Cardiomyopathies in Children and Systemic Disorders When Is It Useful to Look beyond the Heart?

• Published in: Journal of cardiovascular development and disease 2022-01, Vol.9 (2), p.47
• Main Authors: Lodato, Valentina, Parlapiano, Giovanni, Calì, Federica, Silvetti, Massimo Stefano, Adorisio, Rachele, Armando, Michela, El Hachem, May, Romanzo, Antonino, Dionisi-Vici, Carlo, Digilio, Maria Cristina, Novelli, Antonio, Drago, Fabrizio, Raponi, Massimiliano, Baban, Anwar
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; cardiomyopathies; Cardiomyopathy; children; Congenital diseases; Connective tissue; Coronary vessels; Down syndrome; Genes; Heart; heterogeneity; Intellectual disabilities; multisystemic; Pediatrics; personalized approach; Rare diseases; Review; syndromes
• ISSN: 2308-3425; 2308-3425
• DOI: 10.3390/jcdd9020047

Cardiomyopathy (CMP) is a rare disease in the pediatric population, with a high risk of morbidity and mortality. The genetic etiology of CMPs in children is extremely heterogenous. These two factors play a major role in the difficulties of establishing standard diagnostic and therapeutic protocols. Isolated CMP in children is a frequent finding, mainly caused by sarcomeric gene variants with a detection rate that can reach up to 50% of analyzed cohorts. Complex multisystemic forms of pediatric CMP are even more heterogenous. Few studies in literature take into consideration this topic as the main core since it represents a rarity (systemic CMP) within a rarity (pediatric population CMP). Identifying etiology in this cohort is essential for understanding prognosis, risk stratification, eligibility to heart transplantation and/or mechanical-assisted procedures, preventing multiorgan complications, and relatives' recurrence risk calculation. The previous points represent a cornerstone in patients' empowerment and personalized medical care approach. The aim of this work is to propose a new approach for an algorithm in the setting of the diagnostic framework of systemic pediatric CMP. On the other hand, during the literature review, we noticed a relatively common etiologic pattern in some forms of complex/multisystem CMP. In other words, certain syndromes such as Danon, Vici, Alström, Barth, and Myhre syndrome share a common pathway of directly or indirectly defective "autophagy" process, which appears to be a possible initiating/triggering factor for CMPs. This conjoint aspect could be important for possible prognostic/therapeutic implications in this category of patients. However, multicentric studies detailed functional and experimental models are needed prior to deriving conclusions.