Novel compound heterozygous pathogenicBBS5variants in Filipino siblings with Bardet-Biedl syndrome (BBS)

Purpose Bardet-Biedl syndrome (BBS) is rare in the Philippines and only limited information on the prevalent subtypes is available as yet. The purpose of this study is to present the clinical characteristics of two Filipino siblings presenting with mutations inBBS5. Patients and Methods The Filipino female siblings, aged 11 and 14 years underwent comprehensive ophthalmologic evaluation. Fundus photography, macular optical coherence tomography (OCT) and electroretinography (ERG) were also obtained. Systemic workup was performed including radiographic imaging of limb defects, renal ultrasound, blood chemistry, and transvaginal ultrasound. Targeted Bardet-Biedl sequence analysis and deletion/duplication analysis were performed to determine potential pathogenic mutations. Results Both children had poor visual acuity with a myopic refraction. There was a pigmentary retinopathy with retinal pigment epithelium changes and attenuation of vessels without waxy disc pallor. Generalized macular thinning and undetectable ERG responses were recorded. Physical examination revealed obesity, facial anomalies, brachydactyly, postaxial polydactyly, and clinodactyly of fifth digits. Both patients displayed cognitive developmental delay and hypogonadism. Molecular analysis revealed novel compound heterozygous mutations inBBS5with c.143-1 G > A (splice acceptor) and c.925_931del (p.Gln309ilefs*14), each inherited from one asymptomatic parent. Conclusion These are probably the first reportedBBS5mutations causing Bardet-Biedl syndrome in the Philippines. Patients were managed by a multi-disciplinary team and the parents were counseled regarding the prognosis and additional complications associated with the syndrome.