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

Abstract

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.

Sorting Intolerant from Tolerant and PolyPhen-2 Algorithms: A Variation in Exon 14 of ATP7B Gene among 4 West Iraqi Families with Wilson’s Disease

“…As a result, compared to non-consanguineous marriage, the likelihood that the offspring of the first-cousin marriage will have the malformations is anticipated to be very high. This is particularly clear for the genes that cause uncommon autosomal recessive disorders [24].…”

Cardiovascular Involvement in Pediatric FLNC Variants: A Case Series of Fourteen Patients

“…CMPs are a heterogeneous group of diseases, which may lead to progressive heart failure or sudden cardiac death (SCD). They are rare conditions in the pediatric population: DCM is observed in 1:5000 children, HCM in 1:30,000, whereas RCM and ACM are considered extremely rare forms [ 24 , 25 , 26 ]. Familial cases are often autosomal dominant and are characterized by incomplete penetrance and variable expressivity.…”

Rare form of arrhythmogenic cardiomyopathy in a 5-year-old child

“…Для СК характерна триада клинических призна ков: курчаво-шерстистые волосы, присутствуют уже при рождении (волосы вьющиеся, медленно расту щие, трудно расчесываемые, ломкие); ладонно-по дошвенный гиперкератоз, который появляется, когда ребенок начинает самостоятельно ходить и ползать; кардиальная патология в виде дилатации и сниже ния сократительной способности левого желудочка, а также желудочковых нарушений ритма [14,16]. Характерными ЭКГ-маркерами данного синдрома являются низкий вольтаж комплексов QRS, наруше ния внутрижелудочковой проводимости, а также ин версия зубцов Т в V1, V2, V3 или V5 [23][24][25].…”

“…Обычно у детей первых лет жизни отсутствуют клинические проявления со стороны сердечно-со судистой системы, но электрокардиографические и эхокардиографические изменения могут быть выявлены уже в раннем возрасте [23]. В большин стве случаев у пациентов с СК кожные изменения предшествуют возникновению сердечных прояв лений, и дебют ХСН обычно происходит к оконча нию первой декады жизни [16].…”