Ataxia, and Brain atrophy

Kuru, a fatal neurodegenerative condition, is a human prion disease that primarily affected the Fore linguistic group of the Eastern Highlands of Papua New Guinea. Kuru was transmitted by the practice of consuming dead relatives as a mark of respect and mourning ('transumption'). The incidence has fallen dramatically since the cessation of cannibalism in the 1950s (summary by Wadsworth et al., 2008).

• Ataxia
• Mental deterioration
• Abnormality of eye movement
• Unsteady gait
• Neurodegeneration

SOURCES: OMIM MENDELIAN

Cerebellar ataxia, mental retardation, and dysequilibrium syndrome (CAMRQ) is a genetically heterogeneous disorder characterized by congenital cerebellar ataxia and mental retardation (summary by Gulsuner et al., 2011).For a discussion of genetic heterogeneity of CAMRQ, see CAMRQ1 (OMIM ).

CEREBELLAR ATAXIA, MENTAL RETARDATION, AND DYSEQUILIBRIUM SYNDROME 4; CAMRQ4 Is also known as cerebellar ataxia and mental retardation with or without quadrupedal locomotion 4

• Intellectual disability
• Ataxia
• Dysarthria
• Cerebellar atrophy
• Cerebral atrophy

SOURCES: OMIM MENDELIAN

Spinocerebellar ataxia type 12 (SCA12) is a very rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by the presence of action tremor associated with relatively mild cerebellar ataxia. Associated pyramidal and extrapyramidal signs and dementia have been reported.

SPINOCEREBELLAR ATAXIA TYPE 12 Is also known as sca12

• Ataxia
• Cognitive impairment
• Hyperreflexia
• Gait disturbance
• Cerebellar atrophy

SOURCES: ORPHANET MENDELIAN

Charcot-Marie-Tooth disease type 2T (CMT2T) is a slowly progressive autosomal recessive sensorimotor peripheral neuropathy with onset in middle age (Higuchi et al., 2016).For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (OMIM ).

DNAJB2-RELATED CHARCOT-MARIE-TOOTH DISEASE TYPE 2 Is also known as charcot-marie-tooth neuropathy, type 2t|charcot-marie-tooth disease, axonal, autosomal recessive, type 2t|dnajb2-related cmt2

• Ataxia
• Cognitive impairment
• Peripheral neuropathy
• Gait disturbance
• Cerebral atrophy

SOURCES: OMIM ORPHANET MENDELIAN

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Spasticity

SOURCES: OMIM MENDELIAN

Megalencephalic leukoencephalopathy with subcortical cysts-2A is an autosomal recessive neurodegenerative disorder characterized by infantile-onset macrocephaly and later onset of motor deterioration, with ataxia and spasticity, seizures, and cognitive decline of variable severity. Brain MRI shows typical white matter abnormalities, including swelling of the cerebral white matter and subcortical cysts, in all stages of the disease (summary by Lopez-Hernandez et al., 2011).Heterozygous mutations in the HEPACAM gene can cause a similar, but less severe disorder that shows improvement of MRI changes with age (MLC2B ).

• Intellectual disability
• Seizures
• Ataxia
• Spasticity
• Motor delay

SOURCES: OMIM MENDELIAN

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 (OMIM ).

CLN13 DISEASE Is also known as ceroid lipofuscinosis, neuronal, 13, kufs type

• Seizures
• Generalized hypotonia
• Ataxia
• Cognitive impairment
• Hyperreflexia

SOURCES: OMIM ORPHANET MENDELIAN

Spinocerebellar ataxia type 17 (SCA17) is a rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by a variable clinical picture which can include dementia, psychiatric disorders, parkinsonism, dystonia, chorea, spasticity, and epilepsy.

SPINOCEREBELLAR ATAXIA TYPE 17 Is also known as hdl4|sca17|huntington disease-like 4

• Ataxia
• Spasticity
• Gait disturbance
• Cerebellar atrophy
• Behavioral abnormality

SOURCES: ORPHANET MENDELIAN

Autosomal recessive mental retardation-53 is a neurodevelopmental disorder characterized by severely delayed psychomotor development, hypotonia apparent since infancy, and early-onset seizures in most patients. Some patients may have additional features, such as cerebellar hypoplasia and ataxia. MRT53 is one of a group of similar neurologic disorders resulting from biochemical defects in the glycosylphosphatidylinositol (GPI) biosynthetic pathway (summary by Makrythanasis et al., 2016).For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (OMIM ).

MENTAL RETARDATION, AUTOSOMAL RECESSIVE 53; MRT53 Is also known as glycosylphosphatidylinositol biosynthesis defect 13|gpibd13

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Ataxia

SOURCES: OMIM MENDELIAN

Essential tremor may be the most common human movement disorder. The main feature of essential tremor is postural tremor of the arms, but the head, legs, trunk, voice, jaw, and facial muscles also may be involved. Aggravated by emotions, hunger, fatigue, and temperature extremes, the condition may cause a functional disability or even incapacitation. Autosomal dominant inheritance can be demonstrated in most families (summary by Higgins et al., 1997).Deng et al. (2007) provided a detailed review of the genetics of essential tremor. Genetic Heterogeneity of Essential TremorOther forms of hereditary essential tremor include ETM2 (OMIM ), mapped to chromosome 2p25-p22; ETM3 (OMIM ), mapped to chromosome 6p23; ETM4 (OMIM ), caused by mutation in the FUS gene (OMIM ) on chromosome 16p11; and ETM5 (OMIM ), caused by mutation in the TENM4 gene (OMIM ) on chromosome 11q14.

TREMOR, HEREDITARY ESSENTIAL, 1; ETM1 Is also known as fet1|tremor, familial essential, 1

• Hearing impairment
• Ataxia
• Cognitive impairment
• Dysarthria
• Fever

SOURCES: OMIM MENDELIAN