Impact of Local and Systemic Factors on Kidney Dysfunction in Bardet-Biedl Syndrome

Abstract

Bardet Biedl syndrome (BBS) is a rare inherited syndromic condition characterized by renal and extra-renal disorders. Renal defect, at either structural or functional level, is one of the cardinal clinical features, and is a major cause of morbidity. However, the pathogenic mechanism underlying its dysfunction remains largely unknown, and to date only symptomatic treatment with no specific therapy is available for these patients. Elucidating aberrant cellular and/or systemic processes that impact kidney function is therefore a prerequisite to develop targeted innovative therapeutic strategies for the BBS patients. Given the proven role of BBS proteins in the function of the primary cilium (PC) and considering the clinical overlapping of BBS with other ciliopathies, BBS is considered the result of disruption of ciliary activities. The present review aims at giving an updated overview of the spectrum of renal abnormalities in BBS patients according to the existing scientific literature, and discusses the possible role of intrinsic PC dysfunction into the pathogenesis of renal defects based on the most recent findings demonstrating a possible role of systemic factors in favoring the progression of renal disease.

Exploring Key Challenges of Understanding the Pathogenesis of Kidney Disease in Bardet–Biedl Syndrome

“…It is not excluded that kidney disease progression may be affected by the combination of structural abnormalities and common risk factors, such as obesity and hypertension, which are more common in patients with BBS than in the general population. 11 Genetics of BBS Traditional linkage analysis conducted on Bedouin families led to the identification of the first chromosomal disease locus (BBS2). 12 Soon after, a second locus (BBS1) was described, through a genome-wide scan of 31 North American families.…”

Urine Proteomics Revealed a Significant Correlation Between Urine-Fibronectin Abundance and Estimated-GFR Decline in Patients with Bardet-Biedl Syndrome

“…The majority of BBS patients show structural defects of the kidney and the urinary tract [5]; kidney dysfunction ranges from renal hyposthenuria to the end stage renal disease (ESRD) [6-9]. Whether the defective ability to concentrate the urine is an early marker of kidney dysfunction is currently unknown [10-13]. The molecular basis of kidney dysfunction is poorly understood.…”

Expanding the phenotype of Bardet–Biedl syndrome: Newly diagnosed sibling cases

“…Bardet–Biedl syndrome (BBS; OMIN 209900) is a rare autosomal recessive nephronophthisis‐related ciliopathy (NPHP‐RC) characterized by renal abnormalities combined with obesity, mental impairment, rod‐cone dystrophy, polydactyly, and hypogonadism in males . Recently, the identified causative genes for BBS are increased: BBS1 to BBS21, and each gene encodes proteins for the functional maintenance of primary cilia .…”

“…Recently, the identified causative genes for BBS are increased: BBS1 to BBS21, and each gene encodes proteins for the functional maintenance of primary cilia . Thus, the phenotype of BBS is now expanding and in clinical practice, a definite diagnosis of BBS is often difficult to make . Among BBS genes, MKKS, which plays an important role in the assembly of the BBSome, is reportedly attributable to BBS6 .…”

“…The primary clinical features of BBS are rod‐cone dystrophy, post‐ataxia polydactyly, truncal obesity, learning disability, hypogonadism in males, and kidney anomalies . Because of its wide spectrum of phenotypes and case‐by‐case differences in phenotypic severity, clinical diagnosis of BBS is often difficult to make .…”