Anticipation in familial cavernous angioma: ascertainment bias or genetic cause

Anticipation has been linked to unstable trinucleotide repeats in many neurological disorders. We examined the hypothesis of genetic anticipation in familial cavernous angioma (FCA) of the central nervous system.

The mean ASO of affected individuals was compared between successive generations in 55 families. Intergenerational pair-wise comparisons were employed to avoid several ascertainment biases. Regarding severity of disease both type of manifestation and number of cavernous angiomas were compared between generations.

The mean ASO decreased significantly 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 found.

Molecular genetic studies will determine whether trinucleotide repeats are the underlying mechanism for our observation of anticipation in FCA.