Search

Differential diagnosis between autosomal dominant cerebellar ataxia type I (ADCA I) and idiopathic cerebellar ataxia type P (IDCA-P) is very difficult given only clinical and neuroradiological data. The only certain distinctive characteristic is the presence or absence of family history. We observed 7 patients with late-onset cerebellar ataxia associated with other non-cerebellar signs and without a family history of the disease in which clinical signs were comparable to symptoms found in SCA2. The neuroradiological study showed olivopontocerebellar atrophy in all patients and the presence of hyperintensity of the transverse pontine fibers in 6 patients (85. 6%); molecular analysis showed SCA2 mutations in 2 patients. We also report the case of a patient who was initially considered as IDCA-P but who was later correctly identified as SCA2 with an atypical family history (false IDCA-P), after a genetic mutation was found and following an interview with the mother. Our data suggest that spinocerebellar ataxia syndrome should be defined as idiopathic not only after having excluded the possible symptomatic causes but also in the absence of family history, after having excluded the presence of genetic mutation. We believe that family history, in late-onset spinocerebellar ataxia, cannot be considered as the differential criterion among hereditary (ADCA-I) and non-hereditary (IDCA-P) forms; molecular analysis is required for a correct diagnosis.

Autosomal dominant cerebellar ataxias (ADCAs) are a complex group of slowly progressive neurodegenerative disorders characterized by gait and stance ataxia, dysarthria and other symptoms of nervous system involvement. ADCA type I is the commonest form and is genetically heterogeneous; several loci have been identified. Spinocerebellar ataxia type 2 (SCA2) has been mapped to chromosome 12, with expanded cytosine-adenine-guanine (CAG) repeats being identified as the mutational cause of the disease. We investigated 15 families, all originating from mid-eastern Sicily, with ADCA type I; molecular studies performed in 12 families showed the SCA2 mutation to be present in 11 of them (91.6%) - the highest occurrence so far reported in the literature. The CAG repeat of the affected alleles varied between 34 and 44 repeats. Age at onset and repeat length revealed an inverse correlation. Mean age at onset was 37.32 +/- 16. 74 years, and occurred earlier in males than in females. There were no differences in mean CAG repeat units between the sexes. However, a higher instability of CAG repeats was observed for paternal transmission than for maternal transmission. Age at onset and anticipation were not related to parental transmission. Our data suggest that in SCA2 an unknown sex-linked factor may play a role in the modulation of toxic effects of the polyglutamine tract., (Copyright 1999 Lippincott Williams & Wilkins)