Summary Clinical characteristics. Spinocerebellar ataxia type 10 (SCA10) is characterized by slowly progressive cerebellar ataxia that usually starts as poor balance and unsteady gait, followed by upper-limb ataxia, scanning dysarthria, and dysphagia. Abnormal tracking eye movements are common. Recurrent seizures after the onset of gait ataxia have been reported with variable frequencies among different families. Some individuals have cognitive dysfunction, behavioral disturbances, mood disorders, mild pyramidal signs, and peripheral neuropathy. Age of onset ranges from 12 to 48 years. Diagnosis/testing. Diagnosis of SCA10 is established in a proband by identification of a heterozygous ATTCT pentanucleotide-repeat expansion in ATXN10 . Affected individuals have expanded alleles with up to 4,500 ATTCT pentanucleotide repeats; intermediate alleles (280 to 850 repeats) may show reduced penetrance.

Spinocerebellar ataxia type 10 (SCA10) is a subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by slowly progressive cerebellar syndrome and epilepsy, sometimes mild pyramidal signs, peripheral neuropathy and neuropsychological disturbances. Epidemiology Prevalence is unknown. Many kindreds have been found in Mexican and Brazilian populations. SCA10 is the second most common inherited ataxia in these two countries. Clinical description Age of onset ranges from 18 to 45 years (mean age = 32.2 years).

MRCS syndrome is a rare, genetic retinal dystrophy disorder characterized by bilateral microcornea, rod-cone dystrophy, cataracts and posterior staphyloma, in the absence of other systemic features. Night blindness is typically the presenting manifestation and nystagmus, strabismus, astigmatism and angle closure glaucoma may be associated findings. Progressive visual acuity deterioration, due to pulverulent-like cataracts, results in poor vision ranging from no light perception to 20/400.

Generalized pustular psoriasis is a severe inflammatory skin condition that can be life-threatening. Affected people develop episodes of red and tender skin with widespread pustules throughout their body. This is generally accompanied by fever, chills, headache, rapid pulse rate, loss of appetite, nausea and muscle weakness. The condition generally resolves within days or weeks; however, relapses are common. Some cases of generalized pustular psoriasis are caused by changes (mutations) in the IL36RN gene and are inherited in an autosomal recessive manner.

Generalized pustular psoriasis Specialty Dermatology Generalized pustular psoriasis ( GPP ) is an extremely rare type of psoriasis that can present in a variety of forms. Unlike the most general and common forms of psoriasis, GPP usually covers the entire body and with pus-filled blisters rather than plaques. GPP can present at any age, but is rarer in young children. It can appear with or without previous psoriasis conditions or history, and can reoccur in periodic episodes. Contents 1 Signs and symptoms 2 Causes 3 Genetic factors 4 Diagnosis 4.1 Classification 4.1.1 von Zumbusch acute generalized pustular psoriasis 4.1.2 Generalized pustular psoriasis of pregnancy (Impetigo herpetiformis) 4.1.2.1 Infantile and juvenile 4.1.3 Circinate and annular 5 Treatments 6 Prognosis 7 Case reports 7.1 Case report 1 7.2 Case report 2 7.3 Case report 3 7.4 Case report 4 7.5 Case report 5 8 See also 9 References 10 External links Signs and symptoms [ edit ] GPP presents as pustules and plaques over a wide area of the body. It differs from the localized form of pustular psoriasis in that patients are often febrile and systemically ill. [1] However, the most prominent symptom, as described in the Archives of Dermatology , is "sheeted, pinhead-sized, sterile, sub-corneal pustules". [2] The IPC roundtable adds that these pustules often occur either at the edges "of expanding, intensely inflammatory plaques" or "within erythrodermic skin". [3] Causes [ edit ] Most cases of generalized pustular psoriasis present in patients with existing or prior psoriasis conditions. [2] [3] However, there are many cases of GPP that arise without a history of psoriasis. [3] The Department of Dermatology of the University of São Paulo proposed a classification for these two conditions.

Generalized pustular psoriasis is a severe inflammatory skin disease that can be life-threatening and that is characterized by recurrent episodes of high fever, fatigue, episodic erythematous cutaneous eruptions with sterile cutaneous pustules formation on various parts of the body, and neutrophil leukocytosis.

