Autosomal dominant cerebellar ataxia: Phenotypic differences in genetically defined subtypes?
- 1 December 1997
- journal article
- research article
- Published by Wiley in Annals of Neurology
- Vol. 42 (6), 924-932
- https://doi.org/10.1002/ana.410420615
Abstract
Seventy‐seven families with autosomal dominant cerebellar ataxia were analyzed for the CAG repeat expansions causing spinocerebellar ataxia (SCA) types 1, 2, 3, and 6. The SCA1 mutation accounted for 9%, SCA2 for 10%, SCA3 for 42%, and SCA6 for 22% of German ataxia families. Seven of 27 SCA6 patients had no family history of ataxia. Age at onset correlated inversely with repeat length in all subtypes. Yet the average effect of one CAG unit on onset age was different for each SCA subtype. We compared clinical, electrophysiological, and magnetic resonance imaging (MRI) findings to identify phenotypic characteristics of genetically defined SCA subtypes. Slow saccades, hyporeflexia, myoclonus, and action tremor proposed SCA2. SCA3 patients frequently developed diplopia, severe spasticity or pronounced peripheral neuropathy, and impaired temperature discrimination, apart from ataxia. SCA6 presented with a predominantly cerebellar syndrome and patients often had onset after 55 years of age. SCAI was characterized by markedly prolonged peripheral and central motor conduction times in motor evoked potentials. MRI scans showed pontine and cerebellar atrophy in SCA1 and SCA2. In SCA3, enlargement of the fourth ventricle was the main sequel of atrophy. SCA6 presented with pure cerebellar atrophy on MRI. However, overlap between the four SCA subtypes was broad.Keywords
This publication has 34 references indexed in Scilit:
- Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the α1A-voltage-dependent calcium channelNature Genetics, 1997
- Identification of the spinocerebellar ataxia type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECTNature Genetics, 1996
- Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2Nature Genetics, 1996
- The gene for autosomal dominant cerebellar ataxia with pigmentary macular dystrophy maps to chromosome 3p12–p21.1Nature Genetics, 1995
- Retinal degeneration characterizes a spinocerebellar ataxia mapping to chromosome 3pNature Genetics, 1995
- Spinocerebellar ataxia type 5 in a family descended from the grandparents of President Lincoln maps to chromosome 11Nature Genetics, 1994
- The gene for Machado–Joseph disease maps to human chromosome 14qNature Genetics, 1993
- Chromosomal assignment of the second locus for autosomal dominant cerebellar ataxia (SCA2) to chromosome 12q23–24.1Nature Genetics, 1993
- Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1Nature Genetics, 1993
- Hereditary Ataxia and HL-A GenotypesNew England Journal of Medicine, 1974