Table 5 Developmental diseases presenting with cardiac congenital defects
From: The molecular mechanisms of cardiac development and related diseases
Disease | Molecular mechanisms | Genetic Defects | Cardiac phenotypes | Occurrence of CHD | Ref (PMID) |
|---|---|---|---|---|---|
Down syndrome | The presence of three copies of the Homo sapiens chromosome 21 | AVSD, VSD, ASD, PDA and ToF | 40–50% | 36769235 | |
CHARGE syndrome | Pathogenic variants in CHD7 | PDA, VSD, ASD, ToF and aortic abnormalities | 76% | 37675914 | |
Heterotaxy | Abnormalities in cilia; Dysregulation of FGFs, Nodal, Notch, PITX2 and BAF60C | Pathogenic variants in ZIC3, CRYPTIC, NODAL, CFC1, ACVR2B、LEFTY2, CITED2, GDF1, DNAH10, KIF7, FLNA and KMT2D | AVSD (most common), TGA, DORV, ToF, single ventricle, PA, anomalous pulmonary venous drainage, PS, left ventricular outflow tract obstruction, double inlet left ventricle, aortic coarctation, atrial isomerism, bilateral/ hypoplastic/absent sinus node(s), single coronary artery, interrupted inferior vena cava and bilateral superior vena cava | 90% | 27541719, 32738303, 22864291 |
DiGeorge syndrome | Abnormalities in RA signaling | Deletion on the long arm (q) at the 11.2 locus in chromosome 22 (22q11.2) | ToF (most common), IAA, TA, VSD, PA, MAPCA, RAA, ASD, PDA, DORV, APV, PS, BAV | 60–80% | 36897497, 37090828, 32049433 |
Holt-Oram syndrome | Pathogenic variants in TBX5 | ASD (most common), VSD, AVSD, ToF, cardiac arrhythmias, CoA, HLHS, persistent superior vena cava and MVP | 70–95% | 30552424, 35514310 | |
Noonan syndrome | Dysregulation of RAS-MAPK signaling pathway | Pathogenic variants in PTPN11, SOS1, KRAS, NRAS, RAF1, BRAF, SHOC2, CBL | PVS (most common), ASD, VSD, AVCD, AVSD, AS, PDA, ToF, aortic coarctation, peripheral pulmonary stenosis, mitral valve abnormalities and coronary artery abnormalities | 80-90% | 32022400, 27541719 |
Turner syndrome | Monosomy X | BAV (most common), CoA, partial anomalous pulmonary venous connection, left superior vena cava, elongated transverse, arch and dilatation of the brachiocephalic arteries, HLHS, mitral valve anomalies, interrupted inferior vena cava with azygous continuation, cardiac dextroposition, VSD, AVSD, pulmonary valve abnormalities and coronary artery anomalies | 50% | 33307001 | |
Jacobsen Syndrome | Deletion of chromosome 11q | VSD (most common), left ventricular outflow tract defects, mitral valve abnormalities, HLHS, DORV, TGA, AVSD, ASD, dextrocardia, aberrant right subclavian artery, PDA, persistent left superior vena cava, tricuspid atresia, IAA, TA, and PVS | 50% | 36661903 | |
1p36 syndrome | Deletion of chromosome 1p36 | ASD (most common), VSD, valvular abnormalities, PDA, ToF, CoA, infundibular stenosis of the right ventricle, and Ebstein’s anomaly | 71% | 18245432 | |
Alagille syndrome | Pathogenic variants in JAG1 or Notch2 | Peripheral pulmonary artery stenosis and/or hypoplasia (most common), ToF, valvular/supravalvular aortic stenosis, PA | 90% | 35868679 | |
Ellis-van Creveld syndrome | Pathogenic variants in DYNC2H1, DYNC2LI1, EVC, EVC2, GLI, SMO, WDR35, PRKACA or PRKACB | ASD (most common), VSD, single atrium, and left superior vena cava, hypoplastic left ventricle, pulmonary valve stenosis/atresia, and CoA | 66% | 37903214 | |
Costello syndrome | Dysregulation of RAS-MAPK signaling pathway | Pathogenic variants in HRAS | PVS (most common), ASD, VSD | 40%-50% | 21344638 |
Cardiofaciocutaneous syndrome | Dysregulation of RAS-MAPK signaling pathway | Pathogenic variants in BRAF, MAP2K1, MAP2K2, KRAS or YWHAZ | PVS (most common), ASD, VSD, mitral valve dysplasia, arrhythmias, tricuspid valve dysplasia, and BAV | 75% | 38136934 |
Kabuki syndrome | Pathogenic variants in KMT2D or KDM6A | CoA (most common), septal defects, BAV, mitral valve anomalies, conotruncal heart defects, and HLHS | 70% | 21882399 | |
Marfan syndrome | Pathogenic variants in FBN1 | Aortic root dilatation, plurivalvular regurgitation, BAV and MVP | 50-75% | 38667733 | |
Cantu syndrome | Pathogenic variants in ABCC9 or KCNJ8 | Cardiac enlargement (most common), PDA, BAV, mitral valve regurgitation, aortic valve stenosis, dilated aortic root, and pericardial effusion | 75% | 25275207 30571578 | |
Char syndrome | Pathogenic variants in TFAP2B | PDA (most common), VSD | 74% | 20301285 | |
Carpenter Syndrome | Pathogenic variants in RAB23 | VSD, ASD, PDA, PS, ToF | 18%-50% | 25162549 | |
Mowat-Wilson syndrome | Pathogenic variants in ZEB2 | Septal defects and patent ductus arteriosus (most common), PS, CoA, BAV, Aortic valve stenosis, ToF, pulmonary artery sling | 58% | 20301585 | |
Smith-Lemli-Opitz syndrome | Pathogenic variants in DHCR7 | AVCD, anomalous pulmonary venous return, PS | 50% | 20301322 |
