DeCure for Bardet-Biedl syndrome 2

Bardet-Biedl syndrome is a rare autosomal recessive ciliopathic disorder caused by mutations in genes encoding proteins of the BBSome complex, which is essential for ciliary function and cellular signalling. Sixteen causative genes have been identified. The syndrome shows significant clinical and genetic heterogeneity, and recent data have unmasked an oligogenic mode of transmission in which mutations at different BBS loci can interact genetically in some families to cause or modify the phenotype. Diagnosis is based on a group of clinical features, and Beales diagnostic criteria have been used to confirm the syndrome in individual cases.

The core clinical features reported across multiple case reports include postaxial polydactyly or syndactyly, central obesity, retinitis pigmentosa with progressive loss of vision, cognitive impairment, and hypogonadism. In one case, a nine-year-old boy had recent loss of vision in the dark, polydactyly of the feet surgically corrected at seven weeks, significant mental retardation, and a pale optic disc with loss of electroretinographic response under both scotopic and photopic conditions. A 14-year-old boy presented with obesity, difficulty in vision, and hypogonadism. Another 14-year-old male patient exhibited the characteristic features. A 30-year-old man had been entirely blind since age nine with confirmed retinitis pigmentosa, progressive weight gain, cognitive impairment, central obesity, almond-shaped eyes, moon-shaped face, and hexadactyly of the left lower limb; his liver function tests, renal function tests, lipid profile, and abdominal ultrasonography were abnormal. Renal dysfunction, hepatic fibrosis, diabetes mellitus, heart disease, and neurological manifestations are listed as rarer findings.

No pharmacological treatment for the underlying syndrome is described in any of these reports. Management has consisted of symptomatic treatment, appropriate counselling, psychosocial support, nutritional counselling, and a personalised care plan involving a multidisciplinary team with regular monitoring and supportive services including neuropsychological and psychiatric care and family support. One patient was treated for coincident abdominal tuberculosis. What remains missing are any clinical trials of drug interventions, any evidence that a specific molecule modifies the disease course, and any stratification of patients by genotype or phenotype that might guide future therapy.