DEND syndrome is a very rare, generally severe form of neonatal diabetes mellitus (NDM, see this term) characterized by a triad of developmental delay, epilepsy, and neonatal diabetes. Epidemiology Fewer than 40 cases have been reported to date. Clinical description DEND syndrome represents the most severe end of the neonatal diabetes mellitus spectrum. Patients have hyperglycemia requiring insulin therapy that presents within 12 months of birth. The associated neurologic features range from mild psychomotor retardation to severe developmental delay. Patients also have therapy-resistant epilepsy and muscle hypotonia. A less severe, intermediate form has been described and is known as iDEND (see this term).

Fertile eunuch syndrome Other names Pasqualini syndrome Fertile eunuch syndrome is inherited in an autosomal recessive manner. Specialty Medical genetics The fertile eunuch syndrome or Pasqualini syndrome is a cause of hypogonadotropic hypogonadism caused by a luteinizing hormone deficiency. [1] It is characterized by hypogonadism with spermatogenesis . [2] Pasqualini and Bur published the first case of eunuchoidism with preserved spermatogenesis in 1950 in la Revista de la Asociación Médica Argentina. [3] The hypoandrogenism with spermatogenesis syndrome included: (a) eunuchoidism, (b) testis with normal spermatogenesis and full volume, with mature spermatozoids in a high proportion of seminiferous tubes and undifferentiated and immature Leydig cells (c) full functional compensation through the administration of chorionic gonadotropin hormone, while hCG is administered (d) total urinary gonadotrophins within normal limits (e) this definition implies the normal activity of the pituitary and the absence of congenital malformations in general. In describing five other similar cases in 1953, Mc Cullagh & al [4] [5] coined the term fertile eunuch introducing it in the English literature. Unfortunately, this term is incorrect and should not be employed. Indeed, these patients are not really eunuchs. Moreover, as it will be explained later, they are not usually fertile if not treated.

A number sign (#) is used with this entry because of evidence that autosomal recessive oculodentodigital dysplasia is caused by homozygous mutation in the GJA1 gene (121014) on chromosome 6q22. Oculodentodigital dysplasia is usually inherited as an autosomal dominant disorder (164200), which is also caused by mutation in the GJA1 gene. Clinical Features Traboulsi et al. (1986) proposed the existence of a recessive form of oculodentoosseous dysplasia with more severe ocular affection than in the dominant form. They described a single case in a girl with unaffected first-cousin parents. The patient showed long, narrow nose with hypoplastic nasal alae, telecanthus, prominent epicanthal folds, microphthalmia, microcornea, malformed teeth with abnormal enamel, syndactyly of fingers 4 and 5 with clinodactyly of the distal phalanx of the fifth finger in each hand, and soft tissue syndactyly of toes 2, 3, and 4.

Genotype/Phenotype Correlations Wicking et al. (1997) screened 71 unrelated individuals with NBCCS for mutations in the PTCH exons. They identified 28 mutations that were distributed throughout the entire gene and predicted that 86% would cause protein truncation.

Oculodentodigital dysplasia Other names Oculo-dento-digital syndrome , Oculodentodigital dysplasia , and Oculodentoosseous dysplasia Oculodentodigital syndrome (ODD syndrome) is an extremely rare genetic condition that typically results in small eyes, underdeveloped teeth, and syndactyly and malformation of the fourth and fifth fingers. It is considered a kind of ectodermal dysplasia . Contents 1 Signs and symptoms 2 Genetics 3 Epidemiology 4 References 5 External links Signs and symptoms [ edit ] People with ODD syndrome often have a characteristic appearance. Visible features of the condition include: [1] small teeth that are prone to dental caries because of underdeveloped tooth enamel; a long, thin nose; unusually small eyes; and type III syndactyly of the fourth and fifth fingers. Iris atrophy and glaucoma are more common than average. [1] The size of the eyes often interferes with learning to read; special eyeglasses may be required. Hair may be fine, thin, dry, or fragile; in some families, it is curly. [2] Neurologic abnormalities may be seen in adults.

Oculodentodigital dysplasia is a condition that affects many parts of the body, including the eyes (oculo-), teeth (dento-), and fingers (digital). Symptoms of the condition include having small eyes, vision loss, missing teeth, frequent cavities, and bony growths in the fingers. The condition is caused by a mutation in GJA1 and is most typically inherited in an autosomal dominant manner. Oculodentodigital dysplasia can be diagnosed by a clinical examination and confirmed with genetic testing. Management is based on treating the specific symptoms that each affected person exhibits.

Oculodentodigital dysplasia is a condition that affects many parts of the body, particularly the eyes (oculo-), teeth (dento-), and fingers (digital). Common features in people with this condition are small eyes (microphthalmia) and other eye abnormalities that can lead to vision loss. Affected individuals also frequently have tooth abnormalities, such as small or missing teeth, weak enamel, multiple cavities, and early tooth loss. Other common features of this condition include a thin nose and webbing of the skin (syndactyly ) between the fourth and fifth fingers. Less common features of oculodentodigital dysplasia include sparse hair growth (hypotrichosis ), brittle nails, an unusual curvature of the fingers (camptodactyly ), syndactyly of the toes , small head size (microcephaly ), and an opening in the roof of the mouth (cleft palate ).

