Isolated congenital heart defects in first degree relatives of 185 affected children. Prospective study in Mexico City.

Parents (n = 355) and siblings (n = 313) of 185 index cases (IC) with congenital heart disease (CHD) were cardiologically evaluated. In the consecutive sample (2 years) Mendelian and chromosome syndromes were excluded. Four patients and nine siblings had CHD. The frequency of affection in siblings was 2.6% (8 in 313 siblings). All affected relatives are under medical care at the Centro Médico Nacional Siglo XXI, IMSS. In 10 of the 12 affected relatives found, the type of CHD was discordant from that of the IC. Discordance was found also in 9 of 36 IC with two or more CHD. An interpretation is given: if the mutated gene(s) has its effect in early embryological stages, affected relatives may have any type of CHD, but if the alteration occurs later, concordance is expected to be found. This model contributes also in explaining the remarkable genetic heterogeneity that exists in CHD.