Abstract
Various factors are involved in the etiology of congenital heart disease (CHD), but often the cause of CHD is unknown. With the genetic diagnostic’s quality and availability improvement, it is necessary to regularly review the structure of hereditary diseases that are associated with congenital heart disease in order to better predict outcomes.
Objective. To analyze the structure of genetic diseases among newborns with CHD.
Material and methods. A retrospective cohort study was conducted over a two-year period (from January 2021 to November 2022), which included 172 newborns with CHD. The criteria for genetic testing were: (dysembryogenesis stigmas and/or two or more congenital malformations and/or combined CHD). The method was determined by a geneticist. Based on the data obtained, an analysis of the structure of genetic pathology was carried out.
Results. Of 172 newborns with CHD, 96 children met the criteria for genetic testing, of which 24 children were found to have clinically significant genetic mutations. In 34% of cases, Down syndrome was detected, in 29% – DiGeorge syndrome, in 8% – Williams syndrome, and in 29% – other genetic mutations regarded as clinically significant: single rare microdeletions, microduplications, a mosaic form of an additional marker chromosomes and nucleotide sequence changes. Including a child with Fallot’s tetrad, a previously undescribed heterozygous variant of the nucleotide sequence in the NOTCH2 gene (chr1:119916246G>A) was identified.
Conclusions. The current study has demonstrated a pattern of genetic disease among children with congenital heart disease that is broadly consistent with the general population frequency. A number of rare hereditary diseases have been described, including a previously undescribed heterozygous nucleotide sequence variant in the NOTCH2 gene (chr1:119916246G>A), which may be potentially pathogenic. It is necessary to conduct further similar studies on large samples of patients for a more detailed description of the clinical picture of rare genetic mutations.
References
- Xie D., Wang H., Liu Z., Fang J., Yang T., Zhou S. et al. Perinatal outcomes and congenital heart defect prognosis in 53313 non-selected perinatal infants. PLoS One. 2017; 12 (6): e0177229. DOI: 10.1371/journal.pone.0177229
- Bockeria E.L. Perinatal cardiology: the present and the future. Part I: congenital heart disease. Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics). 2019; 64 (3): 5–10 (in Russ.). DOI: 10.21508/1027-4065-2019-64-3-5-10
- Shumakova O.V., Bokeria E.L. Clinical audit of pre- and postnatal diagnostics of obstructive congenital left heart defects at the perinatal center (level III). Russian Journal of Cardiology. 2020; 25 (8): 3788 (in Russ.). DOI: 10.15829/1560-4071-2020-3788
- Cowan J.R., Ware S.M. Genetics and genetic testing in congenital heart disease. Clinics in Perinatology. 2015; 42: 373–93. DOI: 10.1016/j.clp.2015.02.009
- Mone F., Eberhardt R.Y., Morris R.K., Hurles M.E., McMul-lan D.J., Maher E.R. et al. Congenital heart disease and the Diagnostic yield with Exome sequencing (CODE Study): prospective cohort study and systematic review. Ultrasound Obstet Gynecol. 2021; 57: 43–51. DOI: 10.1002/uog.22072
- van Nisselrooij A.E.L., Lugthart M.A., Clur S.A., Linskens I.H., Pajkrt E., Rammeloo L.A. et al. The prevalence of genetic diagnoses in fetuses with severe congenital heart defects. Genetics in Medicine. 2020; 22: 1206–14. DOI: 10.1038/s41436-020-0791-8