Oculodentodigital dysplasia (ODDD) is characterized by craniofacial, neurologic, limb and ocular abnormalities. Epidemiology To date, approximately 250 cases have been described worldwide (the majority of whom were white individuals). Clinical description The disease is characterized by wide intra- and interfamilial phenotypic variability. The typical craniofacial anomalies include a thin nose with hypoplastic alae nasi, small anteverted nares and a prominent columella, mandibular overgrowth, cleft palate, and microcephaly. Skeletal manifestations consist of syndactyly (involving the 4th and 5th fingers and/or 2nd to 4th toes), camptodactyly, and clinodactyly due to hypoplasia or aplasia of the middle phalanges.

A rare benign gastrointestinal disease characterized by the presence of abnormal and nonspecific gastro-intestinal (GI) manifestations, associated with an eosinophilic infiltration of the GI tract, which can affect several segments and involve several layers within the GI wall. Epidemiology Prevalence and incidence are unknown. To date, more than 280 cases have been reported, mainly in Caucasians and with a slight male preponderance. Clinical description EGE can occur at any age, but it is most commonly observed between the ages of 30 and 50 years. It can affect any area of the digestive tract, with the stomach and duodenum being the most commonly affected sites. The clinical presentation is variable and depends on the region of the digestive tract involved and the depth of eosinophilic involvement.

Eosinophilic gastroenteritis occurs when certain white blood cells known as eosinophils get into the digestive tract and cause damage. Symptoms of eosinophilic gastroenteritis usually start in adulthood and may include stomach pain, nausea, vomiting, and the inability to absorb nutrients from food. Sometimes, a blockage in the intestines occurs. In most people, symptoms occur from time to time and may go away completely with treatment. The exact cause of eosinophilic gastroenteritis is unknown, but it may be due to an abnormal response of the immune system to food allergies. Diagnosis is based on the symptoms, a clinical exam, laboratory tests, and by excluding other more common conditions.

Pyruvate dehydrogenase deficiency is characterized by the buildup of a chemical called lactic acid in the body and a variety of neurological problems. Signs and symptoms of this condition usually first appear shortly after birth, and they can vary widely among affected individuals. The most common feature is a potentially life-threatening buildup of lactic acid (lactic acidosis), which can cause nausea, vomiting, severe breathing problems, and an abnormal heartbeat. People with pyruvate dehydrogenase deficiency usually have neurological problems as well. Most have delayed development of mental abilities and motor skills such as sitting and walking.

Autosomal recessive Robinow syndrome (RRS) is the less common type of Robinow syndrome (RS, see this term) characterized by short-limb dwarfism, costovertebral segmentation defects and abnormalities of the head, face and external genitalia. Epidemiology Fewer than 100 cases of this type have been reported in the literature to date. Clinical description The disorder is usually recognizable at birth or in early childhood. The clinical signs are generally far more severe in recessive cases of RS than in the dominant form, particularly skeletal abnormalities. All patients with the recessive form of RS suffer from vertebral segmentation abnormalities, resulting in scoliosis and chest deformities.

A number sign (#) is used with this entry because multicentric osteolysis, nodulosis, and arthropathy (MONA) is caused by homozygous or compound heterozygous mutation in the MMP2 gene (120360) on chromosome 16q12. Description Zankl et al. (2007) defined what they considered to be a continuous clinical spectrum involving Torg syndrome, Winchester syndrome (277950), and NAO syndrome. Torg syndrome is characterized by the presence of multiple, painless, subcutaneous nodules and mild to moderate osteoporosis and osteolysis that is usually limited to the hands and feet. Radiographically, the osteolysis is accompanied by a characteristic widening of the metacarpal and metatarsal bones. Winchester syndrome presents with severe osteolysis in the hands and feet and generalized osteoporosis and bone thinning, similar to NAO, but subcutaneous nodules are characteristically absent.

A rare systemic or rheumatologic disease characterized by peripheral osteolysis (especially carpal and tarsal bones), interphalangeal joint erosions, subcutaneous fibrocollagenous nodules, facial dysmorphism, and a wide range of associated manifestations. Epidemiology Multicentric osteolysis-nodulosis-arthropathy (MONA) spectrum prevalence and incidence of MONA are not known. Fewer than 50 cases have been reported worldwide. Cases have been reported from Saudi Arabia, Italy, Turkey, Algeria, Morocco, the United States, and Korea. Clinical description Onset is usually at preschool age (1-5 years) and the course of the disease is variable. Manifestations of the disorder include multiple peripheral osteolysis beginning at the carpal, tarsal, metacarpal/metatarsal-phalangeal and interphalangeal joints with subsequent generalization.

