Cognitive impairment, and Infertility

Spinocerebellar ataxia type 32 (SCA32) is a subtype of autosomal dominant cerebellar ataxia type 1 (ADCA type 1; see this term) characterized by ataxia, cognitive impairment and azoospermia in males.

SPINOCEREBELLAR ATAXIA TYPE 32 Is also known as cerebellar ataxia with azoospermia and intellectual disability|sca32

• Ataxia
• Cognitive impairment
• Cerebellar atrophy
• Infertility
• Progressive cerebellar ataxia

SOURCES: OMIM ORPHANET MENDELIAN

Boucher-Neuhauser syndrome is an autosomal recessive disorder characterized classically by the triad of spinocerebellar ataxia, hypogonadotropic hypogonadism, and visual impairment due to chorioretinal dystrophy. The age at onset is variable, but most patients develop one or more symptoms in the first decade of life. Chorioretinal dystrophy may not always be present. BNHS is part of a spectrum of neurodegenerative diseases associated with mutations in the PNPLA6 gene that also includes spastic paraplegia-39 (SPG39 ) (summary by Synofzik et al., 2014).See also Gordon Holmes syndrome (GDHS ), caused by mutation in the RNF216 gene (OMIM ), which is also characterized by the combination of cerebellar ataxia and hypogonadotropic hypogonadism.

BOUCHER-NEUHAUSER SYNDROME; BNHS Is also known as spinocerebellar ataxia, hypogonadotropic hypogonadism, and chorioretinal dystrophy

• Ataxia
• Spasticity
• Cognitive impairment
• Visual impairment
• Dysarthria

SOURCES: OMIM MENDELIAN

Gordon Holmes syndrome is an autosomal recessive adult-onset neurodegenerative disorder characterized by progressive cognitive decline, dementia, and variable movement disorders, such as ataxia and chorea. The neurologic phenotype is associated with hypogonadotropic hypogonadism (summary by Santens et al., 2015).

GORDON HOLMES SYNDROME; GDHS Is also known as cahh|cerebellar ataxia and hypogonadotropic hypogonadism|luteinizing hormone-releasing hormone, deficiency of, with ataxia|lhrh deficiency and ataxia

• Hearing impairment
• Ataxia
• Dysarthria
• Abnormality of the skeletal system
• Cerebellar atrophy

SOURCES: OMIM MENDELIAN

Perrault syndrome (PS) is characterized by the association of ovarian dysgenesis in females with sensorineural hearing impairment. In more recent PS reports, some authors have described neurologic abnormalities, notably progressive cerebellar ataxia and intellectual deficit.

PERRAULT SYNDROME Is also known as ovarian dysgenesis with sensorineural deafness|gonadal dysgenesis, xx type, with deafness|xx gonodal dysgenesis-deafness syndrome

• Intellectual disability
• Short stature
• Hearing impairment
• Scoliosis
• Ataxia

SOURCES: ORPHANET OMIM MENDELIAN

Autosomal recessive spastic paraplegia type 46 (SPG46) is a rare, complex type of hereditary spastic paraplegia characterized by an onset, in infancy or childhood, of the typical signs of spastic paraplegia (i.e. spastic gait and weakness of the lower limbs) associated with a variety of additional manifestations including upper limb spasticity and weakness, pseudobulbar dysarthria, bladder dysfunction, cerebellar ataxia, cataracts, and cognitive impairment that can progress to dementia. Brain imaging may show thinning of the corpus callosum and mild atrophy of the cerebrum and cerebellum. SPG46 is due to mutations in the GBA2 gene (9p13.2) encoding non-lysosomal glucosylceramidase.

AUTOSOMAL RECESSIVE SPASTIC PARAPLEGIA TYPE 46 Is also known as spg46

• Intellectual disability
• Hearing impairment
• Scoliosis
• Ataxia
• Nystagmus

SOURCES: OMIM ORPHANET MENDELIAN

Juvenile Huntington disease (JHD) is a form of Huntington disease (HD; see this term), characterized by onset of signs and symptoms before 20 years of age.

JUVENILE HUNTINGTON DISEASE Is also known as huntington chorea|jhd|juvenile huntington chorea

• Seizures
• Ataxia
• Cognitive impairment
• Anemia
• Delayed speech and language development

SOURCES: OMIM ORPHANET MENDELIAN

Myotonic dystrophy (DM) is a multisystem disorder and the most common form of muscular dystrophy in adults. Individuals with DM2 have muscle pain and stiffness, progressive muscle weakness, myotonia, male hypogonadism, cardiac arrhythmias, diabetes, and early cataracts. Other features may include cognitive dysfunction, hypersomnia, tremor, and hearing loss (summary by Heatwole et al., 2011).See also myotonic dystrophy-1 (DM1 ), caused by an expanded CTG repeat in the dystrophia myotonica protein kinase gene (DMPK ) on 19q13.Although originally reported as 2 disorders, myotonic dystrophy-2 and proximal myotonic myopathy are now referred to collectively as DM2 (Udd et al., 2003).

