Bethlem myopathy is a rare disease affecting the skeletal muscles and connective tissue . The disease is characterized by slowly progressive muscle weakness and joint stiffness (contractures). It most often affects the fingers, wrists, elbows, and ankles. Signs and symptoms may begin before birth (with decreased fetal movements), shortly after birth (with low muscle tone or torticollis), in early childhood (with delayed motor skills, muscle weakness, and contractures), or in adulthood (with weakness, Achilles tendon, or finger contractures). Due to the disease's progression, most people with Bethlem myopathy over age 50 require mobility aids (such as a cane, crutches, or wheelchair) for outdoor mobility. Rarely, severe muscle weakness may lead to respiratory difficulties in later life.

Bethlem myopathy Bethlem myopathy has an autosomal dominant pattern of inheritance (autosomal recessive form exists as well [1] ) Bethlem myopathy is an autosomal dominant myopathy , classified as a congenital form of muscular dystrophy , that is caused by a mutation in one of the three genes coding for type VI collagen . [2] These include COL6A1 , COL6A2 , and COL6A3 . [3] Gower's sign , tiptoe -walking and contractures of the joints (especially the fingers) are typical signs and symptoms of the disease. Bethlem myopathy could be diagnosed based on clinical examinations and laboratory tests may be recommended. Currently there is no cure for the disease and symptomatic treatment is used to relieve symptoms and improve quality of life. Bethlem myopathy affects about 1 in 200,000 people. [4] Contents 1 Signs and symptoms 2 Diagnosis 3 Treatment 4 Epidemiology 5 References 6 External links Signs and symptoms [ edit ] The onset of this disease can begin even before birth but is more commonly in childhood or later into adult life. The progression is slow, with symptoms of weakness and walking difficulties sometimes not presenting until middle age.

Collagen VI-related myopathy is a group of disorders that affect skeletal muscles (which are the muscles used for movement) and connective tissue (which provides strength and flexibility to the skin, joints, and other structures throughout the body). Most affected individuals have muscle weakness and joint deformities called contractures that restrict movement of the affected joints and worsen over time. Researchers have described several forms of collagen VI-related myopathy, which range in severity: Bethlem myopathy is the mildest, an intermediate form is moderate in severity, and Ullrich congenital muscular dystrophy is the most severe. People with Bethlem myopathy usually have loose joints (joint laxity) and weak muscle tone (hypotonia) in infancy, but they develop contractures during childhood, typically in their fingers, wrists, elbows, and ankles. Muscle weakness can begin at any age but often appears in childhood to early adulthood.

A number sign (#) is used with this entry because of evidence that Bethlem myopathy-2 (BTHLM2), also known as myopathic-type Ehlers-Danlos syndrome, is caused by heterozygous mutation in the COL12A1 gene (120320) on chromosome 6q. For a discussion of genetic heterogeneity of Bethlem myopathy, see BTHLM1 (158810). Clinical Features Zou et al. (2014) reported a boy with features consistent with Bethlem myopathy. Hypotonia, proximal joint contractures, and distal myopathy were noted during his first year of life. Motor development was delayed, and he started to walk shortly before his second birthday.

Bethlem myopathy is a benign autosomal dominant form of slowly progressive muscular dystrophy. Epidemiology To date, fewer than 100 cases have been reported in the literature, thus illustrating its rarity. Clinical description The clinical features do not differ markedly from those of other mild forms of progressive muscular dystrophy with the exception of finger contractures which are sometimes suggestive of the diagnosis. Etiology Mutations in one of the three subunits of collagen VI are responsible for the disease. Molecular studies are however hampered by the size and expression pattern of the genes.

