Phenotypes of craniofrontonasal syndrome in patients with a pathogenic mutation in EFNB1

Abstract

raniofrontonasal syndrome (CFNS) is an X-linked developmental malformation, caused by mutations in the EFNB1 gene, which \nhave only been described since 2004. A genotype\xe2\x80\x93phenotype correlation seems not to be present. As it is of major importance \nto adequately counsel patients with EFNB1 mutations and their parents, and to improve diagnosis of new patients, more \ninformation about the phenotypic features is needed. This study included 23 patients (2 male, 21 female) with confirmed \nEFNB1 mutations. All patients underwent a thorough physical examination and photographs were taken. If available, \nradiological images were also consulted. Hypertelorism, longitudinal ridging and/or splitting of nails, a (mild) webbed neck and \na clinodactyly of one or more toes were the only consistent features observed in all patients. Frequently observed phenotypic \nfeatures were bifid tip of the nose (91%), columellar indentation (91%) and low implantation of breasts (90%). In comparison \nwith anthropometric data of facial proportions, patients with CFNS had a significantly different face in multiple respects. \nAn overview of all phenotypic features is shown. Patients with EFNB1 mutations have a clear phenotype. This study will \nfacilitate genetic counseling of parents and patients, and contribute to the diagnostic and screening process of patients with \nsuspected CFNS