Prenatal mTOR Inhibitors in Tuberous Sclerosis Complex: Current Insights and Future Directions

Abstract

Background: Tuberous sclerosis complex (TSC) can present prenatally, often with cardiac rhabdomyomas, which, if large, may cause complications such as hydrops fetalis and reduced cardiac output. Prenatal treatment of these lesions with mTOR inhibitors, approved for other TSC manifestations, is under investigation. We hypothesize that mTOR inhibitors could help manage or prevent other TSC-related conditions, particularly neurological issues like epilepsy and CNS lesions, potentially improving neurodevelopmental outcomes. However, the safety of prenatal mTOR treatment remains a concern, especially for foetal development, and limited data are available on neurological outcomes. Methods: We conducted a literature review using PubMed, EMBASE, and Cochrane CENTRAL, focusing on studies involving mTOR inhibitors for prenatal TSC management. The search included case reports and series involving pregnant women diagnosed with TSC or early manifestations like cardiac rhabdomyomas. Keywords included "mTOR Inhibitor", "Rapamycin", "tuberous sclerosis complex", "prenatal", and "rhabdomyoma". Results: Three prenatal mouse studies and eight papers reporting on ten pregnant women treated with mTOR inhibitors were identified. Conclusions: The literature confirms that prenatal mTOR inhibitors may reduce cardiac rhabdomyomas. However, further studies are needed to explore their broader potential, particularly in preventing neurological complications, while carefully considering their impact on intrauterine growth and neurodevelopment.

Keywords: TSC1; TSC2; foetal; mTOR Inhibitors; pregnancy; prenatal; rapamycin; rhabdomyoma; sirolimus; tuberous sclerosis.