Collagen type VI-related disorders are caused by alterations (mutations) of collagen genes ( COL6A1 , COL6A2 , or COL6A3 genes) and include diseases that are mild like Bethlem myopathy or more severe like the Ullrich congenital muscular dystrophy (CMD). Diagnosis depends on typical clinical features, muscle biopsy (for suspected Ullrich CMD) or skin biopsy (for suspected Bethlem myopathy) and genetic testing that shows mutations in the collagen VI genes. The treatment depends on the signs and symptoms that are present and may include physiotherapy regarding stretching exercises, splinting, and mobility aids and orthopedic surgeries.

Summary Clinical characteristics. Chediak-Higashi syndrome (CHS) is characterized by partial oculocutaneous albinism, immunodeficiency, and a mild bleeding tendency. Approximately 85% of affected individuals develop the accelerated phase, or hemophagocytic lymphohistiocytosis, a life-threatening, hyperinflammatory condition. All affected individuals including adolescents and adults with atypical CHS and children with classic CHS who have successfully undergone allogenic hematopoietic stem cell transplantation (HSCT) develop neurologic findings during early adulthood. Diagnosis/testing. The diagnosis of CHS is established in a proband with giant inclusions within leukocytes on peripheral blood smear and/or by the identification of biallelic pathogenic variants in LYST on molecular genetic testing. Management. Treatment of manifestations: Initial chemoimmunotherapy followed by transition to continuation therapy for the accelerated phase; allogenic HSCT as soon as possible to cure hematologic and immunologic defects; L-dopa may be considered for those with parkinsonism; home modifications and intensive rehabilitation for those with ataxia and other neurologic complications; corrective lenses to improve visual acuity; sunglasses to protect sensitive eyes from UV light; sunscreen to prevent sun damage and skin cancer.

Chédiak-Higashi syndrome (CHS) is a rare severe genetic disorder generally characterized by partial oculocutaneous albinism (OCA, see this term), severe immunodeficiency, mild bleeding, neurological dysfunction and lymphoproliferative disorder. A classic, early-onset form and an attenuated, later-onset form (Atypical CHS; see this term) have been described. Epidemiology Exact prevalence is difficult to determine; fewer than 500 cases have been reported. Many patients likely remain undiagnosed because of variability in clinical signs. No gender or ethnic predilection has been found. Clinical description Patients with CHS mostly have partial OCA involving the hair, skin, and eyes.

Chediak-Higashi syndrome is a condition that affects many parts of the body, particularly the immune system. This disease damages immune system cells, leaving them less able to fight off invaders such as viruses and bacteria. As a result, most people with Chediak-Higashi syndrome have repeated and persistent infections starting in infancy or early childhood. These infections tend to be very serious or life-threatening. Chediak-Higashi syndrome is also characterized by a condition called oculocutaneous albinism, which causes abnormally light coloring (pigmentation) of the skin, hair, and eyes. Affected individuals typically have fair skin and light-colored hair , often with a metallic sheen.

This article's lead section may be too short to adequately summarize its key points . Please consider expanding the lead to provide an accessible overview of all important aspects of the article. ( December 2016 ) Béguez-Chédiak–Higashi syndrome Béguez-Chédiak–Higashi syndrome is inherited in an autosomal recessive manner Specialty Endocrinology Béguez-Chédiak–Higashi syndrome [1] ( CHS ) is a rare autosomal recessive disorder that arises from a mutation of a lysosomal trafficking regulator protein, [2] which leads to a decrease in phagocytosis . The decrease in phagocytosis results in recurrent pyogenic infections, albinism , and peripheral neuropathy . In Béguez–Higashi syndrome, the lysosomal trafficking regulator ( LYST ) gene is mutated, leading to disruption of protein synthesis as well as the storage and secretory function of lysosomal granules in white blood cells . [3] This results in defective white blood cell function with enlarged vesicles . This syndrome also leads to neutropenia and phagocyte bactericidal dysfunction due to impaired chemotaxis . [4] Deficiency in serotonin and adenosine-phosphate-containing granules in platelets causes impaired platelet aggregation, leading to prolonged bleeding time.

