Brain Advance Access originally published online on March 3, 2004
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Brain, Vol. 127, No. 5, 1172-1181, 2004
© 2004 Guarantors of Brain
doi: 10.1093/brain/awh139
Dominantly inherited ataxia and dysphonia with dentate calcification: spinocerebellar ataxia type 20
1 Murdoch Childrens Research Institute and 2 Genetic Health Services Victoria, Royal Children’s Hospital, 3 Department of Paediatrics, University of Melbourne, 4 Genetics and Bioinformatics Division, and 5 Australian Genome Research Facility, Walter and Eliza Hall Institute, 6 Department of Otolaryngology, Alfred Hospital, 7 Department of Medicine (Neurosciences), Monash University (Alfred Hospital Campus), Melbourne, Australia and 8 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
Correspondence to: Professor Elsdon Storey, Department of Neurosciences, Alfred Hospital, Melbourne, Victoria 3004, Australia E-mail: elsdon.storey{at}med.monash.edu.au
We describe a pedigree of Anglo-Celtic origin with a phenotypically unique form of dominantly inherited spinocerebellar ataxia (SCA) in 14 personally examined affected members. A remarkable observation is dentate nucleus calcification, producing a low signal on MRI sequences. Unusually for an SCA, dysarthria is typically the initial manifestation. Mild pyramidal signs and hypermetric saccades are noted in some. Its distinguishing clinical features, each present in a majority of affected persons, are palatal tremor, and a form of dysphonia resembling spasmodic dysphonia. Repeat expansion detection failed to identify either CAG/CTG or ATTCT/AGAAT repeat expansions segregating with the disease in this family. The testable SCA mutations have been excluded. On linkage analysis, the locus maps to chromosome 11, which rules out all the remaining mapped SCAs except for SCA5. While locus homogeneity with SCA5 is not formally excluded, we consider it rather unlikely on phenotypic grounds, and propose that this condition may represent an addition to the group of neurogenetic disorders subsumed under the rubric SCA. The International Nomenclature Committee has made a provisional assignment of ‘SCA20’, although firm designation will have to await a definite molecular distinction from SCA5.
Key Words: autosomal dominant spinocerebellar ataxia; spinocerebellar ataxia type 20; dentate nucleus calcification; palatal tremor; linkage analysis
Abbreviations: ADCA= autosomal dominant cerebellar ataxia; AGAAT, adenine–guanine–adenine–adenine–thymine pentanucleotide; ATTCT, adenine–thymine–thymine–cytosine–thymine pentanucleotide; CAG, cytosine–adenine–guanine trinucleotide; cM = centiMorgans; CTG, cytosine–thymine–guanine trinucleotide; DRPLA = dentatorubral-pallidoluysian atrophy; GDB = Genome Database; LOD = logarithm of odds; NCBI = National Center for Biotechnology Information; RED = repeat expansion detection; SCA = spinocerebellar ataxia; VOR = vestibulo-ocular reflex
Received July 30, 2003. Revised December 26, 2003. Accepted January 8, 2004.
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