopathic MCD (iMCD).

The spectrum of disease symptoms and severity is very broad, ranging from gradual enlargement of lymph nodes with mild symptoms to sudden, intense onset of symptoms due to life-threatening organ dysfunction caused by elevated cytokines such as interleukin-6 (IL-6). Symptoms of Castleman disease often overlap with symptoms of other more common illnesses. A Castleman disease diagnosis can therefore only be made with a lymph node biopsy that shows characteristic Castleman disease features and when other illnesses have been evaluated and excluded.

The exact cause of UCD and iMCD is not known. There are no known risk factors; there is no evidence of any food, lifestyle or environmental exposure associated with these diseases. There is no known report of a patient developing UCD or iMCD from contact with another individual with UCD or iMCD. Viruses, genetic mutations acquired over the course of life and inflammation have all been proposed as possible causes of UCD. Recent research suggests that acquired genetic mutations are the likely cause of UCD.

UCD and iMCD affect males and females in equal numbers and there are no known factors that increase the risk of UCD or iMCD. HHV-8-associated MCD affects males at an increased rate compared to females. All types of Castleman disease may affect individuals of any age. Persons with HIV are at increased risk of developing HHV-8-associated MCD. It is estimated that there are approximately 4,300-5,200 cases of CD diagnosed each year in the United States.

Symptoms of the following disorder can be similar to those of Castleman disease. Comparisons may be useful for a differential diagnosis:

Hodgkin lymphoma is a form of cancer of the lymphatic system. Tumors occur in the lymph nodes and/or the areas around the nodes. Symptoms associated with this disorder may include fever, night sweats, weight loss and/or enlarged or swollen lymph nodes. The tumors occur most often in the chest, stomach or spleen. Hodgkin lymphoma is usually progressive and may spread to lymph nodes located in other areas of the body. The exact cause of Hodgkin lymphoma is not known. (For more information on this disorder, choose Hodgkin as your search term in the Rare Disease Database.)


Cat-eye syndrome

Cat eye syndrome (CES) is a rare chromosomal disorder that may be evident at birth. Individuals with a normal chromosomal make-up have two 22nd chromosomes, both of which have a short arm, known as 22p, and a long arm, known as 22q. However, in individuals with CES, the short arm and a small region of the long arm of chromosome 22 (i.e., 22pter-22q11) are present four times (partial tetrasomy) rather than twice in cells of the body. In a small number of people with CES, the 22q11 region is present in 3 copies (partial trisomy).

The classic symptoms associated with CES are ocular coloboma, anal atresia and the minor ear defect preauricular skin tags or pits (see below for explanations). However, the syndrome is extremely variable, and it has been estimated that only 41% of patients with CES have this classic triad of symptoms (Berends et al, 2001). In general the abnormalities associated with CES tend to involve the eyes, ears, anal region, heart, and/or kidneys, but other organs may show involvement and some people show intellectual disability.

CES is a rare disorder associated with the presence of an extra chromosome fragment, in which the short arm (p) and a small portion of the long arm (q) of chromosome 22 are usually present in four copies (partial tetrasomy) rather than two copies in cells of the body. The diagnosis of CES is based on the presence of extra chromosomal material derived from chromosome 22, as described below.

CES has been recognized for more than a century. More than 100 cases have been described in the medical literature, including apparently sporadic and familial cases. Many more affected individuals exist but have not been described in the medical literature. However, the syndrome is very rare, and currently there are no accurate estimates of the incidence of CES in the population. Schinzel et al (1981) estimated an incidence of approximately one in 50,000 to one in 150,000 individuals in Northeastern Switzerland. Because some affected individuals develop few associated features, however, the disorder may in some people remain unrecognized. There is currently no way to estimate how underdiagnosed this syndrome is.

Symptoms of the following disorders may appear similar to those of CES, although the underlying defect would be different. Comparisons may be useful for a differential diagnosis:

The diagnosis of CES is based on the presence of extra chromosomal material derived from chromosome 22q11. (see Causes above).


Catel Manzke Syndrome

Catel-Manzke Type Palatodigital Syndrome

Although researchers have been able to establish a clear syndrome with characteristic or core symptoms, much about the disorder 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 a complete 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.

Alterations (mutations) in the TGDS gene have been identified in individuals with Catel-Manzke syndrome. 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.

The incidence and prevalence of Catel-Manzke syndrome is unknown. More than 33 individuals with the disorder have been reported in the medical literature. Since some individuals may go misdiagnosed or undiagnosed, determining the true frequency of Catel-Manzke syndrome in the general population is difficult. More males have been described with the disorder than females, but this may be a coincidence since so few individuals have been reported in the medical literature.

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

In some cases, Catel-Manzke syndrome may be suspected before birth (prenatally) based upon advanced imaging techniques such as ultrasound. In fetal ultrasonography, reflected sound waves may be used to create an image of the developing fetus, potentially revealing certain findings suggestive of Catel-Manzke syndrome (e.g., abnormal smallness of the jaw, malformation of the index fingers, etc.).


Caudal regression syndrome

The specific symptoms and severity of caudal regression syndrome can vary dramatically from one person to another. Caudal regression syndrome most likely represents a spectrum of disease ranging from cases with milder symptoms to cases with severe, disabling or potentially life-threatening complications. It is important to note that affected individuals may not have all of the symptoms discussed below and that one child’s experience will vary (sometimes dramatically) from another child’s. Parents of affected children should talk to their physician and medical team about their child’s specific case, associated symptoms and overall prognosis.

The exact cause of caudal regression syndrome 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 gene change (mutation). Most likely, caudal regression syndrome 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).

Caudal regression syndrome affects males and females in equal numbers. The incidence of the disorder has been estimated to be 1 in 5 per 100,000 live births. The disorder occurs with greater frequency among women with diabetes.

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

A diagnosis of caudal regression syndrome can often be made before birth (prenatally) usually using a 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 caudal regression syndrome.


Cavernous Malformation

欧洲非罕见：大脑海绵状畸形

Vascular malformations are localized collections of blood vessels that are abnormal in structure or number. Vascular malformations lead to altered blood flow and are not cancerous (nonneoplastic). In the past, researchers believed that most vascular malformations are present at birth (congenital). However, we now know that cavernous malformation lesions display some cancer-like qualities and can develop throughout the lifetime of the affected individual. The four most common types of vascular malformations are capillary telangiectasias, cavernous malformations, venous malformations, and arteriovenous malformations.

Individuals with cerebral cavernous malformations present with a wide variety of symptoms. Some affected individuals may have no symptoms at all while others may experience headaches or neurological deficits, including weakness in the arms or legs, problems with memory or balance, or difficulties with vision or speech. Hemorrhagic stroke and seizures are the most severe symptoms caused by cavernous malformations. Clinical symptoms vary by individual and are dependent on the location of the lesion(s) and on the propensity to bleed. Spinal cord cavernous malformations can cause numbness, weakness, paralysis, tingling, burning, or itching. Cavernous malformations of the spinal cord can also cause problems with bladder and bowel control.

Individuals with only one CCM and no affected relatives most likely have the sporadic (non-inherited) form of the illness. Those with multiple CCMs and/or a family history of the cavernous malformations are much more likely to have the familial type due to a change (mutation) in one of three genes, CCM1 (KRIT1), CCM2, or CCM3 (PDCD10).

In general, cavernous malformations can develop at any age and are present in males and females in equal numbers. Importantly, all ethnic populations are susceptible to the development of a CCM.

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

Magnetic resonance imaging (MRI) is now the standard of care for diagnosing cavernous malformations. Unless an individual has had a recent bleed, CT scans or angiography will not detect CCM lesions. For familial cases, molecular genetic testing for mutations in the CCM1, CCM2, and CCM3 genes is commercially available to confirm the diagnosis and is less expensive than MRI.


Central Core Disease

Central core disease (CCD) is a rare genetic neuromuscular disorder that is classified as a congenital myopathy, meaning that it is present at birth (congenital) and is a disorder that causes muscle weakness (myopathy). Affected infants have low muscle tone (hypotonia) resulting in abnormal floppiness, muscle weakness and a variety of skeletal abnormalities such as side-to-side curvature of the spine (scoliosis). Muscle weakness normally affects the proximal muscles, which are those muscles closest to the center of the body such as the muscles of the shoulder, pelvis and upper arms and legs. Affected infants may experience delays in acquiring motor milestones such as crawling or walking. Some individuals with CCD may be susceptible to developing malignant hyperthermia, a condition in which individuals develop adverse reactions to certain anesthetic drugs during surgical procedures. CCD may be very mild or may cause serious complications. Most cases are inherited in an autosomal dominant pattern and associated with stable or slowly progressive muscle disease and a good prognosis. Some cases are inherited in an autosomal recessive pattern and are more likely to be associated with severe complications.

