EFNB1 was first associated with X-linked craniofrontonasal syndrome as early as 2004 (Wieland et al., PMID: 15124102; Twigg et al., PMID: 15166289). The classical features of this disorder include coronal synostosis, hypertelorism, splitting of the nails, clefting of the nasal tip, and other skeletal anomalies, although a range of phenotypes including non-syndromic craniosynostoses have been observed in probands with variants in EFNB1. Craniofrontonasal syndrome is generally more severe in heterozygous females than in hemizygous males; however, mosaic males with severe phenotypes have been reported. More than 115 unique variants (including missense, nonsense, frameshift, splice site, and multi-exon deletions) in EFNB1 have been seen in humans. This curation includes 13 probands to reach the maximum score for genetic evidence (PMIDs: 15166289, 16639408, 17300690, 15124102, 15959873, 27884935, 29215649, 30651579, 23335590). The mechanism of disease is cellular interference (PMID: 23335590). This gene-disease association is supported by mouse models and expression studies (PMID: 15166289, 12919674, 15037550, 20844017). In summary, EFNB1 is definitively associated with X-linked craniofrontonasal syndrome. This curation was approved by the Craniofacial Malformations Gene Curation Expert Panel on 9/28/20.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. The GenCC does not independently verify the submitted information. Though the information is obtained from sources believed to be reliable, no warranty, expressed or implied, is made regarding accuracy, adequacy, completeness, reliability or usefulness of any information. This disclaimer applies to both isolated and aggregate uses of the information. The information is provided on an "as is" basis, collected through periodic submission and therefore may not represent the most up-to-date information from the submitters. If you have questions about the medical relevance of information contained on this website, please see a healthcare professional; if you have questions about specific gene-disease claims, please contact the relevant sources; and if you have questions about the representation of the data on this website, please contact gencc@thegencc.org.