There have been five studies to date that have identified patients with features consistent with Costello syndrome (CS) and de novo or inherited variants in KRAS (Carta et al., 2006; Nava et al., 2007; Schubbert et al., 2007; Zenker et al., 2007). However, none of the patients possessed features to definitively differentiate their diagnosis from other RASopathies as CS. Variable expressivity, age of ascertainment, and outdated clinical assessments of affected individuals may complicate the clinical diagnosis of CS versus severe forms of cardiofaciocutaneous (CFC) syndrome. Therefore, the evidence for this association is Disputed. Furthermore, the HRAS gene is believed to be the only gene associated with CS (Aoki et al., 2005; Estep, Tidyman, Teitell, Cotter, & Rauen, 2006; Gripp et al., 2006; Kerr et al., 2006; Zampino et al., 2007). Of note, KRAS has also been classified as definitive in association with Noonan syndrome (NS) and as strong in association with CFC syndrome. The ClinGen RASopathy Expert Panel found no evidence associating KRAS with NS-like disorder with loose anagen hair or NS with multiple lentigines. This curation was approved by the ClinGen RASopathy Gene Curation Expert Panel on 7/24/18 (SOP Version 5).
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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