Mol Syndromol 2019 Feb 17;10(1-2):115-123. Epub 2018 Nov 17.
Pediatric Neurosurgery, Hôpital Universitaire Necker-Enfants Malades, Paris, France.
The development of the craniofacial skeleton is a spatial and temporal process where cranial sutures play a role in the regulation of morphogenesis and growth. Disruption of these cellular and molecular interactions may lead to craniosynostosis, the premature obliteration of one or more cranial sutures, yielding skull growth restriction and malformation perpendicular to the affected suture. Facial deformity and various functional CNS anomalies are other frequent complications. Cranial vault expansion and reconstructive surgery remain the mainstay of treatment but pose an elevated risk of morbidity for the infant. While the etiology of nonsyndromic craniosynostosis remains to be deciphered, gain-of-function mutations in and were found to be responsible for more than 3/4 of the most commonly encountered craniofacial syndromes. Animal models have been invaluable to further dissect the role of genes within the cranial sutures and for the development of alternative nonsurgical treatment strategies. In this review, we will present various molecular and pharmacological approaches for the treatment of craniosynostosis that have been tested using in vitro and in vivo assays as well as discuss their potential application in humans focusing on the case of tyrosine kinase inhibitors.