title: Congenital heart defects in oculodentodigital dysplasia: Report of two cases.
abstract: Oculodentodigital dysplasia is caused by mutations in the GJA1 gene. Oculodentodigital dysplasia presents with a spectrum of clinical features including craniofacial, ocular, dental, and limb anomalies. Although recent findings implicate the major role of GJA1 during cardiac organogenesis, congenital heart defects are infrequently reported in oculodentodigital dysplasia. Here we report on two patients with GJA1 mutations presenting with cardiac malformations and type III syndactyly. Patient 1 presented with pulmonary atresia, an intact septum, right ventricular hypoplasia and tricuspid stenosis. The infant had a small nose, thin columella and bilateral 4-5 syndactyly of the fingers. A de novo c.226C>T (p.Arg76Cys) mutation was identified. Patient 2 presented at 6 months with a ventricular septal defect. The child had hypoplastic alae nasi with a thin columella and bilateral 4-5 syndactyly of the digits. A de novo missense mutation, c.145C>G (p.Gln49Glu) was found. Our two patients underscore the importance of cardiac evaluations as part of the initial workup for patients with findings of oculodentodigital dysplasia. Conversely, those patients with type III syndactyly and congenital heart defect should be screened for GJA1 mutations.
authors.affiliation: Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Izumi
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Lippa
authors.forename: Alisha
authors.initials: A
authors.lastname: Wilkens
authors.forename: Holly A
authors.initials: HA
authors.lastname: Feret
authors.forename: Donna M
authors.initials: DM
authors.lastname: McDonald-McGinn
authors.forename: Elaine H
authors.initials: EH
authors.lastname: Zackai
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D018031:Connexin 43 / Q000235:genetics*; D019465:Craniofacial Abnormalities / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D005124:Eye Abnormalities / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005385:Fingers / Q000002:abnormalities / Q000503:physiopathology; D005532:Foot Deformities, Congenital / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D006330:Heart Defects, Congenital / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D006345:Heart Septal Defects, Ventricular / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D011666:Pulmonary Valve Stenosis / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D013576:Syndactyly / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D014071:Tooth Abnormalities / Q000150:complications / Q000235:genetics* / Q000503:physiopathology
chemical_list: D018031:Connexin 43; C500216:GJA1 protein, human
keywords: GJA1; pulmonary stenosis; ventricular septal defect