The specific symptoms and severity of CCD vary greatly from person to person. Some individuals may develop very mild muscle disease that may go unnoticed or get a congenital myopathy incidental finding report from a next-generation sequencing (NGS) genetic test; others may develop serious muscle disease that can delay motor milestones or cause serious breathing (respiratory) difficulties. In most patients, muscle weakness in CCD is not progressive or only progresses very slowly.

Most cases of CCD are thought to be caused by specific variants (mutations) in the ryanodine receptor (RYR1) gene.

Central core disease affects males and females in equal numbers. The exact incidence and prevalence of CCD is unknown. CCD is believed to be the most common form of congenital myopathy, which as a group occurs in 6 out of every 100,000 live births.

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

CCD may be diagnosed based upon a thorough clinical evaluation, detection of characteristic physical findings, patient and family history and specialized tests. However, genetic testing is gradually becoming the first step in the diagnostic process, with other evaluations performed to confirm the genetic results. The disorder may sometimes be diagnosed during the first years of life; however, not infrequently, it may not be recognized until later during childhood, adolescence or adulthood following certain associated musculoskeletal abnormalities (see Symptoms).


Centronuclear myopathy

autosomal dominant centronuclear myopathy (AD-CNM)

The specific symptoms and severity of CNMs can vary greatly among the different forms and from one person to another. Some individuals may only develop mild symptoms; others develop serious life-threatening complications. Unlike the X-linked form, the autosomal dominant form of CNM is rarely fatal during childhood. The autosomal recessive forms can be severe or mild. The course of an individual case is often unpredictable. Because of the variable nature of these disorders, parents should talk to their child’s physician and medical team about their specific case, associated symptoms and overall prognosis.

Centronuclear myopathies are caused by a mutation in a specific gene. The autosomal forms are denoted by their associated gene. DNM2-related myopathy is caused by a mutation in the dynamin 2 (DNM2) gene and is inherited as an autosomal dominant condition. Some cases of DNM2-related CNM may occur spontaneously (sporadically) with no previous family history of the disorder (i.e. new mutations). BIN1-related CNM is caused by mutations to the amphiphysin 2 (BIN1) gene and is inherited as an autosomal recessive condition. RYR1-related CNM is caused by mutations to the skeletal muscle ryanodine receptor (RYR1) gene and is thought to be inherited as an autosomal recessive condition.

Autosomal forms of CNM affect males and females in equal numbers. The disorders are often present at birth, but in mild cases may go undiagnosed into adulthood. The exact incidence of these disorders is unknown. More than 100 families have been reported in the medical literature with DNM2-related CNM. Both BIN1-related CNM and RYR1-related CNM have been reported in fewer than 50 individuals respectively. Because these disorders may go undiagnosed or misdiagnosed, it is difficult to determine the true frequency of CNMs in the general population.

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

CNM should be suspected in newborns with hypotonia and muscle weakness and older children or adults with weakness in the arms and legs. A diagnosis is based upon identification of additional characteristic symptoms, a detailed patient and family history, a thorough clinical evaluation, and a variety of specialized tests.


Cerebellar Agenesis

Cerebellar agenesis is an extremely rare condition. Cerebellar agenesis is a descriptive term implying complete absence of the cerebellum, irrespective of its underlying cause (etiology). Usually, small remnants of the cerebellum are present; therefore, the term subtotal cerebellar agenesis is also used in the literature. It is now recognized that cerebellar agenesis can represent a primary disturbance of embryonic development (also called malformation), but it can also result from a secondary destruction of normally developed tissue (also called a disruption). (See the Causes section below for additional information). It is now established that the cerebellum is not only responsible for motor coordination (of muscles, trunk and limbs, tongue and the eye muscles), but also plays an important role in many non-motor functions, including learning, memory, language and behavior. Therefore, individuals with congenital as well as acquired cerebellar disorders often have learning disabilities, impaired executive functions and variable degree of cognitive impairments.

The signs and symptoms of cerebellar agenesis can vary greatly from one individual to another. According to the medical literature, some individuals with cerebellar agenesis have had only mild symptoms. In fact, in some reported cases, it has been claimed that motor function may be almost normal, perhaps due to partial compensation from other areas of the brain. Reports in the medical literature discuss individuals with cerebellar agenesis who had a normal lifespan, attended regular schools and found employment and lived productive though often simple lives.

The etiology of cerebellar agenesis is varied (heterogeneous). Acquired (prenatal/perinatal) causes include cerebellar destruction caused by hemorrhage, lack of or diminished blood flow (ischemia), prenatal infection (e.g., cytomegalovirus, Zika virus) or other factors. This has been documented in a minority of children with spina bifida (myelomeningocele), also called vanishing cerebellum in myelomeningocele. It is being increasingly recognized in premature babies with very low birth weight (also called cerebellar disruption of prematurity) and is often accompanied by additional anomalies of the brain.

Cerebellar agenesis appears to affect males and females in equal numbers. The exact incidence and prevalence of the disorder in the general population is unknown. Congenital isolated cerebellar agenesis is considered an extremely rare occurrence.

Cerebellar agenesis is defined by neuroimaging and should not be confused with other more prevalent malformations of the cerebellum (e.g., Dandy-Walker malformation and Joubert syndrome) if the detailed neuroimaging pattern is taken into account.

After birth (postnatally) the definite diagnosis of cerebellar agenesis is based on the neuroimaging findings with MRI (magnetic resonance imaging); it cannot be made on clinical grounds. Before birth (prenatally) the diagnosis of cerebellar agenesis is not reliably possible by ultrasound or fetal MRI. Babies have been described with normal brain ultrasound at 20-25 weeks of gestation, with subsequent destruction of the cerebellum during later stages of pregnancy.


Creatine deficiency syndrome

Cerebral creatine deficiency syndromes (CCDS) are inborn errors of creatine metabolism which interrupt the formation or transport of creatine. Creatine is necessary to render available the energy of adenosine triphosphate (ATP) to all cells in the body. Creatine is essential to sustain the high energy levels needed for muscle and brain development.

The severity of CCDS varies from patient to patient. Global developmental delays affect all children with these disorders and may be the first sign, appearing before other symptoms. Speech delay may be particularly severe and is present in all affected children. Intellectual disability of variable severity is typically present in all older children and adults.

CTD is estimated to account for 1-2% of all unexplained X-linked intellectual disabilities. In regard to GAMT deficiency, there have been estimations from 1 out of 250,000 to 1 out of 550,000. As of 2015, there have only been 110 individuals with GAMT deficiency diagnosed worldwide. The prevalence of AGAT is not known because there have been too few studies on record.

CCDS patients are frequently misdiagnosed with cerebral palsy as infants and toddlers. Children are often misdiagnosed with autism or global developmental delays.

CCDS screening is non-invasive.Testing in both urine and plasma is recommended for all three types of CCDS by measuring the concentration of creatine (Cr), guanidinoacetate (GAA) and creatinine (Crn). Follow up genomic testing for specific genes and brain MRI with spectroscopy may be ordered to confirm a CCDS diagnosis. GAMT deficiency is also part of the recommended uniform newborn screening panel and children can be identified at birth in states that have adopted it.


脑叶酸转运缺陷所致神经退行性综合征

Neurodegenerative syndrome due to cerebral folate transport deficiency

Cerebral folate deficiency is a neurological syndrome in which development is usually normal in the first year of life, but at approximately 2 years of age, affected children start to lose mental and motor skills (psychomotor regression). Some early symptoms are intellectual disability, speech difficulties, and development of recurrent seizures in a third of affected children. Motor issues such as tremors and lack of muscle control or coordination of voluntary movements (ataxia) can become severe. Cerebral folate deficiency occurs because of a deficiency of vitamin B folate (vitamin B9) in the brain caused by a low level of 5-methyltetrahydrofolate (5MTHF) in the cerebrospinal fluid due to a disruption in the function of the folate receptor alpha (FRA). The function of the FRA can be disrupted by several causes. The most common etiology involves one of two autoantibodies blinding to the FRA resulting in a disruption in its function. The FRA is highly dependent on mitochondrial function leading to disrupting in FRA function in mitochondrial and other metabolic disorders. Lastly, rare mutation in the FOLR1 gene can result in an autosomal recessive genetic condition which disrupts FRA function. This condition can be treated with leucovorin calcium (aka folinic acid).