Nodulosis–arthropathy–osteolysis syndrome Specialty Dermatology Nodulosis–arthropathy–osteolysis syndrome is a cutaneous condition that shares features with juvenile hyaline fibromatosis . [1] See also [ edit ] Winchester syndrome List of cutaneous conditions References [ edit ] ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set . St. Louis: Mosby. ISBN 978-1-4160-2999-1 . This dermatology article is a stub . You can help Wikipedia by expanding it . v t e

Multicentric osteolysis, nodulosis, and arthropathy (MONA) describes a rare inherited disease characterized by a loss of bone tissue (osteolysis), particularly in the hands and feet . MONA includes a condition formerly called nodulosis-arthropathy-osteolysis (NAO) syndrome. It may also include a similar disorder called Torg syndrome, although it is unknown whether Torg syndrome is actually part of MONA or a separate disorder caused by a mutation in a different gene. In most cases of MONA, bone loss begins in the hands and feet, causing pain and limiting movement. Bone abnormalities can later spread to other areas of the body, with joint problems (arthropathy) occurring in the elbows, shoulders, knees, hips, and spine.

A number sign (#) is used with this entry because of evidence that distal arthrogryposis type 1B (DA1B) is caused by heterozygous mutation in the MYBPC1 gene (160794) on chromosome 12q23. For a general phenotypic description and a discussion of genetic heterogeneity of distal arthrogryposis, see DA1A (108120). Clinical Features Gurnett et al. (2010) described a 5-generation family in which 12 members had distal arthrogryposis type 1. Nine of the 12 had congenital talipes equinovarus (clubfoot) and the 3 others had congenital vertical talus. The lower limb contractures were bilateral in all cases except 1 female with left-sided clubfoot and 1 female with right-sided clubfoot.

Clinical Features Sallis and Beighton (1972) described a new syndrome consisting of flexion deformity of the fingers and 'rocker-bottom' feet due to vertical talus. Fourteen persons in 5 generations were affected but no instance of male-to-male transmission was observed. Stevenson et al. (1975) described the same trait in a large American Black family. They emphasized the ulnar deviation of the fingers. Their patients lacked vertical talus and short stature. Male-to-male transmission was noted. They also noted adduction contraction of the thumb in a newborn in their family.

Summary Clinical characteristics. Pantothenate kinase-associated neurodegeneration (PKAN) is a type of neurodegeneration with brain iron accumulation (NBIA). The phenotypic spectrum of PKAN includes classic PKAN and atypical PKAN. Classic PKAN is characterized by early childhood onset of progressive dystonia, dysarthria, rigidity, and choreoathetosis. Pigmentary retinal degeneration is common. Atypical PKAN is characterized by later onset (age >10 years), prominent speech defects, psychiatric disturbances, and more gradual progression of disease. Diagnosis/testing. The diagnosis of PKAN is established in a proband with the characteristic clinical features and the "eye of the tiger" sign identified on brain MRI (a central region of hyperintensity surrounded by a rim of hypointensity on coronal or transverse T 2 -weighted images of the globus pallidus).

A number sign (#) is used with this entry because neurodegeneration with brain iron accumulation-1 (NBIA1), also known as Hallervorden-Spatz disease, is caused by homozygous or compound heterozygosity mutation in the pantothenate kinase-2 gene (PANK2; 606157) on chromosome 20p13. HARP syndrome (607236) is a rare allelic disorder with a less severe phenotype and the presence of hypobetalipoproteinemia and acanthocytosis. Description Neurodegeneration with brain iron accumulation is a genetically heterogeneous disorder characterized by progressive iron accumulation in the basal ganglia and other regions of the brain, resulting in extrapyramidal movements, such as parkinsonism and dystonia. Age at onset, severity, and cognitive involvement are variable (review by Gregory et al., 2009). Panthothenate kinase-associated neurodegeneration has been classified clinically as 'classic,' 'atypical,' or 'intermediate.'

Pantothenate kinase-associated neurodegeneration (PKAN) is the most common type of neurodegeneration with brain iron accumulation (NBIA; see this term), a rare neurodegenerative disorder characterized by progressive extrapyramidal dysfunction (dystonia, rigidity, choreoathetosis), iron accumulation on the brain and axonal spheroids in the central nervous system. Epidemiology Prevalence is estimated at 1-2/1,000,000. Clinical description Classic PKAN (75% of cases) is characterized by early onset, usually before six years of age, and rapid progression. Atypical PKAN (25% of cases) has later onset, between 13 and 14 years of age, and slower progression. Patients present with symptoms anywhere along a continuum between the two. In classic PKAN, patients present with impaired gait and falling, often related to dystonia, rigidity, impaired balance, or spasticity, and usually lose the ability to ambulate by 10-15 years after onset.

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare disease characterized by a progressive degeneration of the nervous system (neurodegenerative disorder) and buildup of iron in the brain. PKAN is usually classified into two forms: classic and atypical. Classic PKAN causes symptoms in the first ten years of life. The atypical form of PKAN usually occurs after the age of ten and progresses more slowly. All individuals with PKAN have an abnormal buildup of iron in certain areas of the brain. A particular change, called the eye-of-the-tiger sign , which indicates a buildup of iron, is typically seen on magnetic resonance imaging (MRI) scans of the brain in people with this disorder.

Niemann-Pick disease type B is an inherited condition involving lipid metabolism. People with this condition experience a build up of lipids in the spleen, liver, lungs, bone marrow, and brain. Signs and symptoms typically develop in the pre-teen years and may include enlarged liver and spleen (hepatosplenomegaly), short stature, problems with lung function including frequent lung infections, and a low number of platelets in the blood (thrombocytopenia). Niemann-Pick disease type B is caused by changes (mutations or variants) in the SMPD1 gene. It is inherited in an autosomal recessive fashion. Treatment is aimed at addressing the symptoms present in each individual.