Chediak-Higashi syndrome is a genetic syndrome that affects the immune system, as well as other parts of the body. Signs and symptoms include a weakened immune system, repeated and persistent infections beginning in infancy and childhood, oculocutaneous albinism , blood clotting problems, and nervous system abnormalities (e.g., weakness, difficulty walking, and seizures). Complications from this syndrome can become life-threatening. It is caused by mutations in the LYST gene and is inherited in an autosomal recessive fashion.

A number sign (#) is used with this entry because of evidence that right atrial isomerism (RAI) is caused by homozygous mutation in the GDF1 gene (602880) on chromosome 19p12. Description Right atrial isomerism is a severe complex congenital heart defect resulting from embryonic disruption of proper left-right axis determination. RAI is usually characterized by complete atrioventricular septal defect with a common atrium and univentricular AV connection, total anomalous pulmonary drainage, and transposition or malposition of the great arteries. Affected individuals present at birth with severe cardiac failure. Other associated abnormalities include bilateral trilobed lungs, midline liver, and asplenia, as well as situs inversus affecting other organs. Left atrial isomerism (LAI) is a related disorder with a somewhat better prognosis.

A rare heterotaxia characterized by complex congenital heart malformations and abnormal lateralization of other thoracic and abdominal organs due to embryonic disruption of the left-right axis development. Cardiac defects include dextrocardia or mesocardia, common atrioventricular valve associated with complete atrioventricular septal defect or common atrium, transposition or malposition of the great arteries, and total anomalous pulmonary venous drainage, among others. Cardiac arrhythmias are frequently observed. Typical abnormalities of other organs are bilateral trilobed lungs, midline liver, and asplenia. Patients present in the newborn period with severe cardiac failure and cyanosis. Prognosis is poor.

Ivemark syndrome is a rare congenital condition that affects multiple organ systems of the body. Ivemark syndrome is classified as a heterotaxy disorder or a laterality disorder. These terms refer to the failure of the internal organs of the chest and abdomen to be arranged in the proper location within the body. It is characterized by the absence (asplenia) or underdevelopment (hypoplasia) of the spleen , heart malformations , and the abnormal arrangement of the internal organs of the chest and abdomen. Symptoms vary greatly depending on the specific abnormalities present; however if heart malformations are complex, the prognosis is often poor.

A number sign (#) is used with this entry because the phenotype is caused by duplication of genes lying within the critical region for Williams-Beuren syndrome (WBS; 194050) on chromosome 7q11.23. Description The chromosome 7q11.23 duplication syndrome is a multisystem developmental disorder with variable manifestations, most commonly speech delay and mild craniofacial anomalies, and an increased incidence of congenital anomalies such as heart defects, diaphragmatic hernia, and cryptorchidism. Many patients have cognitive defects ranging from mental retardation to autism, although some have normal cognitive abilities (summary by Van der Aa et al., 2009). Clinical Features Somerville et al. (2005) described a boy with growth retardation, mild dysmorphism, and overall developmental delay with a severe impairment in expressive language. Receptive language was found to be in the low average range for age. Hearing was normal.

7q11.23 duplication syndrome is a chromosome abnormality characterized by a variety of neurological and behavioral differences. It is caused by a small amount of additional (duplicated) genetic material from chromosome 7 . Symptoms may include: motor, speech and language delay, behavior problems, intellectual disability, low muscle tone (hypotonia), an increased head circumference ( macrocephaly ), facial dysmorphism, seizures, brain abnormalities, and heart defects such as enlargement of the blood vessel that carries blood from the heart to the rest of the body (aortic dilatation). 7q11.23 duplication syndrome is caused by a duplication of genetic material on the long (q) arm of chromosome 7. Some cases of 7q11.23 duplication syndrome are inherited in an autosomal dominant manner; however, the majority of affected individuals have a new ( de novo ) duplication. While there is no cure for 7q11.23 duplication, treatment options will depend on the type and severity of symptoms present and may involve several specialists.