The symptoms of cerebral folate deficiency may begin as early as four to six months of age with irritability and sleep problems (insomnia). Delays in development may be noted including slow head growth, low muscle tone (hypotonia), ataxia, loss of voluntary movement (dyskinesia), constant contracted muscles (spasticity), speech complications, and epilepsy. Additional signs may involve visual disturbances, hearing loss and autistic features.

Cerebral folate deficiency is caused by a disruption in the function of the folate receptor alpha (FRA).  Folate receptor alpha is located inside the cell membrane and binds to folate, which allows it to be transported into the cell. The protein is created in greatest quantities in the choroid plexus in the brain. The choroid plexus releases cerebrospinal fluid that protects the brain and spinal cord. Folate receptor alpha moves folate through the choroid plexus and into the cerebrospinal fluid that will spread to the brain. Folate is important for constructing myelin and chemical messengers (neurotransmitters) that transmit signals in the brain. The absence of folate in the brain triggers the neurological complications associated with this condition.

Fewer than 20 individuals with cerebral folate deficiency have been reported in scientific literature. The exact prevalence of this condition is unknown.

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

Folinic acid-responsive seizures (FARS) is a condition characterized by myoclonic or clonic seizures, trouble breathing (apnea), and irritability within five days after birth. Brain imaging will demonstrate brain atrophy and numerous white matter abnormalities. FARS is caused by mutations in the ALDH7A1 gene.


Cerebrocostomandibular Syndrome

Cerebrocostomandibular syndrome (CCMS) is a disorder that involves a small chin (micrognathia), an opening in the roof of the mouth (cleft palate), a narrow chest, missing ribs, gaps between ribs, and breathing and feeding difficulties. Other common features include scoliosis, developmental delay or intellectual disability, and hearing loss. Other medical problems can be seen as well. Breathing difficulties can lead to death in childhood, and most babies born with CCMS need surgery in the first year of life to help them breathe. These surgeries can include inserting a breathing tube directly into the throat (tracheostomy), surgeries to make the jaw or chest larger, surgery to insert a feeding tube into the stomach, and surgery to repair the hole in the roof of the mouth. CCMS is caused by changes in the SNRPB gene. A damaging change in one of a person’s two copies of the gene can cause the disorder. Most of the time, these changes are new to a child, and do not show up in family members. Rarely, a parent may have the change as well, and may show no symptoms. The diagnosis of CCMS is usually made in the first year of life based on the clinical features (such as a small jaw, rib gaps, narrow chest, and/or breathing difficulties). Imaging techniques like X-ray or MRI may be needed to take a better look at the ribs and spine. Genetic testing can confirm the diagnosis and help parents to better understand the risk for having another child with the disorder.

CCMS is an extremely rare inherited disorder. Its features mainly stem from problems in how the jaw and ribs are formed. People with CCMS have a small jaw with a small chin and mouth (micrognathia). This can cause the tongue to be in the wrong position (glossoptosis). In turn, the abnormal position of the tongue can cause a gap to form in the roof of the mouth (cleft palate) during development in the womb. This set of features (micrognathia, glossoptosis, and cleft palate) is often called Robin sequence. These features can cause feeding difficulties. Nearly all people with CCMS have a small jaw, and most have cleft palate.

The gene that is changed in patients with CCMS is the SNRPB gene. It is possible that there are other rarer causes of CCMS that have not been discovered yet, since some patients with CCMS do not seem to have a change in SNRPB.

CCMS is a very rare disorder that is apparent at birth (congenital). The disorder appears to affect males and females in equal numbers. Over 80 patients have been reported in the medical literature.

Symptoms of the following disorders can be similar to those of cerebrocostomandibular syndrome (CCMS). Comparisons may be useful for to distinguish between diagnoses:

In some patients, CCMS may be diagnosed before birth (prenatally) using advanced imaging techniques such as ultrasound. Fetal ultrasounds use reflected sound waves to make a picture of the developing fetus, and can show signs of CCMS (e.g., short, improperly formed ribs; small jaw; etc.).


Cerebrotendinous xanthomatosis

The presentation of CTX is highly variable and is associated with a wide range of potential abnormalities. Originally, the disorder was believed only to be a neurological disorder of abnormal fat (lipid) storage not associated with liver disease. It is now known that CTX can occasionally present in childhood with cholestatic liver disease that can be severe or can be mild and resolve on its own in individuals who may later develop other complications of the disorder such as neurological disease. Cholestatic liver disease refers to the interruption or suppression of the flow of bile from the liver (cholestasis). Features of cholestasis include yellowing of the skin, mucous membranes and whites of the eyes (jaundice), failure to thrive, and growth deficiency. Enlargement of the liver (hepatomegaly) and/or spleen (splenomegaly) may also occur.

CTX is caused by a disease-causing (pathogenic) variant in the CYP27A1 gene. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a pathogenic variant of a gene occurs, the protein product or enzyme 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. In CTX, the gene variant is inherited in an autosomal recessive manner.

Recent estimates place CTX incidence ranging from 1:134,970 to 1:461,358 in Europeans, 1:263,222 to 1:468,624 in Africans, 1:71,677 to 1:148,914 in Americans, 1:64,267 to 1:64,712 in East Asians and 1:36,072 to 1:75,601 in South Asians.. Despite this, only around three hundred affected individual of CTX have been described worldwide. This suggests many cases may go undiagnosed or are misdiagnosed. Affected individuals have been reported in the USA, Israel, Italy, Japan, the Netherlands, Belgium, Brazil, Canada, France, Iran, Norway, Tunisia, Spain, China and Sweden. Populations with a higher prevalence of CTX exist, for example in an isolated Israeli Druze community a carrier frequency of 1:11 for the deleterious c.355delC variant was determined, leading to an estimated prevalence of CTX at 1:440 individuals.

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

CTX is diagnosed based on a thorough clinical evaluation, a detailed patient and family history, identification of characteristic clinical findings, and specialized tests including genetic testing and biochemical tests on blood and urine.


Cervical Dystonia

focal dystoniaidiopathic cervical dystonia

Cervical dystonia, also known as spasmodic torticollis, is a rare neurological disorder that originates in the brain. It is the most common form of focal dystonia in an office setting. Cervical dystonia is characterized by involuntary muscle contractions in the neck that cause abnormal movements and postures of the neck and head. In some cases, these abnormal contractions may be sustained or continuous; in others, they may be present as spasms that can resemble tremor. The severity of cervical dystonia can vary, but the disorder can cause significant pain and discomfort as well as difficulty due to the abnormal postures. It can affect quality of life and activities of daily living including employment. Cervical dystonia typically begins in middle age, and rarely begins in adolescence and young adulthood. The cause of cervical dystonia is unknown, although a genetic susceptibility is thought to underlie some cases. If cervical dystonia begins in infancy or early childhood, secondary causes should be investigated.

The symptoms of cervical dystonia may begin slowly and can involve any of the muscles of the neck. The head posture in cervical dystonia can vary. The most common abnormal posture associated with cervical dystonia is the twisting of the chin toward a shoulder so that the head rotates sideways (torticollis). Other abnormal postures associated with cervical dystonia including anterocollis, in which the head tips forward; retrocollis, in which the head is tilted backward; or laterocollis, in which the head tilts toward one side. There can also be shifting of the head on the shoulders in a forward (anterior sagittal shift) or backward (posterior sagittal shift) direction. Often cervical dystonia is complex and combines several angles of head movement. In some people with isolated CD, there may also be a postural tremor of the hands. Symptoms of cervical dystonia vary over the course of the disorder. Studies of the natural history of CD are needed to better understand the natural history of this disorder. Symptoms may temporarily worsen with stress or excitement. The dystonia can be activated by certain postures or positions. This varies in individual patients. Symptoms may improve with the performance of sensory tricks, such as touching the cheek or the back of the head. A small percentage of individuals experience a spontaneous recovery (remission) after symptom onset. This remission is often temporary, lasting days to years, with recurrence of symptoms. It is likely that less than 1 percent of affected individuals have permanent remissions.

