Journal of Pediatric Cardiology and Cardiac Surgery

Noonan syndrome with multiple lentigines (NSML) is frequently associated with hypertrophic cardiomyopathy (HCM) with severe left ventricular tract outflow obstruction (LVOTO); however, standard HCM treatments are often ineffective. Recently, HCM attenuation was observed in the NSML mouse model treated with a mammalian target of rapamycin (mTOR) inhibitor, rapamycin; however, there have been few reports on its clinical experience. Herein, we describe our experience with the treatment using a rapamycin analog, sirolimus, in a 19-year-old adolescent boy with NSML and HCM accompanied by severe LVOTO. The patient was already diagnosed with NSML by genetic examination (heterozygous Q510E mutation in PTPN11). HCM was complicated by severe LVOTO and was refractory to conventional treatment. We initiated sirolimus treatment (1 mg/day) for 16 weeks. Echocardiographic measurement and tissue Doppler evaluation of the left ventricular diastolic function did not significantly change before and after the treatment. Although the brain natriuretic peptide levels temporarily decreased, the values at 16 weeks after sirolimus administration were almost equal to levels before administration. Cardiac magnetic resonance imaging (cMRI) at 8 weeks after sirolimus treatment revealed elevation of native T1 value in the entire left ventricular wall, suggesting fibrosis of the entire left ventricle, which seemed to be irreversible. In our case, the effect of the rapamycin analog sirolimus could not be confirmed. Given the results of cMRI, treatment may have been started too late. It remains possible that the results would have been different if treatment had been started before extensive fibrosis occurred in the myocardium.