Congenital heart defects comprehensive panel

Congenital heart defects span a broad clinical spectrum, from haemodynamically minor septal defects to complex conotruncal and single-ventricle malformations. They occur both as isolated cardiac findings and within multisystem syndromes affecting additional organ systems. Severe lesions are commonly detected prenatally on routine foetal echocardiography or in the neonatal period when cyanosis, heart failure, or low cardiac output becomes clinically apparent; milder lesions may be recognised later in infancy or childhood during evaluation of a heart murmur, exercise intolerance, or incidental imaging findings. Syndromic and nonsyndromic forms both contribute substantially to the overall clinical spectrum. Single-gene syndromes such as 22q11.2 deletion syndrome show highly heterogeneous presentation, ranging from isolated conotruncal defects to overt extracardiac involvement including thymic hypoplasia, palatal anomalies, renal insufficiency, and neurodevelopmental delay. Nonsyndromic presentations typically lack such extracardiac findings and may comprise atrial or ventricular septal defects, bicuspid aortic valve, or other isolated structural lesions.

Congenital heart defects are observed in approximately eight out of every 1,000 live births and represent one of the leading causes of childhood morbidity and mortality worldwide.

The estimated prevalence is 60.2 per 10,000 live births in (2008-2015). Worldwide estimates approximate 1% of live births overall.

The genetic conditions associated with congenital heart defects follow heterogeneous inheritance patterns. The spectrum encompasses autosomal dominant, autosomal recessive, and X-linked forms alongside non-Mendelian contributions including chromosomal and multifactorial inheritance. In a multicentre paediatric CHD cohort with abnormal chromosomal microarray findings, 28% carried genomic disorders with well-recognised CHD association and 67% carried copy-number variants with rare or no prior CHD association.

Using new sequencing technologies (NGS), it is possible to investigate genetic causes of congenital heart defects (including atrial septum defect, ventricular septum defect, tetralogy of Fallot, transposition of the large arteries, hypoplastic left heart syndrome, aortic stenosis, pulmonary stenosis, conotruncal defects, Ebstein anomaly, and heterotaxia), , and other syndromes in familial cases or when an overriding syndrome is suspected.

• Where congenital heart defects are suspected to have a genetic cause, molecular genetic testing can identify the underlying condition and confirm a clinical suspicion.
• The identified entity guides further clinical management and is a prerequisite for targeted medical care; therapeutic options are evaluated individually by the treating physicians.
• Identification of the underlying pathogenic germline variant enables predictive testing of at-risk family members and provides information relevant to family planning.

• Mamasoula C, Addor MC, Carbonell CC, Dias CM, Echevarría-González-de-Garibay LJ, Gatt M, et al. Prevalence of congenital heart defects in Europe, 2008-2015: a registry-based study. Birth Defects Res. 2022;114(20):1404-16. doi:10.1002/bdr2.2117. PMID:; PMCID: PMC10098845.
• Chhatwal K, Smith JJ, Bola H, Zahid A, Venkatakrishnan A, Brand T. Uncovering the genetic basis of congenital heart disease: recent advancements and implications for clinical management. CJC Pediatr Congenit Heart Dis. 2023;2(6 Pt B):464-80. doi:10.1016/j.cjcpc.2023.10.008. PMID:; PMCID: PMC10777202.
• Landis BJ, Helvaty LR, Geddes GC, Lin JI, Yatsenko SA, Lo CW, et al. A multicenter analysis of abnormal chromosomal microarray findings in congenital heart disease. J Am Heart Assoc. 2023;12(18). doi:10.1161/JAHA.123.029340. PMID:; PMCID: PMC10547279.
• Landstrom AP, Kim JJ, Gelb BD, Helm BM, Kannankeril PJ, Semsarian C, et al. Genetic testing for heritable cardiovascular diseases in pediatric patients: a scientific statement from the American Heart Association. Circ Genom Precis Med. 2021;14(5). doi:10.1161/HCG.0000000000000086. PMID:; PMCID: PMC8546375.