7q11.23 duplication syndrome Other names dup7 7q11.23 duplication syndrome (also called dup7 or Duplication of the Williams-Beuren Syndrome Critical Region) is a rare genetic syndrome caused by micro-duplication of 1.5-1.8 mega base in section q11.23 of chromosome 7 . This syndrome is characterized by a wide spectrum of neurological, behavior and other medical problems which may appear in different levels of severity. Common characteristics are speech and sound disorder (CAS - childhood apraxia of speech, dysarthria ), delayed development , delayed motor development and clumsiness, anxiety (especially on social conditions), selective mutism (in 20% of the subjects), ADHD , oppositional disorder , ASD (in 20%), intellectual disability in 18%, cardio-vascular disease (dilation of the ascending aorta in 46%), seizures in 19%, neurological abnormalities ( hypotonia , adventitious movements ). [1] hydrocephalus in 5.6%, [2] chronic constipation. The syndrome was first reported in 2005 [3] Contents 1 Additional symptoms of unknown prevalence 2 Diagnosis 3 Treatment 4 Organization 5 References 6 External links Additional symptoms of unknown prevalence [ edit ] Eyes issues - high strength glasses, strabismus Hypospadias Hypermobility Hypertonia Hearing loss Diagnosis [ edit ] A medical examination is recommended for newly diagnosed including echocardiogram for detection of heart defects (mainly aorta dilation), kidneys ultrasound , consider brain MRI . [1] [4] Treatment [ edit ] Intensive speech/language therapy was found to be important for maximizing long-term outcomes. [5] Organization [ edit ] Duplication Cares is an organization of families affected by dup7. The organization operates a web site and a facebook group. About 500 families are registered in the organization as to 2019.

7q11.23 microduplication syndrome is a rare chromosomal anomaly syndrome resulting from the partial duplication of the long arm of chromosome 7 characterized by a highly variable phenotype that typically manifests with mild-moderate intellectual delay (patients could be in the normal range), speech disorders (particularly of expressive language), and distinctive craniofacial features (brachycephaly, broad forehead, straight eyebows, broad nasal tip, short philtrum, thin upper lip and facial asymmetry). Hypotonia, developmental coordination disorders, behavioral problems (such as anxiety, ADHD and oppositional disorders) and various congenital anomalies, such as heart defects, diaphragmatic hernia, renal malformations and cryptorchidism, are frequently presented. Neurological abnormalities (visible on MRI) have been reported.

A number sign (#) is used with this entry because neuronal ceroid lipofuscinosis-13 (CLN13) is caused by homozygous or compound heterozygous mutation in the CTSF gene (603539) on chromosome 11q13. Description Neuronal ceroid lipofuscinosis-13 is an autosomal recessive neurodegenerative disorder characterized by adult onset of progressive cognitive decline and motor dysfunction leading to dementia and often early death. Some patients develop seizures. Neurons show abnormal accumulation of autofluorescent material (summary by Smith et al., 2013). Adult-onset neuronal ceroid lipofuscinosis is sometimes referred to as Kufs disease. For a discussion of genetic heterogeneity of neuronal ceroid lipofuscinosis (CLN), see CLN1 (256730).

A number sign (#) is used with this entry because neuronal lipofuscinosis-4B (CLN4B) is caused by heterozygous mutation in the DNAJC5 gene (611203) on chromosome 20q13. Description Neuronal ceroid lipofuscinosis-4B is an autosomal dominant neurodegenerative disorder characterized by onset of symptoms in adulthood. It belongs to a group of progressive neurodegenerative diseases characterized by accumulation of intracellular autofluorescent lipopigment storage material in the brain and other tissues. Several different forms have been described according to age of onset (see, e.g., CLN3, 204200). Individuals with the adult form, sometimes referred to as Kufs disease, develop psychiatric manifestations, seizures, cerebellar ataxia, and cognitive decline.

