Type 3 is a more severe presentation of type 1 and is caused by a mutation in the same gene, while type 4 is most often caused by a mutation in SOX10. Mutations in other genes can also cause the different types, and some of these have been given their own lettered subtypes. Most types are autosomal dominant. The estimated prevalence of Waardenburg syndrome is 1 in 42,000. Types 1 and 2 are the most common, comprising approximately half and a third of cases, respectively, while type 4 comprises a fifth and type 3 less than 2% of cases. An estimated 2–5% of congenitally deaf people have Waardenburg syndrome. Descriptions of the syndrome date back to at least the first half of the 20th century, however it is named after Dutch ophthalmologist and geneticist Petrus Johannes Waardenburg, who described it in 1951. Its subtypes were progressively discovered in the following decades and had genes attributed to them mostly in the 1990s and 2000s. Signs and symptoms
Waardenburg syndrome has multiple different types with some variations in symptoms, and symptoms can vary among those with the same type. The two features consistent across all types of Waardenburg syndrome are some degree of congenital sensorineural hearing loss and some degree of pigmentation deficiencies, most consistently in the eyes.
Two 1994 studies first confirmed a link between this type of Waardenburg syndrome and mutations in the MITF gene (now classed as type 2A), located on chromosome 3 at locus 3p14.1–p12.3.Type 2B was first established in 1994 when the same study which found mutations in MITF in patients with Waardenburg syndrome type 2 also found that some patients did not have any mutations in this region. A second 1994 study found a link to chromosome 1 in the locus 1p21–p13.3. This became known as type 2B of the condition (with the gene designated WS2B), however it has not been documented since, and the gene responsible remains unknown.Type 2C was established in 2001 when a study of an Italian family with Waardenburg syndrome type 2 features found that they were due to an unknown gene on chromosome 8 at locus 8q23 that had been broken by a chromosomal translocation. The study established a provisional name for the gene, WS2C. However, mutations in this region in Waardenburg syndrome patients have not been found since.Type 2D was established in 2002 when a study looking to find mutations in the human version of the SNAI2 gene, known to cause depigmentation in mice, found deletions of both copies of this gene in two unrelated individuals with Waardenburg syndrome type 2.