Kidney failure in Bardet-Biedl syndrome

Area of Science:

• Genetics
• Nephrology
• Rare Diseases

Background:

• Bardet-Biedl syndrome (BBS) is a rare genetic disorder associated with multiple congenital anomalies.
• Kidney failure (KF) is a severe complication in BBS, impacting patient morbidity and mortality.
• Understanding genetic and demographic risk factors for KF in BBS is essential for clinical management.

Purpose of the Study:

• To investigate the prevalence and risk factors of kidney failure (KF) in Bardet-Biedl syndrome (BBS).
• To identify specific gene variants and demographic characteristics associated with KF in BBS patients.
• To explore the relationship between KF and other morbidities in the BBS population.

Main Methods:

• Utilized the Clinical Registry Investigating BBS (CRIBBS) database.
• Analyzed data from 607 BBS subjects, identifying 44 with KF.
• Performed molecular confirmation of BBS and analyzed gene variants, demographics, and clinical outcomes.

Main Results:

• Kidney failure (KF) was identified in 7.2% of BBS subjects, with a median age of 12.5 years.
• BBS10 was the most common causal gene (26.6%), while SDCCAG8 showed 100% penetrance for KF.
• Females (77.3%) were disproportionately affected, and truncating variants were present in 67.6% of KF cases.
• KF risk was higher in genes outside the BBSome/chaperonin groups, including TTC21B.
• KF was a significant factor in mortality (73.3% of non-infant deaths).

Conclusions:

• Kidney failure (KF) represents a major risk for premature morbidity and mortality in Bardet-Biedl syndrome (BBS).
• Key risk factors for KF include female sex, truncating variants, and specific genetic mutations.
• Comprehensive genetic investigation is vital for identifying individuals at high risk of KF in BBS.