Genetic and clinical patterns of heritable cerebellar ataxias in adults. I. Genetic analyses.

Family data on 299 probands with spinocerebellar types, 163 with late cortical cerebellar atrophies (LCCA), and 180 with olivopontocerebellar atrophies (OPCA) were analysed. Spinocerebellar types included cases with cerebellar ataxia combined with spasticity. Their family history was not compatible with sex linked inheritance. There were few recessive cases occurring before 24 years of age. The majority of cases were products of non-consanguineous marriages in which one partner was affected. The genetic ratio was 0.5 for each decade at onset between 20 and 59, suggesting that these cases were dominant. The proportion of these familial cases, however, decreased with increasing age at onset, and there were quite a few sporadic cases among the elderly. LCCA and OPCA were considered to represent extremes of a correlated disease spectrum. Although they were weakly familial, single gene heredity was rejected. Sib recurrence rate was 7.5% for LCCA and 9.4% for OPCA. When calculated for different age groups at onset, the rates decreased with increasing age in the two diseases. The rates increased to 25% and 20%, respectively, given two sibs already affected, and to 37.5% and 22.2% when three were affected. These patterns were incompatible with single gene mechanisms and were similar to those in multifactorial diseases with a threshold effect.