MYOTONIC DYSTROPHY 2; DM2 Is also known as promm|proximal myotonic myopathy|dystrophia myotonica 2|myotonic myopathy, proximal|ricker syndrome

• Intellectual disability
• Hearing impairment
• Muscle weakness
• Pain
• Cataract

SOURCES: ORPHANET OMIM MENDELIAN

The hereditary spastic paraplegias are a group of clinically and genetically diverse disorders characterized by progressive, usually severe, lower extremity spasticity; see reviews of Fink et al. (1996) and Fink (1997).SPG is classified according to both the mode of inheritance (autosomal dominant, autosomal recessive (see {270800}), and X-linked (see {303350})) and whether progressive spasticity occurs in isolation ('uncomplicated SPG') or with other neurologic abnormalities ('complicated SPG'), including optic neuropathy, retinopathy, extrapyramidal disturbance, dementia, ataxia, ichthyosis, mental retardation, and deafness. The major neuropathologic feature of autosomal dominant, uncomplicated SPG is axonal degeneration that is maximal in the terminal portions of the longest descending and ascending tracts (crossed and uncrossed corticospinal tracts to the legs and fasciculus gracilis, respectively). Spinocerebellar fibers are involved to a lesser extent. Since the description of 'pure' hereditary spastic paraparesis of late onset by Strumpell (1904), many 'complicated' forms of the disorder have been reported and the question as to whether a 'pure' form exists has been raised off and on. Probably in large part because of their exceptional length, the pyramidal tracts are unusually vulnerable to both acquired and genetic derangement. Although a majority of reported families have displayed recessive inheritance, 10 to 30% of families have a dominant pattern and in fact recessive inheritance of a 'pure' spastic paraplegia may be rare. Genetic Heterogeneity of Autosomal Dominant Spastic ParaplegiaIn addition to SPG3A, other forms of autosomal dominant spastic paraplegia for which the molecular basis is known include SPG4 (OMIM ), caused by mutation in the SPAST gene (OMIM ) on 2p22; SPG6 (OMIM ), caused by mutation in the NIPA1 gene (OMIM ) on 15q11; SPG8 (OMIM ), caused by mutation in the KIAA0196 gene (OMIM ) on 8q24; SPG9A (OMIM ), caused by mutation in the ALDH18A1 gene (OMIM ) on 10q24; SPG10 (OMIM ), caused by mutation in the KIF5A gene (OMIM ) on 12q13; SPG12 (OMIM ), caused by mutation in the RTN2 gene (OMIM ) on 19q13; SPG13 (OMIM ), caused by mutation in the SSPD1 gene (OMIM ) on 2q33.1; SPG31 (OMIM ), caused by mutation in the REEP1 gene (OMIM ) on 2p11; SPG33 (OMIM ), caused by mutation in the ZFYVE27 gene (OMIM ) on 10q24; SPG72 (OMIM ), caused by mutation in the REEP2 gene (OMIM ) on 5q31; and SPG73 (OMIM ), caused by mutation in the CPT1C gene (OMIM ) on 19q13.Autosomal dominant spastic paraplegia has been mapped to chromosomes 9q (SPG19 ), 1p31-p21 (SPG29 ), 12q23-q24 (SPG36 ), 8p21.1-q13.3 (SPG37 ), 4p16-p15 (SPG38 ), and 11p14.1-p11.2 (SPG41 ).

SPASTIC PARAPLEGIA 3, AUTOSOMAL DOMINANT; SPG3A Is also known as spg3|fsp1|strumpell disease|familial spastic paraplegia, autosomal dominant, 1

• Intellectual disability
• Short stature
• Hearing impairment
• Scoliosis
• Ataxia

SOURCES: OMIM MENDELIAN

Autosomal recessive cerebellar ataxia due to STUB1 deficiency is a rare hereditary ataxia characterized by progressive truncal and limb ataxia resulting in gait instability. Dysarthria, dysphagia, nystagmus, spasticity of the lower limbs, mild peripheral sensory neuropathy, cognitive impairment and accelerated ageing have also been associated.

AUTOSOMAL RECESSIVE CEREBELLAR ATAXIA DUE TO STUB1 DEFICIENCY Is also known as scar16|spinocerebellar ataxia autosomal recessive type 16

• Seizures
• Global developmental delay
• Hearing impairment
• Ataxia
• Nystagmus

SOURCES: ORPHANET OMIM MENDELIAN

ACTH-independent macronodular adrenal hyperplasia (AIMAH) is an endogenous form of adrenal Cushing syndrome characterized by multiple bilateral adrenocortical nodules that cause a striking enlargement of the adrenal glands. Although some familial cases have been reported, the vast majority of AIMAH cases are sporadic. Patients typically present in the fifth and sixth decades of life, approximately 10 years later than most patients with other causes of Cushing syndrome (Swain et al., 1998; Christopoulos et al., 2005).Approximately 10 to 15% of adrenal Cushing syndrome is due to primary bilateral ACTH-independent adrenocortical pathology. The 2 main subtypes are AIMAH and primary pigmented nodular adrenocortical disease (PPNAD, see {610489}), which is often a component of the Carney complex (OMIM ) and associated with mutations in the PRKAR1A gene (OMIM ) on chromosome 17q23-q24. AIMAH is rare, representing less than 1% of endogenous causes of Cushing syndrome (Swain et al., 1998; Christopoulos et al., 2005).See also ACTH-independent Cushing syndrome (OMIM ) due to somatic mutation in the PRKACA gene (OMIM ).Cushing 'disease' (OMIM ) is an ACTH-dependent disorder caused in most cases by pituitary adenomas that secrete excessive ACTH. Genetic Heterogeneity of ACTH-Independent Macronodular Adrenal HyperplasiaAIMAH2 (OMIM ) is caused by germline mutation of 1 allele of the ARMC5 gene (OMIM ) coupled with a somatic mutation in the other allele.

ACTH-INDEPENDENT MACRONODULAR ADRENAL HYPERPLASIA; AIMAH1 Is also known as acth-independent macronodular adrenocortical hyperplasia|cushing syndrome, adrenal, due to aimah|corticotropin-independent macronodular adrenal hyperplasia|adrenocorticotropic hormone-independent macronodular adrenal hyperplasia

• Neoplasm
• Failure to thrive
• Muscle weakness
• Cataract
• Visual impairment

SOURCES: OMIM MESH MENDELIAN