The relationship between MSX2 and Enlarged parietal foramina (PFM) was described by Wilkie et al. in 2000 (PMID: 10742103). Parietal foramina are oval defects of the parietal bones caused by deficient ossification around the parietal notch (PMID: 10742103). Notably, MSX2 has also been evaluated by the ClinGen Craniofacial Malformations Gene Curation Expert panel for MSX2-related Craniosynostosis and found it to have a definitive association. At least 8 unique variants (missense, nonsense, frameshift etc.) have been identified in MSX2 in patients with PFM. Evidence supporting this gene-disease relationship includes case-level and experimental evidence. In summary, MSX2 is definitively associated with autosomal dominant Enlarged parietal foramina. 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 Craniofacial Malformations Gene Curation Expert Panel on 7/8/2020 (SOP Version 7).
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).
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