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Autosomal dominant secundum atrial septal defect with various cardiac and noncardiac defects: a new midline disorder
A Mégarbané1, E Stephan, R Kassab
1Unité de Génétique Médicale, Faculté de Médecine, Université Saint-Joseph, Beirut, Lebanon. megarban@dm.net.lb
Insights
A Lebanese family study identified a new autosomal dominant midline disorder affecting the heart and upper body. This condition, characterized by atrial septal defects and other anomalies, shows high penetrance and variable expressivity.
Area of Science:
- Genetics
- Cardiology
- Developmental Biology
Background:
- Atrial septal defects (ASDs) are common congenital heart anomalies.
- Genetic factors play a significant role in the etiology of congenital heart disease.
- Midline developmental disorders can affect multiple organ systems.
Observation:
- A Lebanese family with 12 affected individuals presented with atrial septal defects (ASDs).
- Affected individuals exhibited a spectrum of cardiac anomalies, including conduction defects (left axis deviation, right bundle branch block), arrhythmias (atrial fibrillation, Wolff-Parkinson-White syndrome, nodal atrioventricular rhythm), and valve/outflow tract obstructions (aortic stenosis, pulmonic valve stenosis, Lutembacher syndrome, Ebstein disease).
- Noncardiac abnormalities included hypertelorism, cleft lip, and pectus excavatum, suggesting a broader developmental field defect.
Findings:
- The observed constellation of cardiac and noncardiac anomalies represents a previously undescribed autosomal dominant midline disorder.
- The disorder demonstrates nearly full penetrance and variable expressivity, indicating strong genetic influence with diverse phenotypic manifestations.
- Genetic mapping excluded known loci associated with atrial septal defects or cardiac conduction block, suggesting a novel genetic locus.
Implications:
- This discovery expands our understanding of the genetic basis of congenital heart disease and midline developmental disorders.
- Identification of this novel genetic syndrome provides a new avenue for etiological research and potential therapeutic targets.
- Further investigation into the genetic mutation responsible for this disorder could elucidate fundamental mechanisms of cardiac and craniofacial development.
Abstract:
We report on a Lebanese family in which 12 persons had an atrial septal defect and various cardiac and noncardiac anomalies. Cardiac anomalies are left axis deviation of 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 specially of the presence of hypertelorism, cleft lip, and pectus excavatum. This combination appears to constitute a hitherto undescribed autosomal dominant midline disorder of the heart and upper half of the body with almost full penetrance and variable expressivity. The mutation does not map to any known locus involved in atrial septal defect or conduction block.