Objectives: To characterize the diversity and prevalence of thoraco-abdominal abnormalities in Bardet-Biedl syndrome (BBS), a model ciliopathy for understanding the role of cilia in human health.
Study design: The Clinical Registry Investigating BBS, a worldwide registry exploring the phenotype and natural history of BBS, was used to conduct the study. Protected health information was obtained by subject or family interview and Health Insurance Portability and Accountability Act-approved release of data including imaging studies and genetic testing. Echocardiography and imaging findings were independently confirmed by 2 cardiologists.
Results: Thoraco-abdominal abnormalities were identified in 6 of 368 (1.6%) subjects with a minimum prevalence of 1 in 60 Clinical Registry Investigating BBS participants. Diverse laterality defects were observed suggesting that the underlying ciliopathy randomly alters embryonic left-right axis orientation. Congenital heart disease, common in heterotaxy, was present in 2 subjects. Additional defects, uncommonly reported in BBS, were observed in the central nervous, genitourinary, gastrointestinal, and musculoskeletal systems in the subjects. No BBS genotype was favored in the cohort. One subject had genetic and clinical phenotype diagnostic of both primary ciliary dyskinesia and BBS.
Conclusions: The variety of thoraco-abdominal abnormalities in BBS suggests the pleiotropic nature of these anomalies is not confined to a single pattern or genotype. Clinicians providing care to individuals with BBS should consider the increased prevalence of thoraco-abdominal anomalies in BBS. Individuals with features suggestive of other ciliopathies, such as primary ciliary dyskinesia, should undergo further evaluation for additional genetic disorders.
Trial registration: ClinicalTrials.gov: NCT02329210.
Keywords: cilia; ciliopathy; laterality defects; primary ciliary dyskinesia; rare disease registry.
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