Familial intracranial aneurysms.

Abstract

To the Editor: With interest we have read the study by Wills et al on 346 Finnish families with familial intracranial aneurysms.1 The authors were able to collect an impressively large number of intracranial aneurysms families, defined as at least 2 members with the diagnosis of intracranial aneurysms. In their study, the authors describe different characteristics of the collected families, including the determination of the patterns of inheritance. The authors describe that 198 (57.2%) families were consistent with an autosomal recessive pattern of inheritance, 126 (36.4%) with an autosomal dominant pattern of inheritance, and 19 (5.5%) with an autosomal dominant pattern of inheritance with incomplete penetrance. In 3 (0.9%) families the pattern of inheritance was found to be complex and not consistent with a clear pattern of inheritance.1 However, it is not clear how these patterns of inheritance were determined, as no prespecified criteria for the definition of the modes of inheritance were outlined. Six representative pedigrees of the 346 families were shown in the article. As a representative example of a family with an autosomal recessive pattern of inheritance, the authors showed family no. 10. In this family no. 10, individuals from both the first and second generation were not affected while 10 out of the 19 individuals of the third generation (of 3 different pairs of parents) were affected, compatible with a segregation ratio of 53% (95% CI 29 to 76). This is in strong contrast to the 25% that is expected in families with a true autosomal recessive disease gene. Furthermore, autosomal recessive inheritance in this family is unlikely, as this requires that all parents of the affected children should have carried a disease-causing recessive gene. This would mean that the 3 individuals of the second generation who have affected children …