Fetal cardiac rhabdomyomas treated with maternal sirolimus

Abstract

Objective To review the pathophysiology of rhabdomyomas and the emerging option of prenatal treatment of fetal cardiac rhabdomyomas. Methods We present a case of fetal rhabdomyomas causing significant hemodynamic compromise that received in utero treatment of maternal sirolimus. Genetic amniocentesis confirmed a TSC2 mutation. A treatment program was initiated with a 10‐mg loading dose titrated to a goal maternal trough of 10 to 15 ng/dL. In order to follow fetal cardiac function, a sophisticated method of speckle tracking echocardiography was used before and after treatment. Obstetric ultrasound was used to monitor fetal growth, and clinical surveillance, echocardiography, and brain MRI were used to monitor postnatal growth and development through 6 months of neonatal life. Results Sirolimus was initiated from 28 to 36 weeks of gestation with improvement of cardiac status. During this period, intrauterine growth restriction developed. Postnatally, the infant has had stable rhabdomyomas and cardiac function without reinitiating sirolimus. Brain MRI demonstrated scattered cortical tubers and subependymal nodules, and the infant has not had seizure‐like activity. At 6 months of age, the infant has achieved appropriate developmental milestones. Conclusion In counseling cases of prenatal onset large obstructing rhabdomyomas and cardiac compromise, in utero sirolimus treatment can be considered.

Maternal sirolimus therapy and fetal growth restriction

“…A case report by Pluym et al has described FGR in maternal sirolimus therapy for fetal cardiac rhabdomyoma. However, it was unclear whether left ventricular outflow obstruction or the sirolimus therapy was the factor to which FGR could be attributed [ 11 ]. Park et al did not find FGR in their case report and Barnes et al did not report the birth weight in their case report [ 12 , 13 ].…”

“…The mechanism of placental transfer of sirolimus is not known. From case reports of maternal sirolimus therapy for fetal conditions, it is obvious that placental transfer takes place [ 11 - 13 ]. Unlike adults, most of the fetuses are susceptible to low serum concentration of sirolimus.…”

“…Most of the fetuses lack cytochrome P450 3A isoforms in the liver [ 20 , 21 ]. Based on the enzymology, it is reasonable to infer higher cord blood concentration than maternal level of sirolimus [ 11 , 13 , 21 ].…”

Prenatal Pericardiocentesis and Postnatal Sirolimus for a Giant Inoperable Cardiac Rhabdomyoma

“…The mere presence of inflow or outflow obstruction does not mandate intervention. Prenatal treatment options include conservative management, off-label mTOR inhibitor therapy ( 7 ), pericardiocentesis or shunting, open fetal resection, delivery, and postnatal surgery if pregnancy is advanced ( 6 ). Open fetal resection is an uncommonly performed procedure requiring highly specialized expertise.…”

The Juvenile Ribbons-Foetal Type Rhabdomyoma

“…Lesions appear as triton tumour or cutaneous rhabdomyomatous mesenchymal hamartoma which are exceptionally discerned in young children. Hamartoma is commonly incorporated with neural and/or mature adipose tissue, in addition to skeletal muscle[7,8]  Neuromuscular hamartoma is composed of nerve fibres and skeletal muscle confined to a singular perimysial sheath. Nerve fibres are immune reactive to S100 protein[7,8]  Infantile fibromatosis is a deep-seated neoplasm composed of fascicles of spindle-shaped cells along with an absence of cross striations or undifferentiated cells[7,8] Additionally, foetal rhabdomyoma requires a clinical segregation from conditions such as submucosal cyst, vascular malformation or unspecified benign lesions[9,10].…”