Essas alterações ocorrem no feto enquanto ele se desenvolve no útero durante a gravidez. Anormalidades cromossômicas podem ser uma causa de CHD, embora outras causas incluam o consumo excessivo de álcool durante a gravidez, o uso de medicamentos, infecções virais maternas como rubéola ou sarampo durante o primeiro trimestre, presença de CHD em um pai ou irmão e doença materna (diabetes mellitus, fenilcetonúria).
A herança dessas doenças segue um padrão autossômico dominante, embora possam ser encontradas exceções. CHD abrange uma variedade de defeitos que são comumente agrupados com base na natureza do defeito cardíaco estrutural, padrões de fluxo sanguíneo resultantes, riscos de recorrência familiar observados e genes de suscetibilidade compartilhados. De acordo com o padrão sanguíneo resultante, eles podem ser classificados como:
O painel genético fornece uma análise abrangente dos genes envolvidos nesta doença usando o sequenciamento de nova geração (NGS) para compreender totalmente o espectro de genes relevantes.
A utilidade clínica deste painel é:
| GENE | OMIM DISEASES | INHERITANCE* | % GENE COVERAGE (20X) | HGMD** |
| A2ML1 | Noonan Syndrome |
AD,MU,P |
100% |
23 of 23 |
| ABL1 | Congenital Heart Defects And Skeletal Malformations Syndrome |
AD |
99.93% |
8 of 8 |
| ACTC1 | Atrial Septal Defect Ostium Secundum Type, Dilated Cardiomyopathy, Left Ventricular Noncompaction, Familial Hypertrophic Cardiomyopathy |
AD |
99.93% |
72 of 74 |
| AFF4 | Chops Syndrome |
AD |
99.42% |
6 of 6 |
| ARVCF | 22q11.2 Deletion Syndrome | – |
99.95% |
2 of 2 |
| B3GAT3 | Multiple Joint Dislocations, Short Stature, Craniofacial Dysmorphism, With Or Without Congenital Heart Defects |
AR |
99.86% |
15 of 15 |
| BAZ1B | Williams Syndrome | – |
99.05% |
5 of 5 |
| BCOR | Oculofaciocardiodental Syndrome |
X,XD,G |
99.87% |
NA of NA |
| BMPR2 | Pulmonary Hypertension, Pulmonary Venoocclusive Disease |
AD |
99.99% |
590 of 600 |
| BRAF | Cardiofaciocutaneous Syndrome, Leopard Syndrome, Noonan Syndrome |
AD |
100% |
80 of 80 |
| CBL | Noonan Syndrome |
AD |
100% |
46 of 47 |
| CDK13 | Congenital Heart Defects, Dysmorphic Facial Features, And Intellectual Developmental Disorder |
AD |
92.37% |
31 of 32 |
| CHD7 | Charge Syndrome, Omenn Syndrome |
AD |
96.25% |
823 of 896 |
| CHST3 | CHST3-Related Skeletal Dysplasia, Multiple Joint Dislocations, Short Stature, Craniofacial Dysmorphism, With Or Without Congenital Heart Defects |
AR |
99.97% |
38 of 38 |
| COMT | 22q11.2 Deletion Syndrome |
AD |
99.98% |
5 of 5 |
| CRELD1 | Atrioventricular Septal Defect |
AD |
100% |
14 of 14 |
| CRKL | Distal 22q11.2 Microdeletion Syndrome |
99.93% |
5 of 6 | |
| DGCR2 | Velocardiofacial Syndrome |
AD |
99.94% |
3 of 3 |
| DGCR6 | Velocardiofacial Syndrome |
AD |
94.78% |
NA of NA |
| DGCR8 | Velocardiofacial Syndrome |
AD |
99.98% |
2 of 2 |
| DYNC2H1 | Jeune Syndrome |
AR,MU,D |
99.78% |
214 of 221 |
| EHMT1 | Kleefstra Syndrome |
AD |
98.58% |
58 of 75 |
| ELN | Familial Thoracic Aortic Aneurysm And Aortic Dissection, Supravalvular Aortic Stenosis, Williams Syndrome, Williams-beuren Syndrome |
AD |
99.99% |
95 of 96 |
| ESS2 | Velocardiofacial Syndrome |
AD |
99.91% |
NA of NA |
