Molecular Genetic Testing of Patients with Craniosynostosis

Craniosynostosis is an etiologically heterogeneous condition and includes isolated and syndromal forms, which may result from exogenous as well as genetic factors. Genetic testing of patients with craniosynostosis is today an integral part of the routine diagnostic workup and allows identifying causal genetic alterations in up to 45% of unselected patient cohorts. Test results may provide important information on the expected further clinical course and long-term prognosis of the individual patient and may directly influence further therapy decisions. Furthermore, identification of causal genetic alterations allows individual genetic counseling of the affected families on the mode of inheritance, the recurrence risk for further pregnancies and related aspects including potential options of prenatal genetic diagnosis. In contrast to the preceding chapters, this article will focus on the practical approaches of molecular genetic testing in craniosynostosis patients during direct medical care: Which genetic regions should be tested in which patients? How to proceed? The most frequent clinical situations will be addressed and appropriate workup will be suggested according to current knowledge, but also considering the limited resources available in many health care systems as well as potential implications of the anticipated test results for further medical care.