Transplacental sirolimus therapy for severe fetal cardiac rhabdomyomas in tuberous sclerosis complex: organ-specific
Background:
Transplacental mammalian target of rapamycin (mTOR) inhibition has emerged as a promising therapeutic strategy for severe fetal cardiac rhabdomyomas in tuberous sclerosis complex (TSC). However, its impact on neonatal cardiovascular adaptation and long-term neurological outcomes remains poorly understood.
Case Presentation:
We report a fetus with clinically diagnosed TSC presenting with multiple large cardiac rhabdomyomas causing progressive hemodynamic compromise. Transplacental sirolimus therapy was initiated at 30 weeks of gestation and continued for 7 weeks, resulting in marked regression of cardiac tumors, improved left ventricular outflow tract patency, and recovery of fetal cardiac function. In contrast, serial fetal imaging demonstrated no apparent change in the size or number of intracranial lesions. Elective cesarean delivery was performed at 38 weeks of gestation. Despite favorable prenatal structural improvement, the neonate developed severe left ventricular dysfunction immediately after birth, requiring ductal-dependent circulatory support and intensive cardiovascular management. Postnatal everolimus therapy was initiated on the day of birth, leading to complete regression of cardiac rhabdomyomas by 5 months of age. However, central nervous system lesions persisted, epilepsy developed during infancy, and cognitive and language delays remained evident at 30 months of follow-up. Wolff-Parkinson-White syndrome was also identified during infancy. Genetic analysis ultimately revealed a heterozygous deletion involving exons 11-16 of TSC2.
Conclusions:
This case demonstrates organ- and tissue-specific therapeutic responses to prenatal and postnatal mTOR inhibition in TSC. Although transplacental mTOR inhibition may be life-saving for severe fetal cardiac involvement, prenatal structural improvement may not necessarily predict neonatal cardiovascular stability or favorable long-term neurological outcomes. These findings underscore the importance of careful perinatal planning, realistic prenatal counseling, and extended multidisciplinary follow-up.