| FBN1 | Familial Thoracic Aortic Aneurysm And Aortic Dissection, Marfan Lipodystrophy Syndrome, Marfan Syndrome, Shprintzen-Goldberg Syndrome, Weill-Marchesani Syndrome |
AD |
100% |
2836 of 2845 |
| FGFRL1 | Wolf-Hirschhorn Syndrome |
AD |
99.94% |
1 of 1 |
| FLT4 | Congenital Heart Defects, Tetralogy Of Fallot |
AD |
100% |
119 of 120 |
| GATA4 | 8p23.1 Microdeletion Syndrome, Atrial Septal Defect Ostium Secundum Type, Atrioventricular Septal Defect, Testicular Anomalies With Or Without Congenital Heart Disease, Tetralogy Of Fallot, Ventricular Septal Defect |
AD |
94.69% |
108 of 130 |
| GATA5 | Congenital Heart Defects, Familial Bicuspid Aortic Valve, Tetralogy Of Fallot |
AD,AR |
87.02% |
26 of 32 |
| GATA6 | Atrial Septal Defect Ostium Secundum Type, Atrioventricular Septal Defect, ÇConotruncal Heart Malformations, Truncus Arteriosus Communis, Pancreatic Hypoplasia-Diabetes-Congenital Heart Disease Syndrome, Tetralogy of Fallot |
AD,AR |
84.19% |
66 of 84 |
| GDF1 | Asplenia With Cardiovascular Anomalies, Congenital Heart Defects, Tetralogy Of Fallot |
AD,AR |
75.72% |
11 of 14 |
| GJA5 | Familial Atrial Fibrillation, Chromosome 1q21.1 Deletion Syndrome, Tetralogy Of Fallot |
AD |
99.88% |
13 of 13 |
| GP1BB | 22q11.2 Deletion Syndrome |
AR |
74.08% |
26 of 50 |
| HAND1 | Congenital Heart Disease, Hypoplastic Left Heart Syndrome |
– |
99.89% |
9 of 9 |
| HAND2 | Familial Isolated Dilated Cardiomyopathy |
– |
99.19% |
5 of 6 |
| HDAC8 | Cornelia De Lange Syndrome, Wilson-Turner Syndrome |
X,XD,G |
99.78% |
NA of NA |
| HIRA | 22q11.2 Deletion Syndrome | – |
99.99% |
5 of 5 |
| JAG1 | Tetralogy Of Fallot |
AD |
99.98% |
640 of 641 |
| JMJD1C | 22q11.2 Deletion Syndrome |
– |
99.09% |
27 of 27 |
| KIFBP | Goldberg-Shprintzen Syndrome |
AR |
99.27% |
NA of NA |
| KMT2A | Cornelia De Lange Syndrome, Wiedemann-Steiner Syndrome |
AD |
98.14% |
144 of 149 |
| KRAS | Cardiofaciocutaneous Syndrome, Noonan Syndrome, Toriello-Lacassie-Droste Syndrome |
AD |
100% |
38 of 38 |
| LZTR1 | Noonan Syndrome |
AD |
99.99% |
136 of 136 |
| MAP2K1 | Cardiofaciocutaneous Syndrome, Noonan Syndrome |
AD |
100% |
31 of 31 |
| MAP2K2 | Cardiofaciocutaneous Syndrome, Neurofibromatosis-noonan Syndrome |
AD |
100% |
37 of 37 |
| MAPK1 | Distal 22q11.2 Microdeletion Syndrome |
– |
96.91% |
1 of 1 |
| MRAS | Noonan Syndrome |
AD |
100% |
3 of 3 |
| MYRF | Cardiac-Urogenital Syndrome |
AD |
99.83% |
27 of 27 |
| NF1 | Neurofibromatosis- Noonan Syndrome |
AD |
97.97% |
3082 of 3166 |
| NIPBL | Cornelia De Lange Syndrome |
AD |
99.32% |
409 of 426 |
| NKX2-5 | Atrial Septal Defect With Or Without Atrioventricular Conduction Defects, Atrial Septal Defect, Ostium Secundum Type, Conotruncal Heart Malformations, Truncus Arteriosus Communis, Familial Bicuspid Aortic Valve, Familial Progressive Cardiac Conduction Defect, Hypoplastic Left Heart Syndrome, Tetralogy Of Fallot, Ventricular Septal Defect |
AD,AR |
99.98% |
112 of 116 |
| NKX2-6 | Conotruncal Heart Malformations, Truncus Arteriosus Communis, Tetralogy Of Fallot |
AR |
99.83% |
8 of 8 |
| NOTCH1 | Adams-Oliver Syndrome, Aortic Valve Disease, Familial Bicuspid Aortic Valve |
AD |
99.83% |
178 of 179 |
| NOTCH2 | Acroosteolysis Dominant Type |
AD |
99.88% |
91 of 91 |
| NR2F2 | Congenital Heart Defects, Partial Atrioventricular Septal Defect |
