The neural crest is a temporary embryonic structure that is composed of a population of multipotent cells that delaminate from the ectoderm by epitheliomesenchymal transformation (• Sect. 5.2). These neural-crest-derived cells or neural crest cells (NCC) contribute to a large number of structures, including the spinal, cranial and autonomic ganglia, the enteric nervous system, the medulla of the adrenal gland, the melanocytes, dermal cells, corneal cells and many of the skeletal and connective tissues of the head (• Sect. 5.3). The whole facial and visceral skeleton and part of the neurocranium are formed from neural crest cells (• Sect. 5.4). A number of craniofacial malformations have major NCC involvement, and are referred to as neurocristopathies (• Sect. 5.5). Under this heading, the oculoauriculo-vertebral spectrum, Treacher Collins syndrome, 22q11.2 deletion syndrome, frontonasal dysplasia, craniosynostoses and CHARGE, Mowat-Wilson and Waardenburg syndromes are discussed. An increasing number of craniofacial disorders is currently classified as neurocristopathies. Many other syndromes might be due to NCC defects and form neurocristopathies. Examples are syndromes caused by environmental factors such as retinoic acid syndrome (• Sect. 5.6), ciliopathies, resulting from defects in primary cilia (• Sect. 5.7) and holoprosencephaly (• Sect. 5.8). Holoprosencephaly is an early disorder of pattern formation that may lead to closely related forebrain and facial malformations. Abnormal development of the skull, caused by craniosynostoses, i.e. craniofacial malformations due to agenesis or premature ossification of the cranial sutures, is discussed in • Sect. 5.9. Several clinical cases illustrate these disorders.</p
