Chromosomal abnormalities in children as a predictor of the development of congenital heart and vascular diseases




congenital heart defects, chromosomal pathology, early diagnosis, prognosis, children


Congenital heart defects (CHDs) are the most common of all congenital abnormalities in children and cover a wide range of lesions. They can manifest as minor defects and very complex combined lesions that are incompatible with life. CHDs occur on average in 8-10 cases per 100 live births. The complexity and diversity of cardiovascular defects is traditionally explained by multifactorial etiology, due to the interaction between several genes and environmental factors (the so-called “polygenic model”), but chromosomal abnormalities are often the leading factor in the occurrence of CHDs. The importance of studying chromosomal pathology in the context of CHD lies in the possibility of identifying specific genetic markers that are predictors of the development of these conditions.

The aim - to analyze the current research data on the frequency of CHDs in children with chromosomal pathology; find out the structural features and possibilities of correction of these defects; evaluate the prognostic possibilities of genetic counseling in the prevention and early detection of congenital cardiovascular system pathology in children with chromosomal defects.

The most common chromosomal abnormalities and their impact on the development of the child’s cardiovascular system are considered, and the current state of research in this area is reflected. Clinical signs of the main types of chromosomal abnormalities, their cardiac and extracardiac manifestations are presented. It is established that the largest proportion of CHDs in patients with chromosomal abnormalities are septal defects, which are usually associated with impaired development of endocardial cushions due to an imbalance in the expression of genes located on the affected chromosomes. Genetic testing for congenital cardiovascular abnormality can potentially improve prognosis by providing valuable information on personalized health care, confidence in clinical diagnosis, and patient follow-up.

No conflict of interest was declared by the authors.


Ahmed I, Anjum F. (2023, Jan). Atrioventricular Septal Defect. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. URL:

Alkaya DU, Öztürk B, Ülker AY, Bozlak S, Öztürk E, Dedeoğlu R et al. (2023). Congenital Heart Defects and Outcome in a Large Cohort of Down Syndrome: A Single-Center Experience from Turkey. Turkish Archives of Pediatrics. 58(5): 473.

Antonarakis SE, Skotko BG, Rafii MS, Strydom A, Pape SE, Bianchi DW et al. (2020). Down syndrome. Nature Reviews Disease Primers. 6(1): 9.; PMid:32029743 PMCid:PMC8428796

Asirvatham AR, Pavithran PV, Pankaj A, Bhavani N, Menon U, Menon A et al. (2019). Klinefelter syndrome: clinical spectrum based on 44 consecutive cases from a South Indian tertiary care center. Indian Journal of Endocrinology and Metabolism. 23(2): 263.; PMid:31161115 PMCid:PMC6540891

Bearelly P, Oates R. (2019). Recent advances in managing and understanding Klinefelter syndrome. F1000Research. 8.; PMid:30755791 PMCid:PMC6352920

Benhaourech S, Drighil A, Hammiri AE. (2016). Congenital heart disease and Down syndrome: various aspects of a confirmed association. Cardiovascular journal of Africa. 27(5): 287-290.; PMid:27805241 PMCid:PMC5370349

Bonomi M, Rochira V, Pasquali D, Balercia G, Jannini EA, Ferlin A. (2017). Klinefelter syndrome (KS): genetics, clinical phenotype and hypogonadism. Journal of endocrinological investigation. 40: 123-134.; PMid:27644703 PMCid:PMC5269463

Bull MJ, Trotter T, Santoro SL, Christensen C, Grout RW, Council on Genetics. (2022). Health supervision for children and adolescents with Down syndrome. Pediatrics. 149(5): e2022057010.; PMid:35490285

Butler G, Srirangalingam U, Faithfull J, Sangster P, Senniappan S, Mitchell R. (2023). Klinefelter syndrome: going beyond the diagnosis. Archives of disease in childhood. 108: 166-171.; PMid:35948402 PMCid:PMC7614197

Carey JC. (2021). Trisomy 18 and trisomy 13 syndromes. Cassidy and Allanson's management of genetic syndromes: 937-956.

Chen CP, Ko TM, Chen YY, Su JW, Wang W. (2013). Prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome derived from chromosome 22 associated with cat eye syndrome. Gene. 527(1): 384-388.; PMid:23747353

Cho H, Heo JS, Ahn KH, Hong SC. (2021). Trisomy 9 Mosaicism in an Extremely Low Birth Weight Infant. Perinatology. 32(2): 100-103.

