TWIST1 was first reported by Kim et al. in 2017 in relation to autosomal dominant Sweeney-Cox syndrome, a condition characterized by distinct facial dysostosis. Features include hypertelorism, deficiencies of the eyelids and facial bones, cleft palate/velopharyngeal insufficiency, and low-set cupped ears (PMID: 28369379). Three unique missense variants, all occurring de novo at the Glu117 codon, have been reported in patients (PMIDs: 28369379, 30450715). Evidence supporting this gene-disease relationship includes case-level and experimental evidence. Of note, TWIST1 has also been assessed in association with Saethre-Chotzen syndrome and reached a definitive classification. Indicating it is an ultra-rare condition, only 3 cases of Sweeney-Cox syndrome have been published to date; therefore, there is limited but suggestive evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This classification was approved by the ClinGen Craniofacial malformation expert panel on 3/25/2021.
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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