Genetics of Craniosynostoses: What Is Important for the Neurosurgeon?

Craniosynostosis (CS) is a congenital craniofacial malformation due to the premature fusion of one or more cranial sutures, representing a clinically and genetically heterogeneous anomaly. CS may be a feature in over 100 different Mendelian syndromes, though, in over 70% of cases, it appears as an isolated nonsyndromic defect, with single suture involvement. A genetic cause can be currently ascertained in up to 80% of syndromic CS, whereas it is seldom neglected in nonsyndromic cases. In the last decades, scientific advances allowed the discovering of novel gene-disease and CS-causative mutations, expanding the genetic knowledge of both syndromic and nonsyndromic CS. Taken together, the list of CS-associated genes includes over 100 different genes, functionally implicated in a definite set of interacting pathways, involved in craniofacial morphogenesis and growth, and crucial to the development and maintenance of calvarial sutures. These studies have strongly contributed to defining the influence of specific gene mutations on the surgical outcome and on the overall clinical prognosis for most CS patients offering nowadays unprecedented opportunities for patient-tailored management, improving genetic counseling, and testing and treatment planning.