Fetal Tuberous Sclerosis: Sirolimus for the Treatment of Fetal rhabdomyoma

Dagge, Ana; Silva, Luísa Andrade; Jorge, Sofía; Nogueira, Estela; Rebelo, Mónica; Pinto, Luísa

doi:10.1080/15513815.2021.1948646

Cited by 7 publications

(8 citation statements)

References 15 publications

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“…There have been six reports, including eight cases, to date (see supplement, Table S1 ). The reason to decide on treatment was progressive rhabdomyoma growth and impending heart failure in all reported cases [ 10 , 11 , 13 , 14 , 15 ] except one [ 12 ], in which the main cause was lymphangioleiomyomatosis in the mother that had already been treated with sirolimus before the pregnancy. In another case [ 15 ], the mother received sirolimus for renal angiomyolipomas before becoming pregnant.…”

Section: Discussionmentioning

confidence: 99%

“…The reason to decide on treatment was progressive rhabdomyoma growth and impending heart failure in all reported cases [ 10 , 11 , 13 , 14 , 15 ] except one [ 12 ], in which the main cause was lymphangioleiomyomatosis in the mother that had already been treated with sirolimus before the pregnancy. In another case [ 15 ], the mother received sirolimus for renal angiomyolipomas before becoming pregnant. The decision to treat was usually made in the third trimester of pregnancy, when spontaneous tumor regression with the amelioration of cardiac function could not be expected any more.…”

Section: Discussionmentioning

confidence: 99%

“…Because of the immunosuppressive effect of rapalogs [ 22 ], there may be a risk for a pre- or postnatal infection in the mother or child. In the cases of prenatal sirolimus treatment [ 10 , 11 , 12 , 13 , 14 , 15 ], no severe infections were reported. In our case, we observed low natural killer cells in the mother before treatment as well as in the newborn postnatally.…”

Section: Discussionmentioning

confidence: 99%

“…An adverse neonatal outcome has been significantly associated with tumor size (≥20 mm diameter), fetal dysrhythmia, and the presence of hydrops fetalis [ 6 ]. Addressing this problem, there have been successful trials, albeit few in number, treating the fetus with TSC-related rhabdomyoma by treating the pregnant mother with rapamycin analogs (rapalogs), which act against the constitutive activation of mTORC1 [ 10 , 11 , 12 , 13 , 14 , 15 ]. Sirolimus is used as an immunosuppressive agent to prevent a host vs. graft reaction in transplant patients, but also in patients with TSC1/2 mutation-associated disorders, e.g., for the treatment of renal angiomyolipomas and pulmonary lymphangioleiomyomatosis.…”

Section: Introductionmentioning

confidence: 99%

“…Here, we report the case of a successful treatment of a large, possibly life-threatening cardiac rhabdomyoma in a fetus by administering sirolimus to the mother. We also compare it to the eight cases published to date [ 10 , 11 , 12 , 13 , 14 , 15 ], and discuss the pros and possible cons of this treatment.…”

Section: Introductionmentioning

confidence: 99%

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Successful Prenatal Treatment of Cardiac Rhabdomyoma in a Fetus with Tuberous Sclerosis

et al. 2023

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Cardiac rhabdomyomas are a possible early manifestation of the Tuberous Sclerosis Complex (TSC). They often regress spontaneously but may grow and cause cardiac dysfunction, threatening the child’s life. Treatment with rapalogs can stop the growth of these cardiac tumors and even make them shrink. Here, we present the case of a successful treatment of a cardiac rhabdomyoma in a fetus with TSC by administering sirolimus to the mother. The child’s father carries a TSC2 mutation and the family already had a child with TSC. After we confirmed the TSC diagnosis and growth of the tumor with impending heart failure, we started treatment at 27 weeks of gestation. Subsequently, the rhabdomyoma shrank and the ventricular function improved. The mother tolerated the treatment very well. Delivery was induced at 39 weeks and 1 day of gestation and proceeded without complications. The length, weight, and head circumference of the newborn were normal for the gestational age. Rapalog treatment was continued with everolimus. Metoprolol and vigabatrin were added because of ventricular preexcitation and epileptic discharges in the EEG, respectively. We provide the follow-up data on the child’s development in her first two years of life and discuss the efficacy and safety of this treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Successful Prenatal Treatment of Cardiac Rhabdomyoma in a Fetus with Tuberous Sclerosis

et al. 2023

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Characteristics and Outcomes of Fetal Cardiac Rhabdomyoma With or Without mTOR Inhibitors, a Systematic Review and Meta‐Analysis

Mustafa,

Javinani,

Morning

et al. 2024

Prenatal Diagnosis

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ObjectivesTo investigate the characteristics and outcomes of fetal cardiac rhabdomyoma with or without prenatal use of mammalian target of rapamycin inhibitor (mTORi).Search StrategyWe systematically searched PubMed, Scopus, and Web of Science until June 2023.Selection CriteriaStudies reporting on pregnancies with fetal cardiac rhabdomyoma were included.Data Collection and AnalysisA meta‐analysis of proportions was conducted only on studies that included three or more cases.ResultsA systematic review included 61 studies reporting on 400 fetuses with cardiac rhabdomyoma, of which 52 studies (389 fetuses) had expectant management and 9 studies (11 fetuses) were managed with mTORi. The meta‐analysis included 26 studies reporting on 354 fetuses. Prenatally, 14% (95% CI 4–36) had pericardial effusion, 13% (95% CI 6–27) had arrhythmia, 16% (95% CI 7–31) had outflow tract obstruction, and 10% (95% CI 4–21) had hydrops. Fetal demise occurred in 12% (95% CI 5–30). Before delivery, tumor size reduction was noted in 13%, and after birth in 58%. Following birth, 8% (95% CI 3–14) had neonatal death and 9% (95% 4–17) required cardiac surgery. 60% (95% CI 41–79) of cases were diagnosed with tuberous sclerosis. Seizures were reported only in cases with a tuberous sclerosis diagnosis (41/71 infants). For the 9 studies reporting all together on 11 fetuses with tuberous sclerosis receiving prenatal mTORi, they showed improvement in the size of cardiac rhabdomyoma as well as outflow obstruction and none had fetal demise or neonatal death, and none required postnatal cardiac surgery.ConclusionsWe report on the natural history of prenatal cardiac rhabdomyoma, including characteristics, progression, and survival. We report 11 fetuses with tuberous sclerosis and cardiac rhabdomyoma receiving prenatal mTORi, showing promising results.

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