Atrial Septal Defect, Secundum, With Various Cardiac And Noncardiac Defects

Clinical Features

Megarbane et al. (1999) described a Lebanese family in which 12 persons had secundum atrial defect and various cardiac and noncardiac anomalies. Cardiac anomalies were left axis deviation of the electrocardiographic QRS, right bundle branch block, atrial fibrillation, Wolff-Parkinson-White syndrome, nodal atrioventricular rhythm, aortic stenosis, pulmonic valve stenosis, mitral stenosis (Lutembacher syndrome), and low implantation of the tricuspid valve (Ebstein disease). Noncardiac abnormalities consisted of hypertelorism, cleft lip, and pectus excavatum. The authors suggested that this combination constitutes a hitherto undescribed autosomal dominant midline disorder of the heart and upper half of the body with almost full penetrance and variable expressivity. The disorder occurred in 4 generations and by implication in a fifth because the first generation had 2 affected sibs. There were several instances of male-to-male transmission.

Mapping

Exclusion Studies

Megarbane et al. (1999) stated that genotyping with polymorphic markers covering the 5q34 region, the site of the CSX gene (600584) which is mutant in atrial septal defect with atrioventricular conduction defects (108900), and 19q13, where progressive familial heart block (113900) has been mapped, yielded negative results. Megarbane (1999) also tested for linkage to HLA, which has been claimed for secundum type atrial septal defect (108800). HLA haplotype was determined for 8 persons, 6 affected and 2 unaffected. No linkage was found, as none of the affected persons had the same haplotype. The lack of linkage, as well as the associated defects, indicates that the family suffered from a different disorder than HLA-linked ASD.