Molecular aspects of craniosynostoses: implications in diagnosis and genetic counseling

Abstract

Craniosynostosis is characterized by the premature closure of one or more cranial sutures. It is a highly heterogeneous group, with an incidence of 1 per 2000-3000 births. Both environmental and genetic factors play a role in its etiology. In the last decade, it has been shown that mutations i0 4 genes (FGFR1, FGFR2, FGFR3, TWIST) may cause very well known craniosynostotic syndromes: Apert, Pfeiffer, Crouzon, Jackson-Weiss, Beare-Stevenson and Saethre-Chotzen. Two new conditions associated with the molecular defect have also been elucidated: Muenke's syndrome and Boston type of craniosynostosis. The variability of the phenotype of these two conditions is particularly wide, including patients with only craniosynostosis, classified as non syndromic cases, or those with cloverleaf skull. A precise phenotype and genotype correlation
has not always been possible because of the great clinical overlap and genetic heterogeneity in this group of disorders. A11 the above syndromes present an autossomal dominant pattern of inheritance, and therefore a patient has a 50% chance of having an affected child. Other patterns of inheritance for craniosynostosis have also been described and therefore it is important to perform a careful examination of each case and family. We present two cases seen at our laborato% one with Crouzon and other with Saethre-Chotzen syndrome, to illustrate the importance of the molecular testing for an accurate diagnosis and genetic counseling.