Non-Syndromic Cone-Predominant Retinal Degeneration Associated with Homozygosity for the M390R Mutation in BBS1 Gene

Abstract Introduction: Bardet-Biedl syndrome (BBS) is ciliopathy characterized by retinal degeneration, truncal obesity, post-axial polydactyly, cognitive impairment, male hypogonadotropic hypogonadism, complex female genitourinary malformations, and renal abnormalities (e.g., renal cysts). BBS has an autosomal recessive inheritance pattern, and the most common disease-causing gene is BBS1 , with M390R being the most prevalent mutation. Retinal degeneration in BBS is usually a rod-cone degeneration. Nevertheless, phenotypic variability exists, and cone-rod degeneration has also been reported in BBS1 -related disease, as well as non-syndromic retinitis pigmentosa (RP). We present a case of a patient with homozygous M390R mutations and non-syndromic cone-predominant retinal degeneration. Methods : Case-report conducted at a tertiary-care academic hospital. Results : A 36-year-old male patient with homozygous M390R BBS1 mutations and no family history of retinal disease or consanguinity began follow-up at age 19, after noticing photophobia. Best-corrected visual acuity (BCVA) was 20/32 OD and 20/25 OS. The fundus showed bilateral temporal wedge-shaped pallor of the optic disc and atrophic maculopathy with foveal depigmentation, which translated to hypoautofluorescence on fundus autofluorescence (FAF). Electroretinography revealed cone-rod dysfunction and center-involving maculopathy. Seventeen years later, BCVA was 20/100 OD and 20/80 OS, and the fundus changes overlapped those at baseline. Nevertheless, a slight enlargement of the atrophic lesions was observed on FAF. Despite a thorough systemic evaluation, including abdominal and renal ultrasound, no other major or secondary features of BBS were found. Discussion : To the extent of our knowledge, this is the first reported case of non-syndromic cone-predominant retinal degeneration in a patient harboring homozygous M390R BBS1 mutations.