Serial Kidney Biopsies Reveal Progressive Pathology in Townes-Brocks Syndrome: A Case Report

Townes-Brocks syndrome (TBS) is an autosomal dominant hereditary disorder caused by SALL1 variants, characterized by auricular malformations, anal anomalies, and limb deformities, often accompanied by kidney dysfunction. We describe a case of TBS, which was suspected after birth, in a 27-year-old man presenting with progressive kidney dysfunction and obesity. At age 16, school urinalysis revealed proteinuria and impaired kidney function. A kidney biopsy at that time showed a perihilar variant focal segmental glomerulosclerosis (FSGS) lesion, and the patient was treated with angiotensin II receptor blocker and sodium/glucose cotransporter 2 inhibitor. Kidney function gradually declined, prompting a second biopsy at age 27, which revealed progressive FSGS lesions and interstitial fibrosis/tubular atrophy. Genetic analysis identified a pathogenic SALL1 variant, confirming the diagnosis. This case demonstrates the mechanistic link between SALL1 variants, congenital renal hypoplasia, impaired podocyte repair, and obesity-related hyperfiltration, culminating in rapid development of FSGS. Longitudinal histopathological analysis through repeated biopsy was essential for understanding this progression. The integration of sequential renal biopsies and genetic analysis provided unique pathophysiological insight and diagnostic clarity in TBS-associated kidney disease. In patients with TBS and congenital nephron reduction, weight control is particularly important to mitigate obesity-related hyperfiltration injury.