Adult neuronal ceroid lipofuscinosis is a rare condition that affects the nervous system. Signs and symptoms usually begin around age 30, but they can develop anytime between adolescence and late adulthood. There are two forms of adult neuronal ceroid lipofuscinosis that are differentiated by their underlying genetic cause, mode of inheritance and certain symptoms: Type A is characterized by a combination of seizures and uncontrollable muscle jerks (myoclonic epilepsy); dementia; difficulties with muscle coordination (ataxia); involuntary movements such as tremors or tics; and dysarthria. It is caused by changes (mutations) in the CLN6 or PPT1 gene and is inherited in an autosomal recessive manner. Type B shares many features with type A; however, affected people also experience behavioral abnormalities and do not develop myoclonic epilepsy or dysarthria.

A genetically heterogeneous group of neuronal ceroid lipofuscinoses (NCLs) with onset during the third decade of life, characterized by dementia, seizures and loss of motor capacities, and sometimes associated with visual loss caused by retinal degeneration. Epidemiology Prevalence is unknown. Clinical description The clinical picture is characterized by onset with progressive myoclonic epilepsy or behavioral disturbances, dementia and extrapyramidal motor symptoms that appear at the age of 20-30 years. Vision loss is an uncommon feature and depends on the underlying genetic cause. Etiology The ANCL phenotype was originally designated as CLN4 disease, although the causative gene has not yet been identified. CLN4 may be inherited in an autosomal recessive (CLN4A) or autosomal dominant (CLN4B) manner.

"Kufs" redirects here. For the letter used in Semitic languages, see Qoph . Kufs disease Other names Adult neuronal ceroid lipofuscinosis, ANCL, Adult NCL Kufs disease is one of many diseases categorized under a disorder known as neuronal ceroid lipofuscinosis (NCLs). NCLs are broadly described to create problems with vision, movement and cognitive function. [1] Among all NCLs diseases, Kufs is the only one that does not affect vision, and although this is a distinguishing factor of Kufs, NCLs are typically differentiated by the age at which they appear in a patient [2] Contents 1 Signs and symptoms 2 Genetics 2.1 Type A 2.2 Type B 3 Diagnosis 4 Treatment 5 References 6 External links Signs and symptoms [ edit ] Kufs is a neuronal disease, meaning it affects the nervous system, specifically voluntary movement and intellectual function. Symptoms of Kufs can manifest anytime between adolescence and adulthood, however it usually appears around age 30. There are two types of Kufs: [2] Type A and Type B. Type A causes seizures , myoclonic epilepsy (muscle jerks), dementia , ataxia (compromised muscle coordination), tremors and tics, dysarthria (speech difficulties), confusion, and psychotic behaviour.

Twelve patients had previously been reported, and follow-up information was provided for 9 of them. Mean age of onset was 28 years (range, 12-51 years). Patients typically presented with progressive myoclonus epilepsy with debilitating myoclonic seizures and relatively infrequent tonic-clonic seizures.

Connective tissue disorder due to lysyl hydroxylase-3 deficiency is a rare, genetic disease, caused by lack of lysyl hydrohylase 3 (LH3) activity, characterized by multiple tissue and organ involvement, including skeletal abnormalities (club foot, progressive scoliosis, osteopenia, pathologic fractures), ocular involvement (flat retinae, myopia, cataracts) and hair, nail and skin anomalies (coarse, abnormally distributed hair, skin blistering, reduced palmar creases, hypoplastic nails). Patients also present intrauterine growth retardation, facial dysmorphism (flat facial profile, low-set ears, shallow orbits, short and upturned nose, downturned corners of mouth) and joint flexion contractures. Growth and developmental delay, bilateral sensorineural deafness, friable diaphragm and later-onset spontaneous vascular ruptures are additional reported features.