A number sign (#) is used with this entry because of evidence that susceptibility to pustular psoriasis-15 (PSORS15) is conferred by heterozygous mutation in the AP1S3 gene (615781) on chromosome 2q36. For a discussion of genetic heterogeneity of psoriasis, see PSORS1 (177900). Molecular Genetics Setta-Kaffetzi et al. (2014) performed whole-exome sequencing in 9 patients with acral pustular psoriasis (acrodermatitis continua of Hallopeau) who were negative for mutation in the CARD14 (607211) and IL36RN (605507) genes, and identified heterozygosity for a missense mutation in the AP1S3 gene (R33W; 615781.0001) in 4 patients. Subsequent screening of 119 unrelated British patients with pustular psoriasis, including 112 with the palmoplantar form (PPP), 5 with the generalized form (GPP), and 2 with the acral form, revealed the same R33W missense mutation in 5 additional patients, 4 with PPP and 1 with GPP; in addition, 6 patients, 5 with PPP and 1 with GPP, were heterozygous for another missense mutation (F4C; 615781.0002) in the AP1S3 gene. Overall, Setta-Kaffetzi et al. (2014) observed that AP1S3 variants were detected in all forms of pustular psoriasis but were noticeably enriched among patients with the acral form and significantly underrepresented within the PPP dataset.

Mucopolysaccharidosis type IIIB (MPS IIIB) is an genetic disorder that makes the body unable to break down large sugar molecules called glycosaminoglycans (GAGs, formerly called mucopolysaccharides). Specifically, people with this condition are unable to break down a GAG called heparan sulfate. Affected individuals can have severe neurological symptoms, including progressive dementia, aggressive behavior, hyperactivity, seizures, deafness, loss of vision, and an inability to sleep for more than a few hours at a time. MPS IIIB is caused by alterations (mutations) in the NAGLU gene. This gene provides the instructions for producing an enzyme called N-alpha-acetylglucosaminidase, which is needed to completely break down heparan sulfate. MPS IIIB is inherited in an autosomal recessive manner. There is no specific treatment for this condition.

Mucocutaneous venous malformations (VMCMs) are hereditary vascular malformations characterized by the presence of small, multifocal, bluish-purple venous lesions involving the skin and mucosa. Epidemiology Prevalence is unknown but around 20 families have been identified so far. Clinical description The multifocal venous lesions are usually small (< 2cm in diameter), and are present at birth. They are soft and usually compressible and undergo proportionate growth with age. There is significant clinical variation with respect to the size, location and number of lesions, even between affected individuals from the same family.

Multiple cutaneous and mucosal venous malformations (also known as VMCM) are bluish patches (lesions) on the skin (cutaneous) and the mucous membranes, such as the lining of the mouth and nose. These lesions represent areas where the underlying veins and other blood vessels did not develop properly (venous malformations). The lesions can be painful, especially when they extend from the skin into the muscles and joints, or when a calcium deposit forms within the lesion causing inflammation and swelling. Most people with VMCM are born with at least one venous malformation. As affected individuals age, the lesions present from birth usually become larger and new lesions often appear.

Summary Clinical characteristics. The condition multiple cutaneous and mucosal venous malformations (VMCM) is characterized by the presence of small, multifocal bluish cutaneous and/or mucosal venous malformations. They are usually present at birth. New lesions appear with time. Small lesions are usually asymptomatic; larger lesions can invade subcutaneous muscle and cause pain. Malignant transformation has not been reported. Diagnosis/testing. The diagnosis of VMCM is established in a proband with small, multifocal cutaneous and/or mucosal bluish-purple vascular malformations with slow blood flow on Doppler ultrasound AND/OR by the identification of a heterozygous gain-of-abnormal-function pathogenic variant in TEK by molecular genetic testing. Management. Treatment of manifestations: Sclerotherapy, alone or in combination with plastic and reconstructive surgery, is used depending on the size and location of the lesions. Low molecular-weight heparin (LMWH) should be administered prior to any invasive procedure.

