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Waardenburg Syndrome

What Is Waardenburg Syndrome?

Waardenburg syndrome (WS) is a group of genetic conditions that can cause hearing loss and changes in pigmentation (color) of the hair, skin and eyes. There are at least four different types of Waardenburg Syndrome, and several subtypes within the four types. Types I and II are the most common types of the syndrome, whereas types III and IV, which include intestinal malformations are relatively rare. Other names used to describe Waardenburg Syndrome include: Klein-Waardenburg syndrome, Mende's syndrome II, Van der Hoeve-Halbertsma-Waardenburg syndrome, Ptosis-Epicanthus syndrome, Van der Hoeve-Halbertsma-Gualdi syndrome, Waardenburg type Pierpont, Van der Hoeve-Waardenburg-Klein syndrome, Waardenburg's syndrome II, and Vogt’s syndrome.

The degree of hearing loss can vary, it can be either unilateral or bilateral (one or both ears) and mild to profound. Waardenburg Syndrome accounts for approximately 3% of the population with congenital deafness. Vestibular symptoms including vertigo, dizziness and balance problems have been reported in Waardenburg Syndrome, even without hearing loss. Waardenburg Syndrome is a form of syndromic deafness, which means that there are additional medical issues in some other area of the body above and beyond the hearing loss.

Signs of Waardenburg Syndrome

Individuals with Waardenburg Syndrome often have very pale blue eyes or two different colored eyes (complete heterochromia). Sometimes one eye has sections of two different colors (sectional heterochromia). Individuals with this condition frequently also have distinctive hair coloring, such as a patch of white hair (poliosis) or hair that prematurely turns gray. Other facial features common in individuals with Waardenburg Syndrome include wide-set eyes (hypertelorism) due to a prominent, broad nasal root (dystopia canthorum—particularly associated with type I), a low hairline, or eyebrows that touch in the middle. Waardenburg Syndrome has a higher than average association with intestinal and spinal defects, cleft lip and palate, scapular elevation, and patches of white pigmentation on the skin similar to vitiligo.

How does Waardenburg Syndrome Affect Hearing?

The genes that cause Waardenburg Syndrome are involved in the development and formation of several types of cells, including the pigment producing cells called melanocytes. Melanocytes produce a pigment called melanin which contributes to skin, hair and eye color and additionally plays a pivotal role in the normal function of the middle ear. Melanocytes are required in the stria vascularis for normal cochlear function. Histopathologic examination of the inner ears of individuals with Waardenburg Syndrome shows absent Organs of Corti, atrophy of the spinal ganglion and reduced numbers of nerve fibers.

Causes of Waardenburg Syndrome

Identified causes of Waardenburg Syndrome include mutations in the EDN3, EDNRB, MITF, PAX3, SNAI2, and SOX10 genes, depending on which type of Waardenburg Sydrome is involved.

  • Type 1 and Type 3 Waardenburg Syndrome results from a mutation of the PAX3 gene located on chromosome band 2q35.
  • The primary subtype of Type 2 Waardenburg Syndrome is associated with mutations in the microphthalmia-associated transcription factor (MITF) on the SNA12 gene located on chromosome band 3p14. Mutations at loci 1-p12.3, 8p23, and 8q11 are responsible for other subtypes of Type 2 Waardenburg Syndrome, while some other cases which are symptomatically suspected to be Type 2 Waardenburg Syndrome do not have mutations in any of these locations.
  • Type 4 Waardenburg Syndrome is associated with mutations in the SOX10, EDN3 or EDNRB. These genes, in addition to their connection to the development of melanin, are also linked to the development of nerve cells within the large intestine. Mutations in any of these genes results in hearing loss, problems with pigmentation and intestinal issues related to Hirschsprung disease.

How is Waardenburg Syndrome Transmitted?

Waardenburg syndrome is typically inherited in an autosomal dominant pattern, which means that one copy of the defective gene is sufficient to cause the disorder. In most cases, an affected individual has one parent with the condition. A small percentage of cases result from new mutations in the gene where there is no history of the disorder in the affected person’s family.