AD |
97.37% |
16 of 18 |
| NRAS | Noonan Syndrome, Schimmelpenning– Feuerstein-Mims Syndrome |
AD |
100% |
15 of 15 |
| NSD1 | 5q35 Microduplication Syndrome, Sotos Syndrome, Weaver Syndrome |
AD |
99.80% |
451 of 459 |
| NSD2 | Wolf-Hirschhorn Syndrome |
AD |
99.91% |
NA of NA |
| PPP1CB | Noonan Syndrome-like Disorder With Loose Anagen Hair |
AD |
99.87% |
12 of 12 |
| PRDM16 | 1p36 Deletion Syndrome, Familial Isolated Dilated Cardiomyopathy, Left Ventricular Noncompaction, Dilated Cardiomyopathy |
AD |
98.81% |
20 of 20 |
| PRDM6 | Patent Ductus Arteriosus |
AD |
99.63% |
4 of 4 |
| PRKD1 | Congenital Heart Defects And Ectodermal Dysplasia |
AD |
97.39% |
8 of 9 |
| PTPN11 | Leopard Syndrome, Noonan Syndrome |
AD |
100% |
150 of 151 |
| RAD21 | Cornelia De Lange Syndrome, Mungan Syndrome |
AD,AR |
99.80% |
16 of 17 |
| RAF1 | Dilated Cardiomyopathy, Leopard, Noonan Syndrome |
AD |
100% |
64 of 64 |
| RASA2 | Noonan Syndrome |
– |
99.82% |
5 of 5 |
| RBM10 | Tarp Syndrome |
X,XR,G |
100% |
NA of NA |
| RBPJ | Adams-Oliver Syndrome |
AD |
99.98% |
8 of 8 |
| RIT1 | Noonan Syndrome |
AD |
99.85% |
27 of 27 |
| RRAS | Noonan Syndrome | – |
95.86% |
3 of 3 |
| RRAS2 | Noonan Syndrome |
AD |
99.80% |
6 of 6 |
| RREB1 | 22q11.2 Deletion Syndrome |
99.92% |
8 of 8 | |
| SEC24C | 22q11.2 Deletion Syndrome |
– |
99.98% |
NA of NA |
| SETD5 | Cornelia De Lange Syndrome |
AD |
99.77% |
37 of 37 |
| SHOC2 | Noonan Syndrome-like Disorder With Loose Anagen Hair |
AD |
99.98% |
8 of 8 |
| SKI | 1p36 Deletion Syndrome, Shprintzen-Goldberg Craniosynostosis Syndrome |
AD |
99.66% |
39 of 39 |
| SMC1A | Cornelia De Lange Syndrome, Wiedemann-Steiner Syndrome |
X,XR,XD,G |
100% |
NA of NA |
| SMC3 | Cornelia De Lange Syndrome |
AD |
100% |
30 of 30 |
| SOS1 | Noonan Syndrome |
AD |
100% |
103 of 104 |
| SOS2 | Noonan Syndrome |
AD |
99.48% |
6 of 7 |
| STAG2 | Xq25 Microduplication Syndrome |
X,XR,G |
99.09% |
NA of NA |
| TAB2 | Congenital Heart Defects, Polyvalvular Heart Disease Syndrome |
AD |
99% |
13 of 13 |
| TBX1 | 22q11.2 Deletion Syndrome, Conotruncal Heart Malformations, Truncus Arteriosus Communis, DiGeorge Syndrome, Tetralogy Of Fallot, Velocardiofacial Syndrome |
AD,AR |
88.70% |
35 of 42 |
| TBX20 | Atrial Septal Defect Ostium Secundum Type |
AD |
99.98% |
33 of 34 |
| TBX5 | Holt-Oram Syndrome |
AD |
100% |
143 of 152 |
| TFAP2B | Char Syndrome, Patent Ductus Arteriosus |
AD |
100% |
19 of 19 |
| TKT | Short Stature, Developmental Delay, And Congenital Heart Defects |
AR |
99% |
6 of 6 |
| TLL1 | Atrial Septal Defect Ostium Primum Type, Atrial Septal Defect Ostium Secundum Type |
AD |
99.96% |
8 of 8 |
| TMEM94 | Intellectual Developmental Disorder With Cardiac Defects And Dysmorphic Facies |
AR |
98% |
NA of NA |
| UFD1 | 22q11.2 Deletion Syndrome | – |
99.98% |
NA of NA |
| VPS33A | Mucopolysaccharidosis-like Syndrome With Congenital Heart Defects And Hematopoietic Disorders |
AR |
97.86% |
1 of 1 |
| WDPCP | Bardet-Biedl Syndrome, Congenital Heart Defects |
AR |
99.30% |
8 of 8 |
| ZFPM2 | Tetralogy Of Fallot |
AD |
99.40% |
44 of 46 |
| ZIC3 | X-linked Visceral Heterotaxy |
X,XR,G |
99.98% |
NA of NA |
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