Targeted Therapy in Neonatal Cardiac Rhabdomyoma: Expanding mTOR-Inhibition Beyond TSC Germline Mutations

All articles of this category (opens in new window) Background: Cardiac rhabdomyomas are the most common pediatric heart tumor and are often associated with tuberous sclerosis complex (TSC). While usually asymptomatic, they may cause heart failure or arrhythmia. The use of mTOR inhibitors can lead to tumor reduction. While routine genetic testing from lymphocytes only addresses germline mutations, somatic mosaicism can only be detected in tissue samples. Methods: We report a term newborn in whom, following a systolic murmur, echocardiography revealed a mass with subtotal obstruction of the left ventricular outflow tract (LVOT). Suspecting a TSC-associated rhabdomyoma, mTOR inhibitor therapy was initiated. During follow-up, the patient developed heart failure with reduced cardiac output and elevated troponin levels, leading to surgical resection. Postoperatively, LVOT flow was unobstructed with mild aortic regurgitation. Histology confirmed rhabdomyoma. Routine genetic testing revealed no TSC germline mutation, but molecular analysis of tumor tissue showed a pathogenic somatic TSC2 mosaicism. Further evaluation revealed no evidence of other TSC manifestations. Conclusion: Identifying a somatic mosaic TSC2 mutation suggests that limiting mTOR inhibitor use to patients with TSC germline mutations may be too restrictive. In this case, surgery was ultimately required due to hemodynamic compromise, resulting in stopping mTOR inhibitor therapy. Nonetheless, the potential presence of somatic TSC variants in cardiac rhabdomyomas offers a plausible biological rationale for considering mTOR inhibition in certain high-risk cases, such as preterm neonates with low birth weight, to possibly delay or prevent early surgical intervention even if the classical TSC genetic diagnostic is negative. Ultimately, the impact of mTOR inhibition in this group of patients needs further assessment. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany