Bardet–Biedl syndrome: Genetics, molecular pathophysiology, and disease management

Abstract

Primary cilia play a key role in sensory perception and various signaling pathways. Any defect in them leads to group of disorders called ciliopathies, and Bardet–Biedl syndrome (BBS, OMIM 209900) is one among them. The disorder is clinically and genetically heterogeneous, with various primary and secondary clinical manifestations, and shows autosomal recessive inheritance and highly prevalent in inbred/consanguineous populations. The disease mapped to at least twenty different genes (BBS1-BBS20), follow oligogenic inheritance pattern. BBS proteins localizes to the centerosome and regulates the biogenesis and functions of the cilia. In BBS, the functioning of various systemic organs (with ciliated cells) gets deranged and results in systemic manifestations. Certain components of the disease (such as obesity, diabetes, and renal problems) when noticed earlier offer a disease management benefit to the patients. However, the awareness of the disease is comparatively low and most often noticed only after severe vision loss in patients, which is usually in the first decade of the patient's age. In the current review, we have provided the recent updates retrieved from various types of scientific literature through journals, on the genetics, its molecular relevance, and the clinical outcome in BBS. The review in nutshell would provide the basic awareness of the disease that will have an impact in disease management and counseling benefits to the patients and their families.

Ophthalmic manifestations of endocrine disorders—endocrinology and the eye

“…Primary findings include obesity, developmental disability, kidney dysfunction, rod-cone dystrophy, dystrophic extremities, and hypogonadism. Generally, children develop obesity by age three and ocular disturbances by age nine, at which point suspicion for Bardet-Biedl arises (67).…”

“…Rods and cones are photoreceptor cells in the retina responsible for day and night vision, respectively. The outer segments of these cells are modified sensory cilia, which aid in the processes of photon capture and visual transduction (67).…”

“…The first associated ocular finding is night blindness or nyctalopia, which typically manifests in early childhood. In fact, a decrease in rod and cone amplitudes may be detected as early as 2 years of age by electroretinogram testing (67). By the second decade of life, patients suffer a loss in peripheral vision, which eventually affects the central visual field (68).…”

“…By the second decade of life, patients suffer a loss in peripheral vision, which eventually affects the central visual field (68). With disease progression in the third decade, 98% of patients report complete loss of vision (67). Additional ophthalmologic features that often accompany a diagnosis of Bardet-Biedl include myopia, strabismus, and cataract formation (52).…”

“…As a result, infertility, progressive retinal dystrophy, and vision decline are inevitable outcomes of the disease (67). However, supplementation with high doses of vitamin A may aid in preservation of retinal function (61).…”