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Purpose: Bardet-Biedl Syndrome (BBS) is a rare autosomal recessive ciliopathy. Within corneal development, primary cilia serve a critical role. We sought to investigate the association of BBS with corneal astigmatism among a cohort of patients with BBS., Methods: This was a cross-sectional, retrospective study performed at a pediatric ophthalmology department of a tertiary hospital. The study enrolled 45 patients with genetically confirmed Bardet-Biedl syndrome, encompassing a total of 90 eyes observed from February 2011 to August 2021. Spherical and cylindrical refractive errors and keratometry outcome measures, including diopter (D) values at the flattest and steepest axes, were recorded. Corneal astigmatism of greater than 3D is considered extreme corneal astigmatism based on previously published data., Results: Among 45 patients (M:26; F:19), the mean age was 16.4 ± 8.2 years, and the mean best-corrected visual acuity was 20/60. The most common molecular diagnosis was BBS1 , seen in 24 of 45 (53.3%). Among all the patients, the mean spherical refractive error was -2.9 ± 3.8D. The mean cylindrical refractive error was 2.6 ± 1.5D. The mean keratometry values at the flattest axis was 43.5 ± 5.3D (39.4-75.0) and at the steepest axis was 47.2 ± 7.3D(41.5-84.0). Among all the patients with BBS, the mean corneal astigmatism was 3.7 ± 1.0D(0.5-7.1), which is considered extreme., Conclusion: A cohort of individuals with BBS demonstrated high corneal astigmatism. These results suggest an association between corneal astigmatism and primary ciliary dysfunction and may assist in clinical management and future therapeutic targets among BBS and other corneal disorders.

Background: Bardet-Biedl syndrome (BBS) is known to be associated with hydrocephalus, but not with idiopathic intracranial hypertension (IIH). Case presentation: We describe such a case and propose the pathogenesis. We also discuss the challenges of diagnosis, treatment, and monitoring outcomes in this population that is already at high risk of vision loss from retinal dystrophy., Conclusion: IIH can result from a combination of risk factors in conjunction with the underlying dysfunctional cilia in BBS patients. Monitoring disease progression is difficult, and as such IIH may be underdiagnosed or missed. Management must be adjusted to account for BBS patients' impaired metabolic and renal physiology. It is important that clinicians be aware of these challenges in this vulnerable population, and regular monitoring should be done to avoid preventable vision loss.

Bardet-Biedl syndrome (BBS) is a pleiotropic and clinically and genetically heterogeneous ciliopathy. Primary features are early-onset retinal dystrophy that is typically rod-cone, obesity, polydactyly, renal abnormalities, hypogonadism, and learning difficulties, but most patients do not present with the full clinical picture. In a BBS patient from a consanguineous marriage we performed next-generation sequencing targeting all known BBS genes and other genes known or hypothesized to cause ciliopathies. While no mutation was present in any of the recognized genes for BBS, we were able to identify the homozygous non-conservative mutation c.529C>T (p.Arg177Trp) in C8orf37 that segregated with the phenotype, affects an evolutionarily highly conserved residue, and is bioinformatically predicted to be pathogenic. The same mutation has been described in unrelated patients with non-syndromic cone-rod dystrophy and other C8orf37 changes were found in individuals with retinitis pigmentosa. We conclude that C8orf37 should be added to BBS screening panels as a probable rare cause of the disease and that individuals with C8orf37-related retinal dystrophy should be screened for BBS features.

Purpose: To describe a case of choroidal neovascularization in a young patient with genetically-proven Bardet-Biedl syndrome., Methods: Case description with fundus and anatomical photography and optical coherence tomography., Patients: Single patient case description., Results: Fundus photography and optical coherence tomography reveal the presence of previously-active choroidal neovascularization. Anatomical, historical, and genetic evidence confirm Bardet-Biedl syndrome in this individual., Discussion: Choroidal neovascularization accompanying this syndrome has not been reported. Herein we describe the first published description of choroidal neovascularization in an individual with genetically-proven Bardet-Biedl syndrome.

Purpose: To assess for SDCCAG8 mutations in Bardet-Biedl syndrome (BBS) subjects with renal involvement and no polydactyly, and to describe phenotypic characteristics of SDCCAG8-related disease., Material and Methods: Five patients (from 4 pedigrees) with clinical diagnosis of BBS, who had retinal and renal involvement and no polydactyly, were assessed. Sequence analysis of SDCCAG8 was undertaken and a detailed clinical review of an affected sibship was performed., Results: A sibship of East Indian origin who carried a putative clinical diagnosis of BBS had compound heterozygous mutations in SDCCAG8 (p.Thr482LysfsX12/p.Asp543AlafsX24). The renal involvement was early and required transplant in both cases. Both were short statured and had asthma since childhood. The younger sister also had non-alcoholic fatty liver disease. Visual acuity and central fields were preserved in the teenage years in both patients. The optical coherence tomography showed preservation of the retinal lamination at the fovea; fundus autofluorescence demonstrated a perifoveal ring of hyperfluorescence as commonly observed in other forms of retinitis pigmentosa. Full-field electroretinogram revealed rod function to be more severely affected than cone function in both cases., Conclusion: Our results and prior literature suggest that SDCCAG8 could play an important role in presumed BBS patients affected with severe kidney disease and absent polydactyly. This report enhances the phenotypic description of SDCCAG8-related disease.

