Laurence-Moon-Bardet-Biedl syndrome. Clinical,electrophysiological and genetic aspects

Sammanfattning: The study included 44 Scandinavian individuals with the autosomal recessive inherited Laurence-Moon-Bardet-Biedl syndrome. Inclusion criteria were retinal dystrophy plus at least 2 more of the remaining traditional cardinal signs of the syndrome: obesity, polydactyly, hypogenitalism and mental retardation. The study showed that the patients had an early onset of night blindness and a poor visual prognosis. No rod ERG-responses to dim blue light were found, even in the youngest-3 years old. No one exceeding the age of 16 had a best corrected visual acuity of more than 0.1. The fundus picture was an atypical retinitis pigmentosa with macular pigments previous to any bone spicules. Birth weight and -length were within normal limits, but obesity appeared in early childhood and proceeded to profuse overweight during adolecence. Final height was slightly reduced. Typical skeletal anomalies were polydactyly, short and broad metacarpal bones and flat joint surfaces of the metacarpo- or metatarso-phalangeal joints. Hypogenitalism was noted in nearly all the men but only as an exception in the women. Most patients seemed to have good mental resources. Renal disease was a common cause of death. We found significantly higher frequencies of small or missing teeth and short roots compared to a control group. Substantial variation of the clinical signs was demonstrated both between families and between affected siblings in 11 families with 2-3 syndrome members. These families were included in a genetic study of 29 similar families where linkage was confirmed to the BBS1, BBS4 and BBS2 loci on chromosomes 11, 15 and 16. No clear clinical distinctions were apparent between the families linked to the different loci. Overlapping of clinical signs from the subgroups Laurence-Moon, Bardet-Biedl and Alström syndromes were observed within the same patient or family. The typical features in our Laurence-Moon-Bardet-Biedl syndrome patients were: retinal dystrophy, obesity, dental anomalies, skeletal anomalies of hands and feet, hypogenitalism in men and renal disease.