Townes-Brocks Syndrome Revealed by Kidney Gene Panel Testing

Area of Science:

• Genetics
• Nephrology
• Rare Diseases

Background:

• Townes-Brocks syndrome (TBS) is a rare genetic disorder linked to SALL1 variants, typically presenting with anorectal malformations, ear anomalies, and hand/thumb abnormalities.
• While kidney involvement is known in TBS, its prevalence and spectrum in individuals undergoing genetic testing for kidney disease are not well-characterized.

Purpose of the Study:

• To determine the incidence of SALL1 variants in patients tested for monogenic kidney disease.
• To identify and quantify the renal and extrarenal features associated with SALL1 variants in this cohort.

Main Methods:

• Retrospective analysis of genetic data from a 385-gene panel.
• Identification of pathogenic or likely pathogenic SALL1 variants.
• Collection of clinical data including age, features, and disease progression.

Main Results:

• SALL1 variants were found in 1:1592 patients tested for monogenic kidney disease (22/35,044 samples).
• 91% of patients with SALL1 variants had chronic kidney disease (CKD); common renal features included renal agenesis/hypoplasia, FSGS, and cysts.
• Extrarenal features such as hearing loss, ear anomalies, anorectal malformations, and hand/thumb abnormalities were present in a significant proportion of cases.

Conclusions:

• SALL1 variants are an under-recognized cause of monogenic kidney disease.
• Genetic testing for SALL1 variants should be considered in individuals with unexplained kidney disease, even with atypical or mild TBS features.