Type 4C is caused by an autosomal dominant or autosomal-recessive mutation in the gene SOX10, the same gene as in type 2E.A study was done on a rare case of a double heterozygous child with each parent having only single mutations in MITF or PAX3. The effect of double heterozygous mutations in the genes MITF and PAX3 in WS1 and WS2 can increase the pigment-affected symptoms. It leads to the conclusion that the double mutation of MITF is associated with the extremity of Waardenburg syndrome and may affect the phenotypes or symptoms of the syndrome. Classification table
Treatment
There is currently no treatment or cure for Waardenburg syndrome. The symptom most likely to be of practical importance is deafness, and this is treated as any other irreversible deafness would be. In marked cases, there may be cosmetic issues. Other abnormalities (neurological, structural, Hirschsprungs disease) associated with the syndrome are treated symptomatically. Epidemiology
The prevalence of all types of Waardenburg syndrome is estimated at around 1 in 42,000. Types 1 and 2 are by far the most common, with type 1 appearing to be slightly more common. In a 2015 review looking at 417 patients, type 1 was found to be the most common type, encompassing around half of all cases (47%), while type 2 was the second-most common type, encompassing around a third (33%). The vast majority (around 85%) of type 2 cases are type 2A. The prevalence of type 2B is unknown, as it was only reported in one 1996 study.
If two individuals with a mutation in this gene have a child carrying both mutations (homozygous), for which there is 25% chance, additional symptoms are present in the child, such as a hole in the iris (coloboma), small eyes (microphthalmia), hardened bones (osteopetrosis), macrocephaly, albinism and deafness.There have been two known patients identified with mutations in both copies of SNAI2 (classified as type 2D); these individuals presented with Waardenburg syndrome type 2 but did not have hair pigmentation deficiencies.When Waardenburg syndrome type 2 is caused by a mutation in SOX10 (classified as type 2E), it can on some occasions present with multiple neurological symptoms. These can include developmental delay, early childhood nystagmus, increased muscle tone, white matter anomalies or hypomyelination in the brain, autistic-like behaviour and the underdevelopment or complete absence of many inner-ear structures such as the vestibular system or cochlea. Lack of a sense of smell (anosmia) due to a missing olfactory bulb in the brain may also be present. Type 3
Also known as Klein–Waardenburg syndrome, or Waardenburg–Klein syndrome, type 3 has the same symptoms as type 1 (and is caused by mutations in the same gene) but has additional symptoms that affect the arms and hands. These can include joint contractures of the fingers (camptodactyly), due to underdeveloped muscles, as well as fused digits (syndactyly) or winged scapulae. Microcephaly and developmental delay are also possible. Type 4
Also known as Shah–Waardenburg syndrome, or Waardenburg–Shah syndrome, type 4 has most of the same features as type 2 (i.e.