FGFR1 has been repeatedly described in association with autosomal dominant Pfeiffer Syndrome Type I (PS1), a mild form of Pfeiffer Syndrome characterized by craniofacial anomalies, broad thumbs and big toes, and prematurely closed cranial sutures in some cases (Muenke et al. 1994; PMID: 7874169). One missense variant in FGFR1 is associated with PS1, and has been reported in at least 16 probands from 8 publications (PMIDs: 10861678, 14564217, 7874169, 16957473, 25251565, 24127277, 23348274, 24776567). This gene-disease association is also supported by experimental evidence including animal models, and an in vitro functional assay (PMIDs: 21538817, 10942429, 14613973). In summary, FGFR1 is definitively associated with autosomal dominant Pfeiffer Syndrome Type I. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Craniofacial Malformations Gene Curation Expert Panel on 5/20/2021. Gene Clinical Validity Standard Operating Procedures (SOP) – Version 8.
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.