PURPOSE: Because a tracheal cartilaginous sleeve (TCS) confers a significant mortality risk that can be mitigated with appropriate intervention, we sought to describe the prevalence and associated genotypes in a large cohort of children with syndromic craniosynostosis. METHODS: Chart review of patients with syndromic craniosynostosis across two institutions. RESULTS: In a cohort of 86 patients with syndromic craniosynostosis, 31 required airway evaluation under anesthesia. TCS was found in 19, for an overall prevalence of 22%. FGFR2, TWIST1, and FGFR3 mutations were identified in children with TCS. All five children with a W290C mutation in FGFR2 had TCS, and most previously reported children with W290C had identification of TCS or early death. In contrast, TCS was not associated with other mutations at residue 290. CONCLUSION: There is an association between TCS and syndromic craniosynostosis, and it appears to be particularly high in individuals with the W290C mutation in FGFR2. Referral to a pediatric otolaryngologist and consideration of operative airway evaluation (i.e., bronchoscopy or rigid endoscopy) in all patients with syndromic craniosynostosis should be considered to evaluate for TCS. Results from genetic testing may help providers weigh the risks and benefits of early airway evaluation and intervention in children with higher-risk genotypes.Genet Med 19 1, 62-68.
PURPOSE: Because a tracheal cartilaginous sleeve (TCS) confers a significant mortality risk that can be mitigated with appropriate intervention, we sought to describe the prevalence and associated genotypes in a large cohort of children with syndromic craniosynostosis. METHODS: Chart review of patients with syndromic craniosynostosis across two institutions. RESULTS: In a cohort of 86 patients with syndromic craniosynostosis, 31 required airway evaluation under anesthesia. TCS was found in 19, for an overall prevalence of 22%. FGFR2, TWIST1, and FGFR3 mutations were identified in children with TCS. All five children with a W290C mutation in FGFR2 had TCS, and most previously reported children with W290C had identification of TCS or early death. In contrast, TCS was not associated with other mutations at residue 290. CONCLUSION: There is an association between TCS and syndromic craniosynostosis, and it appears to be particularly high in individuals with the W290C mutation in FGFR2. Referral to a pediatric otolaryngologist and consideration of operative airway evaluation (i.e., bronchoscopy or rigid endoscopy) in all patients with syndromic craniosynostosis should be considered to evaluate for TCS. Results from genetic testing may help providers weigh the risks and benefits of early airway evaluation and intervention in children with higher-risk genotypes.Genet Med 19 1, 62-68.
Authors: M Gonzales; S Heuertz; J Martinovic; S Delahaye; A Bazin; P Loget; L Pasquier; M Le Merrer; J Bonaventure Journal: Clin Genet Date: 2005-08 Impact factor: 4.438
Authors: Yingli Wang; Miao Sun; Victoria L Uhlhorn; Xueyan Zhou; Inga Peter; Neus Martinez-Abadias; Cheryl A Hill; Christopher J Percival; Joan T Richtsmeier; David L Huso; Ethylin Wang Jabs Journal: BMC Dev Biol Date: 2010-02-22 Impact factor: 1.978
Authors: Greg Holmes; Courtney O'Rourke; Susan M Motch Perrine; Na Lu; Harm van Bakel; Joan T Richtsmeier; Ethylin Wang Jabs Journal: Development Date: 2018-10-05 Impact factor: 6.868
Authors: Emma Peskett; Samin Kumar; William Baird; Janhvi Jaiswal; Ming Li; Priyanca Patel; Jonathan A Britto; Erwin Pauws Journal: Biol Open Date: 2017-02-15 Impact factor: 2.422
Authors: Austin S Lam; Carrie C Liu; Gail H Deutsch; Joshua Rivera; Jonathan A Perkins; Greg Holmes; Ethylin W Jabs; Michael L Cunningham; John P Dahl Journal: Laryngoscope Date: 2020-09-04 Impact factor: 3.325