Multicystic Kidney Disease in a Family With Tuberous Sclerosis Complex

Tuberous sclerosis complex (TSC) is a multisystem condition associated with disease-causing variants of either TSC1 or TSC2 genes. Significant kidney involvement in TSC is most often due to development of angiomyolipomas (AMLs) and occurs more frequently in people with TSC2 variants. Kidney cysts are also commonly seen; however, these are usually small and not recognised as problematic. A subset of patients has a severe polycystic kidney disease due to a contiguous gene deletion involving PKD1 and TSC2 on chromosome 16. End-stage kidney disease (ESKD) occurs commonly in patients with TSC2/PKD1 deletions but is otherwise rare. We report a family with a TSC1 variant. The father, a 34-year-old male, presented with chronic kidney disease with eGFR 31 mL/min, proteinuria 1.2 g/day and hypertension. Ultrasound showed small cystic kidneys. Coincidentally, his 2-year-old daughter presented with seizures and had skin lesions and neurological signs consistent with TSC. Her 1-year-old brother also met TSC diagnostic criteria. Further investigations of the father showed typical skin lesions and cerebral tubers. Genetic testing identified a variant in TSC1. The father progressed to ESKD and subsequently received a kidney transplant. His two children have similar renal ultrasounds with multiple cysts; now aged 18 and 16 years, they have normal eGFR and no proteinuria. This family manifests a rarely described multicystic phenotype and TSC1 variant. The father's case demonstrates the risk of progressive kidney disease in TSC, even in the absence of AMLs or TSC2/PKD1 contiguous deletion, and highlights the importance of renal monitoring of all adults with TSC.