Sirolimus therapy for fetal cardiac rhabdomyoma in a pregnant woman with tuberous sclerosis

Abstract

Rhabdomyoma is the most common fetal cardiac tumor, and its development is related to tuberous sclerosis. Fetal cardiac rhabdomyomas often spontaneously regress in utero or after birth, but large tumors can cause hemodynamic obstruction. Sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been used as an immunosuppressant after organ transplantation. The mTOR inhibitors are well-known to have anti-tumor activity, and they have been used for the treatment of patients with tuberous sclerosis. In the current case, fetal cardiac rhabdomyoma was completely resolved in utero during oral sirolimus treatment in the mother with tuberous sclerosis. This case shows that oral sirolimus therapy in pregnancy may be a treatment for multiple or large fetal cardiac rhabdomyomas.

Fetal cardiac rhabdomyomas treated with maternal sirolimus

“…The tumor began regrowing, and the fetus was delivered at 39 weeks. The third report by Park et al documents maternal sirolimus treatment at 23 weeks for 1.2‐cm nonobstructing rhabdomyomas with complete resolution by delivery.…”

“…The new development of mitral valve regurgitation and worsening inflow obstruction were ominous signs of impending hydrops and possible fetal demise. She was then offered options of continued expectant management or off‐label in utero therapy with maternal sirolimus, which has been previously described . A multidisciplinary team was developed, and extensive counseling was performed including discussion of the risks of sirolimus, which included potential maternal bone marrow suppression, transaminitis, proteinuria, hypertriglyceridemia, immunosuppression and infection, oral mucositis, and pneumonitis.…”

“…She was then offered options of continued expectant management or off-label in utero therapy with maternal sirolimus, which has been previously described. [21][22][23] A multidisciplinary team was developed, and extensive counseling was performed including discussion of the risks of sirolimus, which included potential maternal bone marrow suppression, transaminitis, proteinuria, hypertriglyceridemia, immunosuppression and infection, oral mucositis, and pneumonitis. A treatment program was initiated as previously described with a 10-mg loading dose, and doses were titrated to a goal maternal trough of 10 to 15 ng/dL.…”

“…In the postnatal period, mechanistic target of rapamycin (mTOR) inhibitors, sirolimus, and everolimus have been used for symptomatic rhabdomyomas. More recently, single case reports of in utero treatment with maternal sirolimus administration have been used to address fetal rhabdomyomas . Herein, we present an additional case of prenatal treatment of fetal rhabdomyomas with sirolimus that decreased the tumor burden and improved the cardiac function as demonstrated with a novel method of speckle tracking echocardiography.…”

Multiple cutaneous nodules in a 7-month-old boy

“…Clinical trials and scientific evidence support the use of sirolimus in TSC patients with specific manifestations, including SEGA and skin lesions(2-4). Darcy AK et al conducted a multicenter clinical investigation on the safety of mTOR inhibitors in TSC patients before the age of two years(9).Sirolimus has been reported to treat fetus with TSC presenting cardiac rhabdomyoma(10). Our patient started sirolimus treatment at the age of eight months and the symptoms improved significantly, especially the JXG skin lesions.The patient had pulmonary isolated subpleural nodule in the left lower lobe via chest CT.…”