Cervical dystonia is classified as an isolated dystonia if there are no other associated abnormal findings, such as spasticity, Parkinsonism or ataxia. Most isolated cervical dystonia had no identifiable underlying causes. However, in some cases, cervical dystonia can arise from another underlying cause and be considered secondary (occurring as consequence of another disorder or condition). In most cases, isolated cervical dystonia is idiopathic although a genetic susceptibility may be present as evidenced by a positive family history in approximately 10-25% of cases. Cervical dystonia is associated with changes (mutations) in several genes (GNAL, THAP1, CIZ1, ANO3 genes) and several possible environmental factors. However, at this time there is no gene test that is recommended for clinical purposes in people with cervical dystonia. Some cases of cervical dystonia may have an identifiable cause (secondary cervical dystonia). In these cases, cervical dystonia may develop due to the use of certain drugs such as anti-psychotics or certain nausea medications with dopamine receptor blocking activity. In most secondary cases, such as those due to toxins or degenerative brain diseases, there are additional signs and symptoms other than cervical dystonia. Whether trauma to the neck could cause cervical dystonia remains controversial. Cervical dystonia is a neurological disorder. However, there are some non-neurological conditions that may mimic cervical dystonia. In children with slippage of the vertebrae in the neck (atlanto-axial subluxation), there may be a twisting of the head that is very painful and requires specialized orthopedic treatments. Some infants are born with a shortening of one of the muscles in the neck (congenital infantile torticollis) that causes a head turn. In some children with esophageal reflux, there can also be posturing of the head. There are additional conditions, including functional movement disorders that may appear similar to cervical dystonia but are non-neurologic in origin.

Cervical dystonia affects women approximately twice as often as men. It is the most common form of focal dystonia in an office setting. Cervical dystonia may affect individuals of any age, but typically develops in people between 40 and 60 years of age. Cervical dystonia affects people of all ethnic backgrounds. The exact incidence or prevalence of cervical dystonia in the general population is unknown but is estimated to be about 60,000 people in the United States.

A diagnosis of cervical dystonia is based upon clinical examination, a detailed patient history, and knowledge of the disorder. No specific laboratory or imaging test confirms a diagnosis of cervical dystonia. There are no abnormalities in laboratory or imaging tests. Magnetic resonance imaging (MRI) of the brain is normal, and MRI of the neck does not help with the diagnosis unless compression of the spinal cord is suspected. Electromyography is not indicated unless there are additional signs of nerve irritation.


Neutral lipid storage disease with ichthyosis

Chanarin-Dorfman syndrome can affect many systems. All patients have skin findings that are usually present at birth: redness, fine scaling, dark pigmentation and severe itching which leads to scratching and skin-picking (excoriation). The skin appearance is referred to ichthyosiform nonbullous erythroderma. Patients also have liver disease with lipid storage which can lead to liver failure. About 60% of patients also have muscle problems. They have slowly progressive weakness of the proximal arms and legs. When the muscles are affected they release their enzymes in the blood, which can be detected by the presence of a CK elevation. Exercise intolerance has never been reported, but many patients reported early fatigability.

Chanarin-Dorfman syndrome is caused by changes (mutations) in the ABHD5 gene located on chromosome 3. This gene produces a protein involved in fat metabolism called CGI-58. This protein is called a co-factor because it helps the activity of the main enzyme, which is adipose triacylglycerol lipase (ATGL). The function of this enzyme is to break down a type of fat called triacylglycerol (TAG). This process is disturbed when either the enzyme or the helper protein doesn’t work properly. When the fat (triacylglycerol) cannot be broken down, it accumulates in various parts of the body as lipid droplets and causes different symptoms. This is what happens in a group of disorders called ‘neutral lipid storage disease’. It comprises two entities:

There have been over 128 patients reported worldwide, especially in the Mediterranean and Middle East region. Many of the reported patients have been children born to couples who are related by blood (consanguineous). This condition affects males and females equally.

There are a few disorders other than Chanarin-Dorfman syndrome that have similar skin changes at birth and involve many systems. Among those, there is Neherton syndrome, Sjögren-Larsson syndrome, Conradi-Heunermann-Happle syndrome, Ichthyosis follicularis, atrichia and photophobia (IFAP) syndrome and Refsum syndrome.

Newborns usually have characteristic skin changes (ichthyosiform changes), but the combination of skin appearance, liver abnormalities and other system involvement is what raises the suspicion for Chanarin-Dorfman syndrome. The suspected diagnosis is made with a peripheral blood smear test, where fat deposits (lipid droplets) are seen in white blood cells (called Jordan’s anomaly). Molecular genetic testing for mutations in the ABHD5 gene is available to confirm the diagnosis.


Iridocorneal endothelial syndrome

Chandler’s syndrome (CS) is a rare eye disorder in which the endothelium, the single layer of cells lining the interior of the cornea, proliferates causing corneal edema, distortion of the iris, and unusually high pressure in the eye (glaucoma). CS is one of three syndromes affecting the eyes (progressive iris atrophy and Cogan-Reese syndrome are the other two) that make up the iridocorneal endothelial syndrome (ICE syndrome). The spectrum is an acquired, unilateral disorder, which typically occurs in early to middle adulthood and predominantly affects women.  Chandler’s syndrome is the most commonly encountered clinical variant of this spectrum.

Chandler’s syndrome is characterized by proliferation of the cells lining the cornea, swelling of the cornea with distortion of the iris and glaucoma (optic nerve damage from high pressure) within the eye.

The single layer of cells lining the inside of the surface of the cornea is known as the endothelium. One of the roles played by the endothelium is to pump aqueous humor (fluid inside the eye) from the cornea. If the behavior of the endothelium is interrupted (as in Chandler’s syndrome), the pumping action fails, and fluid accumulates in the cornea (corneal edema) resulting in blurred vision. In addition, the abnormal endothelial cells can migrate as a membrane over adjacent structures, including the iris and the trabecular meshwork (the drainage canal of the eye). Contraction of this membrane leads to associated iris changes (corectopia) and iridotrabecular synechiae causing obstruction of aqueous outflow in the trabecular meshwork resulting in secondary glaucoma.

Chandler’s syndrome is a very rare disorder that affects females more often than it does males. The disorder usually appears during young adult to middle aged years. However, its occurrence in a child and a teenager has been reported. ICE syndrome has been described in different ethnic groups, although the prevalence of the 3 clinical variants may vary among ethnicities.

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

Progressive (or essential) iris atrophy is a very similar disorder to Chandler’s syndrome and their symptoms may even overlap. Progressive iris atrophy is characterized by gross distortion of the pupil eye and the development of holes in the iris. This condition also causes increased intraocular pressure and corneal edema. If left untreated, vision loss may occur.


Charcot-Marie-Tooth Disease

腓骨肌萎缩症/遗传性运动感觉性神经病

Charcot-Marie-Tooth (CMT) disease is a group of disorders in which the motor and/or sensory peripheral nerves are affected, resulting in muscle weakness and atrophy as well as sensory loss. Symptoms occur first in the distal legs and later in the hands. The nerve cells in individuals with this disorder are not able to send electrical signals properly because of abnormalities in the nerve axon or abnormalities in the insulation (myelin) around the axon. In CMT specific gene mutations are responsible for the abnormal function of the peripheral nerves. In many forms of CMT these genes are known and in others, while the condition is known to be inherited, the specific gene has not yet been identified.

Symptoms of CMT disease usually begin gradually in adolescence, but can begin earlier or later. In almost all patients, the longest nerve fibers are affected first. Over time, affected individuals may lose the normal use of their feet, hands, legs and arms. Common early signs and symptoms can include decreased sensitivity to heat, touch or pain, muscle weakness in the hand, foot or lower leg, trouble with fine motor skills, high-stepped gait (foot drop), loss of muscle mass in the lower leg, frequent tripping or falling, hammertoe, high foot arch and flat feet. Stretch reflexes may be lost. The disease is slowly progressive and variable, and those affected may remain active for years and live a normal life span. In the most severe cases, breathing difficulties can hasten death.

CMT is known to be a genetic condition caused by genes that have abnormal changes affecting their function. There are now over 100 genes that are known to be responsible for various forms of CMT. A single gene, PMP22, when duplicated, is the cause of around 50% of cases of CMT, while damaging changes in some genes that cause CMT can be extremely rare and found only in a few families. In around 40% of cases of CMT, no responsible gene has yet been identified.

CMT is found worldwide in people of all races and ethnic groups. Prevalence rate estimates from epidemiological studies are highly variable due in part to the wide variation of clinical symptoms and different disease forms as well as discrepancies in what conditions are included within CMT. Recent prevalence estimates range from 9 to 28 per 100,000. Symptoms of CMT usually begin gradually in adolescence, early adulthood or middle age.