Description Malignant melanoma is a neoplasm of pigment-producing cells called melanocytes that occurs most often in the skin, but may also occur in the eyes, ears, gastrointestinal tract, leptomeninges, and oral and genital mucous membranes (summary by Habif, 2010). Genetic Heterogeneity of Susceptibility to Cutaneous Malignant Melanoma The locus for susceptibility to familial cutaneous malignant melanoma-1 (CMM1) has been mapped to chromosome 1p36. Other CMM susceptibility loci include CMM2 (155601), caused by variation in the CDKN2A gene (600160) on chromosome 9p21; CMM3 (609048), caused by variation in the CDK4 gene (123829) on chromosome 12q14; CMM4 (608035), mapped to chromosome 1p22; CMM5 (613099), caused by variation in the MC1R gene (155555) on chromosome 16q24; CMM6 (613972), caused by variation in the XRCC3 gene (600675) on chromosome 14q32; CMM7 (612263), mapped to chromosome 20q11; CMM8 (614456), caused by variation in the MITF gene (156845) on chromosome 3p13; CMM9 (615134), caused by variation in the TERT gene (187270) on chromosome 5p15; and CMM10 (615848), caused by mutation in the POT1 gene (606478) on chromosome 7q31. Somatic mutations causing malignant melanoma have also been identified in several genes, including BRAF (164757), STK11 (602216), PTEN (601728), TRRAP (603015), DCC (120470), GRIN2A (138253), ZNF831, BAP1 (603089), and RASA2 (601589). A large percentage of melanomas (40-60%) carry an activating somatic mutation in the BRAF gene, most often V600E (164757.0001) (Davies et al., 2002; Pollock et al., 2003).

Dysplastic nevus syndrome Other names Atypical mole syndrome (AMS), familial atypical multiple mole–melanoma (FAMMM) syndrome, familial melanoma syndrome, [1] B-K mole syndrome, atypical mole syndrome Large numbers of moles are characteristic features of familial atypical multiple mole–melanoma syndrome. Specialty Oncology , medical genetics Dysplastic nevus syndrome , also known as familial atypical multiple mole–melanoma (FAMMM) syndrome, is an inherited cutaneous condition described in certain families, and characterized by unusual nevi and multiple inherited melanomas . [2] [3] First described in 1820, the condition is inherited in an autosomal dominant pattern, and caused by mutations in the CDKN2A gene . In addition to melanoma, individuals with the condition are at increased risk for pancreatic cancer . The diagnosis of dysplastic nevus syndrome is based on clinical presentation and family history. Treatment consists of resection of malignant skin lesions (melanoma).

A rare form of hereditary spastic paraplegia which usually presents in late adolescence or early adulthood as a pure phenotype of lower limb spasticity with hyperreflexia and extensor plantar responses, as well as mild bladder disturbances and pes cavus. Rarely, it can present as a complex phenotype with additional manifestations including epilepsy, variable peripheral neuropathy and/or memory impairment.

A number sign (#) is used with this entry because of evidence that Pallister-Hall syndrome (PHS) is caused by heterozygous mutation in the GLI3 gene (165240) on chromosome 7p14. Description Pallister-Hall syndrome is a pleiotropic autosomal dominant disorder comprising hypothalamic hamartoma, pituitary dysfunction, central polydactyly, and visceral malformations (Biesecker et al., 1996). Clinical Features Hall et al. (1980) reported 6 infants with a neonatally lethal malformation syndrome of hypothalamic hamartoblastoma, postaxial polydactyly, and imperforate anus. Some had laryngeal cleft, abnormal lung lobation, renal agenesis or dysplasia, short fourth metacarpals, nail dysplasia, multiple buccal frenula, hypoadrenalism, microphallus, congenital heart defect, and intrauterine growth retardation. All cases were sporadic and chromosomes were apparently normal. The parents were nonconsanguineous.

