INTRAFAMILIAL VARIATION OF THE PHENOTYPE IN BARDET-BIEDL SYNDROME

Aims - To describe the variation of the phenotype within families with several individuals with Bardet-Biedl syndrome. Methods - The phenoty pes of affected siblings in 11 Scandinavian families were compared wit h two or more members who had at least three of the features: retinal dystrophy, polydactyly, obesity, hypogenitalism, and mental retardatio n. Individuals without retinal dystrophy were excluded. Results - Intr afamilial variation of expressivity of the features obesity, polydacty ly, abnormal radiograms of the extremities, hypogenitalism, short stat ure, paraplegia, and dental abnormalities was found. The retinal dystr ophy varied with respect to both the onset of symptoms and the course of the disease. The morphology of the fundus, however, was consistent within the families. The disorder showed statistically significant gen etic Linkage to the BBS4 locus on chromosome 15 in the affected siblin gs in two of the families, but the clinical features in these patients did not differ from the other cases of Bardet-Biedl syndrome. Conclus ion - Comparison of siblings with the Bardet-Biedl syndrome showed var iation of the typical features. In addition, the course of retinal dys trophy varied. No distinctive clinical features were found to separate the BBS4 phenotype from the remaining patients.