New insights into craniosynostosis

Abstract

Craniosynostosis is a congenital developmental disorder involving premature fusion of cranial sutures, often associated with multiple neurological manifestations. The perspective of this group of disorders has changed dramatically in the new era of molecular genetics. In the last decade a large literature with new concepts in craniosynostosis has appeared. More than 100 syndromes associated with craniosynostosis have been described, and in about a dozen, the molecular defect has been identified. Pediatric neurologists are less aware than geneticists, neurosurgeons, and craniofacial surgeons of these changes. General concepts about craniosynostosis are here presented with updates of clinical and genetic aspects of well-defined syndromes such as Apert, Crouzon, Pfeiffer, Saethre-Chotzen. Evidence of their relationship with fibroblast growth factor receptors (FGFRs) 1, 2, and 3, and with causative genes such as TWIST has been documented. New and other less common syndromes also are discussed. The differences between positional and synostotic plagiocephaly are important, as well as the cause of nonsyndromic craniosynostosis. The prognosis and neurological outcome of patients, including "benign" forms of craniosynostosis, are other important aspects. Major advances have occurred in understanding pathogenesis, diagnosis, and treatment of craniosynostosis. The role of local dura mater and apoptosis; modalities of imaging such as prenatal ultrasound and three-dimensional and spiral CT have improved the accuracy in diagnosis, and the new approaches in surgical treatment involving efficient and less invasive methods, are evidence of these advances.