Personalized Genetic Diagnosis of Congenital Heart Defects in Newborns

Abstract

Congenital heart disease is a group of pathologies characterized by structural malformations of the heart or great vessels. These alterations occur during the embryonic period and are the most frequently observed severe congenital malformations, the main cause of neonatal mortality due to malformation, and the second most frequent congenital malformations overall after malformations of the central nervous system. The severity of different types of congenital heart disease varies depending on the combination of associated anatomical defects. The causes of these malformations are usually considered multifactorial, but genetic variants play a key role. Currently, use of high-throughput genetic technologies allows identification of pathogenic aneuploidies, deletions/duplications of large segments, as well as rare single nucleotide variants. The high incidence of congenital heart disease as well as the associated complications makes it necessary to establish a diagnosis as early as possible to adopt the most appropriate measures in a personalized approach. In this review, we provide an exhaustive update of the genetic bases of the most frequent congenital heart diseases as well as other syndromes associated with congenital heart defects, and how genetic data can be translated to clinical practice in a personalized approach.

Probing single ventricle heart defects with patient‐derived induced pluripotent stem cells and emerging technologies

“…Yet, with an incidence in the United States of 1 in 3,841 live births, HLHS is rare compared with most congenital cardiac disorders (Mai et al, 2019). Although only about 1,025 infants are born yearly with HLHS in the United States, this type of SVHD is responsible for 25% of cardiac‐related infant deaths (Diz et al, 2021; Mai et al, 2019). HLHS is characterized by underdevelopment of the structures that constitute the left side of the heart (Figure 1) including the mitral valve, left ventricle, aortic valve, and aorta (Reamon‐Buettner, Ciribilli, Inga, & Borlak, 2008).…”

“…The cardiovascular system is the first organ system to develop during fetal development (Donovan & Cascella, 2020). During the early stages of heart development, structural malformations of the heart and its associated vessels can emerge, producing congenital heart disease (CHD) in newborns (Diz et al, 2021). Approximately one third of infants with CHD must undergo at least one surgery within the first year of life to survive (Dittrich et al, 2003).…”

“…Approximately one third of infants with CHD must undergo at least one surgery within the first year of life to survive (Dittrich et al, 2003). CHD occurs in less than 1% of live births, with a higher incidence in males (Diz et al, 2021). CHD is a broad term for all structural heart defects present at or before birth.…”

Genetics and genetic diagnostics of congenital heart disease

“…Вариаций нарушений нормального развития сердца очень много, как и подходов к классификации. Одной из первых клинических классификаций, используемых до сих пор, было выделение синих (цианотичных) и белых (нецианотичных) пороков сердца на основе ведущего нарушения гемодинамики [11]. В 2007 г. L.D.…”

Prenatal Diagnosis of Chromosome 22q11.21 Microduplication Syndrome in a Fetus with Congenital Malformation of the Cardiovascular System: Case Report

“…Вади серцево-судинної системи, як одна з найбільш поширених патологій, зустрічаються з різною частотою залежно від регіону дослідження і за даними світової статистики цей показник коливається в межах від 4-5 до 9 випадків на 1000 живонароджених [1,2,3]. Вроджені вади серця (ВВС) займають провідне місце серед інших вад розвитку (до 30 %) і є частиною найважчих станів -множинних вроджених вад розвитку [4,5,6].…”