Table 1.
Genetic Causes of CHD
| Species / Genetic abnormality | CHD incidence, % |
Ref. |
|---|---|---|
| Human | ||
|
| ||
| 1q21.1 deletion | 23 | 16 |
|
| ||
| Turner syndrome (45, XO karyotype) | 30 | 17 |
|
| ||
| Cornelia de Lange (NIPBL, SMC1A, SMC3) | 31 | 18 |
|
| ||
| Down syndrome (trisomy 21) | 44 | 19 |
|
| ||
| Holt-Oram syndrome (TBX5) | 62 | 20 |
|
| ||
| DiGeorge syndrome (22q11.2 deletion) | 75 | 21 |
|
| ||
| NKX2–5 mutation | 88 | 22 |
|
| ||
| Mouse | ||
|
| ||
| Gata4+/− | 12–76 | 23 |
|
| ||
| Nkx2–5+/− | 5–50 | 24 |
|
| ||
| Tbx5+/− | 40–80 | 25 |
Genetic causes of CHD show high, but never complete penetrance. Examples of human copy number variants, chromosomal, and genetic abnormalities are shown in which cases were ascertained by the presence of the genetic abnormality. CHD incidence in mouse mutant models depends on the genetic background, which can be systematically varied via inbred strain crosses. The variability is a sign of interactions between the mutated CHD gene and polymorphic modifier genes.
CHD, congenital heart defects.