Niemann-Pick disease type B is a mild subtype of Niemann-Pick disease, an autosomal recessive lysosomal disease, and is characterized clinically by onset in childhood with hepatosplenomegaly, growth retardation, and lung disorders such as infections and dyspnea

Clinical findings included the following: Gait disturbance (89%), the most frequent being ataxia and spasticity together or ataxia alone Action limb dystonia (86%) Mild chorea (75%) Cerebellar action tremor (70%) Non-epileptic paroxysmal events (28%) Dyspraxia (21%) Myoclonus (16%) The 40 individuals on a ketogenic diet had less severe gait disturbances, but more complex movement disorders than those on a conventional diet [Pons et al 2010], an observation suggesting that the extrapyramidal and cerebellar findings are more apparent in the milder phenotypes.

Glucose transporter type 1 (GLUT1) deficiency syndrome is characterized by an encephalopathy marked by childhood epilepsy that is refractory to treatment, deceleration of cranial growth leading to microcephaly, psychomotor retardation, spasticity, ataxia, dysarthria and other paroxysmal neurological phenomena often occurring before meals. Symptoms appear between the age of 1 and 4 months, following a normal birth and gestation. Epidemiology The prevalence is unknown. Etiology In the majority of cases the disease is associated with de novo mutations in the SLC2A1 gene. Diagnostic methods Diagnosis is based on the clinical picture and biochemical analysis of the cerebrospinal fluid (CSF). Genetic counseling GLUT1 deficiency syndrome is transmitted as an autosomal dominant trait and in these cases the affected parent presents with a mild form of the disease.

De Vivo disease Other names De Vivo disease De Vivo disease has an autosomal dominant pattern of inheritance Specialty Medical genetics GLUT1 deficiency syndrome , also known as GLUT1-DS , De Vivo disease or Glucose transporter type 1 deficiency syndrome, is an autosomal dominant , genetic metabolic disorder associated with a deficiency of GLUT1 , the protein that transports glucose across the blood brain barrier. [1] Glucose Transporter Type 1 Deficiency Syndrome has an estimated birth incidence of 1 in 90,000. [2] This birth incidence translates to an estimated prevalence of 3,000 to 7,000 in the U.S. [2] Contents 1 Presentation 1.1 Effects 2 Genetics 3 Diagnosis 4 Management 5 References 6 External links Presentation [ edit ] GLUT1 deficiency is characterized by an array of signs and symptoms including mental and motor developmental delays, infantile seizures refractory to anticonvulsants, ataxia , dystonia , dysarthria , opsoclonus , spasticity , other paroxysmal neurologic phenomena and sometimes deceleration of head growth also known as microcephaly . The presence and severity of symptoms vary considerably between affected individuals. Individuals with the disorder generally have frequent seizures (epilepsy), often beginning in the first months of life. In newborns, the first sign of the disorder may be involuntary eye movements that are rapid and irregular. [3] Patients typically begin to experience seizures between three and six months of age, but some occur much later. [4] Other seizure types may occur, including generalized tonic clonic, focal, myoclonic, atypical absence, atonic, or unclassified. [4] Mothers of infants with this disorder usually have uneventful pregnancies and deliveries, with the child appearing normal and within typical birth weight and length ranges. Infants with GLUT1 deficiency syndrome have a normal head size at birth, but the growth of the brain and skull is slow, in severe cases resulting in an abnormally small head size ( microcephaly ). [3] Typically, seizures start between one and four months in 90% of cases with abnormal eye movements and apneic episodes preceding the onset of seizures in some cases. [5] Seizures usually are complex to begin with and later become more generalized.

Glucose transporter type 1 deficiency syndrome (GLUT1 deficiency syndrome) is an inherited condition that affects the nervous system. Signs and symptoms generally develop within the first few months of life and may include recurrent seizures (epilepsy) and involuntary eye movements. Affected people may also have microcephaly (unusually small head size) that develops after birth, developmental delay, intellectual disability and other neurological problems such as spasticity, ataxia (difficulty coordinating movements), and dysarthria. Approximately 10% of affected people have the "non-epileptic" form of GLUT1 deficiency syndrome which is associated with all the typical symptoms of the condition without seizures. GLUT1 deficiency syndrome is caused by changes (mutations) in the SLC2A1 gene and is inherited in an autosomal dominant manner.

Pulmonary arterial hypertension associated with portal hypertension (PAH-PH) is a form of pulmonary arterial hypertension (PAH), characterized by an elevated pulmonary arterial resistance leading to right heart failure observed as a complication of portal hypertension.

