Severe Renal Phenotype Across A Multigenerational Tuberous Sclerosis Complex (TSC) Family.

backgroundTuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by the formation of hamartomas in the brain, kidney, and heart, along with other complex clinical manifestations, including TSC-associated neuropsychiatric disorder (TAND). Development of genotype-phenotype correlations within TSC can aid clinicians in providing prognostic data and improve clinical management. We present here a multigenerational family who has a pathogenic variant in TSC2 displaying a severe renal phenotype.

methodsA 23-year-old Caucasian male (Patient 1) was determined to have a molecularly confirmed diagnosis of TSC at approximately 2 months of age. The nonsense pathogenic variant (c.1372C>T (p.Arg458*)) in TSC2 had been previously identified in his father (Patient 6), grandmother (Patient 5), and other extended paternal family members (Patient 2, 3, 4, 7).

resultsClinical evaluations revealed that the affected family members display a severe renal phenotype characterized by large angiomyolipoma burden (AMLs), renal cystic disease, and chronic kidney disease leading to renal failure.

conclusionOur clinical report is of significance as it illustrates a possible genotype-phenotype correlation between a specific TSC2 pathogenic variant and a severe renal phenotype. Our case series highlights the importance of establishing genotype-phenotype interactions to provide anticipatory guidance using prognostic data and clinical management.