Regression Of Cardiac Rhabdomyoma Research Articles

Rapamycin therapy for neonatal tuberous sclerosis complex with cardiac rhabdomyomas: A case report and review.

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease that varies greatly in its expression. The current study reports a novel case of TSC caused by a TSC2 mutation (TSC2c.1642_1643insA or TSC2p.K549fsX589), in which multiple cardiac rhabdomyomas were detected by fetal echocardiography in week 31 of pregnancy. The infant was delivered successfully; however, seizures began 16 days following birth. Subsequent genetic tests confirmed a diagnosis of TSC. Rapamycin treatment resulted in regression of cardiac rhabdomyomas and controlled seizures. The current study demonstrates the value of fetal echocardiography in the diagnosis of TSC and suggests that inhibition of the mammalian target of the rapamycin (mTOR) signaling pathway may be considered as a potential antiepileptogenic therapy for neonatal TSC. In addition, it was demonstrated that rapamycin treatment was therapeutically beneficial for preventing disorders caused by abnormal mTOR signaling, such as cancer. According to the literature, cardiac rhabdomyomas, seizures and skin lesions are well established markers for TSC in neonates. MRI scans of the brain and genetic screening of TSC1 and TSC2 genes may facilitate an early diagnosis of TSC.

Everolimus treatment of a fetal intracardiac rhabdomyoma not associated with the tuberous sclerosis complex: a case report

Abstract Introduction Benign cardiac rhabdomyomas are the most common cardiac tumors in fetuses and children. They are most often located in the ventricles and may disturb myocardial function, the severity correlating with location and size of the tumor. Rhabdomyomas are commonly associated with the tuberous sclerosis complex (TSC) and are the first clinical manifestation in 50–80% of the cases [Isaacs H Jr. Fetal and neonatal cardiac tumors. Pediatr Cardiol. 2004;25:252–73, Colosi E, Russo C, Macaluso G, Musone R, Catalano C. Sonographic diagnosis of fetal cardiac rhabdomyomas and cerebral tubers: a case report of prenatal tuberous sclerosis. J Prenat Med. 2013;7:51–5]. Several authors have documented the sensitivity of TSC-associated rhabdomyomas to everolimus treatment [Hoshal SG, Samuel BP, Schneider JR, Mammen L, Vettukattil JJ. Regression of massive cardiac rhabdomyoma on everolimus therapy. Pediatr Int. 2016;58:397–9, Mlczoch E, Hanslik A, Luckner D, Kitzmüller E, Prayer D, Michel-Behnke I. Prenatal diagnosis of giant cardiac rhabdomyoma in tuberous sclerosis complex: a new therapeutic option with everolimus. Ultrasound Obstet Gynecol. 2015;45:618–21, Tiberio D, Franz DN, Phillips JR. Regression of a cardiac rhabdomyoma in a patient receiving everolimus. Pediatrics. 2011;127:e1335–7]. The present study provides convincing evidence of successful everolimus therapy in a newborn without the TSC complex. Case presentation A cardiac rhabdomyoma measuring 35 × 28 × 24 mm was seen in a fetus in pre- and postnatal echocardiography. There was no family history for TSC and amniocentesis showed no mutations in the TSC1/TSC2 genes. Off-label treatment with everolimus began when the neonate was 11 days old and was discontinued when the infant was 11 months old after echocardiography showed marked regression of tumor size and improvement of the tricuspid valve insufficiency. Echocardiography 3 months later showed an increase in size to 13.2 × 9 mm, so that everolimus therapy was re-instated. The next echocardiography, 10 weeks later, showed renewed regression of tumor size and a residual moderate tricuspid valve insufficiency under everolimus therapy. Discussion The present report of a rhabdomyoma in a newborn without an association with TSC is of interest because it identifies a treatment effect of everolimus. A medical approach in patients with cardiac decompensation due to intracardiac rhabdomyomas offers an attractive alternative to surgery.

Successful treatment of arrhythmia-induced cardiomyopathy in an infant with tuberous sclerosis complex

BackgroundTuberous sclerosis complex (TSC) is an autosomal-dominant tumor suppressor gene syndrome that is characterized by the development of distinctive benign tumors and malformations in multiple organ systems (N Eng J Med 355:1345-1356, 2006). Cardiac rhabdomyomas are intracavitary or intramural tumors observed in 50–70 % of infants with TSC but only cause serious clinical problems in a very small fraction of these patients (N Eng J Med 355:1345-1356, 2006; Pediatrics 118:1146-1151, 2006; Eur J Pediatr 153:155-7, 1994); most individuals have no clinical symptoms and their tumors spontaneously regress. However, despite being clinically silent, these lesions can provoke arrhythmias and heart failure (Pediatrics 118:1146-1151, 2006; Eur J Pediatr 153:155-7, 1994).Case presentationWe here report the clinical findings of an infant suffering from TSC complicated with dilated cardiomyopathy (DCM) after the regression of cardiac rhabdomyomas. Although his tumors improved spontaneously, tachycardia and irregular heart rate due to frequent premature ventricular and supraventricular contractions persisted from the newborn period and were refractory to several medications. His cardiomyopathy was suspected to have been induced by the tachycardia or arrhythmia. We found carvedilol therapy to be safe and highly effective in treating the cardiomyopathy. To our knowledge, this is the first case report of TSC with DCM after regression of cardiac tumors and its successful treatment.ConclusionThe patient’s clinical course suggests that careful life-long disease management is important, even in TSC patients without apparent symptoms.

Regression of Cardiac Rhabdomyomas in a Neonate after Everolimus Treatment.

Cardiac rhabdomyoma often shows spontaneous regression and usually requires only close follow-up. However, patients with symptomatic inoperable rhabdomyomas may be candidates for everolimus treatment. Our patient had multiple inoperable cardiac rhabdomyomas causing serious left ventricle outflow-tract obstruction that showed a dramatic reduction in the size after everolimus therapy, a mammalian target of rapamycin (mTOR) inhibitor. After discontinuation of therapy, an increase in the diameter of masses occurred and everolimus was restarted. After 6 months of treatment, rhabdomyomas decreased in size and therapy was stopped. In conclusion, everolimus could be a possible novel therapy for neonates with clinically significant rhabdomyomas.

Everolimus投与後に心臓横紋筋腫が急速に退縮した結節性硬化症の1乳児例

mTOR阻害薬のeverolimusは，結節性硬化症に伴う腎血管筋脂肪腫や上衣下巨細胞性星細胞腫に対する有効性が報告されているが，心臓横紋筋腫に対する報告は稀である．症例は生後10か月の男児．胎児期から両側側脳室上衣下結節と多発性心臓腫瘍を指摘され結節性硬化症（TS）と診断された．出生後，小さな心臓腫瘍は自然退縮したが，右室中隔，左室自由壁，左室心尖部の大きな腫瘍は残存した．流入路，流出路狭窄はなかった．生後3か月から難治性痙攣が出現し，頭部MRIで上衣下巨細胞性星細胞腫を認めたため，生後10か月から同腫瘍に対してeverolimusを開始した（3.0 mg/m2/日）．その結果，上衣下巨細胞性星細胞腫は縮小し，痙攣も抑制できた．心臓腫瘍は，everolimus投与後1か月で左室自由壁の腫瘍が消失し，投与後7か月で左室心尖部の腫瘍も消失した．残存した右室中隔の腫瘍もeverolimus投与前は最大23.4×16.7 mmあったものが，投与後1か月で16.1×4.3 mmまで急速に縮小した．Everolimusは，TSに合併した心臓横紋筋腫を急速に退縮させる可能性がある．