Paroxysmal exercise-induced dystonia Other names Paroxysmal exertion-induced dyskinesia This condition is inherited in an autosomal dominant manner Specialty Neurology Paroxysmal exercise-induced dystonia or PED is a rare neurological disorder characterized by sudden, transient, involuntary movements, often including repetitive twisting motions and painful posturing triggered by exercise or other physical exertion. [1] PED is in the class of paroxysmal dyskinesia which are a group of rare movement disorders characterized by attacks of hyperkinesia with intact consciousness. [2] The term paroxysmal indicates that the episodes are sudden and short lived and usually unpredicted, and return to normal is rapid. [1] The number of reported cases of people with PED is very small leading to difficulty in studying and classifying this disease and most studies are limited to a very small number of test subjects. Contents 1 Symptoms and signs 2 Causes 2.1 Familial 2.2 Sporadic 3 Diagnosis 3.1 Related disorders 4 Treatments 5 Epidemiology 6 Research 7 See also 8 References 9 External links Symptoms and signs [ edit ] Episodes are relatively short-lived, lasting anywhere from 5–30 minutes, and in most cases disappear completely after cessation of the physical exercise. Most patients will experience 1 to 5 episodes per month, but some can have attacks daily. [1] The muscles most often affected are usually in the legs and feet (75% of reported cases), but the upper body muscles such as the arms, face, neck, and trunk have also been observed to be affected during the episodes of dystonia . [3] Age of onset is usually sometime in childhood, but can range from 1–30 years old. [4] In one study it was found that the mean age of onset was around 8 years. Similarly in the study, the legs were the most common affected part of the body and the attacks were reported as stiffening and cramps by those affected. During an episode of PED patients find walking nearly impossible. [5] Cerebral spinal fluid analysis showed a two-fold increase of homovanillic acid and 5-hydroxyindoleacetic acid immediately following exercise compared to normal levels.

Paroxysmal exertion-induced dyskinesia (PED) is a form of paroxysmal dyskinesia (see this term), characterized by painless attacks of dystonia of the extremities triggered by prolonged physical activities. Epidemiology The prevalence is unknown but 20 sporadic cases and 9 families have been described to date. Clinical description The age of onset is usually in childhood, but may range from 1 to 30 years. PED is characterized by dyskinesias induced by prolonged exercise of 15-60 minutes of duration. The attacks last between 5 minutes and 2 hours and are typically restricted to the exercised limbs.

Summary Clinical characteristics. Lymphedema-distichiasis syndrome (referred to as LDS in this GeneReview ) is characterized by lower-limb lymphedema, and distichiasis (aberrant eyelashes ranging from a full set of extra eyelashes to a single hair). Lymphedema typically appears in late childhood or puberty, is confined to the lower limbs with or without involvement of the external genitalia, and is often asymmetric; severity varies within families. Males develop edema at an earlier age and have more problems with cellulitis than females. Distichiasis, which may be present at birth, is observed in 94% of affected individuals. About 75% of affected individuals have ocular findings including corneal irritation, recurrent conjunctivitis, and photophobia; other common findings include varicose veins and ptosis.

Lymphedema - distichiasis is a rare syndromic lymphedema disorder characterized by lower-limb lymphedema and varying degrees of abnormal growth of eyelashes from the orifices of the Meibomian glands (distichiasis), with occasional associated manifestations.

Lymphedema–distichiasis syndrome Other names Lymphedema with distichiasis [1] Lymphedema–distichiasis syndrome is inherited in an autosomal dominant manner Lymphedema–distichiasis syndrome is a medical condition associated with the FOXC2 gene. [2] : 849 People with this hereditary condition have a double row of eyelashes , which is called distichiasis , and a risk of swollen limbs due to problems in the lymphatic system . Contents 1 Genetics 2 Mutations 3 Symptoms 4 Syndrome diagnosis and management 5 See also 6 Notes 7 References 8 External links Genetics [ edit ] Lymphedema-distichiasis is inherited in an autosomal dominant fashion. [3] It is estimated that only ¼ of diagnosed individuals did not inherit the condition but rather acquired the syndrome via a de novo mutation. [4] Symptoms emerge between the life stages of puberty to early adulthood (around 30 years old). [ citation needed ] This is the result of a mutation in the FOXC2 gene. [5] Mutations [ edit ] p.Y41F, a missense mutation, is also located in FOXC2 AD-1. p.Y41F is one of eleven mutations found in the FOXC2 gene. It was determined that of these 11 mutations, one was nonsense, six were missense, and four were frameshift mutations. [6] Symptoms [ edit ] The main symptoms of lymphedema-distichiasis are limb swelling and a double row of eyelashes. Symptoms that have been noted in some but not all cases include cysts, light sensitivity, cardiac defects, cleft palate, and eye problems such as astigmatism and cornea scarring. [5] Syndrome diagnosis and management [ edit ] Currently, the most accurate test to determine if an individual is affected by lymphedema-distichiasis syndrome is done via Sanger sequencing , which includes whole genome analysis and single gene and multigene testing. [3] [7] Sequenced DNA that exhibits mutations in the FOXC2 gene are considered confirmed clinical diagnoses. In addition to Sanger sequencing, Multiplex Ligation Probe Amplification (MLPA) can be used to determine if duplications and deletions in FOXC2 are present in an individual, making it a practical testing mechanism. [3] Lastly, diagnosis is sometimes determined without genome testing.

Lymphedema-distichiasis syndrome is a condition that affects the normal function of the lymphatic system , which is a part of the circulatory and immune systems. The lymphatic system produces and transports fluids and immune cells throughout the body. People with lymphedema-distichiasis syndrome develop puffiness or swelling (lymphedema ) of the limbs, typically the legs and feet. Another characteristic of this syndrome is the growth of extra eyelashes (distichiasis), ranging from a few extra eyelashes to a full extra set on both the upper and lower lids. These eyelashes do not grow along the edge of the eyelid, but out of its inner lining.