Chou YY, Wang CJ, Lin CH, Chung HT, Lo FS. (2020). Association between cardiovascular anomalies and karyotypes in Turner syndrome patients in Taiwan: A local cohort study. Pediatrics & Neonatology. 61(2): 188-194.; PMid:31672476

Cooper DS, Riggs KW, Zafar F, Jacobs JP, Hill KD, Pasquali SK et al. (2019). Cardiac surgery in patients with trisomy 13 and 18: an analysis of the society of thoracic surgeons congenital heart surgery database. Journal of the American Heart Association. 8(13): e012349.; PMid:31237190 PMCid:PMC6662341

Corbitt H, Maslen C, Prakash S, Morris SA, Silberbach M. (2018). Allometric considerations when assessing aortic aneurysms in Turner syndrome: Implications for activity recommendations and medical decision‐making. American Journal of Medical Genetics Part A, 176(2): 277-282.; PMid:29243875 PMCid:PMC5831410

Davis C, Grischkan J, Tobias JD. (2020). Perioperative Care of a Child With Cri Du Chat Syndrome. Journal of Medical Cases. 11(9): 279.; PMid:34434412 PMCid:PMC8383670

Donato B, Ferreira MJ. (2018). Cardiovascular risk in Turner syndrome. Revista portuguesa de cardiologia. 37(7): 607-621.; PMid:29866389

Fiot E, Alauze B, Donadille B, Samara-Boustani D, Houang M, De Filippo G et al. (2022). Turner syndrome: French national diagnosis and care protocol (NDCP; national diagnosis and care protocol). Orphanet Journal of Rare Diseases. 17(1): 1-39.; PMid:35821070 PMCid:PMC9277788

Franconeri A, Ballati F, Pin M, Carone L, Danesino GM, Valentini A. (2020). Interrupted aortic arch: A case report. Indian Journal of Radiology and Imaging. 30(01): 81-83.; PMid:32476755 PMCid:PMC7240901

Freeman SB, Taft LF, Dooley KJ, Allran K, Sherman SL, Hassold TJ et al. (1998). Population‐based study of congenital heart defects in Down syndrome. American journal of medical genetics. 80(3): 213-217.<213::AID-AJMG6>3.3.CO;2-#

Gaspar NS, Rocha G, Grangeia A, Soares HC. (2022). Cat-eye syndrome: a report of two cases and literature review. Cureus. 14(6).

Gözgeç E, Kantarci M, Guven F, Ogul H, Ceviz N, Eren S. (2021). Determination of anomalous pulmonary venous return with high-pitch low-dose computed tomography in paediatric patients. Folia Morphologica. 80(2): 336-343.; PMid:32459365

Gravholt CH, Andersen NH, Conway GS, Dekkers OM, Geffner ME, Klein KO et al. (2017). Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting. European journal of endocrinology. 177(3): G1-G70.; PMid:28705803

Heinrich T, Nanda I, Rehn M, Zollner U, Frieauff E, Wirbelauer J et al. (2013). Live-born trisomy 22: patient report and review. Molecular Syndromology. 3(6): 262-269.; PMid:23599696 PMCid:PMC3569106

Kozel BA, Barak B, Kim CA, Mervis CB, Osborne LR, Porter M, Pober BR. (2021). Williams syndrome. Nature Reviews Disease Primers. 7(1): 42.; PMid:34140529 PMCid:PMC9437774

Kwak JH, Lee SW, Cha HR, Huh J, Kang IS, Jun TG et al. (2022). Long-Term Observational Outcomes after Total Correction of Congenital Heart Disease in Korean Patients with Down Syndrome: A National Cohort Study. Children. 9(9): 1329.; PMid:36138638 PMCid:PMC9497944

Lee CL, Lin SM, Chen MR, Chuang CK, Syu YM, Chiu HC et al. (2022). Long-term cardiovascular findings in Williams syndrome: a single medical center experience in Taiwan. Journal of Personalized Medicine. 12(5): 817.; PMid:35629241 PMCid:PMC9146911

Li M, Glass J, Du X, Dubbs H, Harr MH, Falk M et al. (2021). Trisomy 9 mosaic syndrome: sixteen additional patients with new and/or less commonly reported features, literature review, and suggested clinical guidelines. American Journal of Medical Genetics Part A. 185(8): 2374-2383.; PMid:33969943 PMCid:PMC8662755

Lin AE, Lippe BM, Geffner ME, Gomes A, Lois JF, Barton CW et al. (1986). Aortic dilation, dissection, and rupture in patients with Turner syndrome. The Journal of pediatrics. 109(5): 820-826.; PMid:3772661

Mollo N, Scognamiglio R, Conti A, Paladino S, Nitsch L, Izzo A. (2023). Genetics and Molecular Basis of Congenital Heart Defects in Down Syndrome: Role of Extracellular Matrix Regulation. International Journal of Molecular Sciences. 24(3): 2918.; PMid:36769235 PMCid:PMC9918028

