1288 CONOTRUNCAL DEFECTS IN CHARGE ASSOCIATION: EVIDENCE FOR NEURAL CREST INVOLVEMENT

Abstract

Defects in CHARGE association may include choanal atresia, coloboma, cardiac anomalies, growth and mental deficiency, genital hypoplasia, and ear anomalies, as well as other facial defects such as cleft palate, micrognathia, facial palsy and velopharyngeal problems. Previous studies have demonstrated that cephalic neural crest plays a major role in facial morphogenesis. Recent studies using quail/chick chimeras have shown that mesenchyme of the aorticopulmonary septum is also derived from cells of the cephalic neural crest. There is overlap between CHARGE association and DiGeorge Syndrome, and when tissue from cephalic neural crest is ablated, conotruncal septation defects and thymic deficiency may result. We hypothesized that abnormalities in the formation, proliferation, or migration of cephalic neural crest cells might result in an association between craniofacial and conotruncal anomalies in CHARGE association. We tested this hypothesis by examining the types of cardiac defects among 34 previously published and 17 new CHARGE association patients with congenital heart disease. Conotruncal defects were present in 35% of these patients, versus an expected prevalence of 16-22% in large series of patients with congenital heart disease. These data suggest a possible pathogenetic link between certain craniofacial and cardiac defects that may involve the cephalic neural crest.