Peripheral neuropathy is part of at least 100 inherited syndromes, though it is typically overshadowed by other manifestations. Expert opinions differ on exactly which disorders are similar to but separate from, the same as, or have some overlap with conditions within the CMT group of disorders.

The diagnosis of CMT disease can be challenging. Diagnosis is based on physical symptoms, family history and clinical tests. Clinical tests include nerve conduction velocity (NCV) which measures the speed at which impulses travel along the nerves and electromyogram (EMG) which records the electrical activity of muscle cell. With recent advances in molecular genetic testing using both deletion duplication analysis and next generation sequencing (NGS) for patients with a clinical diagnosis of CMT, a genetic cause can be found in about 60% of patients. For CMT1 a genetic cause can be identified in 56-92% of patients. For axonal CMT, genetic causes can be found 17-44% of the time. Panels to test multiple genes can include from 7 to 150 genes, while abnormalities in 4 genes, (PMP22 duplication, GJB1, MFN2, and MPZ) account for about 90% of these genetic diagnoses.


CHARGE syndrome

CHARGE syndrome is a rare disorder that arises during early fetal development and affects multiple organ systems. The CHARGE acronym comes from the first letter of some of the more common features seen in these children: (C) = coloboma (usually retinochoroidal) and cranial nerve defects (80-90%); (H) = heart defects in 75-85%, especially tetralogy of Fallot; (A) = atresia of the choanae (blocked nasal breathing passages) (50-60%); (R) = retardation of growth (70-80%) and development; (G) = genital underdevelopment due to hypogonadotropic hypogonadism; (E) = ear abnormalities and sensorineural hearing loss (>90%). In addition to the CHARGE features above, many children with CHARGE syndrome have other features, including characteristic facial features: asymmetric facial nerve palsy, cleft lip or palate, esophageal atresia (blind-ending food pipe) or tracheoesophageal fistula (connection between the windpipe and the food pipe). The symptoms of CHARGE syndrome vary greatly from one child to another.

CHARGE syndrome affects multiple organ systems, resulting in multiple problems apparent at birth. Other characteristics of CHARGE syndrome may not become apparent until later in life. The diagnosis of CHARGE syndrome should be made by a medical geneticist based on the presence of at least one major criterion and several minor and/or occasional criteria of CHARGE syndrome (see below).

The cause of CHARGE syndrome is usually a new variant (change) in the CHD7 gene, or rarely, genomic alterations in the region of chromosome 8 (8q12.2) where the CHD7 gene is located. CHD7 function is required for the development of the retina and cranial motor neurons. Over 70-90 % of typical CHARGE syndrome patients have variants in the CHD7 gene.

CHARGE syndrome is a rare disorder, affecting 1:10,000-15,000 live births. It affects males and females in equal numbers and has been seen in all races and on every continent. There are far more cases of CHARGE syndrome than those described in the medical literature. Many cases are misdiagnosed or undiagnosed, especially in children with fewer problems. Although many features of CHARGE syndrome are apparent at birth, some features will not become apparent for weeks, months or perhaps years later. The recurrence risk of CHARGE syndrome for parents with one affected child is low, around 2-3 percent. The recurrence risk for an adult with CHARGE syndrome to have an affected child may be as high as 50 percent.

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

A medical geneticist or other specialist familiar with CHARGE syndrome should do a complete physical exam and order tests to look for the major and minor features of CHARGE syndrome listed above.


Chediak Higashi Syndrome

Chediak-Higashi syndrome (CHS) is a rare, inherited, complex, immune disorder that usually occurs in childhood characterized by reduced pigment in the skin and eyes (oculocutaneous albinism),  immune deficiency with an increased susceptibility to infections, and a tendency to bruise and bleed easily. Neurological deficits are also common. CHS is transmitted as an autosomal recessive genetic condition.

The symptoms of CHS may be apparent during early infancy. Hair is typically blond or light brown with a silvery tint. Affected children may be abnormally sensitive to light (photosensitivity) because of the reduced pigment in the eyes and skin, and may exhibit rapid, involuntary, eye movements (nystagmus). More important and more serious are the effects of CHS on the patient’s immune and nervous systems.

Chediak-Higashi syndrome is inherited as an autosomal recessive genetic trait. The responsible gene has been mapped to chromosomal locus 1q42.1-q42.2 and is known as LYST gene.

Chediak-Higashi syndrome is a very rare disorder that affects males and females in equal numbers. It is often obvious at birth or shortly thereafter. There does not appear to be a higher risk for any particular ethnic or racial group. There are less than 500 cases of the disease on record. 85% of affected individuals progress to the accelerated phase.

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

Griscelli syndrome, also known as Chediak-Higashi-like syndrome, is a rare inherited disorder characterized by partial albinism and abnormalities of platelets and white blood cells. The symptoms are similar to those of CHS.  There are 3 different types of Griscelli syndrome. Type 2 is very similar to CHS as patients have reduced pigment and immune abnormalities. These patients are also at risk for the accelerated phase. On laboratory analysis, the white blood cells do not have the giant granules like those seen in Chediak- Higashi syndrome; therefore, the diagnoses are made differentially based on these WBC granules.


Chiari Malformations

The signs and symptoms of Chiari malformation can vary greatly from one person to another. Some individuals may not have any symptoms (asymptomatic) upon diagnosis as an incidental finding; others may have serious manifestations such as neurological deficits. Symptoms may go through periods of exacerbation and remission. Chiari malformations are highly variable conditions that will affect every individual person differently. Specific symptoms can occur in different combinations and generally reflect dysfunction of the cerebellum, the brainstem, the spinal cord and lower cranial nerves. 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.

The exact cause of Chiari malformations is unknown. These malformations and the associated central nervous system abnormalities are extremely complex. Chiari malformations appear to be due to a developmental failure of the brainstem and upper spinal cord (cervical region) within a developing fetus with no known cause. Some investigators believe that an abnormally small posterior fossa, which is the space in which the cerebellum normally resides, contributes to the development of a Chiari malformation. In many individuals, the posterior fossa is abnormally small, which may lead to the growing brain being pushed down through the normal opening (foramen magnum) where the brain and spinal cord meet.

Chiari malformations affect individuals of every race and ethnicity. Some studies suggest that females are affected more often than males. In most cases, a Chiari malformation is thought to be present at birth (congenital), although some cases may not be discovered until adulthood (sometimes incidentally when a brain scan is done for another reason). The incidence and prevalence of Chiari malformations are unknown. Some cases may go undiagnosed or misdiagnosed, making it difficult to determine the true frequency of these disorders in the general population.

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

A diagnosis of a Chiari malformation is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a neurological exam that includes a variety of specialized tests including specialized imaging techniques.


Chikungunya

Chikungunya is a rare viral infection transmitted by the bite of an infected mosquito. It is characterized by a rash, fever, and severe joint pain (arthralgias) that usually lasts for three to seven days. Because of its effect on the joints, Chikungunya has been classified among the Arthritic Viruses. It primarily occurs in tropical areas of the world.

The early symptoms of Chikungunya include fever, headache, and joint pain (arthralgias) that may be so severe that they may be disabling.  The knees, elbows, wrists, ankles, and/or fingers are generally effected.  Joint pain increases with movement and is worse in the morning.  However, it may take several weeks before the symptoms improve.  Chikungunya is not associated with permanent joint damage.

Chikungunya is an infectious tropical disease caused by a virus that belongs to the group of A arboviruses.  It is transmitted by various species of mosquitoes.  Monkeys may also be infected with this virus.  Some cases of this infection appear to have occurred through casual human to human contact, but it is not known how it is transmitted among humans.

Chikungunya is a viral disease that affects males and females in equal numbers.  It primarily affects children and young adults in Africa, Southeast Asia, and India.  A large outbreak of Chikungunya occurred in Tanganyika, Africa in 1953. This disorder is rare outside of tropical areas of the world.

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

O’Nyong-Nyong Virus is an infectious disease that first appeared in Africa in the late 1950’s.  The symptoms are similar to those of Chikungunya and include fever, joint pain, and skin rashes.  People with O’Nyong-Nyong Virus usually have swollen lymph nodes.  Typically the fever is short in duration and the joint pain is mild.

