Tracheal cartilaginous sleeves in children with syndromic craniosynostosis

Genet Med. 2017 Jan;19(1):62-68. doi: 10.1038/gim.2016.60. Epub 2016 May 26.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / physiopathology
  • Adolescent
  • Adult
  • Cartilage / metabolism
  • Cartilage / pathology
  • Child
  • Child, Preschool
  • Craniosynostoses / diagnosis
  • Craniosynostoses / genetics*
  • Craniosynostoses / physiopathology
  • Female
  • Genetic Testing
  • Genotype
  • Humans
  • Male
  • Mutation
  • Nuclear Proteins / genetics*
  • Receptor, Fibroblast Growth Factor, Type 2 / genetics*
  • Receptor, Fibroblast Growth Factor, Type 3 / genetics*
  • Trachea / metabolism
  • Trachea / pathology
  • Twist-Related Protein 1 / genetics*

Substances

  • Nuclear Proteins
  • TWIST1 protein, human
  • Twist-Related Protein 1
  • FGFR2 protein, human
  • FGFR3 protein, human
  • Receptor, Fibroblast Growth Factor, Type 2
  • Receptor, Fibroblast Growth Factor, Type 3