Interrupted aortic arch vsd genetic8/4/2023 Syndromic: Chromosomal aneuploidy, microdeletion or gene/locus/inheritance Non syndromic: Locus/inheritance Phenotype associated with structural heart disease Syndromic: Syndrome name Non syndromic: Gene implicated We review known implicated genes and chromosomal abnormalities, discussed when and how to perform genetic testing, and shared our perspective regarding clinical applications. The focus of this review is on the genetics of structural CHD, as opposed to other disease categories such as inherited channelopathies. Genetics carries the potential to unravel etiological mysteries that underpin CHD, provide pathophysiological insights, assist in risk assessment, inform clinical management, and counsel families regarding future offspring. The fact that monogenic and chromosomal abnormality models account for a substantial proportion of CHD enhances the potential value of genetic investigation and testing. Furthermore, the rate of CHD increases with consanguinity, as described in Arabic countries. In so-called multiplex families with several affected members, identified candidate genes have been consistent with monogenetic models with Mendelian inheritance. Chromosomal abnormalities have been associated with cardiac defects, particularly in the setting of syndromic phenotypes ( e.g., trisomy 21, DiGeorge, and Williams-Beuren syndromes). However, some forms of CHD could not be explained by a polygenic model, with much higher recurrence risks in first-degree relatives than predicted. Technological advances have permitted the confirmation of clinically suspected monogenetic subtypes of CHD, with dominant or recessive inheritance patterns. Other implicated maternal factors include pregestational diabetes, pollakiuria, febrile illnesses, rubeola, influenza, alcohol consummation, cigarette smoking, and teratogenic pharmacological agents such as thalidomide, warfarin, angiotensin converting enzyme inhibitors, and certain anticonvulsant and anti-inflammatory drugs. Early investigations into environmental factors spawned recommendations for maternal multivitamin supplementation containing folic acid to reduce risks of developing CHD. The complexity and heterogeneity of CHD has traditionally been attributed to multifactorial etiologies arising from interactions between multiple genes and environmental factors (so-called “polygenic model”). While much progress has been made regarding the management of children and adults with CHD, a greater understanding of underlying etiologies could potentially lead to further advances in preventive care and therapeutic strategies. The spectrum of severity ranges from insignificant and even self-resolving lesions, such as ventricular septal defects that spontaneously close, to highly complex and multiorgan manifestations that are incompatible with natural survival. It is the most common type of birth defect and encompasses a wide range of malformations. Although genetics may appear to constitute a highly specialized sector of cardiology, basic knowledge regarding inheritance patterns, recurrence risks, and available screening and diagnostic tools, including their strengths and limitations, could assist the treating physician in providing sound counsel.Ĭongenital heart disease (CHD) afflicts 2 to 3 children per 100 live births. In some circumstances, prenatal or preimplantation genetic screening could identify fetuses or embryos at high risk for CHD. Moreover, genetic assessment may serve as a tool to predict recurrence risk, define the pattern of inheritance within a family, and evaluate the need for further family screening. Genetic investigation in CHD may carry the potential to improve prognosis by yielding valuable information with regards to personalized medical care, confidence in the clinical diagnosis, and/or targeted patient follow-up. The selection of a genetic test is contingent upon the particular diagnostic hypothesis generated by clinical examination. A family tree with a detailed phenotypic description serves as the initial screening tool to identify potentially inherited defects and to guide further genetic investigation. In such instances, genetic investigation and testing may potentially play an important role in clinical care. For example, monogenic models and chromosomal abnormalities have been associated with various syndromic and non-syndromic forms of CHD. It is now understood that the contribution of genetics to CHD extends beyond a single unified paradigm. Traditionally, a polygenic model defined by the interaction of multiple genes and environmental factors was hypothesized to account for different forms of CHD. Congenital heart disease (CHD) is the most common type of birth defect.
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