The diagnosis of Chikungunya may be confirmed by a specialized blood test that detects immune responses to the virus (ELISA test). The symptoms of Chikungunya improve spontaneously after several weeks. There is no specific treatment. However, bed rest and antiinflammatory medications (i.e., ibuprofen) may be useful. As with other viral diseases, antibiotics are not effective in treating this disease.


Cholangiocarcinoma

Cholangiocarcinomas are cancers that arise from the cells lining the bile duct. They originally were grouped according to the location from which they arise as intrahepatic (arising from the bile ducts inside the liver), perihilar (arising from the bile ducts where they exit the liver), or distal (arising from the bile ducts outside the liver). Gallbladder cancers are also biliary tract cancers but arise from the cells lining the inside of the gallbladder.

Most patients have no symptoms, particularly when the cancer is at an early stage. Occasionally biliary tract cancers are diagnosed incidentally when a CT or MRI scan is done for another reason, or when the gallbladder is removed due to symptomatic gallstones. Patients may have non-specific symptoms including weight loss, abdominal pain, fevers, night sweats and fatigue. Distal and perihilar cholangiocarcinoma or gallbladder cancers more frequently cause patients to develop jaundice due to tumor or lymph nodes blocking a major bile duct.

Most cases of biliary tract cancer are sporadic, with no identifiable predisposing factors. There are several known risk factors for development of cholangiocarcinoma, however, including liver cirrhosis, hepatitis B and C, biliary tract stones, liver fluke infections, a congenital anatomical abnormality called a choledochal cyst and the chronic condition of inflamed bile ducts also called primary sclerosing cholangitis. Exposure to some industrial chemicals such as nitrosamines, dioxin, asbestos and polychlorinated biphenyls are also thought to increase the risk of developing cholangiocarcinoma. In the U.S., gallbladder cancer is commonly associated with the presence of long-standing gallstones resulting in calcification of the gallbladder wall or porcelain gallbladder. Gallbladder polyps are also associated with increased risk of gallbladder cancer. The incidence of bile duct cancers differs worldwide, likely reflecting both differing genetic predisposition and variable exposure to known risk factors.

Approximately 20,000 new cases of bile duct cancers are diagnosed in the U.S. each year, of which over 12,000 are gallbladder cancers and distal/perihilar cholangiocarcinoma and 6,000 are intrahepatic cholangiocarcinoma. The incidence of intrahepatic cholangiocarcinoma in the U.S. is approximately 1.49 per 100,000 people.  Recently, the incidence of bile duct cancers has been increasing. This trend may be explained by the improved diagnostic techniques including imaging, increased disease awareness among physicians and wider acceptance of liver biopsy by patients.  Unlike intrahepatic and extrahepatic bile duct cancer, gallbladder cancer is more common in females than males, and in some countries the rates are three times higher for females. Certain geographic areas have a high incidence of gallbladder cancer, including Chile, Bolivia and India. A high incidence also has been reported in North American Native Americans and Mexican Americans.

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

A diagnosis of cholangiocarcinoma or gallbladder cancer is based on identification of characteristic symptoms (if present), a detailed patient history, clinical examination and several specialized tests including blood tests, imaging tests and endoscopic procedures. Either CT or MRI scans may be used to assess the tumor size and to look for blockage of the bile ducts and sites of spread. Endoscopic retrograde cholangiopancreatography (ERCP) may be used to insert a stent into a blocked bile duct to relieve jaundice. A biopsy is usually required to confirm the pathologic diagnosis and may be obtained by a CT or endoscopic ultrasound (EUS) guided biopsy. It is critical that genetic testing using next generation sequencing be performed on the biopsy sample. Some patients with gallbladder cancer are incidentally diagnosed following elective removal of their gallbladder due to gallstones, where the cancer is only detected on pathologic examination.


Cholera

Cholera is an acute infectious disease caused by the bacterium vibrio cholerae, which lives and multiples (colonizes) in the small intestine but does not destroy or invade the intestinal tissue (noninvasive). The major symptom of cholera is massive watery diarrhea that occurs because of a toxin secreted by the bacteria that stimulates the cells of the small intestine to secrete fluid. There are several strains of V. cholerae and the severity of the disease is based on the particular infectious strain.

The symptoms of cholera vary according to the severity of the disease.  Some infected individuals may only experience a few days of mild diarrhea.  Others may have more serious symptoms and prolonged diarrhea may be so severe that there is excessive fluid loss leading to shock.  Rapid onset of life- threatening complications may occur in very severe cases.

Cholera is caused by the bacterium vibrio cholerae which is a rod-shaped gram negative organism.  There are several different types of this bacteria which can produce mild or more severe forms of the disease.  The symptoms of cholera develop due to the release of a toxin (Vibrio c. 01) by the bacteria.

Outbreaks of cholera are typically limited to specific geographic areas (endemic) in India and parts of the Middle East, Asia, South America, and Africa.  The disease affects males and females in equal numbers.  Children are more susceptible to cholera than adults, especially those children under the age of five years.  Major outbreaks of cholera usually occur during the warmest part of the year.  Cholera occasionally spreads to Europe, Japan, Australia, and South America where epidemics can occur any time of the year and affect persons of all ages equally.

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

Escherichia coli are bacteria found in the intestines of humans and many animals.  They usually do not cause disease (nonpathogenic) but certain strains may cause acute inflammation in some cases.  When these infections occur in the small intestine, symptoms may include bloody and watery diarrhea accompanied by fever.  When severe infection occurs in newborns, it is called Winckel’s Disease and may cause overwhelming infection of the blood stream (septicemia).  An outbreak of E. coli infection from under cooked hamburger meat occurred in the Unites States during the early 1990’s.  Several children died from this infection; others experience varying symptoms.

The diagnosis of cholera is confirmed by clinical evaluation and the isolation of the V. cholerae from cultures grown with samples of fresh stool from an infected individual.


Cholesteryl ester storage disease

acid cholesteryl ester hydrolase deficiency, type 2

The symptoms and severity of CESD are highly variable. Some individuals may develop symptoms during childhood; others may have extremely mild cases that cause few symptoms. Still other individuals may not have any noticeable symptoms (asymptomatic) and may go undiagnosed until well into adulthood. It is important to note that affected individuals will not have all of the symptoms discussed below. The disorder often goes misdiagnosed or undiagnosed, making it difficult to determine its true frequency in the general population.

CESD is caused by pathogenic variants in the lysosomal acid lipase (LIPA) gene. The LIPA gene contains instructions for producing the enzyme lysosomal lipase acid. This enzyme is essential for breaking down (metabolizing) certain fats in the body, especially cholesteryl esters (a form of cholesterol) and to a lesser degree triglycerides. Without proper levels of this enzyme, these fats abnormally accumulate in and damage various tissues and organs of the body. Variants in the LIPA gene result deficient levels of active, functional LIPA enzyme. There is no direct linear relation between residual LAL activity and the severity of the disease.

CESD affects males and females in equal numbers. Approximately 50 cases have been reported in the medical literature. It is likely that there are more patients with CESD who have been misdiagnosed with other conditions.

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

A diagnosis of CESD may be suspected based upon identification of characteristic symptoms such as abnormally enlarged liver. A diagnosis may be confirmed by a thorough clinical evaluation, a detail patient history (including family history) and specialized tests that reveal deficient activity of the LIPA enzyme in certain cells and tissues of the body. Testing for CESD is easy to perform and reliable through the measurement of enzyme activity in circulating leukocytes using dry blood spot (DBS) technology. In these cells, LAL activity is more severely depressed than in the body. Molecular genetic testing for variants in the LIPA gene is also available. This is usually a two-step procedure where testing for the highly prevalent E8SJM variant is done first and, if needed, sequencing of the LIPA gene is the second step.


Chordoma

A chordoma can develop anywhere along the spine from the base of the skull to the tailbone (coccyx). The most common locations for a chordoma are at the triangular bone near the base of the spine (sacrum), the coccyx, and the clivus, which is a bone in the base of the skull. The clivus is located in front of the brainstem and behind the back of the throat.

The underlying causes of chordoma are unknown. Most cases arise spontaneously and are not due to an inherited genetic change. A prevailing theory is that acquired genetic abnormalities or mutations result in cancerous growth of notochordal remnants. These genetic abnormalities may arise spontaneously for unknown reasons or, more rarely, be inherited.

