neurocristopathies

Neurocristopathies are a group of disorders arising from defects in neural crest cell development, migration, differentiation, or survival. The neural crest is a transient, multipotent cell population that forms along the embryonic neural tube and gives rise to diverse cell types, including peripheral neurons and glia of the autonomic and sensory systems, adrenal medullary chromaffin cells, melanocytes, and much of the craniofacial skeleton and connective tissue, as well as certain endocrine cells. Disruption of these processes can produce a wide range of phenotypes, from isolated abnormalities to multisystem syndromes.

Most neurocristopathies are genetic, involving mutations in neural crest regulatory genes and signaling pathways such as SOX10, PAX3, EDNRB, EDN3, RET, and MITF, among others. They can occur as part of syndromes, such as DiGeorge syndrome (22q11.2 deletion) and Treacher Collins syndrome, where neural crest derivatives contribute abnormally to craniofacial or cardiac structures, or as isolated conditions affecting a single crest-derived lineage. Environmental factors during development may also contribute in some cases.

Representative conditions in this group include Hirschsprung disease, caused by failure of enteric neural crest cells to populate the intestinal wall; neuroblastoma, a tumor of sympathetic-origin neural crest cells typically seen in children; pheochromocytoma and extra-adrenal paragangliomas arising from neural crest–derived chromaffin cells; and medullary thyroid carcinoma, derived from neural crest–origin parafollicular C cells. Pigmentary and craniofacial disorders such as Waardenburg syndrome reflect defects in crest derivatives. Diagnosis relies on clinical assessment, imaging, and genetic testing, with management typically requiring multidisciplinary care.