This later led to the synonym Mende syndrome being recorded in some databases.In 1929, Dutch physician K. T. A. Halbertsma described a familial pattern to dystopia canthorum, and in 1930, Italian physician Vincenzo Gualdi (1891–1976) also confirmed a hereditary pattern to dystopia canthorum. This later led to the synonym Van der Hoeve–Halbertsma–Waardenburg–Gualdi syndrome being recorded in some databases.In 1947, Swiss ophthamologist David Klein (1908–1993) first reported a patient with bilateral deafness, pigmentation deficiencies, characteristic facial features and malformation of the arms. Although this was the first full description of a patient with Waardenburg syndrome type 3, contemporary clinicians did not consider the syndrome he described to be the same as that described by Waardenburg four years later, in part due to how severe the arm malformations were in his patient.The syndrome was first fully formalised and described by Dutch ophthalmologist and geneticist Petrus Johannes Waardenburg (1886–1979) in 1951. The condition he described is now categorised as Waardenburg syndrome type 1. Descriptions of subtypes
Type 2 was first established in 1971 when a study noticed that some Waardenburg syndrome patients did not have dystopia canthorum. A 1977 study confirmed a familial pattern to this other presentation.
no telecanthus, or apparent wider eye gap), but with the addition of Hirschsprungs disease, which is a congenital lack of nerves in the intestines leading to bowel dysfunction. Additionally, hearing loss is not as common as in type 2. Rarely, cleft lip has been reported in this form of Waardenburg syndrome.Type 4 can also be caused by a mutation in SOX10 (the same gene as in type 2E), in which it is known as type 4C; hearing loss is very common and severe in this type. PCWH
A mutation in SOX10, the gene involved in type 2E and type 4C, can sometimes result in the symptoms of both types (neurological symptoms, as sometimes seen in type 2E, and Hirschsprungs disease, as seen in type 4). When this happens, it is called peripheral demyelinating neuropathy–central dysmyelinating leukodystrophy–Waardenburg syndrome–Hirschsprung disease (PCWH). Cause
Waardenburg syndrome is caused by mutations in any of several genes that affect the operation of neural crest cells in embryonic development. Most types of Waardenburg syndrome are caused by autosomal dominant mutations. The few that are autosomal recessive are rare. In most cases, an affected person has inherited it from one parent with one of the dominant forms of the condition. A small percentage of cases result from spontaneous new mutations in the gene, where no family history of the condition exists.The neural crest is a group of temporary migratory cells that are left over after the neural tube has closed (neurulation), around the fourth week of embryonic development.