Nelson KE, Rosella LC, Mahant S, Guttmann A. (2016). Survival and surgical interventions for children with trisomy 13 and 18. Jamaю 316(4): 420-428.; PMid:27458947

Noordman ID, Fejzic Z, Bos M, Duijnhouwer AL, Weijers G, Kempers M et al. (2021). Cardiac abnormalities in girls with Turner syndrome: ECG abnormalities, myocardial strain imaging, and karyotype-phenotype associations. American Journal of Medical Genetics Part A. 185(8): 2399-2408.; PMid:33969942 PMCid:PMC8359841

Phung V, Singh KE, Danon S, Tan CA, Dabagh S. (2023). Non-mosaic trisomy 22 and congenital heart surgery using the shared decision making model: a case report. BMC pediatrics. 23(1): 122.; PMid:36932325 PMCid:PMC10024442

Pierpont ME, Brueckner M, Chung WK, Garg V, Lacro RV, McGuire AL et al. (2018). Genetic basis for congenital heart disease: revisited: a scientific statement from the American Heart Association. Circulation. 138(21): e653-e711.; PMid:30571578 PMCid:PMC6555769

Quezada E, Lapidus J, Shaughnessy R, Chen Z, Silberbach M. (2015). Aortic dimensions in Turner syndrome. American Journal of Medical Genetics Part A. 167(11): 2527-2532.; PMid:26118429

Rodríguez Caballero Á, Torres-Lagares D, Rodríguez Pérez A, Serrera Figallo MA, Hernández Guisado JM, Machuca Portillo G. (2010). Cri du chat syndrome: a critical review. Med Oral Patol Oral Cir Bucal. 15(3): 473-478.; PMid:20038906

Romeo JL, Etnel JR, Takkenberg JJ, Roos-Hesselink JW, Helbing WA, van de Woestijne P et al. (2020). Outcome after surgical repair of tetralogy of Fallot: a systematic review and meta-analysis. The Journal of Thoracic and Cardiovascular Surgery. 159(1): 220-236.; PMid:37452468

Rosenblum JM, Kanter KR, Shashidharan S, Shaw FR, Chai PJ. (2022). Cardiac surgery in children with trisomy 13 or trisomy 18: How safe is it? JTCVS open. 12: 364-371.; PMid:36590710 PMCid:PMC9801274

Santoro M, Coi A, Spadoni I, Bianchi F, Pierini A. (2018). Sex differences for major congenital heart defects in Down Syndrome: A population based study. European journal of medical genetics. 61(9): 546-550.; PMid:29753092

Sharma D, Murki S, Pratap T, Vasikarla M. (2014). Cat eye syndrome. Case Reports. 2014: bcr2014203923.; PMid:24842361 PMCid:PMC4039909

Silberbach M, Roos-Hesselink JW, Andersen NH, Braverman AC, Brown N, Collins RT et al. (2018). Cardiovascular health in Turner syndrome: a scientific statement from the American Heart Association. Circulation: Genomic and Precision Medicine. 11(10): e000048.; PMid:30354301

Springett A, Wellesley D, Greenlees R, Loane M, Addor MC, Arriola L et al. (2015). Congenital anomalies associated with trisomy 18 or trisomy 13: A registry‐based study in 16 European countries, 2000-2011. American journal of medical genetics Part A. 167(12): 3062-3069.; PMid:26347425

Swanson SK, Schumacher KR, Ohye RG, Zampi JD. (2021). Impact of trisomy 13 and 18 on airway anomalies and pulmonary complications after cardiac surgery. The Journal of Thoracic and Cardiovascular Surgery. 162(1): 241-249.; PMid:32981701

Tinkle BT, Walker ME, Blough‐Pfau RI, Saal HM, Hopkin RJ. (2003). Unexpected survival in a case of prenatally diagnosed non‐mosaic trisomy 22: Clinical report and review of the natural history. American Journal of Medical Genetics Part A. 118(1): 90-95.; PMid:12605450

Williams JL, McDonald MT, Seifert BA, Deak KL, Rehder CW, Campbell MJ. (2020). An unusual association: total anomalous pulmonary venous return and aortic arch obstruction in patients with cat eye syndrome. Journal of Pediatric Genetics. 10(01): 035-038.; PMid:33552636 PMCid:PMC7853914

Xu C, Li M, Peng J, Zhang Y, Li H, Zheng G, Wang D. (2023). Case report: A case report and literature review of complete trisomy 9. Frontiers in Genetics. 14.

Yuan SM. (2017). Congenital heart defects in Williams syndrome. Turkish Journal of Pediatrics. 59(3).; PMid:29376566

Zucker EJ. (2018). Syndromes with aortic involvement: pictorial review. Cardiovascular Diagnosis and Therapy. 8; Suppl 1: S71.; PMid:29850420 PMCid:PMC5949600