ID #70 Oncogenetic and Reproductive Management in TSC
Nouha Bouayed AbdelmoulaAbstract
Introduction
Tuberous sclerosis complex (TSC) is a multisystem neurocutaneous disorder caused by mutations in TSC1 or TSC2. Clinical expression is highly variable, involving the brain, kidneys, skin, lungs, and eyes, with CNS tumors and renal disease being primary causes of morbidity. Genotype-phenotype correlations are incompletely understood, and intra-familial variability is common. Early genetic diagnosis is critical for both management and reproductive planning.
Methods
We investigated a Tunisian family with two brothers affected by TSC. Clinical assessment included neurological, renal, dermatological, and imaging studies. Molecular analysis of TSC1 and TSC2 was performed using Sanger sequencing. Genetic counseling was offered to assess reproductive risks and options for future conceptions.
Results
Both brothers carried a 2 bp deletion in exon 5 of TSC1. Clinical severity differed markedly: the 26-year-old exhibited moderate TSC with late-onset epilepsy, small renal angiomyolipomas, and pulmonary micronodules; the 36-year-old presented earlier epilepsy onset, multiple large renal lesions, subependymal nodules, and rapid progression to renal cell carcinoma and astrocytomas.
Conclusion
This case illustrates the phenotypic variability associated with a single TSC1 mutation. Early genetic testing enables accurate diagnosis, anticipatory surveillance, and informed reproductive decision-making. For families with known pathogenic TSC1 variants, options to secure future conceptions include preimplantation genetic testing, prenatal genetic testing, and detailed genetic counseling to minimize transmission risk. These approaches, combined with longitudinal clinical follow-up, optimize outcomes and reduce uncertainty for affected families.