Lymphedema-distichiasis syndrome is a condition that affects the normal function of the lymphatic system (part of the immune system that produces and transports fluids and immune cells throughout the body). People with this syndrome have extra eyelashes (distichiasis) and develop puffiness or swelling (lymphedema) of the limbs, most often the legs and feet. The abnormal eyelashes, which grow along the inner lining of the eyelid, often touch the eyeball and can cause damage to the clear covering of the eye (cornea). Other eye problems such as an irregular curvature of the cornea causing blurred vision ( astigmatism ) or scarring of the cornea may also occur. Other health problems that may occur in lymphedema-distichiasis syndrome include varicose veins , droopy eyelids (ptosis), and an opening in the roof of the mouth (cleft palate).

1p36 deletion syndrome is a disorder that typically causes severe intellectual disability. Most affected individuals do not speak, or speak only a few words. They may have temper tantrums, bite themselves, or exhibit other behavior problems. Most have structural abnormalities of the brain, and seizures occur in more than half of individuals with this disorder. Affected individuals usually have weak muscle tone (hypotonia) and swallowing difficulties (dysphagia). People with 1p36 deletion syndrome have a small head that is also unusually short and wide in proportion to its size (microbrachycephaly).

1p36 deletion syndrome Other names Monosomy 1p36 A toddler showing facial symptoms of the syndrome. 1p36 deletion syndrome is a congenital genetic disorder characterized by moderate to severe intellectual disability , delayed growth, hypotonia , seizures, limited speech ability, malformations, hearing and vision impairment, and distinct facial features . The symptoms may vary, depending on the exact location of the chromosomal deletion. [1] The condition is caused by a genetic deletion (loss of a segment of DNA) on the outermost band on the short arm (p) of chromosome 1 . It is one of the most common deletion syndromes. It is estimated that the syndrome occurs in one in every 5,000 to 10,000 births. Contents 1 Signs and symptoms 1.1 Developmental and behavioral 1.2 Neurologic 1.2.1 Vision 1.3 Distinct facial features 1.4 Other congenital defects 1.4.1 Skeletal 1.4.2 Heart 1.4.3 Genitourinary and kidneys 2 Genetics 3 Diagnosis 4 Treatment 5 Epidemiology 6 References Signs and symptoms [ edit ] There are a number of signs and symptoms characteristic of monosomy 1p36, but no one individual will display all of the possible features. In general, children will exhibit failure to thrive and global delays. [2] Developmental and behavioral [ edit ] Most young children with 1p36 deletion syndrome have delayed development of speech and motor skills.

1p36 deletion syndrome is a chromosomal anomaly characterized by distinctive facial dysmorphic features, hypotonia, developmental delay, intellectual disability, seizures, heart defects, hearing impairment and prenatal onset growth deficiency. Epidemiology 1p36 deletion syndrome is considered one of the most common chromosome deletion syndromes, with an incidence of 1/ 5,000 to 1 /10,000 live births occurring equally in both genders, across all ethnicities. Clinical description Patients share recognizable craniofacial dysmorphism with straight eyebrows, deep-set eyes, broad and flat nasal root/bridge, midface hypoplasia, long philtrum, pointed chin, and frequently observed large late-closing anterior fontanel (>3 cm at birth), microbrachycephaly and posteriorly rotated, low-set, abnormal ears. Brachydactyly, camptodactyly and short feet are also characteristic. Almost all patients suffer from congenital hypotonia, contributing to feeding difficulties, delay in motor development and fine motor skills, and delayed or absent speech. A variable level of intellectual deficit is observed in all patients.

A number sign (#) is used with this entry because of evidence that this neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (NEDBEH) is caused by heterozygous mutation in the RERE gene (605226) on chromosome 1p36. Description Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart is an autosomal dominant syndrome characterized by onset in infancy of developmental delay, intellectual disability, and behavioral disorders, such as autism spectrum disorders. About half of patients have additional abnormalities, most commonly involving the eye, heart, and genitourinary system. The phenotype is reminiscent of that observed in patients with 1p36 deletion syndrome (607872); RERE is located in the proximal 1p36 critical region (summary by Fregeau et al., 2016). Clinical Features Fregeau et al. (2016) reported 10 unrelated children with a neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, and autistic spectrum disorder, variably associated with additional congenital abnormalities.

1p36 deletion syndrome is a chromosome disorder that typically causes severe intellectual disability. Most affected individuals do not speak, or speak only a few words. They may have temper tantrums, bite themselves, or exhibit other behavior problems. Most have structural abnormalities of the brain, and seizures occur in more than half of individuals with this disorder. Affected individuals usually have weak muscle tone (hypotonia) and swallowing difficulties (dysphagia). Other features include a small head that is unusually short and wide; vision and hearing problems; abnormalities of the skeleton, heart, gastrointestinal system, kidneys, or genitalia; and distinctive facial features. 1p36 deletion syndrome is caused by a deletion of genetic material from a specific region in the short (p) arm of chromosome 1 .

