They are responsible for differentiating into a diverse group of cells that reach different areas of the body. The neural tube and neural crest are derived from the ectoderm; the neural tube goes on to form the brain and spinal cord, while the neural crest cells eventually go on to form various bones and cartilage of the skull and face by migrating through the pharyngeal arches. They also differentiate into the stria vascularis of the cochlea, the nerves and glia of the intestines (myenteric plexus), Schwann cells, which myelinate the peripheral nervous system to allow sufficient conductivity, odontoblasts, which produce dentin deep in the teeth, some neuroendocrine cells, connective tissue around the salivary, lacrimal, pituitary, thymus and thyroid glands, connective tissue of the eye, such as the stroma of the iris and cornea and the trabecular meshwork, and melanocytes, including those in the stroma of the iris that give rise to brown eye colour through melanin. Neural crest cells also have a role in muscle formation, including the wall muscle of certain cardiac arteries. Causes of subtypes
Type 1 is caused by an autosomal dominant mutation in the gene PAX3. PAX3, or paired box 3, is a transcription factor that has a role in maintaining an open window of time for certain neural crest cells (such as those of the head and eyes) to divide and migrate before their terminal differentiation (i.e. to maintain them in the stem-cell state).
Type 2C has so far only been found in one Italian family, and type 2D had only been found in 2 unrelated patients as of 2018. The number of known cases of type 2E that involved neurological abnormalities was reported to be 23 as of 2017, while the number of the rest is unknown. Type 3 is rarer than types 1, 2 and 4, comprising less than 2% of cases. Type 4 appears to encompass around a fifth of cases (19%). Of its subtypes, type 4C is by far the most common (about 71% of type 4), followed by type 4A (19%) and type 4B (10%).It is estimated that Waardenburg syndrome is present in 2–5% of congenitally deaf people. Congenital deafness comprises around half of deafness as a whole. About 1 in 30 students in schools for the deaf have Waardenburg syndrome. The variable presentation of the syndrome makes it difficult to arrive at precise figures for its prevalence. History
Early descriptions
In 1916, Dutch ophthalmologist Jan van der Hoeve (1878–1952) described a pair of twin girls with deafness and a particular type of blepharophimosis, believed to be the dystopia canthorum found in Waardenburg syndrome types 1 and 3. Blepharophimosis describes eyelids which are underdeveloped such that they permanently cover part of the eyes. In 1926, German physician Irmgard Mende described a family of four generations in which five children had symptoms of depigmentation of hair, skin and eyes, deafness and a "mongoloid" appearance. (Waardenburg later attributed this description to the dystopia canthorum.)