Author + information
- Received October 10, 1988
- Revision received March 8, 1989
- Accepted March 25, 1989
- Published online September 1, 1989.
- Charlotte Ferencz, MD, MPH, FACC1,
- Joann A. Boughman, PHD,
- Catherine A. Neill, MD,
- Joel I. Brenner, MD, FACC,
- Lowell W. Perry, MD, FACC,
- The Baltimore-Washington Infant Study Group
- ↵1Address for reprints: Charlotte Ferencz, MD, MPH, University of Maryland School of Medicine, Howard Hall, Room 146-D, 660 West Redwood Street, Baltimore, Maryland 21201.
The Baltimore-Washington Infant Study, an epidemiologic investigation of congenital heart disease, searches for genetic and environmental risk factors. Among 2,102 infants with heart disease, 17.5% had a noncardiac abnormality of chromosomal or genetic origin, whereas among 2,328 control infants, only 0.7% had a genetic abnormality.
Familial cardiovascular malformations encountered can be grouped into five distinct etiologic mechanisms. Single gene effects may be responsible for the specific histologic and biochemical changes in familial atrial septal defect with conduction disturbance and also in idiopathic ventricular hypertrophy. Left heart lesions showed familial concordance by the presumed morphogenetic mechanism of abnormal embryonic blood flow with phenotypes of varying severity. Pulmonary stenosis appeared with familial heritable disorders, as well as a partially concordant lesion with tetralogy of Fallot. Ventricular septal defect with transposition of the great arteries (one sibling pair) and with truncus arteriosus (two sibling pairs) indicate forme fruste expression of conotruncal defects. Endocardial cushion defect occurred with and without Down's syndrome in members of three families, suggesting inheritance of a defect affecting cellular migration. Heritable blood coagulopathies occurred in case families and not in control families. The association of hemophilia and transposition, observed also by others, is extremely unlikely by chance and suggests genetic errors of endothelial cell function.
The description of specific families from a populationbased study emphasizes biologic questions on the nature of the inheritance of cardiovascular malformations.
☆ This study was supported by Grant no. R37 HL25629 from the National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland. The Baltimore-Washington Infant Study co-investigators who supported this research are Judith D. Rubin, MD, MPH, Robert J. McCarter, SeD, Seymour I. Hepner, MD, FACC, and John W. Downing, MD, FACC.
- Received October 10, 1988.
- Revision received March 8, 1989.
- Accepted March 25, 1989.