Congenital heart diseases [113 genes]

Congenital heart diseases are the most frequent cause of congenital malformations in newborns, and are the first cause of infant death related to congenital malformations. Most congenital heart diseases have a multifactorial etiology. It is estimated that in 8%-10% of cases the cause is a chromosomal abnormality, and 3%-5% present within the context of a monogenic syndrome.

• 8-14/1,000 live newborns

Specific molecular diagnosis for a genetic syndrome allows for appropriate advice and early medical follow-up. The American Heart Association (AHA) and the American Academy of Pediatrics have pointed out the main reasons to determine the genetic cause of congenital heart diseases:

• Identifying other organs and systems susceptible of medical follow-up.
• Obtaining specific information about the prognosis.
• Informing families about risks of recurrence.
• Identifying relatives at risk and providing them with the necessary studies, including genetic study.

• Individuals suspected or clinically diagnosed with a syndromic or non-syndromic (i.e. isolated) congenital heart disease. Upon familial history of congenital heart disease with a risk of recurrence, it is always necessary to try to determine its molecular etiology.
• Familial study: relatives of patients with a syndromic or non-syndromic congenital heart disease in which a causal mutation has been previously identified.

It is recommended to rule out chromosomal abnormalities (karyotype, CGH-arrays, SNP arrays) in order to improve the yield of the test, especially when other malformations are present.

The NGS panel allows identifying mutations in some of the genes previously associated with the development of syndromic or non-syndromic congenital heart diseases.

Case analysis using whole-exome sequencing can be considered in cases where there is suspicion of a genetic cause for a congenital heart disease without an identified molecular cause, but the individual yield over our NGS panels is low.