A Multidisciplinary Approach in Prenatal Diagnosis of TSC With Cardiac Rhabdomyoma as the Initial Symptom

The long-term prognosis of a fetus with cardiac rhabdomyoma (CR) depends on the correlation with tuberous sclerosis complex (TSC). In recent years, the numerous variations of uncertain significance (VUS) of TSC genes produced by high-throughput sequencing have made counseling challenging, studies until now have tended to side-step the tricky topics. Here, we integrated detailed parental phenotype, echocardiography, neuro MRI, and genetic information to conduct a comprehensive evaluation of 61 CR fetuses. As a result, multiple CRs and cerebral lesions appeared in 90 and 80%, respectively of fetuses with pathogenic (P)/likely pathogenic (LP) TSC1/TSC2 variations. Overall, 85.7% of the live-born infants with P/LP presented with TSC-associated signs. While, 85.7% of VUS without nervous findings had good prognoses. Genetic evidence and cerebral MRI findings are the most sensitive index to assess long-term prognosis, which complement and confirm each other for a TSC diagnosis. In total, 68.9% of fetuses with CR could benefit from this multidisciplinary approach, which turned out to be potentially clinically actionable with precise clinical/genetic diagnosis or had a foreseeable outcome. Our practice provides a practical and feasible solution for perinatal management and prognostic guidance for fetuses with CR.