OC29 - Genotype over phenotype: the road less travelled in diagnosing Bardet- Biedl syndrome

Introduction Bardet-Biedl Syndrome (BBS) is a rare autosomal recessive disorder classified under ciliopathies. It typically presents with a combination of features such as retinal dystrophy, polydactyly, renal abnormalities, hypogonadism, intellectual disability, and obesity. While obesity is a hallmark feature, its occurrence in isolation—without other classical manifestations—is uncommon. With advancements in molecular diagnostics, atypical presentations of BBS are being increasingly identified. Purpose This case report highlights a rare phenotype of BBS, where metabolic abnormalities appeared in the absence of traditional clinical signs. Case Summary A 19-year-old male presented with progressive weight gain beginning at age 5. At the time of evaluation, he weighed 135 kg and had a blood pressure of 158/108 mmHg. Clinical examination revealed acanthosis nigricans and multiple skin tags. Notably, he lacked typical BBS features such as polydactyly, retinal dystrophy, genital anomalies, or cognitive impairment. He had normal neurodevelopment and reported no visual issues. Given the early-onset severe obesity and metabolic features, genetic testing was pursued, which identified a pathogenic mutation in the IFT172 gene—associated with BBS20. This confirmed the diagnosis despite the absence of classical clinical features. Treatment and Follow-up Following genetic confirmation and absence of retinal involvement, the patient was initiated on lifestyle modification and oral semaglutide, starting at 3 mg daily with uptitration to 7 mg over six months. Follow-up at 3 months showed a weight reduction of 10 kg, and by 6 months, a total weight loss of 20 kg was achieved. The treatment was well tolerated with a favorable safety profile. Conclusion This case underscores a mild, atypical presentation of Bardet-Biedl Syndrome, manifesting solely with obesity and features of metabolic syndrome. It emphasizes the critical role of genetic testing in evaluating individuals with early- onset obesity, especially when phenotypic hallmarks are absent. Early diagnosis facilitates timely intervention, genetic counselling, and longitudinal monitoring, as additional features of BBS may develop over time.The positive metabolic response to semaglutide underscores its therapeutic potential in syndromic obesity, even in the absence of classical phenotypic markers.