title: Autosomal dominant inheritance of cardiac valves anomalies in two families: extended spectrum of left-ventricular outflow tract obstruction.
abstract: Only a limited number of families with clear monogenic inheritance of nonsyndromic forms of congenital valve defects have been described. We describe two multiplex pedigrees with a similar nonsyndromic form of heart valve anomalies that segregate as an autosomal dominant condition. The first family is a three-generation pedigree with 10 family members affected with congenital defects of the cardiac valves, including six patients with aortic stenosis and/or aortic regurgitation. Pulmonary and/or tricuspid valve abnormalities were present in three patients, and ventricular septal defect (VSD) was present in two patients. The second family consists of 11 patients in three generations with aortic valve stenosis in seven patients, defects of the pulmonary valves in two patients, and atrial septal defect (ASD) in two patients. Incomplete penetrance was observed in both families. Although left-ventricular outflow tract obstruction was present in most family members, the co-occurrence with pulmonary valve abnormalities and septal defects in both families is uncommon. These families provide evidence that left-sided obstructive defects and thoracic aortic aneurysm may be accompanied by right-sided defects, and even septal defects. These families might be instrumental in identifying genes involved in cardiac valve morphogenesis and malformation.
authors.affiliation: Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands. m.w.wessels@erasmusmc.nl
authors.forename: Marja W
authors.initials: MW
authors.lastname: Wessels
authors.forename: Ingrid M B H
authors.initials: IM
authors.lastname: van de Laar
authors.forename: Jolien
authors.initials: J
authors.lastname: Roos-Hesselink
authors.forename: Sipke
authors.initials: S
authors.lastname: Strikwerda
authors.forename: Danielle F
authors.initials: DF
authors.lastname: Majoor-Krakauer
authors.forename: Bert B A
authors.initials: BB
authors.lastname: de Vries
authors.forename: Wilhelmina S
authors.initials: WS
authors.lastname: Kerstjens-Frederikse
authors.forename: Yvonne J
authors.initials: YJ
authors.lastname: Vos
authors.forename: Bianca M
authors.initials: BM
authors.lastname: de Graaf
authors.forename: Aida M
authors.initials: AM
authors.lastname: Bertoli-Avella
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Willems
mesh_terms: D005192:Family Health; D005799:Genes, Dominant; D006345:Heart Septal Defects, Ventricular / Q000235:genetics; D006351:Heart Valves / Q000002:abnormalities*; D006801:Humans; D019683:Penetrance; D014694:Ventricular Outflow Obstruction / Q000235:genetics*