Craniosynostosis and syndromes with craniosynostosis: Incidence, genetics, penetrance, variability, and new syndrome updating

Different classifications of the same phenomena may be equally valid for different purposes. Craniosynostosis can be viewed from 2 different perspectives - anatomic and genetic. When the main interest is clinical description, growth and development, or surgical management of craniosynostosis, the perspective is anatomic. In this context, which particular suture is synostosed is of primary importance. In genetic perspective, classifying syndromes on the basis of which particular suture is synostosed can be very misleading. Since patients with the same genetic condition may have fusion of different sutures, which specific suture is synostosed is of secondary importance in this context. The clinical geneticist's main concern is with the overall pattern of anomalies (from which syndrome dignosis follows) and with those family members who are affected (from which genetic counseling follows). Thus, in genetic perspective craniosynostosis and syndromes with craniosynostosis should not be classified on the basis of which sutures are synostosed. Craniosynostosis and syndromes with craniosynostosis should not be classified on the basis of presence or absence of mental deficiency. It cannot be stated categorically that mental deficiency occurs in one craniosynostosis syndrome but not in another. The risk of retardation is probably present to some extent in all conditions with craniosynostosis. Some conditions have a higher frequency of retardation and, in some, the degree of retardation tends to be more severe. Analysis of syndromes in which craniosynostosis is a feature shows that certain types of anomalies occur more commonly than others. These are listed in a table. The greatest diagnostic mileage in syndromes with craniosynostosis seems to be in evaluating the limbs, the ear, and the cardiovascular system. Obviously, abnormalities of the eye and brain occur with high frequency and are important. They are not included here simply because they are so frequently secondary to craniosynostosis; our concern here is with the overall pattern of primary anomalies, from which syndrome diagnosis can be made. At the present time, syndromes with craniosynostosis and syndactyly, polydactyly, or polysyndactly are very likely to be monogenic. In contrast, if the limb defects are of the 'deficiency' or 'other defect' type and occur with growth deficiency of prenatal onset, the condition is more likely to be chromosomal or even teratogenic. Without growth deficiency, it is likely to be monogenic.