Table 1.
Genes and loci commonly associated with syndromic congenital heart disease.
| Syndrome | Genes | Loci | Cardiac Disease | % CHD |
|---|---|---|---|---|
| Alagille |
JAG 1
NOTCH2 |
20p12.2 1p12-p11 |
PPS, TOF, PA | >90 |
| CFC |
BRAF
KRAS MAP2K1 MAP2K2 |
7q34 12p12.1 15q22.31 19p13.3 |
PVS, ASD, HCM | 75 |
| Cantu | ABCC9 | 12p12.1 | PDA, BAV, HCM, CoA, PE, AS | 75 |
| Char | TFAP2B | 6p12.3 | PDA, VSD | 58 |
| CHARGE | CHD7 | 8q12 | TOF, PDA, DORV, AVSD, VSD | 75–85 |
| Costello | HRAS | 11p15.5 | PVS, ASD, VSD, HCM, arrhythmias | 44–52 |
| DiGeorge | TBX1 | 22q11.2 deletion |
Conotruncal defects, VSD, IAA, ASD, VR |
74–85 |
| Ellis-van Creveld |
EVC
EVC2 |
4p16.2 4p16.2 |
Common atrium | 60 |
| Holt-Oram | TBX5 | 12q24.1 | VSD, ASD, AVSD, conduction defects | 50 |
| Kabuki |
KMT2D
KDM6A |
12q13 Xp11.3 |
CoA, BAV, VSD, TOF, TGA, HLHS | 50 |
| Noonan |
PTPN11
SOS1 RAF1 KRAS NRAS RIT1 SHOC2 SOS2 BRAF |
12q24.13 2p22.1 3p25.2 12p12.1 1p13.2 1q22 10q25.2 14q21.3 7q34 |
Dysplastic PVS, ASD, TOF, AVSD, HCM, VSD, PDA |
75 |
| Williams-Beuren | 7q11.23 deletion (ELN) |
7q11.23 | SVAS, PAS, VSD, ASD | 80 |
| Carpenter | RAB23 | 6p11.2 | VSD, ASD, PDA, PS, TOF, TGA | 50 |
| Coffin-Siris |
ARID1B
SMARCB1 ARID1A SMARCB1 SMARCA4 SMARCE1 |
6q25 22q11 1p36.1 22q11.23 19p13.2 17q21.2 |
ASD, AVSD, VSD, MR, PDA, PS, DEX, AS | 20–44 |
| Cornelia de Lange |
NIPBL
SMC1L1 SMC3 |
5p13 Xp11.22 10q25 |
PVS, VSD, ASD, PDA | 33 |
| Mowat-Wilson | ZEB2 | 2q22.3 | VSD, CoA, ASD, PDA, PAS | 54 |
| Rubinstein-Taybi |
CBP
EP300 |
16p13.3 22q13.2 |
PDA, VSD, ASD, HLHS, BAV | 33 |
| Smith-Lemli-Opitz | DHCR7 | 11q12-13 | AVSD, HLHS, ASD, PDA, VSD | 50 |
Abbreviations: AS, aortic stenosis; ASD, atrial septal defect; AVSD, atrioventricular septal defect; BAV, bicuspid aortic valve; CFC, cardiofaciocutaneous; CHARGE, coloboma, heart defects, choanal atresia, retarded growth and development, genital anomalies, and ear anomalies; CoA, coarctation of the aorta; DEX, dextrocardia; DORV, double-outlet right ventricle; HCM, hypertrophic cardiomyopathy; CHD, congenital heart disease; HLHS, hypoplastic left heart syndrome; IAA, interruption of aortic arch; MR, mitral regurgitation; PA, pulmonary atresia; PAS, pulmonary artery stenosis; PDA, patent ductus arteriosus; PE, pericardial effusion; PPS, peripheral pulmonary stenosis; PS, pulmonary stenosis; PVS, pulmonary valve stenosis; SVAS, supravalvular aortic stenosis; TGA, transposition of great arteries; TOF, tetralogy of Fallot; VR, vascular ring; and VSD, ventricular septal defect. Note: % CHD denotes the proportion of patients with the particular genetic syndrome affected by CHD. Adapted from [7].