Chordomas can affect individuals of any age, including young children, but most often are diagnosed in individuals between 40-75 years of age (the average age at diagnosis is 55 years). Collectively, chordomas affect males more often than females by a ratio of approximately 2:1. However, skull base tumors have an equal (1:1) gender distribution. Children are more likely to have skull base tumors. Chordomas account for approximately 1-4% of all malignant bone tumors and around 20% of primary tumors of the spinal column. The incidence of chordoma is estimated to be approximately 1 per 1,000,000 people. About 300 new cases of chordoma are diagnosed in the United States each year. Some reports state that these tumors are more common in individuals of European ancestry.

Chondrosarcoma is a general term for a type of bone cancer that arises from cartilage cells. Cartilage is the specialized tissue that serves as a buffer or cushion at joints. Most of the skeleton of an embryo consists of cartilage, which is slowly converted into bone. Chondrosarcomas typically affect the arms, legs, and pelvis, but can affect any area that contains cartilage including the skull base and spinal column. Most cases are diagnosed in adults between the ages of 20 and 60. Chondrosarcomas are malignant and may spread to other areas of the body. (For more information on this disorder, choose chondrosarcoma as your search term in the Rare Disease Database.)

The symptoms of chordoma are not specific. Therefore the diagnosis is based on characteristic radiologic pathologic findings.


Choroideremia

Choroideremia is a genetic disorder of sight that usually affects males. Female carriers may have mild symptoms without loss of vision. Major symptoms are difficulty seeing in the dark leading to progressive loss of peripheral vision, followed by tunnel vision. The rate and degree of vision loss differs among individuals. Night blindness, usually the first noticeable symptom, generally occurs during childhood.

Choroideremia is characterized by extensive loss of all retinal layers in the eyes. This disorder usually begins during childhood with wasting (atrophy) of the pigmented retinal epithelium, retina, and choroid. The retina is the light sensitive, most internal layer, consisting of many nerve containing layers. A layer of single pigmented cells is the layer outside of the retina. The choroid is the next layer located between the retina and the white section of the eye (the sclera); this layer contains small blood vessel).

Choroideremia can be caused by many different changes (called variants or mutations) in the CHM gene. The CHM gene encodes REP1 (RAB escort protein 1), a protein that takes part in targeting vesicles (small sacs of substances) into, out of and within cells.

Choroideremia affects primarily males. Female carriers generally have few or no symptoms. However, a small number of females develop the disorder because of a genetic process that inactivates the normal gene and leaves only the dysfunctional gene active. In the Salla area of northern Finland, an unusually high number of people have been diagnosed with choroideremia; approximately one in forty persons.

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

X linked retinitis pigmentosa (RP) is the most common inherited vision disorder that has similar symptoms to choroideremia. X linked RP is passed from a mother (who carries or has RP) to a son. In RP, the retina degenerates, vision decreases and can be lost. Symptoms include night blindness leading to progressive loss of peripheral vision, followed by tunnel vision. Night blindness is usually the first noticeable symptom, generally occurring during childhood. This is followed by tunnel vision (loss of peripheral vision). The extent and progression of symptoms is variable. An eye doctor (ophthalmologist) can differentiate between RP and choroideremia with an eye exam. (For more information on this disorder, choose retinitis pigmentosa as your search term in the Rare Disease Database.)

The symptoms of choroideremia can be treated but the disease itself cannot yet be cured. Organizations providing services to sight impaired people help patients and their families.


Choroiditis, Serpiginous

Serpiginous Choroiditis is one of the conditions in a group termed the white dot syndromes which all involve inflammation of the retina and choroid and are defined by the appearance of white dots in the posterior inner part of the eye (fundus). Serpiginous Choroiditis is a rare recurrent eye disorder characterized by irregularly shaped (serpiginous) lesions involving two layers of the eye surface (the retinal pigment epithelium and the choriocapillaris). No symptoms are apparent unless a specific area of the retina (macula) is damaged. A sudden, painless decrease in vision in one or both eyes may be the first sign of Serpiginous Choroiditis. Patients may also notice blind gaps in the visual field (scotomata) or a sensation of flashes of light (photopsia). Both eyes are commonly affected, although the second eye may not develop lesions for weeks to years after the first eye. The exact cause of Serpiginous Choroiditis is not known.

Serpiginous Choroiditis is a rare disorder characterized by recurrent lesions affecting two layers of the eye (the retinal pigment epithelium and the choriocapillaris).  The retina is the light-sensitive internal coat of the eyeball, consisting of eight layers.  Seven of these layers contain nerves, and one layer contains pigmentation (retinal pigment epithelium).  The choroid is a vascular membrane located between the retina inside the eye and the white section on the outside of the eye (sclera).  The choriocapillaris is the layer of the choroid next to the retina.

The exact cause of Serpiginous Choroiditis is not known.  Symptoms develop due to lesions that damage the part of the retina that absorbs short wavelengths of light (macular region).  Vision loss may also occur if a membrane composed of fibers and blood vessels (subretinal neovascular membrane) develops and then moves into the macular region.  It has been suggested in the medical literature that an abnormal immune response may cause inflammation of the blood vessels (localized vasculitis) of the eye, leading to the development of Serpiginous Choroiditis.  Some scientists suggest that the disorder is one of impaired blood circulation in the eye membranes.  A few affected individuals have been reported to have had chronic exposure to an unusual variety of chemicals, but the relationship between this exposure and the development of Serpiginous Choroiditis is not clear at this time.

Serpiginous Choroiditis is a rare disorder that affects males more often than females.  Symptoms usually appear during the early to middle adult years.

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

Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE) is a rare acquired eye disorder characterized by the sudden onset of vision loss and inflammation of the outer retina and the pigmented layer of the retina (retinal pigment epithelium).  Multiple yellow-white plaque-like lesions appear in the posterior pole of the retina in each eye.  The rapid but temporary vision loss often subsides without treatment.  Pigment alterations usually remain after resolution of the lesions.  Vision loss may be permanent if the lesions affect a specific area on the retina (subfoveally), but more than 90 percent of affected individuals recover visual clarity within a few months of onset.  (For more information on this disorder, choose APMPPE as your search term in the Rare Disease Database.)

Diagnosis of Serpiginous Choroiditis may be made by clinical evaluation and specialized ophthalmologic examinations such as electroretinography, electro-oculography, and/or fluorescein angiography. Widespread wasting (atrophy) of the choroid and retinal pigment epithelium membranes of the eye, pigment clumping, and/or deposits of fibrous tissue under the retina are characteristic findings.


Chromosome 10, Distal Trisomy 10q

10号染色体长臂远端三体

chromosome 10, partial trisomy 10q24-qter

Chromosome 10, distal trisomy 10q is an extremely rare chromosomal disorder in which the end (distal) portion of the long arm (q) of one chromosome 10 (10q) appears three times (trisomy) rather than twice in cells of the body. The disorder is characterized by unusually slow growth before and after birth); abnormally diminished muscle tone (hypotonia); mild to severe intellectual disability; and mild to severe delays in the acquisition of skills requiring coordination of mental and muscular activities. Affected infants and children may also have distinctive malformations of the head and facial (craniofacial) area; defects of the hands and/or feet; and/or skeletal, heart (cardiac), kidney (renal), and/or respiratory (pulmonary) abnormalities. The range and severity of symptoms and physical findings may vary from person to person, depending upon the exact length and location of the duplicated portion of chromosome 10q. In most cases, chromosome 10, distal trisomy 10q is due to a chromosomal balanced translocation in one of the parents.

In individuals with chromosome 10, distal trisomy 10q, an extremely rare chromosomal disorder, the end (distal) portion of the long arm (q) of one chromosome 10 (10q) is duplicated (trisomic). Symptoms and physical characteristics associated with the disorder may vary greatly in range and severity, depending upon the exact size and location of the duplicated portion of chromosome 10q. However, in most patients, the disorder is characterized by mild to severe intellectual disability; distinctive malformations of the head and facial (craniofacial) area; also, there are sometimes defects of the hands and/or feet; and/or skeletal, heart (cardiac), kidney (renal), and/or respiratory (pulmonary) abnormalities. It is important to note that affected infants will not have all of the abnormalities listed below.

Chromosome 10, distal trisomy 10q is an extremely rare chromosomal disorder in which part of the end (distal) portion of the long arm (q) of one chromosome 10 is duplicated. Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Pairs of human chromosomes are numbered from 1 through 22, and an additional 23rd pair of sex chromosomes which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm designated p and a long arm designated q. Chromosomes are further sub-divided into many bands that are numbered. For example, chromosome 11p13 refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Chromosome 10, distal trisomy 10q is an extremely rare but well-defined chromosomal disorder that appears to affect males and females at about the same rate. More than 35 cases have been reported in the medical literature since the disorder was originally described in 1974 (J.J. Yunis). Many of the symptoms and physical features associated with the disorder are apparent at birth (congenital).

