title: Tracheal cartilaginous sleeves in children with syndromic craniosynostosis.
abstract: 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.
  
  
  
  Chart review of patients with syndromic craniosynostosis across two institutions.
  
  
  
  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.
  
  
  
  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.affiliation: Department of Pediatrics, Division of Craniofacial Medicine, Seattle Children's Hospital, Seattle, Washington, USA.
authors.forename: Tara L
authors.initials: TL
authors.lastname: Wenger
authors.affiliation: Department of Surgery, Division of Otolaryngology, Seattle Children's Hospital, Seattle, Washington, USA.
authors.forename: John
authors.identifier: 0000-0002-3576-6167
authors.initials: J
authors.lastname: Dahl
authors.affiliation: Department of Pediatrics, Division of Human Genetics and Molecular Biology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Bhoj
authors.affiliation: Department of Pediatrics, Division of Craniofacial Medicine, Seattle Children's Hospital, Seattle, Washington, USA.
authors.forename: Anna
authors.identifier: 0000-0002-8266-9204
authors.initials: A
authors.lastname: Rosen
authors.affiliation: Department of Pediatrics, Division of Human Genetics and Molecular Biology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Donna
authors.initials: D
authors.lastname: McDonald-McGinn
authors.affiliation: Department of Pediatrics, Division of Human Genetics and Molecular Biology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Elaine
authors.initials: E
authors.lastname: Zackai
authors.affiliation: Department of Surgery, Division of Otolaryngology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: Jacobs
authors.affiliation: Department of Pediatrics, Division of Craniofacial Medicine, Seattle Children's Hospital, Seattle, Washington, USA.
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Heike
authors.affiliation: Department of Pediatrics, Division of Craniofacial Medicine, Seattle Children's Hospital, Seattle, Washington, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Hing
authors.affiliation: Department of Pediatrics, Division of Human Genetics and Molecular Biology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Avni
authors.identifier: 0000-0003-2871-4307
authors.initials: A
authors.lastname: Santani
authors.affiliation: Department of Surgery, Division of Otolaryngology, Seattle Children's Hospital, Seattle, Washington, USA.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Inglis
authors.affiliation: Department of Surgery, Division of Otolaryngology, Seattle Children's Hospital, Seattle, Washington, USA.
authors.forename: Kathleen C Y
authors.initials: KC
authors.lastname: Sie
authors.affiliation: Department of Pediatrics, Division of Craniofacial Medicine, Seattle Children's Hospital, Seattle, Washington, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Cunningham
authors.affiliation: Department of Surgery, Division of Otolaryngology, Seattle Children's Hospital, Seattle, Washington, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Perkins
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000503:physiopathology; D000293:Adolescent; D000328:Adult; D002356:Cartilage / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003398:Craniosynostoses / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*; D014132:Trachea / Q000378:metabolism / Q000473:pathology; D051879:Twist-Related Protein 1 / Q000235:genetics*
chemical_list: D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; C496353:FGFR2 protein, human; C496365:FGFR3 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3