Craniofrontonasal syndrome (CFNS; OMIM # 304110) is a rare X-linked disorder with greater severity in heterozygous females than in hemizygous males. CFNS is characterized by coronal craniosynostosis, frontal bossing, severe hypertelorism, craniofacial asymmetry, downslant palpebral fissure, broad nasal root, bifid nasal tip, grooved fingernails, curly wiry hair, and abnormalities of the thoracic skeleton. There are very few cases describing association of CFNS with heart defects. We discuss a very rare feature: atrial septal defect in a molecularly confirmed case of CFNS.
AdamsR.H.WilkinsonG.A.WeissC.DiellaF.GaleN.W.DeutschU.RisauW.KleinR.Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis. Genes Dev.1999; 13: 295–306.
2.
GrutznerE.GorlinR.J.Craniofrontonasal dysplasia: phenotypic expression in females and males and genetic considerations. Oral Surg Oral Med Oral Pathol.1988; 65: 436–444.
3.
KleinR.Eph/ephrin signaling in morphogenesis, neural development and plasticity. Curr Opin Cell Biol.2004; 16: 580–589.
4.
MakarovR.SteinerB.GucevZ.TasicV.WieackerP.WielandI.The impact of CFNS-causing EFNB1 mutations on ephrin-B1 function. BMC Med Genet.2010; 11: 98.
5.
SaavedraD.Richieri-CostaA.Guion-AlmeidaM.L.CohenMMJr. Craniofrontonasal syndrome: study of 41 patients. Am J Med Genet.1996; 61: 147–151.
6.
TwiggS.R.BabbsC.van den ElzenM.E.GorielyA.TaylorS.McGowanS.J.. Cellular interference in craniofrontonasal syndrome: males mosaic for mutations in the X-linked EFNB1 gene are more severely affected than true hemizygotes. Hum Mol Genet.2013; 22: 1654–1662.
7.
van den ElzenM.E.TwiggS.R.GoosJ.A.HoogeboomA.J.van den OuwelandA.M.WilkieA.O.MathijssenI.J.Phenotypes of craniofrontonasal syndrome in a patients with a pathogenic mutation in EFNB1. Eur J Hum Genet.2014; 22: 995–1001.
8.
WengerhoffS.M.WeissA.R.DwyerK.L.DettmanR.W.Migratory role for Ephrin B ligands in avian epicardial mesothelial cells. Dev Dyn.2010; 239: 598–609.
9.
WieackerP.WielandI.Clinical and genetic aspects of craniofrontonasal syndrome: towards resolving a genetic paradox. Mol Genet Metab.2005; 86: 110–116.
10.
WielandI.Craniofrontonasal syndrome: molecular genetics, EFNB1 mutations and the concept of cellular interference. In: MuenkeM.KressW.CollmannH.SolomonB.D., eds. Craniosynostoses: Molecular Genetics, Principles of Diagnosis, and Treatment.Basel, Switzerland: Karger; 2011: 107–119. Monographs in Human Genetics, vol 19.
11.
WielandI.JakubiczkaS.MuschkeP.CohenM.ThieleH.GerlachK.L.AdamsR.H.WieackerP.Mutations of the ephrin-B1 gene cause craniofrontonasal syndrome. Am J Hum Genet.2004; 74: 1209–15.
