Table 2.
Well-Characterized Syndromes Caused by Single-Gene Variation Associated with CHD
| Syndrome | Gene | Loci | Cardiac Defect | Percent with CHD | Clinical findings | References |
|---|---|---|---|---|---|---|
| Alagille syndrome |
JAG1
NOTCH2 |
20p12.2 1p12-p11 |
PPS, TOF, PA | >90 | Bile duct paucity, posterior embryotoxon, butterfly vertebrae, renal defects | 21934706 16773578 |
| Char syndrome | TFAP2B | 6p12.3 | PDA, VSD | 58% | Wide-set eyes, down-slanting palpebral fissures, thick lips, hand anomalies | 10802654 |
| CHARGE syndrome | CHD7 | 8q12 | TOF, PDA, DORV, AVSD, VSD | 75–85% | Coloboma, choanal atresia, genital hypoplasia, ear anomalies, hearing loss, developmental delay, growth retardation, intellectual disability | 28160409 |
| Ellis-van Creveld syndrome |
EVC
EVC2 |
4p16.2 4p16.2 |
Common atrium | 60% | Skeletal dysplasia, short limbs, polydactyly, short ribs, dysplastic nails, respiratory insufficiency | 10700184 12571802 |
| Holt-Oram syndrome | TBX5 | 12q24.1 | VSD, ASD, AVSD, conduction defects | 50% | Absent, hypoplastic, or triphalangeal thumbs; phocomelia; defects of radius; limb defects more prominent on left | 16183809 |
| Kabuki syndrome |
KMT2D
KDM6A |
12q13 Xp11.3 |
CoA, BAV, VSD, TOF, TGA, HLHS | 50% | Growth deficiency, wide palpebral fissures, large protuberant ears, fetal finger pads, intellectual disability, clinodactyly | 12002156 21671394 |
| Noonan syndrome |
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% | Short stature, hypertelorism, down-slanting palpebral fissures, ptosis, low posterior hairline, pectus deformity, bleeding disorder, chylothorax, cryptorchidism | 20876176 |
ASD, atrial septal defect; AVSD, atrioventricular septal defect; BAV, bicuspid aortic valve; CHARGE, coloboma, heart defects, choanal atresia, retarded growth and development, genital anomalies, and ear anomalies; CHD, congenital heart disease; CoA, coarctation of the aorta; DORV, double-outlet right ventricle; HCM, hypertrophic cardiomyopathy; HLHS, hypoplastic left heart syndrome; PA, pulmonary atresia; PDA, patent ductus arteriosus; PPS, peripheral pulmonary stenosis; PVS, pulmonary valve stenosis; TGA, transposition of great arteries; and VSD, ventricular septal defect.