Challenges in the Management of Giant Cardiac Rhabdomyoma in a Toddler: Unresponsive to Everolimus Therapy

Introduction

Primary cardiac tumors are rarely detected in fetuses and children. Rhabdomyoma is the most prevalent cardiac tumor found in children (1). These cases are also associated with tuberous sclerosis complex (TSC). More recent analysis shows that 50% of rhabdomyomas disappear spontaneously in the first two years (Lazea C et al., Children 2024; 11: 674). These tumors can also be potentially fatal, and surgery is the best treatment option. Tuberous sclerosis complex (TSC) is a multisystem-acquired disorder that shows itself by benign hamartoma. The disorder affects the kidneys, brain, heart, and skin. Approximately 90% of cases of TSC have damaging variants in one of the two central suppressor genes, TSC1 or TSC2. Their primary functions are regulating cell cycle and differentiation by hindering the mammalian target of rapamycin (mTOR). If a damaging variant of the TSC1 or TSC2 gene impairs the correct function of the Tuberous Sclerosis protein complex. Everolimus is a partially selective mTORC1 inhibitor. mTORC1 is regulated by upstream signaling events that regulate the phosphorylation and activity state of the Tuberous Sclerosis protein complex (TSC), which consists of TSC1 (Hamartin), TSC2 (Tuberin) and TBC1D7. The inhibitory action of Everolimus is NOT by inhibiting the production of TSC1 and TSC2, but rather by inhibiting mTORC1 activity downstream of the Tuberous Sclerosis protein complex (Moavero R et al., Ital J Pediatr 2013; 39: 57. Veerharen HA et al., J Pediatr 2003; 132: 258–263). Since 2012, numerous reported cases have proven that Everolimus is an effective treatment modality for tuberous sclerosis and rhabdomyoma (Hoshal SG., Pediatr Int 2016; 58: 397–399. Veerharen HA et al., J Pediatr 2003; 132: 258–263). Everolimus primarily targets mTORC1. Also, other clinically approved mTOR inhibitors, such as Sirolimus, likely have equal efficacy as other mTOR inhibitors. Herein, we report a case of a giant inoperable cardiac rhabdomyoma that does not respond to the use of oral Everolimus in a two-year-old boy.

Publication History

Article published online:
30 August 2024