The neurocristopathies: reinterpretation based upon the mechanism of abnormal morphogenesis

This review sets forth a broadened interpretation of the neurocristopathies based on the current understanding of the role of neural crest cells in normal development. Two general types of cristopathies are defined predicated on the abnormal mechanism involved in production of the defect or condition. Defects and disorders which constitute the originally defined neurocristopathies including pheochromocytoma, neurofibromatosis, and the multiple endocrine adenomatoses are best explained as dysplasias of neural crest derivatives. Affected individuals rarely exhibit true malformation of structure but do carry a lifetime risk for disordered growth of crest derived tissue. On the other hand, defects and disorders which derive from migrational abnormalities primarily of cranial neural crest cells such as frontonasal dysplasia, the DiGeorge sequence, and Waardenberg syndrome represent true malformations. The spectrum of involvement is usually definable at the time of diagnosis and disordered growth of crest derived tissue does not occur. The clinical implications of this distinction are discussed.