title: The pathogenesis of premature craniosynostosis in acrocephalosyndactyly (Apert's syndrome). A reconsideration.
abstract: A detailed examination of a stillborn fetus with Apert's syndrome showed several unexpected findings, which prompted a reevaluation of the heretofore generally accepted hypotheses regarding the cause of the dysmorphic craniofacial features in this syndrome. (1) The characteristic clinical features of Apert's syndrome were present at 24 to 26 weeks of gestation, and presumably much earlier. (2) However, there was no evidence, clinical or histological, of premature fusion of any of the cranial sutures or basilar synchondroses in this fetus. From our observations, and from a critical review of the literature, we conclude that the characteristic craniofacial malformations of Apert's syndrome are not caused by premature fusion of the cranial sutures, as has been commonly postulated. Rather, a malformation of the skull base is the most likely primary morphological event, and it leads to the characteristic dysmorphic facies, then secondarily to premature craniosynostosis. We believe the nature of the malformation is related to an abnormality in the bones which comprise the cranial base base (e.g. the sphenoid, ethmoid, and occipital bones) and to abnormal spatial relationships between the cribriform plate and the crista galli, resulting in a positional disarrangement of the points of basal attachment of the dura matter. The latter, then, precludes the normal response of the neurocranium to the forces produced by the growing brain. The synostosis is viewed as a symptom, rather than as a cause, of the dysmorphic craniofacial features typical of Apert's syndrome.
mesh_terms: D000168:Acrocephalosyndactylia / Q000150:complications* / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics; D000293:Adolescent; D000328:Adult; D003398:Craniosynostoses / Q000000981:diagnostic imaging / Q000209:etiology*; D005004:Ethmoid Bone / Q000002:abnormalities; D005260:Female; D005528:Foot / Q000000981:diagnostic imaging; D006225:Hand / Q000000981:diagnostic imaging; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009777:Occipital Bone / Q000002:abnormalities; D011247:Pregnancy; D011859:Radiography; D012886:Skull / Q000000981:diagnostic imaging; D013100:Sphenoid Bone / Q000002:abnormalities; D013577:Syndrome