Pancreatic hypoplasia-diabetes-congenital heart disease syndrome is characterized by partial pancreatic agenesis, diabetes mellitus, and heart anomalies (including transposition of the great vessels, ventricular or atrial septal defects, pulmonary stenosis, or patent ductus arteriosis). Epidemiology It has been described in one Japanese family, in which the mother and at least two of her four children were affected (another two children died shortly after birth). Genetic counseling The syndrome appears to be inherited as an autosomal dominant trait.

GM1 gangliosidosis is a rare lysosomal storage disorder characterized biochemically by deficient beta-galactosidase activity and clinically by a wide range of variable neurovisceral, ophthalmological and dysmorphic features. Epidemiology The disorder is panethnic but worldwide prevalence is not known. Prevalence at birth is estimated to be approximately 1:100,000 to 200,000 live births. High prevalence has been found in Malta and Brazil, and in the Cypriot and Roma populations. Clinical description There are three types of GM1 gangliosidosis based on the age of onset: a severe rapidly progressive infantile form with onset before six months of age (type 1 GM1 gangliosidosis), a late infantile or juvenile form with onset between seven months and 3 years of age with delayed motor and cognitive development (type 2 GM1 gangliosidosis), and an adult, chronic form with late onset between 3 and 30 years of age (type 3 GM1 gangliosidosis) characterized primarily by generalized dystonia (see these terms).

GM1 gangliosidosis is an inherited lysosomal storage disorder that progressively destroys nerve cells (neurons) in the brain and spinal cord. The condition may be classified into three major types based on the general age that signs and symptoms first appear: classic infantile ( type 1 ); juvenile ( type 2 ); and adult onset or chronic ( type 3 ). Although the types differ in severity, their features may overlap significantly. GM1 gangliosidosis is caused by mutations in the GLB1 gene and is inherited in an autosomal recessive manner. Treatment is currently symptomatic and supportive.

A number sign (#) is used with this entry because GM1-gangliosidosis is caused by mutation in the gene encoding beta-galactosidase-1 (GLB1; 611458). Description GM1-Gangliosidosis is an autosomal recessive lysosomal storage disease characterized by accumulation of ganglioside substrates in lysosomes. Clinically, patients show variable degrees of neurodegeneration and skeletal abnormalities. There are 3 main clinical variants categorized by severity and variable residual beta-galactosidase activity. Type I, or infantile form, shows rapid psychomotor deterioration beginning within 6 months of birth, generalized central nervous system involvement, hepatosplenomegaly, facial dysmorphism, macular cherry-red spots, skeletal dysplasia, and early death.

A number sign (#) is used with this entry because of evidence that 3-methylcrotonylglycinuria II, or MCC2 deficiency (MCC2D), is caused by homozygous or compound heterozygous mutation in the gene encoding the beta subunit of 3-methylcrotonyl-CoA carboxylase (MCCC2; 609014) on chromosome 5q13. Also see 3-methylcrotonylglycinuria I (MCC1D; 210200), caused by mutation in the alpha subunit of 3-methylcrotonyl-CoA carboxylase (MCCC1; 609010). Clinical Features Beemer et al. (1982) reported 2 Vietnamese sibs with isolated 3-methylcrotonyl-CoA carboxylase deficiency who presented in early childhood shortly after arriving as immigrants to the Netherlands. Both children excreted large amounts of 3-methylcrotonylglycine (MCG) and 3-hydroxyisovaleric acid (HIVA). There was no in vivo or in vitro response to biotin. One patient had transient alopecia.

A rare inherited disorder of leucine metabolism characterized by a highly variable clinical picture ranging from metabolic crisis in infancy to asymptomatic adults. Epidemiology The birth prevalence in Europe is estimated at 1/50,000-1/30,000. The introduction of neonatal screening programs based on tandem mass spectrometry has revealed a high frequency of this disorder, and it now appears to be the most common organic aciduria in some populations. Clinical description Patients with 3-methylcrotonyl-CoA carboxylase deficiency (3-MCCD) have a variable clinical phenotype with the vast majority of patients being asymptomatic and a small subgroup displaying symptoms of an organic aciduria, usually in association with environmental triggering factors. Many newborns now diagnosed through expanded newborn screening tests remain asymptomatic, indicating that the disease has a very low clinical penetrance.

