Haqq, Andrea M.

ABSTRACT Bardet‐Biedl syndrome (BBS) is a rare autosomal recessive disorder characterized by clinical and genetic heterogeneity. Data on the prevalence of clinical manifestations and comorbidities in BBS, particularly in pediatric patients, are limited. This study aimed to assess the prevalence and various manifestations of endocrine and other clinical comorbidities among pediatric and adult patients with BBS. This retrospective chart review included pediatric and adult patients with BBS evaluated at an academic tertiary care center in the United States between 2000 and 2024. The study included 31 patients (7 children and 24 adults) with seven identified pathogenic variants associated with BBS. The most common genetic etiology was biallelic variants in BBS1 (36%). Obesity was diagnosed in 86% of children and 100% of adults. No children had diabetes or prediabetes, whereas 46% of adults were affected. Dyslipidemia was identified in 29% of children and 46% of adults. No thyroid abnormalities were identified in children, whereas 25% of adults were affected. Retinal dystrophy was present in 71% of children and 96% of adults. Polydactyly was observed in 100% of children and 75% of adults. Chronic kidney disease was present in 29% of children and 63% of adults. This study highlights the clinical heterogeneity and substantial multisystem burden of BBS across pediatric and adult patients. The greater prevalence of diabetes/prediabetes, dyslipidemia, thyroid abnormalities, chronic kidney disease, and visual impairment among adults suggests that these complications may emerge or progress over time. Early recognition, proactive longitudinal surveillance, and comprehensive multidisciplinary care are essential to optimize management across the lifespan.

Abstract Disclosure: D. Hassan: None. M. Salama: None. K. Muthusamy: None. A.M. Haqq: None. S. Kumar: None. Introduction: Bardet-Biedl syndrome (BBS) is a rare genetic condition characterized by obesity and considerable clinical and genetic heterogeneity. While cardiometabolic and endocrine comorbidities are commonly associated with BBS, data on their prevalence, particularly in children, remain limited. Objective: To assess the prevalence of cardiometabolic and endocrine comorbidities among pediatric and adult patients with BBS. Methods: This is a retrospective chart review of pediatric and adult patients with BBS evaluated in the outpatient setting at Mayo clinic. The cohort included individuals aged 0-50 years with either a clinical or genetic diagnosis of BBS, identified from January 1, 2000, onward. Demographic, anthropometric, phenotypic, and biochemical data were reviewed. Results: The study comprised 34 patients, including 9 children (median age 8 years (IQR: 3.5-11)) and 25 adults (median age 33.5 years (IQR: 27-42)). Females constituted 56% of the cohort and White individuals accounted for 76%. The median age at diagnosis of BBS was 9 years (IQR: 3-16). Phenotypic characteristics included retinal dystrophy in 33% of children and 92% of adults, polydactyly in 78% of children and 52% of adults, and learning disabilities in 56% of children and 52% of adults. Obesity was prevalent in 56% of children and 80% of adults. Among children, their median maximum BMI % of the 95th percentile was 149% (IQR: 136-163%). Adults had a a median maximum BMI of 50 kg/m² (IQR: 43-55). There was insufficient data to determine the onset of hyperphagia; however, the median age of obesity onset for the cohort was 7 years (IQR: 4-11). No cases of diabetes or prediabetes were identified among children, whereas 40% of adults were diagnosed with type 2 diabetes. Cardiometabolic characteristics included hypertension in 11% of children and 48% of adults, kidney dysfunction in 33% of children and 56% of adults. Dyslipidemia was noted in 22% of children and 44% of adults, with median triglyceride levels 133 mg/dL (IQR: 93-153) in children and 142 mg/dL (IQR: 120-200) in adults. No cases of cardiovascular disease were identified in children, whereas 8% of adults were diagnosed with the condition. Endocrine characteristics included hypothyroidism in 11% of children and in 24% of adults. Of the 34 patients, genotype data were available for 28 individuals (82%). The most prevalent genotype was BBS1, comprising 27% of the cases. This was followed by BBS2 and BBS10, which each accounted for 15% of the cohort. Genotypes BBS4, BBS6 (MKKS2), IFT172, and SCLT1 were each observed in 3% of the cohort. Conclusion: This study highlights the significant clinical, cardiometabolic, and endocrine burden associated with BBS across children and adults. These findings underscore the importance of early and comprehensive multidisciplinary management of BBS. Keywords: Bardet-Biedl syndrome, obesity, cardiometabolic, endocrine comorbidities. Presentation: Monday, July 14, 2025