Epigenetics and Congenital Heart Diseases

Abstract

Congenital heart disease (CHD) is a frequent occurrence, with a prevalence rate of almost 1% in the general population. However, the pathophysiology of the anomalous heart development is still unclear in most patients screened. A definitive genetic origin, be it single-point mutation or larger chromosomal disruptions, only explains about 35% of identified cases. The precisely choreographed embryology of the heart relies on timed activation of developmental molecular cascades, spatially and temporally regulated through epigenetic regulation: chromatin conformation, DNA priming through methylation patterns, and spatial accessibility to transcription factors. This multi-level regulatory network is eminently susceptible to outside disruption, resulting in faulty cardiac development. Similarly, the heart is unique in its dynamic development: growth is intrinsically related to mechanical stimulation, and disruption of the intrauterine environment will have a direct impact on fetal embryology. These two converging axes offer new areas of research to characterize the cardiac epigenetic regulation and identify points of fragility in order to counteract its teratogenic consequences.

Chromatinopathies: insight in clinical aspects and underlying epigenetic changes

“…It has been shown that congenital heart defects noted in CPs may encompass a wide spectrum of abnormalities such as (1) tetralogy of Fallot (Coffin-Siris syndrome, CHARGE syndrome, Sifrim-Hitz-Weiss syndrome, Kleefstra syndrome, and Cornelia de Lange syndrome), (2) atrial septal defect (Coffin-Siris syndrome, Sifirim-Hitz-Weiss syndrome, Kabuki syndrome, Kleefstra syndrome, Wolf-Hirschorn syndrome, Rubinstein-Taybi syndrome, Microphthalmia syndromic 2, Cornelia de Lange syndrome, Intellectual disability-hypotonic facies syndrome X-linked, and Immunodeficiency-centromeric instability-facial anomalies syndrome 1), (3) ventricular septal defect (Coffin-Siris syndrome, CHARGE syndrome, Sifrim-Hitz-Weiss syndrome, Kabuki syndrome, Kleefstra syndrome, Rubinstein-Taybi syndrome, Microphthalmia syndromic 2, Cornelia de Lange syndrome, and Immunodeficiency-centromeric instability-facial anomalies syndrome 1), (4) interrupted aortic arch (CHARGE syndrome), (5) pulmonary stenosis (CHARGE syndrome, Kleefstra syndrome, Cornelia de Lange syndrome, and Intellectual disability-hypotonic facies syndrome X-linked), (6) aortic stenosis (Intellectual disability-hypotonic facies syndrome X-linked), (7) patent ductus arteriosus (Coffin-Siris syndrome, CHARGE syndrome, Sifrim-Hitz-Weiss syndrome, Cornelia de Lange syndrome, and Intellectual disability-hypotonic facies syndrome X-linked), (8) mitral valve anomalies (Microphthalmia syndromic 2), and (9) double-outlet right ventricle (CHARGE syndrome) (Linglart and Bonnet 2022 ).…”

Adenosine deaminase acting on RNA 1 (ADAR1) as crucial regulators in cardiovascular diseases: structures, pathogenesis, and potential therapeutic approach

“…Congenital heart disease (CHD) is currently the most common type of birth defect in the general population with an incidence of about 1% ( Linglart and Bonnet, 2022 ). Interestingly, few studies have identified the role of RNA editing in CHD.…”

Biological Age in Congenital Heart Disease—Exploring the Ticking Clock

“…These encompass chromosomal aneuploidy such as Down syndrome and Turner syndrome, copy number variants such as 22q11 deletion syndrome and Williams-Beuren syndrome, single gene mutation syndromes like Alagille, Noonan, or CHARGE syndromes [20][21][22][23][24], and several monogenic non-syndromic lesions. Genetic entities are characterized by incomplete penetration and variable expression [23,25]. In addition to genetics, maternal obesity, diabetes, tobacco exposure, alcohol intake, teratogenic medications, and infections such as rubella are known causes [23,25].…”

“…Genetic entities are characterized by incomplete penetration and variable expression [23,25]. In addition to genetics, maternal obesity, diabetes, tobacco exposure, alcohol intake, teratogenic medications, and infections such as rubella are known causes [23,25]. The majority of disease presentations are non-syndromic with no distinct cause [18,21].…”