Introduction: Early onset retinal degeneration associated with obesity can present a diagnostic challenge in paediatric ophthalmology practice. Clinical overlap between Bardet-Biedl syndrome (BBS) and Alström syndrome has been described, although the two entities are genetically distinct. To date, 16 genes are known to be associated with BBS (BBS1-16) and only one gene has been identified for Alström syndrome (ALMS1)., Materials and Methods: In collaboration with the French National Center for Sequencing (CNS, Evry), all coding exons and flanking introns were sequenced for 27 ciliopathy genes (BBS1-12, MGC1203, TTC21b, AHI1, NPHP2-8 (NPHP6=BBS14), MKS1(BBS13), MKS3, C2ORF86, SDCCAG8, ALMS1) in 96 patients referred with a clinical diagnosis of BBS. ALMS1 gene analysis included sequencing of all coding exons., Results: BBS known gene mutations were found in 44 patients (36 with two mutations and 8 heterozygous). ALMS1 mutations were found in four cases. The rate of ALMS1 mutations among patients suspected of having BBS was 4.2%., Discussion: Clinically, all four patients presented early-onset severe retinal degeneration with congenital nystagmus associated with obesity. The difficult early differential diagnosis between the two syndromes is outlined. One mutation had already been reported (c.11310delAGAG/p.R3770fsX) and three were novel (c.2293C > T/p.Q765X, c.6823insA/p.R2275fsX, c.9046delA/p.N3016fsX)., Conclusions: Ciliopathy genes sequencing can be very helpful in providing a timely diagnosis in this group of patients, hence appropriate genetic counselling for families and adequate medical follow-up for affected children.

Background: To report the clinical findings in two brothers presenting with a pigmentary retinopathy and post-axial polydactyly, who were found to have a mutation in the BBS1 gene, confirming a diagnosis of Bardet-Biedl syndrome (BBS)., Materials and Methods: Documentation of the clinical history, electrophysiological investigations, clinical examination and ocular findings of two brothers born to non-consanguineous white parents, with careful delineation of their clinical phenotypes. Screening of the BBS 1 gene on chromosome 11q13 by PCR-amplified exon alterations followed by direct sequencing was carried out to identify pathogenic mutations., Results: Although both probands had polydactyly and the characteristic ocular signs of BBS on both ophthalmological examination and electro-retinography, neither of them had dysmorphic facial features, obesity, hypogonadism, cognitive impairment, or renal anomalies. The first proband did have mild learning difficulties, although this did not restrict him in activities of daily living. Both probands were homozygous positive for the presence of a c.1169T > G (p.Met390Arg) mutation in BBS1., Conclusion: Although neither proband fulfilled the typical criteria for BBS, this diagnosis was confirmed on mutation analysis. These cases serve to highlight the degree of clinical variability observed in BBS which may be under-diagnosed in patients with milder phenotypes.

Purpose: To determine whether retinal dysfunction in obligate carriers of the Bardet-Biedl syndrome (BBS) could be observed in local electroretinographic responses obtained with the multifocal electroretinogram (mfERG)., Methods: Six obligate carriers of the BBS were examined for the study. Examination of each carrier included an ocular examination and mfERG testing of one eye. For the mfERG, we used a 103-scaled hexagonal stimulus array that subtended a retinal area of approximately 40 degrees in diameter. The amplitudes and implicit times in each location for the mfERG were compared with the corresponding values determined for a group of 34 normally sighted, age-similar control subjects., Results: Mapping of 103 local electroretinographic response amplitudes within a central 40 degrees area with the mfERG showed regions of reduced mfERG amplitudes in three of six carriers. Implicit time measurements in the 6 carriers were all normal except for those locations associated with abnormal amplitude reductions in 3 of the carriers. When present, retinal dysfunction was evident in the presence of a normal-appearing fundus., Conclusions: Multifocal ERG testing can demonstrate areas of retinal dysfunction in carriers of the BBS. This test may therefore be useful for identifying some heterozygous carriers of this disease.

Bardet-Biedl Syndrome (BBS) is a multisystemic disorder diagnosed on the basis of a combination of primary and secondary clinical features that include retinal dystrophy, obesity, polydactyly, cognitive dysfunction, and renal malformations. We report a unique case of BBS in a 13-year old girl of African-American descent who presented with retinitis pigmentosa, obesity, polydactyly, learning disabilities, precocious puberty, hypertension, renal cysts, and Hirschprung disease. Further evaluation revealed a history of precocious puberty, which is antithetical to the common manifestations of BBS, while neuroimaging was suggestive of periventricular leukomalacia and neuro-electrophysiologic studies revealed diffuse cerebral disturbance, which may contribute to her neurological abnormalities. The patient was also diagnosed with hydrometrocolpos, a finding typical of McKusick-Kaufman Syndrome (MKKS) but infrequent in other disorders. This observation, together with recent findings in some mouse models of BBS, raises the question of whether hydrometrocolpos should be considered as an additional diagnostic criterion for BBS to be used in females in parallel to the criterion of hypogonadism in males, thereby improving diagnostic sensitivity.