Some cases of Type 2 and Type 4 Waardenburg are genetically transmitted from parent to child in a recessive manner, which means that an affected individual must inherit one copy of the non-functioning gene from each parent. Carriers who only have one copy of the gene (i.e. one normal gene and one mutated gene) do not manifest any of the signs of the condition, but have a 1 in 2 chance of passing on the defective gene to their children (who would then also be carriers only), and a 1 in 4 chance of having an affected child if the other parent is also a carrier.

Treatment

Waardenburg Syndrome is relatively easy to diagnose because of the many common visible facial features. Genetic testing can confirm a symptomatic diagnosis. A specialized interdisciplinary team of professionals is necessary to treat all of the issues associated with Waardenburg Syndrome. This group of individuals should include an Otologist or Otolaryngologists, audiologists, speech-language pathologists, a clinical geneticist and a genetic counselor. Depending on the type of Waardenbug syndrome, this team may need to be expanded to include an ophthalmologist, dermatologist, craniofacial surgeon, and gastrointestinal specialist. All of these individuals should have extensive experience in pediatrics.

The California Ear Institute is a leading global center for otological, otolaryngological and audiological treatment. Dr. Joseph Roberson, a board certified neurotologist, has performed thousands of successful hearing related surgeries on children and adults, including many whose hearing impairment is due to Waardenburg Syndrome.

Consequences of Avoiding Treatment

If it is the desire of the family for their child to hear and speak as normally as possible, it is necessary to seek medical evaluation as soon as possible after birth of a child who is referred by their newborn hearing screening program for additional testing, regardless of whether or not Waardenburg Syndrome is suspected to be the source of the hearing loss. Delays in treatment for profound sensorineural hearing loss will result in the inability for the patient to develop normal spoken speech and language skills. Additionally, candidacy for cochlear implantation, currently the only medical treatment available for the treatment of profound sensorineural hearing loss, cannot be established without a comprehensive medical examination. Avoiding medical evaluation for Waardenburg Syndrome or any other hearing impairment related disorder is not recommended.

Additional Notes

Patients searching the internet for information about Waardenburg Syndrome or any other medical issue should know when reading about individual case histories, that generally it is the patients with the most severe symptoms who either post their own experiences or are included in medical review journals. As a result, it is easy to become overly alarmed and assume the worst. Patients should keep this in mind as they explore the available resources, and look for sources that are certified by HON or other reputable health reviewing organizations. As with all medical conditions, prompt treatment by experienced medical personnel give the best chance for a positive outcome.

Additional Reading

  1. Kujat A, Veith VP, Faber R, Froster UG. Prenatal diagnosis and genetic counseling in a case of spina bifida in a family with Waardenburg syndrome type I. Fetal Diagn Ther. 2007;22(2):155-8. Epub 2006 Nov 28
  2. Sato-Jin K, Nishimura EK, Akasaka E, Huber W, Nakano H, Miller A, Du J, Wu M, Hanada K, Sawamura D, Fisher DE, Imokawa G.Epistatic connections between microphthalmia-associated transcription factor and endothelin signaling in Waardenburg syndrome and other pigmentary disorders.FASEB J. 2007 Nov 26; [Epub ahead of print]
  3. Bondurand N, Dastot-Le Moal F, Stanchina L, Collot N, Baral V, Marlin S, Attie-Bitach T, Giurgea I, Skopinski L, Reardon W, Toutain A, Sarda P, Echaieb A, Lackmy-Port-Lis M, Touraine R, Amiel J, Goossens M, Pingault V. Deletions at the SOX10 gene locus cause Waardenburg syndrome types 2 and 4. Am J Hum Genet. 2007 Dec;81(6):1169-85. Epub 2007 Oct 22.
  4. Ruiz-Maldonado R. Hypomelanotic conditions of the newborn and infant.Dermatol Clin. 2007 Jul;25(3):373-82, ix.
  5. Charrow J. Different colored eyes. Waardenburg syndrome.Pediatr Ann. 2007 May;36(5):277-8.
  6. Hornyak TJ. The developmental biology of melanocytes and its application to understanding human congenital disorders of pigmentation. Adv Dermatol. 2006;22:201-18. Review.
  7. http://www.nidcd.nih.gov/health/hearing/waard.asp
  8. http://en.wikipedia.org/wiki/Waardenburg_syndrome
  9. http://ghr.nlm.nih.gov/condition=waardenburgsyndrome
  10. http://www.nlm.nih.gov/medlineplus/ency/article/001428.htm

 

 

 


 
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