Retinal Degeneration and Visual Outcomes in Patients With Bardet-Biedl Syndrome: Genotypic Influences From a Caribbean Cohort

TL;DR

This study examines how different genetic mutations in Bardet-Biedl Syndrome affect vision in a Puerto Rican population, finding that BBS1 mutations are most common and lead to severe visual impairment.

Contribution

The study identifies BBS1 as the most prevalent mutation in Puerto Rico and links it to worse visual outcomes compared to other genotypes.

Findings

BBS1 mutations were most common (86%) and associated with worse vision than compound heterozygotes.

Patients with advanced disease showed near-absent visual fields and significant retinal thinning.

Structural retinal damage was linked to disruption of the inner/outer segments on OCT.

Abstract

Background

The Bardet-Biedl syndrome (BBS) is a rare multisystem ciliopathy characterized by retinal degeneration, polydactyly, truncal obesity, hypogonadism, and hypogonadotropism. Progressive rod-cone dystrophy leads to early-onset vision loss. Despite increased genetic screening, BBS remains underdiagnosed in Caribbean populations. This study aims to describe the genetic and ocular phenotype of patients with BBS in Puerto Rico and explore genotype-phenotype correlations.

Methods

We conducted a retrospective chart review of 36 genetically confirmed BBS patients from a hereditary retinal disease clinic in Puerto Rico. Data collected included best-corrected visual acuity (BCVA), refractive error, visual field mean deviation (MD), and macular optical coherence tomography (OCT) measurements (volume and thickness). Genetic testing identified the BBS subtype and zygosity. Descriptive and statistical analyses were performed. The study was approved by a certified institutional review board (IRB).

Results

Age ranged from three to 69 years old. Mutations in the BBS1 gene were most frequent (86%), followed by BBS7 (8%), BBS10 (3%), and BBS19 (3%). Most patients had homozygous mutations in the BBS1 (%). The mean BCVA was 2.0 logMAR OD and 2.1 logMAR OS. Patients with homozygotic mutations in the BBS1 had worse vision than compound heterozygotes (p=0.025). Upon visual field examination, the MD was -27.6 dB OD and -28.3 dB OS. Near-absent visual fields occurred in patients with advanced disease. Macular volume and thickness averaged 8.2 mm³/227 µm (OD) and 7.7 mm³/216 µm (OS). Structural damage was associated with inner/outer segment disruption on OCT.

Conclusions

Mutations in the BBS1 are the most frequent in Puerto Rico, often associated with profound visual impairment and retinal thinning. These findings underscore the importance of early ophthalmic evaluation and genetic testing in patients with syndromic retinitis pigmentosa. Genotype-specific differences in visual decline support personalized surveillance and future therapeutic planning.