What to Ask to the Geneticist in Craniosynostosis?

Craniosynostoses (CS) are a group of congenital conditions characterized by premature fusion of one or more cranial sutures, affecting skull growth and leading to distinct head shape abnormalities. Depending on the affected sutures, CS result in various head shape abnormalities: scaphocephaly (long and narrow head), brachycephaly (short and wide head), trigonocephaly (triangular forehead), or plagiocephaly (asymmetrical head shape). CS can be isolated (non-syndromic craniosynostosis/NSCS) or may be a manifestation of more complex conditions such as systemic skeletal bone disorders (secondary CS) or multiple malformations syndromes (syndromic craniosynostosis/SCS). Various etiologies have been reported including chromosomal or gene abnormalities as well as teratogenic factors. The availability of exome and whole genome sequencing has led to the characterization of the molecular bases of an increasing number of CS, thus emphasizing the genetic heterogeneity of these conditions and blurring the limits between NSCS and SCS. Patients affected by CS should be referred to a clinical genetics team in order to rule out possible associated signs suggesting secondary or syndromic CS and to perform appropriate molecular tests, depending either on the clinical picture (NSCS vs. secondary CS vs. SCS) or the specific suture involved. An early diagnosis is particularly important in cases of secondary CS and SCS, for an appropriate management of the possible multisystemic complications. The molecular characterization of CS leads to appropriate genetic counseling and prognosis estimation. This is particularly important in a prenatal setting. Overall, patients with CS should be systematically referred to multidisciplinary teams including neurosurgeons, clinical geneticists, molecular geneticists, genetic counselors, and psychologists, in order to provide a patient-tailored appropriate genetic assessment.