Human disease Tuber cinereum hamartoma Other names Hypothalamic hamartoma A hypothalamic hamartoma (black arrows) on MRI Tuber cinereum hamartoma is a benign tumor in which a disorganized collection of neurons and glia accumulate at the tuber cinereum of the hypothalamus on the floor of the third ventricle . It is a congenital malformation, included on the spectrum of gray matter heterotopias . Formation occurs during embryogenesis , typically between days 33 and 41 of gestation. Size of the tumor varies from one to three centimeters in diameter, with the mean being closer to the low end of this range. It is estimated to occur at a frequency of one in one million individuals. [1] Contents 1 Signs and symptoms 1.1 Associated conditions 2 Diagnosis 2.1 Anatomic and imaging findings 3 Treatment 4 In popular culture 5 References 6 External links Signs and symptoms [ edit ] Electroencephalography is used to find the source of electrical activity causing the gelastic seizure.

This article needs additional citations for verification . Please help improve this article by adding citations to reliable sources . Unsourced material may be challenged and removed. Find sources: "Pallister–Hall syndrome" – news · newspapers · books · scholar · JSTOR ( August 2011 ) ( Learn how and when to remove this template message ) Pallister–Hall syndrome (PHS) Pallister–Hall syndrome is inherited in an autosomal dominant pattern. Specialty Medical genetics Pallister–Hall syndrome (abbreviated PHS) [1] is a disorder that affects the development of many parts of the body. It is named for Judith Hall and Philip Pallister . [2] [3] Contents 1 Presentation 1.1 Seizures 2 Genetics 3 Diagnosis 4 Treatment 5 Notable Cases 6 References 7 External links Presentation [ edit ] Most people with this condition have extra fingers and/or toes ( polydactyly ), and the skin between some fingers or toes may be fused ( cutaneous syndactyly ). An abnormal growth in the brain called a hypothalamic hamartoma is characteristic of this disorder.

Hypothalamic hamartomas (HH) are rare, tumor-like malformations that occur during fetal development and are present at birth. The lesions usually do not change in size or spread to other locations. Both the type and severity of symptoms vary greatly among patients with hypothalamic hamartomas. Common symptoms include frequent gelastic seizures (spontaneous laughing, giggling and/or smirking) or dacrystic seizures (crying or grunting); developmental delays; and/or precocious puberty . Additional symptoms may include cognitive impairment; emotional and behavioral difficulties; and endocrine disturbances.

A number sign (#) is used with this entry because of evidence that pontocerebellar hypoplasia type 2C (PCH2C) is caused by homozygous mutation in the TSEN34 gene (608754) on chromosome 19q13. One such patient has been reported. Description Pontocerebellar hypoplasia (PCH) represents a heterogeneous group of disorders characterized by an abnormally small cerebellum and brainstem. PCH type 2 is characterized by progressive microcephaly from birth combined with extrapyramidal dyskinesia and chorea, epilepsy, and normal spinal cord findings (Barth, 1993). For a phenotypic description and a discussion of genetic heterogeneity of PCH, see PCH1 (607596). Molecular Genetics In an individual of Turkish origin with PCH2, Budde et al. (2008) identified homozygosity for a missense mutation in the TSEN34 gene (R58W; 608754.0001).

A number sign (#) is used with this entry because pontocerebellar hypoplasia type 2D (PCH2D), also known as progressive cerebellocerebral atrophy (PCCA), is caused by homozygous or compound heterozygous mutation in the SEPSECS gene (613009) on chromosome 4p15. Description PCH2D is an autosomal recessive disorder characterized by progressive microcephaly, postnatal onset of progressive atrophy of the cerebrum and cerebellum, profound mental retardation, spasticity, and variable seizures (summary by Ben-Zeev et al., 2003). For a general phenotypic description and a discussion of genetic heterogeneity of pontocerebellar hypoplasia type 2, see PCH2A (277470). Clinical Features Ben-Zeev et al. (2003) reported 4 unrelated patients with profound mental retardation, postnatal progressive microcephaly, spasticity, and progressive cerebellocerebral atrophy (PCCA). All patients were from nonconsanguineous Sephardic Jewish families: 2 were of Iraqi origin, and 2 were of combined Iraqi and Moroccan origin.