- Williams K., Carson J., Lo C. Genetics of Congenital Heart Disease. MDPI Biomolecules. 2019; 96: 879–902. DOI: 10.3390/biom9120879
- Qiao F., Wang Y., Zhang C., Zhou R., Wu Y., Wang C. et al. Comprehensive evaluation of genetic variants using chromosomal microarray analysis and exome sequencing in fetuses with congenital heart defect. Ultrasound Obstet Gynecol. 2021; 58 (3): 377–87. DOI: 10.1002/uog.23532
- Liu Y., Chen S., Zühlke L., Black G.C., Choy M.K., Li N. et al. Global birth prevalence of congenital heart defects 1970–2017: updated systematic review and meta-analysis of 260 studies. International Journal of Epidemiology. 2019; 48 (2): 455–63. DOI: 10.1093/ije/dyz009
- Shabana N.A., Shahid S.U., Irfan U. Genetic Contribution to Congenital Heart Disease (CHD). Pediatric Cardiology. 2020; 41 (1):12–23. DOI: 10.1007/s00246-019-02271-4 11. Twite M.D., Stenquist S., Ing R.J. Williams syndrome. Paediatr Anaesth. 2019; 29 (5): 483–90. DOI: 10.1111/pan. 13620
- Yuan S.M. Congenital heart defects in Williams syndrome. Turk. J. Pediatr. 2017; 59 (3): 225–32. DOI: 10.24953/turkjped.2017.03.001
- Redaelli S., Conconi D., Sala E., Villa N., Crosti F., Roversi G. et al. Characterization of Chromosomal Breakpoints in 12 Cases with 8p Rearrangements Defines a Continuum of Fragility of the Region. International Journal Molecular Sciences. 2022; 23 (6): 33–47. DOI: 10.3390/ijms23063347
- Landis B.J., Helvaty L.R., Geddes G.C., Lin J.I., Yatsenko S.A., Lo C.W. et al. A Multicenter Analysis of Abnormal Chromosomal Microarray Findings in Congenital Heart Disease. Journal of the American Heart Association. 2023; 12 (18): e029340. DOI: 10.1161/JAHA.123.029340
- Li B., Zhou T., Zou Y. Mid1/Mid2 expression in craniofacial development and a literature review of X-linked opitz syndrome. Mol. Genet. Genomic. Med. 2015; 4 (1): 95–105. DOI: 10.1002/mgg3.183
- Cho E.K., Kim J., Yang A., Cho S.Y., Jin D.K. 2q37 Deletion syndrome confirmed by high-resolution cytogenetic analysis. Ann. Pediatr. Endocrinol. Metab. 2017; 22 (2): 129–32. DOI: 10.6065/apem.2017.22.2.129
- Giraldo-Ocampo S., Pachajoa H. 2q37 deletion syndrome in a Colombian patient with macrocephaly: a case report. BMC Pediatr. 2022; 22 (1): 569. DOI: 10.1186/s12887-022-03620-8
- Palumbo O., Palumbo P., Ferri E., Riviello F.N., Cloroformio L., Carella M. et al. Report of a patient and further clinical and molecular characterization of interstitial 4p16.3 microduplication. Mol. Cytogenet. 2015; 8: 15. DOI: 10.1186/s13039-015-0119-6
- Schönewolf-Greulich B., Ravn K., Hamborg-Petersen B., Brøndum-Nielsen K., Tümer Z. Segregation of a 4p16.3 duplication with a characteristic appearance, macrocephaly, speech delay and mild intellectual disability in a 3-generation family. Am. J. Med. Genet. A. 2013; 161A (9): 2358–62. DOI: 10.1002/ajmg.a.36099
- Faassen M.V. RAS-pathies: Noonan syndrome and other related diseases. The literature review. Problems of Endocrinology. 2014; 60 (6): 45–52 (in Russ.). DOI: 10.14341/probl201460645-52
About the authors
- Ekaterina L. Bockeria, Dr. Med. Sci., Professor, Leading Researcher; ORCID
- Oksana V. Shumakova, Cand. Med. Sci., Neonatologist, Department Assistant; ORCID
- Alina A. Dokshukina, Neonatologist, Researcher; ORCID
- Olga V. Grebneva, Neonatologist; ORCID
- Grigory S. Vasiliev, Geneticist; ORCID
- Elena V. Grosheva, Cand. Med. Sci., Neonatologist, Head of Department; ORCID