Description Usher syndrome type I an autosomal recessive disorder characterized by profound congenital hearing impairment with unintelligible speech, early retinitis pigmentosa, and constant vestibular dysfunction (summary by Chaib et al., 1997). For a discussion of genetic heterogeneity of USH type I, see 276900. Mapping Using homozygosity mapping in a consanguineous family in Morocco, Chaib et al. (1997) identified a genetically distinct form, which they called USH1E and mapped to 21q21. The delimited 15-cM interval was flanked by D21S1905 and D21S1913. INHERITANCE - Autosomal recessive HEAD & NECK Ears - Hearing loss, congenital sensorineural - Vestibular areflexia, complete Eyes - Retinitis pigmentosa ▲ Close

A number sign (#) is used with this entry because Usher syndrome type IIIA (USH3A) is caused by homozygous or compound heterozygous mutation in the CLRN1 gene (606397) on chromosome 3q25. Mutation in the same gene can cause a form of nonsyndromic retinitis pigmentosa (RP61; 614180). Description Usher syndrome type III is characterized by postlingual, progressive hearing loss, variable vestibular dysfunction, and onset of retinitis pigmentosa symptoms, including nyctalopia, constriction of the visual fields, and loss of central visual acuity, usually by the second decade of life (Karjalainen et al., 1985; Pakarinen et al., 1995). For a discussion of phenotypic heterogeneity of Usher syndrome, see USH1 (276900). Genetic Heterogeneity of Usher syndrome Type III Usher syndrome type IIIB (614504) is caused by mutation in the HARS gene (142810) on chromosome 5q31.3.

A number sign (#) is used with this entry because of evidence that a retinitis pigmentosa-deafness syndrome is due to mutation in the MTTS2 gene (590085). Clinical Features Kumar-Singh et al. (1993) reported an extensive Irish kindred segregating retinitis pigmentosa and deafness. Affected members usually presented first with hearing difficulties in their teens. In their twenties, patients noted symptoms referable to impairment of night vision and loss of peripheral visual fields. Affected individuals showed abnormal electroretinographic responses before the onset of symptoms, however.

A number sign (#) is used with this entry because Usher syndrome type IC is caused by homozygous or compound heterozygous mutation in the gene encoding harmonin (605242) on chromosome 11p15. Description Usher syndrome type I is an autosomal recessive condition characterized by profound congenital hearing impairment with unintelligible speech, early retinitis pigmentosa (usually evident within the first decade), and constant vestibular dysfunction. Type I is distinguished from type II (276901) on the basis of severity of hearing loss and the extent of vestibular involvement. Type I patients are profoundly deaf, whereas type II patients are 'hard of hearing.' Vestibular function is defective in type I patients, whereas type II patients have normal vestibular function (Moller et al., 1989).

Description Usher syndrome type I is an autosomal recessive condition characterized by profound congenital hearing impairment with unintelligible speech, early retinitis pigmentosa (usually evident within the first decade), and constant vestibular dysfunction. Type I is distinguished from type II (276901) on the basis of severity of hearing loss and the extent of vestibular involvement. Type I patients are profoundly deaf, whereas type II patients are 'hard of hearing.' Vestibular function is defective in type I patients, whereas type II patients have normal vestibular function (Moller et al., 1989). Patients with type III (USH3; 276902) have progressive hearing loss. For a discussion of genetic heterogeneity of Usher syndrome type I, see USH1 (276900).

Usher syndrome is a genetic disorder characterized by sensorineural hearing loss or deafness and progressive vision loss due to retinitis pigmentosa . Sensorineural hearing means it is caused by abnormalities of the inner ear . Retinitis pigmentosa is an eye disease that affects the layer of light-sensitive tissue at the back of the eye ( the retina ). Vision loss occurs as the light-sensing cells of the retina gradually deteriorate. Night vision loss begins first, followed by blind spots that develop in the side (peripheral) vision, that can enlarge and merge to produce tunnel vision (loss of all peripheral vision).

A number sign (#) is used with this entry because of evidence that Usher syndrome type IJ (USH1J) is caused by homozygous mutation in the CIB2 gene (605564) on chromosome 15q24. Mutation in the same gene causes autosomal recessive deafness-48 (DFNB48; 609439). Description Usher syndrome type I is an autosomal recessive condition characterized by profound congenital hearing impairment with unintelligible speech, early retinitis pigmentosa (usually evident within the first decade), and constant vestibular dysfunction. Type I is distinguished from type II (276901) on the basis of severity of hearing loss and the extent of vestibular involvement. Type I patients are profoundly deaf, whereas type II patients are 'hard of hearing.'

Description Usher syndrome type I is an autosomal recessive condition characterized by profound congenital hearing impairment with unintelligible speech, early retinitis pigmentosa (usually evident within the first decade), and constant vestibular dysfunction. Type I is distinguished from type II (276901) on the basis of severity of hearing loss and the extent of vestibular involvement. Type I patients are profoundly deaf, whereas type II patients are 'hard of hearing.' Vestibular function is defective in type I patients, whereas type II patients have normal vestibular function (Moller et al., 1989). Patients with type III (USH3; 276902) have progressive hearing loss. For a discussion of genetic heterogeneity of Usher syndrome type I, see USH1 (276900).

