Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Ataxias, spinocerebellar autosomal dominant (SCA) [G11.9]

OMIM numbers: 164400 (SCA1), 601556 (ATXN1), 183090 (SCA2), 601517 (ATXN2), 109150 (MJD), 607047 (ATXN3), 183086 (SCA6), 601011 (CACNA1A), 164500 (SCA7), 607640 (ATXN7), 607136 (SCA17), 600075 (TBP)

Dr. rer. biol. hum. Soheyla Chahrokh-Zadeh

Scientific Background

Autosomal dominant spinocerebellar ataxias are a clinically and genetically heterogenous group of diseases, comprising approx. 40 subtypes. Prevalence is estimated to be at least 3 in 100,000 (in the Netherlands). The genetic cause is yet unknown for some of the types. All of them share progressive ataxia as their most common clinical sign. Apart from unsteady gait, speech and oculomotor dysfunction, ataxia of the torso and extremities as well as intention tremor and other neurological signs and symptoms may occur. There are 3 clinical forms: type 1 with signs and symptoms affecting the eyes and various other neurological signs (SCA1–4, 8, 12, 13, 17), type 2 with pigmentary macular degeneration (SCA7), type 3 as pure cerebellar ataxia (SCA5, 6, 10, 11, 14).

Onset of the disease is usually between the 30th and 50th year of life; however, it may also be during childhood or after the 6th decade. The subtypes SCA1, 2, 3, 6 and 7 are caused by pathologic CAG triplet-repeat expansions within various genes. Like other triplet-repeat diseases, SCAs exhibit anticipation within one family, i.e. onset of the disease at a younger age and an increasingly severe course in successive generations. SCA17 is phenotypically more variable and complex. The CAG repeat expansion is located within a complex CAG/CAA repeat region. Due to the broad clinical spectrum, SCA17 may be mistaken for other neurodegenerative diseases such as Huntington's disease, Parkinson's disease and other movement disorders and cerebellar diseases. Some patients solely show psychiatric signs and symptoms (e.g. dementia, bipolar psychosis, paranoia) without ataxia or movement disorders. Due to the similarity of the clinical signs and symptoms to Huntington's disease, SCA17 has also been termed “Huntington's Disease-like 4 Syndrome (HDL4)”. If the clinical signs and symptoms are not clear, moleculargenetic diagnostics may aid in the classification of the disease.