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 phenotypes of affected siblings in 11 Scandinavian families with two or more members who had at least three of the features: retinal dystrophy, polydactyly, obesity, hypogenitalism, and mental retardation, were compared [corrected]. Individuals without retinal dystrophy were excluded.

Results: Intrafamilial variation of expressivity of the features obesity, polydactyly, abnormal radiograms of the extremities, hypogenitalism, short stature, paraplegia, and dental abnormalities was found. The retinal dystrophy 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 genetic linkage to the BBS4 locus on chromosome 15 in the affected siblings in two of the families, but the clinical features in these patients did not differ from the other cases of Bardet-Biedl syndrome.

Conclusion: Comparison of siblings with the Bardet-Biedl syndrome showed variation of the typical features. In addition, the course of retinal dystrophy varied. No distinctive clinical features were found to separate the BBS4 phenotype from the remaining patients.