Symptoms of the following disorders may be similar to those of Chromosome 10, Distal Trisomy 10q. Comparisons may be useful for a differential diagnosis:

Chromosome 10, Monosomy 10p is a very rare chromosomal disorder in which the end (distal) portion of the short arm (p) of one chromosome 10 is missing (deleted or monosomic). The disorder is characterized by growth delays and short stature, developmental delays, characteristic abnormalities of the head and facial (craniofacial) area, congenital heart defects, urinary tract malformations, and/or failure of one or both of the testes to descend into the scrotum (cryptorchidism) in affected males. Characteristic craniofacial malformations may include an abnormally small head (microcephaly) with an unusually prominent forehead (frontal bossing); a small, underdeveloped jaw (micrognathia); drooping of the upper eyelid(s) (ptosis); downslanting eyelid folds (palpebral fissures); small, misshapen ears; and/or other abnormalities. In most cases, the disorder is due to a spontaneous (de novo) genetic change (mutation) that occurs for unknown reasons (sporadic). (For more information on this disorder, choose Monosomy 10p as your search term in the Rare Disease Database.)


Chromosome 10, Monosomy 10p

10号染色体短臂远端单体

Chromosome 10, monosomy 10p is a rare chromosomal disorder in which the end (distal) portion of the short arm (p) of chromosome 10 is missing (deleted or monosomic). The range and severity of symptoms and findings may be variable, depending upon the exact size or location of the deletion on chromosome 10p. However, associated features often include severe intellectual disability; growth delays after birth (postnatal growth retardation); distinctive malformations of the skull and facial (craniofacial) region; a short neck; and/or structural defects of the heart that are present at birth (congenital heart defects). Several cases have also been reported in which affected individuals have some features of DiGeorge syndrome (DGS). DGS is a congenital disorder characterized by underdevelopment or absence of the thymus and parathyroid glands, potentially causing abnormalities of the immune system, deficient production of parathyroid hormone (hypoparathyroidism), a heart defect, and associated findings. In many cases, chromosome 10, monosomy 10p appears to occur spontaneously (de novo) for unknown reasons.

The symptoms and physical findings associated with chromosome 10, monosomy 10p may vary in range and severity from case to case. However, according to reports in the medical literature, most individuals with the disorder are affected by severe intellectual disability and delays in the acquisition of skills requiring the coordination of mental and motor activities (psychomotor retardation). Monosomy 10p is also frequently associated with growth delays after birth, resulting in short stature.

Chromosome 10, monosomy 10p is a rare chromosomal abnormality in which there is deletion (monosomy) of the end (distal) portion of the short arm (p) of chromosome 10. 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.

Chromosome 10, monosomy 10p is typically evident at birth (congenital). Since the disorder was originally reported in the medical literature in 1970, over 46 cases have been recorded. In such observed cases, males appear to be more frequently affected than females.

Symptoms of the following disorders may also be similar to those of chromosome 10, monosomy 10p. Comparisons may be useful for a differential diagnosis:

Chromosome 22, deletion 22q11.2 is a rare chromosomal disorder in which there is deletion of the long arm of chromosome 22. Individuals with deletions involving band q11.2 (i.e., DGCR) are affected by DiGeorge syndrome, including underdevelopment or absence of the thymus and potentially increased susceptibility to certain infections; hypoparathyroidism; and, in some cases, cardiovascular defects. Deletions that involve the end (distal) portion of chromosome 22q may also be associated with severe mental and psychomotor retardation; poor muscle tone (hypotonia); characteristic craniofacial features; and skeletal defects. Craniofacial abnormalities may include an abnormally small head (microcephaly); deeply set eyes; vertical skin folds that cover the eyes’ inner corners (epicanthal folds); low, full eyebrows and long eyelashes; a broad, bulbous nose; and an abnormally long vertical groove in the center of the upper lip (philtrum). Affected individuals may also have abnormal front-to-back curvature of the spine (kyphosis), unusually short fingers, and/or other abnormalities. This syndrome may appear to occur spontaneously (de novo) for unknown reasons or result from a parental balanced translocation involving chromosome 22q and another chromosome.


Chromosome 11, Partial Monosomy 11q

11号染色体长臂部分缺失

Partial monosomy 11q syndrome is a rare chromosomal disorder in which a portion of the long arm of chromosome 11 is deleted (missing). Jacobsen syndrome is observed in SOME  patients with 11q partial deletion. The region consistently missing in individuals with this disorder (JS) is band q24.1 (11q24.1) suggesting that the absence of this specific area is critical to developing the disorder (this chromosome region is called the Jacobsen syndrome critical region). It is important to stress that a complete genetic assessment requires both traditional chromosome tests (with or without the FISH staining technique), and CGH array.

Symptoms and physical characteristics associated with partial monosomy 11q vary greatly depending on the exact size and gene content of the deleted material on chromosome 11. For a complete genetic assessment it is important that both traditional chromosome tests and CGH array are performed. No specific feature has been seen in every person, so it is important to note that affected children will not have all of the symptoms discussed below.

Partial monosomy 11q is a rare disorder in which a portion of the long arm (q) of chromosome 11 is missing (deleted). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Each human cell has 46 chromosomes: 23 are derived from the father and 23 from the mother. Pairs of human chromosomes are numbered from 1 through 22, and the additional 23rd pair is that of sex chromosomes which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm designated p and a long arm designated q. When stained, chromosomes are further sub-divided into many bands that are numbered. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Partial monosomy 11q is an extremely rare chromosomal disorder that is apparent at birth. The disorder was initially described in the medical literature in 1973. Since that time, more than 200 cases have been described in the medical literature. According to some sources, more females are affected than males. The prevalence has been estimated at 1/100,000 births.

Symptoms of the following disorders can be similar to those of partial monosomy 11q. Comparisons may be useful for a differential diagnosis.

Partial monosomy 11q may be diagnosed based upon a thorough clinical evaluation, the identification of characteristic physical findings, including low platelets and chromosomal studies and/or array comparative genomic hybridization (CGH) studies that demonstrate missing (deleted) material on chromosome 11q. Chromosome studies can be done on a blood sample. Chromosomes are analyzed after a laboratory procedure that includes a culture of cells obtained from a small amount of blood, and staining procedures. These chromosomes are stained so that they can be viewed more easily and are then examined under a microscope where the missing segment of chromosome 11q can be detected (high resolution karyotype). To determine the precise breakpoint on 11q, more a sensitive test may be necessary such as: fluorescent in situ hybridization (FISH), a diagnostic test in which probes marked by a specific color of fluorescent dye attach to a specific chromosome allowing researchers to better view that specific region of a chromosome.


Chromosome 11, Partial Trisomy 11q

11号染色体长臂部分重复

Chromosome 11, Partial Trisomy 11q is a rare chromosomal disorder in which the end (distal) portion of the long arm (q) of the 11th chromosome appears three times (trisomy) rather than twice in cells of the body. Although associated symptoms and findings may vary, the disorder is often associated with delayed growth before and after birth (prenatal and postnatal growth retardation); varying degrees of mental retardation; distinctive abnormalities of the skull and facial (craniofacial) region; and/or other features. Chromosomal analysis is necessary for a definite diagnosis.

Chromosome 11, Partial Trisomy 11q is commonly characterized by growth retardation before and after birth, delayed acquisition of skills requiring the coordination of mental and motor activities (psychomotor retardation), mild to moderate mental retardation, and distinctive craniofacial abnormalities.

In individuals with Chromosome 11, Partial Trisomy 11q, the end (distal) region of the long arm (q) of chromosome 11 is present three times (i.e., trisomic or duplicated) rather than twice in cells of the body.  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.

Chromosome 11, Partial Trisomy 11q is a very rare chromosomal disorder that is reported to affect more females than males.  Approximately 45 cases of this disorder have been documented in the medical literature.

Symptoms of the following disorders can be similar to those of Chromosome 11, Partial Trisomy 11q.  Comparisons may be useful for a differential diagnosis:

Many chromosomal disorders have features similar to Chromosome 11, Partial Trisomy 11q.  The only way to determine which chromosomal disorder an individual has is through genetic testing.  (For more information on these disorders, choose Chromosomal Disorder as your search term in the Rare Disease Database.)