Anticipation in familial cavernous angioma: ascertainment bias or genetic cause

Objectives - Anticipation has been linked to unstable trinucleotide repeats in many neurological disorders. We examined the hypothesis of genetic anti cipation in familial cavernous angioma (FCA) of the central nervous system. Material and methods - The mean ASO of affected individuals was compared b etween successive generations in 55 families. Intergenerational pair-wise c omparisons were employed to avoid several ascertainment biases. Regarding s everity of disease both type of manifestation and number of cavernous angio mas were compared between generations. Results - The mean ASO decreased sig nificantly both from the first to the second generation (31.6 vs 17.8 years ; P=0.000) and from the second to the third generation (17.8 vs 6.7 years; P=0.002). The pair-wise comparisons also showed significantly earlier ASO. No clear evidence for anticipation with regard to severity of disease was f ound. Conclusions - Molecular genetic studies will determine whether trinuc leotide repeats are the underlying mechanism for our observation of anticip ation in FCA.