Hypertrophic Cardiomyopathy in Children: Pathophysiology, Diagnosis, and Treatment of Non-sarcomeric Causes.

Emanuele Monda,Martina Caiazza,Francesco Di Fraia,Fabio Fimiani,Michele Lioncino,Paolo Calabrò,Giuseppe Pacileo,Giuseppe Palmiero,Marta Rubino,Annapaola Cirillo,Maria Giovanna Russo,Adelaide Fusco,Federica Verrillo,Giuseppe Limongelli,Roberta Pacileo,Augusto Esposito

doi:10.3389/fped.2021.632293

Abstract

Hypertrophic cardiomyopathy (HCM) is a myocardial disease characterized by left ventricular hypertrophy not solely explained by abnormal loading conditions. Despite its rare prevalence in pediatric age, HCM carries a relevant risk of mortality and morbidity in both infants and children. Pediatric HCM is a large heterogeneous group of disorders. Other than mutations in sarcomeric genes, which represent the most important cause of HCM in adults, childhood HCM includes a high prevalence of non-sarcomeric causes, including inherited errors of metabolism (i.e., glycogen storage diseases, lysosomal storage diseases, and fatty acid oxidation disorders), malformation syndromes, neuromuscular diseases, and mitochondrial disease, which globally represent up to 35% of children with HCM. The age of presentation and the underlying etiology significantly impact the prognosis of children with HCM. Moreover, in recent years, different targeted approaches for non-sarcomeric etiologies of HCM have emerged. Therefore, the etiological diagnosis is a fundamental step in designing specific management and therapy in these subjects. The present review aims to provide an overview of the non-sarcomeric causes of HCM in children, focusing on the pathophysiology, clinical features, diagnosis, and treatment of these rare disorders.

Highlights

Hypertrophic cardiomyopathy (HCM) is a myocardial disease characterized by left ventricular (LV) hypertrophy not solely explained by abnormal loading conditions [1]
The present review aims to provide an overview of the specific causes of HCM in children, focusing on the pathophysiology, diagnosis, and treatment of these rare disorders
The prognosis of the patients affected by Noonan syndrome (NS) and HCM is influenced by the high prevalence of pulmonary valve stenosis, and the coexistence of complex congenital heart disease (CHD) as atrioventricular septal defects (10%), atrial septal defect (10%), and rarely tetralogy of Fallot, patent ductus arteriosus, and left-sided obstructions resulting in mitral valve (MV) abnormalities [17, 21]

Summary

INTRODUCTION

Hypertrophic cardiomyopathy (HCM) is a myocardial disease characterized by left ventricular (LV) hypertrophy not solely explained by abnormal loading conditions [1]. Other than mutations in sarcomeric genes, which represent the most important cause of HCM both in adults and in children (40–60% of cases) [1,2,3,4,5,6,7], the other causes of HCM include inherited errors of metabolism (i.e., glycogen storage diseases (GSDs), lysosomal storage diseases, and fatty acid oxidation disorders), neuromuscular diseases, malformation syndromes (i.e., RASopathies), and mitochondrial disease (Table 1), which. HCM presenting before 1 year of age shows a worse prognosis [2] and is principally caused by inherited errors of metabolism or malformation syndrome (e.g., RASopathies) (Figure 3). The present review aims to provide an overview of the specific causes of HCM in children, focusing on the pathophysiology, diagnosis, and treatment of these rare disorders

Introduction

Findings

CONCLUSIONS