Table 18.
Categories of CHD
| Category | Definition | Primary type/s of causative genetic variants | Diagnostic yielda | ||
|---|---|---|---|---|---|
| CMA | WES | WGSb | |||
| Syndromic (CHD+ECA) | CHD seen in conjunction with extracardiac anomalies including (but not limited to) neurological, cranio-facial, limb, growth, skeletal, and genitourinary differences | de novo c or inherited CNVs and SNVs | ∼3–25% | ∼25% | ∼41% |
| Non-syndromic, inherited | CHD seen without features suggestive of a genetic syndrome, often affecting multiple family members | Inherited SNVs | Unknown | ∼31–46% | ∼36% |
| Sporadic | CHD without a suspected hereditary component and without being associated with a known syndrome | Multiple variants contributing synergistically | ∼3–10% | ∼2–10%d | ∼10% |
a
Based on literature with clinically applicable results, i.e. studies conducting clinical evaluations of variants according to ACMG guidelines.69
b
Based on our clinical experience in conjunction with Alankarage et al., 2019.441
c
De novo, not inherited from either parent.
d
Based on large cohort-based studies without clinical evaluation of variants. Information presented is collated from research reported in refs439–442,444,454–457 and modified from ref.458
CHD, congenital heart disease; CMA, chromosome microarray; CNV, copy number variant; ECA, extracardiac anomaly; SNV, single-nucleotide variant; WES, whole-exome sequencing; WGS, whole-genome sequencing.