title: Syndromic craniosynostosis: from history to hydrogen bonds.
abstract: The syndromic craniosynostoses, usually involving multiple sutures, are hereditary forms of craniosynostosis associated with extracranial phenotypes such as limb, cardiac, CNS and tracheal malformations. The genetic etiology of syndromic craniosynostosis in humans is only partially understood. Syndromic synostosis has been found to be associated with mutations of the fibroblast growth factor receptor family (FGFR1, -R2, -R3), TWIST1, MSX2, and EFNB1. Apert, Pfeiffer, Crouzon, and Jackson-Weiss syndromes are due to gain-of-function mutations of FGFR2 in either the Ig II-III linker region (Apert) or Ig III domain. Loss of function mutations of TWIST1 and gain-of-function mutations of MSX2 lead to Saethre-Chotzen and Boston-type syndromes, respectively. The mutations in Pfeiffer (FGFR1), Muenke (FGFR3), and Apert syndrome (FGFR2) are caused by the same amino acid substitution in a highly conserved region of the Ig II-III linker region of these proteins, which suggests that these receptor tyrosine kinases have an overlapping function in suture biology. In this review we will discuss the historical descriptions, current phenotypes and molecular causes of the more common forms of syndromic craniosynostosis.
authors.affiliation: Division of Craniofacial Medicine, University of Washington Department of Pediatrics and Children's Craniofacial Center, Children's Hospital and Regional Medical Center, Seattle, WA, USA. mcunning@u.washington.edu
authors.forename: Machael L
authors.initials: ML
authors.lastname: Cunningham
authors.forename: Marianne L
authors.initials: ML
authors.lastname: Seto
authors.forename: Chootima
authors.initials: C
authors.lastname: Ratisoontorn
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Heike
authors.forename: Anne V
authors.initials: AV
authors.lastname: Hing
mesh_terms: D000168:Acrocephalosyndactylia / Q000235:genetics / Q000266:history; D003394:Craniofacial Dysostosis / Q000235:genetics / Q000266:history; D003398:Craniosynostoses / Q000235:genetics* / Q000266:history*; D049669:History, 16th Century; D049672:History, 19th Century; D049673:History, 20th Century; D049690:History, Ancient; D006801:Humans; D006860:Hydrogen Bonding; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D017434:Protein Structure, Tertiary; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D013577:Syndrome; D051879:Twist-Related Protein 1 / Q000235:genetics
chemical_list: D009687:Nuclear Proteins; D017468:Receptors, Fibroblast Growth Factor; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1