Table 1

Common congenital heart disease resulting from chromosomal abnormalities

DisorderCausative gene(s)LocusInheritanceClinical featuresAssociated cardiac anomaliesReference(s)
Chromosomal aneuploidy associated with CHDTrisomy 21
(Down syndrome)
UnknownChr21Error in meiosisDistinctive facial features, mental retardation, hypotonia, conductive hearing loss; CHD.AVSD, ASD, VSD and TOF.1 2
Trisomy 18
(Edward syndrome)
UnknownChr18Error in meiosisSevere mental retardation, biliary atresia, hypotonia, distinctive facial features, distinctively clenched fingers, poor survival and CHD.ASD, VSD, PDA, TOF, BAV and CoA.8 9
Trisomy 13
(Patau syndrome)
UnknownChr13Error in meiosisMicrocephaly, orofacial clefts, severe mental retardation, postaxial polydactyly, omphalocele, microphthalmia, poor survival and CHD.ASD, VSD, PDA and HLHS.8
Monosomy X
(Turner syndrome)
UnknownChrXError in meiosisShort stature, webbed neck, primary amenorrhea, lymphedema and CHD.CoA, HLHS, BAV and AS.1
47, XXY
(Klinefelter syndrome)
UnknownChrXError in meiosisDevelopmental delay, tall stature, hypoplastic testes, delayed puberty and CHD.PDA, ASD and mitral valve prolapses.7
Copy number variations associated with CHD1q21.1 deletionGJA5, BCL9, CHD1L, FMO5 and ACP61q21.1De novo, AD, N/AMild to moderate mental retardation, microcephaly, cataracts and CHD.TOF, VSD, AS and CoA.24–26
4p16.3 deletion (Wolf-Hirschhorn syndrome)WHSC1 and FGFRL14p16.3De novo and N/ADistinctive facial features,neurological and growth delay, seizures and CHD.Mild septal defects and arterial ductus persistency.27
4q22.1 deletionPPM1K4q22.1De novo and ADDementia, Lewy body, Parkinson diseases and CHD.TOF.26 28
7q11.23 deletion (Williams-Beuren syndrome)ELN7q11.23De novo and AD (minority of cases)Developmental delay, mental retardation; elfin facies, hypercalcemia, renal disorders, hearing loss and CHD.PAS, PPS, AV and MV defects and SVAS.16 17
8p23.1 deletionGATA48p23.1N/AHernia, Testicular anomalies, Congenital diaphragmatic 2, Ebstein anomaly, CHD.ASD, AVSD, TOF, VSD and Ebstein anomalies.18
9q34.3 deletionNOTCH1and EHMT19q34.3De novo and ADDistinctive facial features and CHD.HLHS, TOF and CoA.26 29
11q23 deletion (Jacobsen syndrome)ETS111q23De novo and ADDistinctive facial features, growth and psychomotor retardation, strabismus, thrombocytopenia, hammertoes and CHD.HLHS and LVOT defects.22 23
15q11.2 deletionTUBGCP5, CYFIP1, NIPA2 and NIPA115q11.2N/ADelayed psychomotor development, speech delay, autism spectrum disorder, attention deficit- hyperactivity disorder, obsessive–compulsive disorder, possibly seizures and CHD.ASD, VSD, CoA, TAPVD and complex left sided.28
22q11.2 deletion (DiGeorge Syndrome)TBX122q11.2De novo and AD (28% of cases).Thymus and parathyroid aplasia or hypoplasia, immunodeficiency, hypocalcemia, distinctive facial features, OFT abnormalities and CHD.TOF, IAA type B, VSD, TA, aortic arch anomalies and truncus arteriosus.13 14
Distal 22q11.2 deletionCRKL and ERK2/MAPK122q11.22De novo and AR (minority of cases)Distinctive facial features, psychiatric and cognitive deficits, sepsis and CHD.Interrupted aortic arch and truncus arteriosus.15
  • AD, autosomal dominant; AR, autosome recessive; AS, aortic stenosis; ASD, atrial septal defect; AV, aortic valve; AVSD, atrioventricular septal defect; BAV, bicuspid aortic valve; CHD, congenital heart disease; Chr, chromosome; CoA, coarctation of the aorta; HLHS, hypoplastic left heart syndrome; IAA, interrupted aortic arch; LVOT, left ventricular outflow tract; MV, mitral valve; N/A, not available; OFT, outflow tract; PAS, pulmonary artery stenosis; PDA, patent ductus arteriosus; PPS, peripheral pulmonic stenosis; SVAS, supravalvar aortic stenosis; TA, tricuspid atresia; TAPVD, total anomalous pulmonary venous drainage; TOF, tetralogy of Fallot; VSD, ventricular septal defect.