3-methylcrotonyl-CoA carboxylase deficiency (3-MCC deficiency) is an inherited condition in which the body is unable to breakdown the amino acid, leucine (a building block of protein). Some children with 3-MCC deficiency will begin developing signs and symptoms during infancy or early childhood; however, more recent studies suggest that many affected babies identified through newborn screening will never experience symptoms of the condition. 3-MCC deficiency may be associated with episodes of " metabolic crisis " in which affected people experience poor appetite, lack of energy, irritability, weakness, nausea and/or vomiting. If metabolic crises are untreated, the condition can lead to developmental delay, seizures, coma, and even death. 3-MCC deficiency is caused by changes (mutations) in MCCC1 or MCCC2 gene and is inherited in an autosomal recessive manner. Treatment may include a low-leucine diet and appropriate supplements.

3-Methylcrotonyl-CoA carboxylase deficiency Other names 3MCC deficiency Methylcrotonyl-CoA This article includes a list of general references , but it remains largely unverified because it lacks sufficient corresponding inline citations . Please help to improve this article by introducing more precise citations. ( July 2011 ) ( Learn how and when to remove this template message ) 3-Methylcrotonyl-CoA carboxylase deficiency also known as 3-Methylcrotonylglycinuria or BMCC deficiency is an inherited disorder in which the body is unable to process certain proteins properly. People with this disorder have inadequate levels of an enzyme that helps break down proteins containing the amino acid leucine . This condition affects an estimated 1 in 50,000 individuals worldwide. Contents 1 Presentation 2 Genetics 3 Screening 4 Treatment 5 References 6 External links Presentation [ edit ] Infants with this disorder appear normal at birth but usually develop signs and symptoms during the first year of life or in early childhood.

3-methylcrotonyl-CoA carboxylase deficiency (also known as 3-MCC deficiency) is an inherited disorder in which the body is unable to process certain proteins properly. People with this disorder have a shortage of an enzyme that helps break down proteins containing a particular building block (amino acid) called leucine. Infants with 3-MCC deficiency appear normal at birth but usually develop signs and symptoms in infancy or early childhood. The characteristic features of this condition, which can range from mild to life-threatening, include feeding difficulties, recurrent episodes of vomiting and diarrhea, excessive tiredness (lethargy), and weak muscle tone (hypotonia). If untreated, this disorder can lead to delayed development, seizures, and coma.

Hypokalemic periodic paralysis Other names hypoKPP This condition is inherited in an autosomal dominant manner Specialty Neurology , neuromuscular medicine Hypokalemic periodic paralysis ( hypoKPP ), also known as familial hypokalemic periodic paralysis ( FHPP ), [1] is a rare, autosomal dominant channelopathy characterized by muscle weakness or paralysis when there is a fall in potassium levels in the blood . In individuals with this mutation, attacks sometimes begin in adolescence and most commonly occur with individual triggers such as rest after strenuous exercise (attacks during exercise are rare), high carbohydrate meals, meals with high sodium content, sudden changes in temperature, and even excitement, noise, flashing lights, cold temperatures and stress. Weakness may be mild and limited to certain muscle groups, or more severe full-body paralysis. During an attack, reflexes may be decreased or absent. Attacks may last for a few hours or persist for several days. Recovery is usually sudden when it occurs, due to release of potassium from swollen muscles as they recover.

A number sign (#) is used with this entry because hypokalemic periodic paralysis type 2 (HOKPP2) is caused by heterozygous mutation in the SCN4A gene (603967). Mutations in the SCN4A gene can also cause hyperkalemic periodic paralysis (HYPP; 170500). For a general phenotypic description and a discussion of genetic heterogeneity of HOKPP, see HOKPP1 (170400), which is caused by mutation in the CACNL1A3 gene (CACNA1S; 114208). Clinical Features Bulman et al. (1999) reported 2 cousins with HOKPP. The proband experienced a first paralytic attack at age 14 on awakening in the morning, and was found to have a serum potassium of 2.2 mmol/L.

