title: Risk of congenital heart disease in relatives of probands with conotruncal cardiac defects: an evaluation of 1,620 families.
abstract: Current recurrence risk counseling for conotruncal cardiac defects (CTD) is based on empiric estimates from multiple studies. We examined the risk of congenital heart disease (CHD) in relatives of probands with CTDs to assist in counseling practices in the current era. One thousand six-twenty probands with CTDs and no reported chromosomal or genetic abnormalities were recruited sequentially. A three-generation pedigree was obtained for each proband by a genetic counselor detailing the presence and type of CHD in each family member. Risks and 95% confidence intervals (CI) were calculated for sub-groups of relatives based on degree of relationship for all probands and by individual lesion of the proband. For pairs of affected relatives, concordance rates were calculated. Severity of CHD in the affected relative was assessed. The risk of CHD was higher in siblings (4.4%, 95% CI 3.4-5.4) than in parents (1.5%, 95% CI 1.1-1.9). Risk varied by the cardiac lesion of the proband with the highest risk in first-degree relatives of probands with tetralogy of Fallot and the lowest in D-transposition of the great arteries. 39% of affected parents and 69% of affected siblings had a concordant lesion (i.e., CTD). Most affected siblings of probands with severe CTDs had complex defects (58%), whereas very few affected parents had complex defects (20%). These data suggest that recurrence risk varies by lesion and relationship, with substantial concordance observed by cardiac lesion and complexity of disease, particularly among siblings. These findings contribute to risk counseling in the current era.
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatrics, Perelman School of Medicine, The Children's Hospital of Philadelphia, The University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Shabnam
authors.initials: S
authors.lastname: Peyvandi
authors.forename: Eitan
authors.initials: E
authors.lastname: Ingall
authors.forename: Stacy
authors.initials: S
authors.lastname: Woyciechowski
authors.forename: Jennifer
authors.initials: J
authors.lastname: Garbarini
authors.forename: Laura E
authors.initials: LE
authors.lastname: Mitchell
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Goldmuntz
mesh_terms: D005190:Family; D005260:Female; D006330:Heart Defects, Congenital / Q000453:epidemiology* / Q000235:genetics; D006801:Humans; D008297:Male; D010375:Pedigree; D012008:Recurrence; D012306:Risk
keywords: congenital heart defects; conotruncal cardiac defects; genetic counseling; recurrence risk