Table 1

Common congenital heart disease resulting from chromosomal abnormalities

	Disorder	Causative gene(s)	Locus	Inheritance	Clinical features	Associated cardiac anomalies	Reference(s)
Chromosomal aneuploidy associated with CHD	Trisomy 21 (Down syndrome)	Unknown	Chr21	Error in meiosis	Distinctive facial features, mental retardation, hypotonia, conductive hearing loss; CHD.	AVSD, ASD, VSD and TOF.	1 2
	Trisomy 18 (Edward syndrome)	Unknown	Chr18	Error in meiosis	Severe 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)	Unknown	Chr13	Error in meiosis	Microcephaly, orofacial clefts, severe mental retardation, postaxial polydactyly, omphalocele, microphthalmia, poor survival and CHD.	ASD, VSD, PDA and HLHS.	8
	Monosomy X (Turner syndrome)	Unknown	ChrX	Error in meiosis	Short stature, webbed neck, primary amenorrhea, lymphedema and CHD.	CoA, HLHS, BAV and AS.	1
	47, XXY (Klinefelter syndrome)	Unknown	ChrX	Error in meiosis	Developmental delay, tall stature, hypoplastic testes, delayed puberty and CHD.	PDA, ASD and mitral valve prolapses.	7
Copy number variations associated with CHD	1q21.1 deletion	GJA5, BCL9, CHD1L, FMO5 and ACP6	1q21.1	De novo, AD, N/A	Mild to moderate mental retardation, microcephaly, cataracts and CHD.	TOF, VSD, AS and CoA.	24–26
	4p16.3 deletion (Wolf-Hirschhorn syndrome)	WHSC1 and FGFRL1	4p16.3	De novo and N/A	Distinctive facial features，neurological and growth delay, seizures and CHD.	Mild septal defects and arterial ductus persistency.	27
	4q22.1 deletion	PPM1K	4q22.1	De novo and AD	Dementia, Lewy body, Parkinson diseases and CHD.	TOF.	26 28
	7q11.23 deletion (Williams-Beuren syndrome)	ELN	7q11.23	De 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 deletion	GATA4	8p23.1	N/A	Hernia, Testicular anomalies, Congenital diaphragmatic 2, Ebstein anomaly, CHD.	ASD, AVSD, TOF, VSD and Ebstein anomalies.	18
	9q34.3 deletion	NOTCH1and EHMT1	9q34.3	De novo and AD	Distinctive facial features and CHD.	HLHS, TOF and CoA.	26 29
	11q23 deletion (Jacobsen syndrome)	ETS1	11q23	De novo and AD	Distinctive facial features, growth and psychomotor retardation, strabismus, thrombocytopenia, hammertoes and CHD.	HLHS and LVOT defects.	22 23
	15q11.2 deletion	TUBGCP5, CYFIP1, NIPA2 and NIPA1	15q11.2	N/A	Delayed 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)	TBX1	22q11.2	De 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 deletion	CRKL and ERK2/MAPK1	22q11.22	De 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.