[Craniosynostosis]

ABSTRACT

Craniosynostosis, the premature fusion of one or more cranial sutures, is a common malformation occurring in 1 of 2,000 live births. The function of the suture is to permit molding at the birth canal, adjustment for the expanding brain, and absorption of mechanical trauma in childhood. Craniosynostosis results from premature ossification and fusion of the skull sutures and generally results in alteration of the shape of the cranial vault and/or premature closure of the fontanelles. When associated anomalies or delays are present, the possibility of a syndrome should be considered. There are more than 180 syndromes that manifest craniosynostosis, and significant progress has been made in understanding their clinical and molecular aspects. Mutations in the FGFR1, FGFR2, FGFR3, TWIST1, and MSX2 genes cause the most common and/or well-characterized syndromes. Approximately 85% of cases are believed to be nonsyndromic with no identifiable gene mutation. Clinical evaluations should include in-depth antenatal history and documentation of any teratogenic exposure, a 3-generation family history and a comprehensive review of systems. The autosomal dominant inheritance and variable expressivity of many disorders mandates that patients and available first-degree relatives should undergo detailed clinical examination, including subtle malformations. Because of variable expressivity, the identification of a mutation in an affected individual should be followed by parental testing. In autosomal dominant types of craniosynostosis, mutation carriers have a 50% risk of passing the affected gene to their offspring. Negative parental mutation testing still leaves a small [1%] risk of recurrence because of potential gonadal mosaicism. Truly nonsyndromic craniosynostosis is thought to be a multifactorial trait with recurrent risk around 5% for coronal and around 1% for sagittal suture fusion