Craniosynostosis syndromes in the genomic era

Abstract

The origin of craniosynostosis is heterogeneous: hereditary, mechanical, teratogenic, and idiopathic. Craniosynostosis is further defined by the suture(s) involved and whether it is syndromic or nonsyndromic. Syndromic craniosynostosis typically involves cranial sutures plus central nervous system and extracranial skeletal changes. Nonsyndromic craniosynostosis is usually confined to cranial changes. The most common syndromic synostoses reflect changes in fibroblast growth factor receptor (FGFR) activity related to mutations in the genes coding for these receptors. Other genes have been implicated in craniosynostosis syndromes. Several craniosynostosis syndromes are caused by mutation of the same FGFR, making the eponymic designation (eg, Crouzon's or Pfeiffer's syndrome) unclear. Ultimately, syndrome eponyms may be replaced by designation of the underlying mutation. Neurologic complications may include mental retardation, increased intracranial pressure, and cranial nerve abnormalities. Craniosynostosis syndromes require careful physical examination, radiological investigation, and now molecular evaluation to predict outcome and risk of recurrence.