Endocrine Characteristics in Bardet Biedl Syndrome from a Large Single-Centre Paediatric Multidisciplinary Clinic

Abstract Objective Bardet-Biedl syndrome (BBS) is a rare genetic ciliopathy characterised by obesity, rod-cone dystrophy, polydactyly, hypogonadism, cognitive impairment and renal abnormalities. Additional endocrine associations include short stature and hypothyroidism. The endocrine characteristics in children are not well described. Methods A retrospective analysis of prospectively collected data in paediatric patients with genetically confirmed BBS from a single multidisciplinary BBS service. Data related to endocrine function were extracted from the electronic patient record. Height was reported for patients ≥4 years old and ≥15 years old. Short stature was defined as a height Z-score (standard deviation score, SDS) -2 or height 1.6 SDS below the mid-parental height. Results 135 patients were included: 69 (51%) were female, ranging from 1.2-19.4 years old. At ≥15 years, 21.1% (12/57) had short stature and 77.6% (45/58) had obesity. On average, BMI worsened over time. Triglycerides were raised in 55.5% (66/119). No patients demonstrated biochemical or clinical evidence of persistent primary or secondary hypogonadism, and none required pubertal induction or sex steroid replacement therapy. Primary hypothyroidism and subclinical hypothyroidism were identified in 1.7% (2/121) and 0.8% (1/121), respectively. Type 1 diabetes, Type 2 diabetes and impaired glucose tolerance were identified in 1.5% (2/135), 2.2% (3/135) and 1.5% (2/135), respectively. Conclusions This is the largest analysis of endocrine characteristics in paediatric patients with BBS. Short stature and obesity are characteristic of paediatric BBS. However, hypogonadism, hypothyroidism, and insulin resistance are less prevalent compared with adult BBS populations. Longitudinal studies spanning paediatric and adult populations may further characterise the natural history of these endocrine conditions associated with BBS.