A rare ciliopathy characterized by congenital or childhood onset sensorineural hearing loss (HL) and retinitis pigmentosa (RP) that occurs in a second step with a night blindness and a progressive vision loss and, in some cases, vestibular dysfunction. Epidemiology Prevalence of Usher syndrome (US) is estimated at 1/30,000. It is by far the most common cause of hereditary, combined deafness-blindness. Clinical description Sensorineural hearing loss is typically congenital and three clinical entities have been defined according to severity of hearing loss severity. Type 1 (around 40% of cases) is characterized by profound, nonprogressive congenital deafness, typically associated with vestibular areflexia that leads to delayed acquisitions (delayed head control, unassisted sitting and walking).

A number sign (#) is used with this entry because of evidence that Usher syndrome type IIIB (USH3B) is caused by homozygous mutation in the HARS gene (HARS1; 142810) on chromosome 5q31. Description Usher syndrome type III is characterized by postlingual, progressive hearing loss, variable vestibular dysfunction, and onset of retinitis pigmentosa symptoms, including nyctalopia, constriction of the visual fields, and loss of central visual acuity, usually by the second decade of life (Karjalainen et al., 1985; Pakarinen et al., 1995). For a discussion of genetic heterogeneity of type III Usher syndrome, see USH3A (276902). Clinical Features Puffenberger et al. (2012) studied Usher syndrome patients from Old Order Amish families in Pennsylvania. Growth and development were normal during infancy. Visual impairment became evident during early childhood with the emergence of fine horizontal nystagmus, light aversion, and optic pallor.

A number sign (#) is used with this entry because Usher syndrome type IF (USH1F) can be caused by homozygous or compound heterozygous mutation in the protocadherin-15 gene (PCDH15; 605514) on chromosome 10q. See 601067 for a form of Usher syndrome type I (USH1D/F) caused by digenic mutation in the CDH23 (605516) and PCDH15 genes. For a general description and a discussion of genetic heterogeneity of USH1, see 276900. Description Usher syndrome constitutes a group of autosomal recessive disorders characterized by progressive pigmentary retinopathy and sensorineural hearing loss. Phenotypic distinctions are based on auditory and vestibular differences.

A number sign (#) is used with this entry because Usher syndrome type ID (USH1D) is caused by homozygous or compound heterozygous mutation in the gene encoding cadherin-23 (CDH23; 605516) on chromosome 10q22. The same gene is the site of mutation in a form of nonsyndromic autosomal recessive deafness, DFNB12 (601386). Type ID/F Usher syndrome is caused by digenic mutation in the CDH23 and PCDH15 (605514) genes. Description Usher syndrome type I is an autosomal recessive condition characterized by profound congenital hearing impairment with unintelligible speech, early retinitis pigmentosa (usually evident within the first decade), and constant vestibular dysfunction. Type I is distinguished from type II (276901) on the basis of severity of hearing loss and the extent of vestibular involvement.

A number sign (#) is used with this entry because Usher syndrome type IG can be caused by homozygous or compound heterozygous mutation in the SANS gene (USH1G; 607696) on chromosome 17q25. For a discussion of genetic heterogeneity of Usher syndrome type I, see 276900. Description Usher syndrome is an autosomal recessive disorder associated with sensorineural hearing impairment and progressive visual loss attributable to retinitis pigmentosa. The syndrome is both clinically and genetically heterogeneous. Of the 3 different clinical types that have been described, USH1 (276900), consisting of the association of profound congenital deafness, constant vestibular dysfunction, and prepubertal onset retinitis pigmentosa, is the most severe. Clinical Features Bashir et al. (2010) reported 4 affected members of a consanguineous Pakistani family with Usher syndrome type IG.

A number sign (#) is used with this entry because Usher syndrome type IIC (USH2C) is caused by homozygous or compound heterozygous mutation in the ADGRV1 gene (602851) on chromosome 5q14. It is also caused by biallelic digenic mutation in the ADGRV1 and PDZD7 (612971) genes. Description Usher syndrome is a clinically and genetically heterogeneous autosomal recessive disorder characterized by sensorineural hearing deficiencies at birth and later development of progressive retinitis pigmentosa (RP). It is the most frequent cause of combined deafness and blindness in adults and affects 3 to 6% of children born with hearing impairment. In brief, patients with Usher syndrome type II have mild hearing impairment with normal vestibular responses.

Vestibular response was abolished in 3 patients with type I and was normal in 3 patients with type II and in 1 patient with type III. In Norway, Grondahl (1987) found 28 patients from 18 families with Usher syndrome.

A number sign (#) is used with this entry because of evidence that type IID Usher syndrome (USH2D) is caused by homozygous or compound heterozygous mutation in the WHRN gene (607928) on chromosome 9q32. WHRN mutation has also been shown to cause a form of autosomal recessive nonsyndromic deafness, DFNB31 (607084). Description Usher syndrome is a clinically and genetically heterogeneous autosomal recessive disorder characterized by sensorineural hearing deficiencies at birth and later development of progressive retinitis pigmentosa (RP). It is the most frequent cause of combined deafness and blindness in adults and affects 3 to 6% of children born with hearing impairment. In brief, patients with Usher syndrome type II have mild hearing impairment with normal vestibular responses.