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

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.

Characteristics and Long-Term Ablation Outcomes of Supraventricular Arrhythmias in Hypertrophic Cardiomyopathy: A 10-Year, Single-Center Experience

“…Some etiologies might be associated with arrhythmia. Monda et al and Limongelli et al concluded that pre-excitation, atrioventricular block, and concentric left ventricular hypertrophy might be diagnostic clues for non-sarcomeric etiologies ( 32 , 33 ).…”

Pathogenic Mechanisms of Hypertrophic Cardiomyopathy beyond Sarcomere Dysfunction

“…In addition to altered calcium signaling, congenital mutations in genes encoding components of the RAS/mitogen-activated protein kinase (MAPK) pathway are also linked to HCM as a part of the developmental disorders, collectively called RASopathies [33,34]. Patients with RASopathies, such as Noonan, Costello, and cardio-facio-cutaneous syndromes, are typically born with facial dysmorphism, skeletal defects, and later in life develop various types of cardiomyopathies among which HCM is the most common myocardial pathology, represents poor prognosis and is the leading cause of death [35][36][37].…”

Pathogenic Mechanisms of Hypertrophic Cardiomyopathy Beyond Sarcomere Dysfunction

“…In addition to altered calcium signaling, congenital mutations in genes encoding components of the RAS/mitogen-activated protein kinase (MAPK) pathway are also linked to HCM as a part of the developmental disorders, collectively called RASopatheis [30,31]. Patients with RASopathies, such as Noonan, Costello and cardio-facio-cutaneous syndromes are typically born with facial dysmorphism, skeletal defects and later in life develop various types of cardiomyopathies among which HCM is the most common myocardial pathology, represents poor prognosis and is the leading cause of death [32][33][34].…”