A number sign (#) is used with this entry because of evidence that pontocerebellar hypoplasia type 2F (PCH2F) is caused by homozygous mutation in the TSEN15 gene (608756) on chromosome 1q25. Description Pontocerebellar hypoplasia type 2F is an autosomal recessive neurodevelopmental disorder characterized by progressive microcephaly and variable neurologic signs and symptoms, including cognitive and motor delay, poor or absent speech, seizures, and spasticity (summary by Breuss et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of pontocerebellar hypoplasia type 2, see PCH2A (277470). Clinical Features Alazami et al. (2015) reported a boy (13DG0167), born of consanguineous parents, with primary microcephaly and global developmental delay. Breuss et al. (2016) reported follow-up on this patient, who was born to Saudi parents.

A number sign (#) is used with this entry because of evidence that pontocerebellar hypoplasia type 2A (PCH2A) is caused by homozygous mutation in the TSEN54 gene (608755) on chromosome 17q25. Description Pontocerebellar hypoplasia (PCH) represents a heterogeneous group of disorders characterized by an abnormally small cerebellum and brainstem. PCH type 2 is characterized by progressive microcephaly from birth combined with extrapyramidal dyskinesia and chorea, epilepsy, and normal spinal cord findings (Barth, 1993). For a phenotypic description and a discussion of genetic heterogeneity of PCH, see PCH1 (607596). Genetic Heterogeneity of Pontocerebellar Hypoplasia Type 2 PCH2B (612389) is caused by mutation in the TSEN2 gene (608753) on chromosome 3p25, and PCH2C (612390) is caused by mutation in the TSEN34 gene (608754) on chromosome 19q13.

Pontocerebellar hypoplasia type 2 (PCH2) is a rare condition that affects the development of the brain. Signs and symptoms vary but may include microcephaly, developmental delay with lack of voluntary motor development, intellectual disability and movement disorders (i.e. chorea , dystonia, and spasticity). Affected people may also experience dysphagia (difficulty swallowing), impaired vision, seizures and an inability to communicate. Children with this condition often pass away prior to age 10 years, although survival beyond age 20 years has been reported. PCH2 is caused by changes (mutations) in the TSEN54 , TSEN2 , TSEN34 , or SEPSECS gene and is inherited in an autosomal recessive manner.

A rare, genetic form of pontocerebellar hypoplasia characterized by pontocerebellar hypoplasia and progressive neocortical atrophy that manifests clinically with uncoordinated sucking and swallowing, and generalized clonus in the neonate. In early childhood, spasticity, chorea/dyskinesia, seizures and progressive microcephaly develop. Voluntary motor development is lacking. Epidemiology Pontocerebellar hypoplasia type 2 (PCH2) is reported in at least 81 families to date. It is the most common form of pontocerebellar hypoplasia. Clinical description After an uneventful pregnancy and birth without dysmorphic features, affected neonates present usually, but not always, with dysphagia due to bucco-pharyngeal incoordination, respiratory and feeding difficulties and generalized clonus. Extrapyramidal dyskinesia with mixed spasticity such as chorea, athetosis and dystonia develop later.

A rare autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome characterized by early-childhood onset of cerebellar ataxia associated with generalized tonic-clonic epilepsy and psychomotor development delay, dysarthria, gaze-evoked nystagmus and learning disability. Other features in some patients include upper motor neuron signs with leg spasticity and extensor plantar responses, and mild cerebellar atrophy on brain MRI.

Peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome is a rare, syndromic genetic deafness characterized by a combination of muscle weakness, chronic neuropathic and myopathic features, hoarseness and sensorineural hearing loss. A wide range of disease onset and severity has been reported even within the same family.