It was present in all 11 affected individuals from the same family ranging from age 33 to 74 years [Links et al 1990] and in 28% of a study group with a mean age of 39 years (range 8-66 years) [Sternberg et al 2001].

Hypokalemic periodic paralysis (HOKPP) is characterized by episodes of muscle paralysis associated with a fall in blood potassium levels ( hypokalemia ). Episodes typically involve a temporary inability to move muscles in the arms and legs. The first attack usually occurs in childhood or adolescence. Attacks can last for hours or days, and the frequency of attacks varies among people with HOKPP. The frequency is usually highest between the ages of 15 and 35, and then decreases with age. Some people with HOKPP also develop late-onset proximal myopathy . HOKPP can be caused by mutations in the CACNA1S , SCN4A , or KCNJ18 gene.

A form of oculocutaneous albinism characterized by light hair at birth that darkens with age, white skin, transparent irides, photophobia, nystagmus, foveal hypoplasia and reduced visual acuity.

Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare immunodeficiency syndrome , with susceptibility to mycobacteria, such as the vaccine against tuberculosis (bacillus Calmette-Guérin (BCG) and environmental mycobacteria . It is characterized by severe, recurrent infections, either systemic (widespread) or localized. It has many subtypes. The most serious types are the autosomal recessive complete interferon gamma receptor 1 (IFN-gammaR1) and receptor 2 (IFN-gammaR2) deficiencies. MSMD due to partial IFN-gammaR1, partial IFN-gammaR2, complete IL-12R-beta1, complete IL12B, complete ISG15, partial STAT1 and partial IRF8 deficiencies and MSMD due to partial X-linked recessive (XR) mutations are less severe subtypes. Only about half of patients with MSMD have an identified genetic cause.

Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare immunodeficiency syndrome, characterized by a narrow vulnerability to poorly virulent mycobacteria, such as bacillus Calmette-Guérin (BCG) vaccines and environmental mycobacteria (EM), and defined by severe, recurrent infections, either disseminated or localized. Epidemiology The prevalence is unknown. Clinical description MSMD due to autosomal recessive (AR) complete interferon gamma receptor 1 (IFN-gammaR1) and receptor 2 (IFN-gammaR2) deficiencies (see these terms), the most serious variants, develop in early childhood with first infections generally occurring around the age of 3. Serious, disseminated infections with BCG and EM are observed and can involve soft tissue, bone marrow, lungs, skin, bones and lymph nodes. Other infections with Salmonella spp. , Listeria monocytogenes and viruses have been reported. MSMD due to partial IFN-gammaR1, partial IFN-gammaR2, complete IL-12R-beta1, complete IL12B, complete ISG15, partial STAT1 and partial IRF8 deficiencies and MSMD due to partial X-linked recessive (XR) mutations (see these terms) are usually less severe.

Description Although primary lateral sclerosis (PLS) is similar to amyotrophic lateral sclerosis (ALS; 105400), they are considered to be clinically distinct progressive paralytic neurodegenerative disorders. Following a period of diagnostic confusion, the clinical distinction between ALS and PLS became clear and diagnostic criteria were established (Pringle et al., 1992). PLS is characterized by degeneration of the upper motor neurons and the corticospinal and corticobulbar tracts, whereas ALS is a more severe disorder characterized by degeneration of both the upper and lower motor neurons. See 606353 for autosomal recessive juvenile-onset PLS, which is caused by mutations in the ALS2 gene (606352). Clinical Features Pringle et al. (1992) reported 8 unrelated patients with adult-onset sporadic PLS and suggested diagnostic criteria.

Microcephalic primordial dwarfism due to RTTN deficiency is a rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by primary microcephaly, profound short stature, moderate to severe intellectual disability, global developmental delay, craniofacial dysmorphism (e.g. sloping forehead, high and broad nasal bridge) and variable brain malformations, including simplified gyration, pachygyria, polymicrogyria, reduced sulcation, dysgenesis of corpus callosum and deformed ventricles. Renal anomalies, bilateral hearing loss, multiple joint contractures, severe failure to thrive and a sacral lesion cephalad to the gluteal crease have also been reported.