What is the definition of Waardenburg Syndrome Type 2?
Waardenburg syndrome type 2 (WS2) is a type of Waardenburg syndrome characterized by varying degrees of deafness and pigmentation (coloring) abnormalities of the eyes, hair and/or skin. WS2 differs from type 1 and some other types of WS by the absence of dystopia canthorum (lateral displacement of the inner canthi of the eyes). Sensorineural hearing loss occurs in the majority of people with WS2, and heterochromia iridis (differences in eye coloring) occurs in about half. Progressive hearing loss has also been reported in some people with WS2.
WS2 may be caused by changes (mutations) in any of several genes, but in many cases the genetic cause is unknown. While inheritance is usually autosomal dominant, sometimes WS2 is not inherited, occurring for the first time in someone with no family history of the condition. Treatment may include the use of hearing aids and/or cosmetic products or treatments (if desired) for skin hypopigmentation.
Waardenburg syndrome type 2 can be further divided into subtypes based on the genetic cause, when the responsible gene can be identified.
What are the alternative names for Waardenburg Syndrome Type 2?
What are the symptoms for Waardenburg Syndrome Type 2?
Waardenburg syndrome type 2 (WS2) is characterized by varying degrees of deafness and pigmentation (coloring) anomalies of the eyes, hair and skin, but without dystopia canthorum (lateral displacement of the inner canthi of the eyes). Sensorineural hearing loss is present in the majority of people with WS2 (almost 80%), and heterochromia iridum (differences in eye coloring) is present in almost half. Progressive hearing loss has also been reported in some people with WS2. In some people, particularly those with WS type 2E, signs of Kallmann syndrome are present.
How is Waardenburg Syndrome Type 2 diagnosed?
Waardenburg syndrome type 2 (WS2) is diagnosed by the presence of 2 of the 5 major criteria needed for a general diagnosis of Waardenburg syndrome, with no dystopia canthorum (lateral displacement of the inner canthi of the eyes).
In contrast to the general diagnosis of WS2, made based on symptoms, the diagnosis of a subtype of WS2 relies on identifying the genetic cause of WS2. For some subtypes, the general location (locus) of the responsible gene is known, but the specific responsible gene has not yet been identified. There are currently 5 subtypes of WS2:
- Type 2A is caused by a change (mutation) in the MITF gene on chromosome 3
- Type 2B is associated with a locus on chromosome 1
- Type 2C is associated with a locus on chromosome 8
- Type 2D is caused by mutations is the SNAI2 gene on chromosome 8
- Type 2E is caused by mutations in the SOX10 gene on chromosome 22
Is Waardenburg Syndrome Type 2 an inherited disorder?
Waardenburg syndrome type 2 (WS2) is usually inherited in an autosomal dominant manner. This means that having a change (mutation) in only one copy of the responsible gene in each cell is enough to cause features of the condition.
In some cases, an affected person inherits the mutated gene from an affected parent. In other cases, the mutation occurs for the first time in a person with no family history of the condition. This is called a de novo mutation. When a person with a mutation that causes an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit that mutation.
WS type 2D is the only subtype reportedly inherited in an autosomal recessive manner. This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. Affected people inherit one mutated copy of the gene from each parent, who is referred to as a carrier. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When 2 carriers of an autosomal recessive condition have children, each child has a:
- 25% (1 in 4) chance to be affected
- 50% (1 in 2) chance to be an unaffected carrier like each parent
- 25% chance to be unaffected and not be a carrier
Identifying the gene responsible for WS2 is necessary to determine the subtype that is present in a person or family.
People with questions about genetic risks or genetic testing for themselves or family members should speak with a genetic counselor or other genetics professional. A genetics professional can help by:
- thoroughly evaluating the family history
- addressing questions and concerns
- assessing recurrence risks
- facilitating genetic testing if desired
- discussing reproductive options