Neurocristopathy is a diverse class of pathologies that may arise from defects in the development of tissues containing cells commonly derived from the embryonic

neural crest Neural crest cells are a temporary group of cells unique to vertebrates that arise from the embryonic ectoderm germ layer, and in turn give rise to a diverse cell lineage—including melanocytes, craniofacial cartilage and bone, smooth muscle, per ...

cell lineage. The term was coined by Robert P. Bolande in 1974. After the induction of the

, the newly formed neural crest cells (NCC) delaminate from their tissue of origin and migrate from the entire neural axis of the vertebrate embryo to specific locations where they will give rise to different cell derivatives. The formation of this cell population therefore requires a timely and spatially controlled interplay of inter- and intra-cellular signals. An alteration in the occurrence and timing of these signals leads to a set of syndromes called Neurocristopathies (NCP), which comprises a broad spectrum of congenital malformations affecting an appreciable percentage of newborns. Moreover, since NCC migrate along the embryo, they are susceptible to subtle changes in the environment both during their migration and upon arrival at their destination. This means that even little modifications, either genetically or environmentally caused, in the external cues that modulate NCC migration have a deep effect on the normal migration and differentiation of these cells, thus becoming a causative factor for the development of NCP. Recently, a new classification for this group of diseases has been proposed. This new criteria takes into account the axial origin of the NC population that contributes to the derived tissue affected in a particular NCP. According to this, some diseases have a single axial origin, i.e, they arise from an alteration in the development of only one NC population (e.g cranial NCP, such as Auriculo Condylar Syndrome). However, other NCP arise from a defect in two or more NC populations (such as the CHARGE syndrome). Accepted examples of NCP are

piebaldism Piebaldism refers to the absence of mature melanin-forming cells (melanocytes) in certain areas of the skin and hair. It is a rare autosomal dominant disorder of melanocyte development.James, William; Berger, Timothy; Elston, Dirk (2005). ''Andrews ...

Waardenburg syndrome Waardenburg syndrome is a group of rare genetic conditions characterised by at least some degree of congenital hearing loss and pigmentation deficiencies, which can include bright blue eyes (or one blue eye and one brown eye), a white foreloc ...

Hirschsprung disease Hirschsprung's disease (HD or HSCR) is a birth defect in which nerves are missing from parts of the intestine. The most prominent symptom is constipation. Other symptoms may include vomiting, abdominal pain, diarrhea and slow growth. Symptoms ...

Ondine's curse Central hypoventilation syndrome (CHS) is a sleep-related breathing disorder that causes ineffective breathing, apnea, or respiratory arrest during sleep (and during wakefulness in severe cases). CHS can either be congenital (CCHS) or acquired ( ...

(congenital central hypoventilation syndrome),

pheochromocytoma Pheochromocytoma (PHEO or PCC) is a rare tumor of the adrenal medulla composed of chromaffin cells, also known as pheochromocytes. When a tumor composed of the same cells as a pheochromocytoma develops outside the adrenal gland, it is referred t ...

paraganglioma A paraganglioma is a rare neuroendocrine neoplasm that may develop at various body sites (including the head, neck, thorax and abdomen). When the same type of tumor is found in the adrenal gland, they are referred to as a pheochromocytoma. They a ...

Merkel cell carcinoma Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer occurring in about 3 people per 1,000,000 members of the population. It is also known as cutaneous APUDoma, primary neuroendocrine carcinoma of the skin, primary small cell carcin ...

multiple endocrine neoplasia Multiple endocrine neoplasia (abbreviated MEN) is a condition which encompasses several distinct syndromes featuring tumors of endocrine glands, each with its own characteristic pattern. In some cases, the tumors are malignant, in others, benig ...

, neurofibromatosis type I, CHARGE syndrome,

familial dysautonomia Familial dysautonomia (FD), also known as Riley-Day Syndrome, is a rare, progressive, recessive genetic disorder of the autonomic nervous system that affects the development and survival of sensory, sympathetic and some parasympathetic neurons ...

DiGeorge syndrome DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a syndrome caused by a microdeletion on the long arm of chromosome 22. While the symptoms can vary, they often include congenital heart problems, specific facial features, frequent i ...

, Axenfeld-Rieger syndrome,

Goldenhar syndrome Goldenhar syndrome is a rare congenital defect characterized by incomplete development of the ear, nose, soft palate, lip and mandible on usually one side of the body. Common clinical manifestations include limbal dermoids, preauricular skin ta ...

(a.k.a.

hemifacial microsomia Hemifacial microsomia (HFM) is a congenital disorder that affects the development of the lower half of the face, most commonly the ears, the mouth and the mandible. It usually occurs on one side of the face, but both sides are sometimes affected. ...

), craniofrontonasal syndrome,

congenital melanocytic nevus The congenital melanocytic nevus is a type of melanocytic nevus (or mole) found in infants at birth. This type of birthmark occurs in an estimated 1% of infants worldwide; it is located in the area of the head and neck 15% of the time. Signs a ...

, melanoma, and certain

congenital heart defect A congenital heart defect (CHD), also known as a congenital heart anomaly and congenital heart disease, is a defect in the structure of the heart or great vessels that is present at birth. A congenital heart defect is classed as a cardiovascul ...

s of the outflow tract. Recently, many diseases have been incorporated as NCP, mainly based on the finding of new NC derivatives. In particular, Multiple sclerosis has been suggested as being neurocristopathic in origin. The usefulness of the definition resides in its ability to refer to a potentially common

etiological Etiology (pronounced ; alternatively: aetiology or ætiology) is the study of causation or origination. The word is derived from the Greek (''aitiología'') "giving a reason for" (, ''aitía'', "cause"); and ('' -logía''). More completely, e ...

factor for certain neoplasms and/or congenital malformation associations that are otherwise difficult to group with other means of nosology. Moreover, the classification of NCP is intended to help physicians understand the causal mechanism that drives the formation of a certain NCP, and therefore the selection of the correct diagnostic test and therapies.

References

{{reflist Animal developmental biology Medical terminology 1974 in biology Congenital disorders Genetic diseases and disorders Embryology of nervous system