Reviewed April 2006
What is Waardenburg syndrome?
Waardenburg syndrome is a group of genetic conditions that can cause hearing loss and changes in coloring (pigmentation) of the hair, skin, and eyes. Although most people with Waardenburg syndrome have normal hearing, moderate to profound hearing loss can occur in one or both ears. People with this condition often have very pale blue eyes or different colored eyes, such as one blue eye and one brown eye. Sometimes one eye has segments of two different colors. Distinctive hair coloring (such as a patch of white hair or hair that prematurely turns gray) is another common sign of the condition. The features of Waardenburg syndrome vary among affected individuals, even among people in the same family.
The four known types of Waardenburg syndrome are distinguished by their physical characteristics and sometimes by their genetic cause. Types I and II have very similar features, although people with type I almost always have eyes that appear widely spaced and people with type II do not. In addition, hearing loss occurs more often in people with type II than in those with type I. Type III (sometimes called Klein-Waardenburg syndrome) includes abnormalities of the upper limbs in addition to hearing loss and changes in pigmentation. Type IV (also known as Waardenburg-Shah syndrome) has signs and symptoms of both Waardenburg syndrome and Hirschsprung disease, an intestinal disorder that causes severe constipation or blockage of the intestine.
How common is Waardenburg syndrome?
Waardenburg syndrome affects an estimated 1 in 10,000 to 20,000 people. In schools for the deaf, 2 percent to 3 percent of students have this condition. Types I and II are the most common forms of Waardenburg syndrome, while types III and IV are rare.
What genes are related to Waardenburg syndrome?
Mutations in the EDN3, EDNRB, MITF, PAX3, SNAI2, and SOX10 genes cause Waardenburg syndrome.
The genes that cause Waardenburg syndrome are involved in the formation and development of several types of cells, including pigment-producing cells called melanocytes. Melanocytes make a pigment called melanin, which contributes to skin, hair, and eye color and plays an essential role in the normal function of the inner ear. Mutations in any of these genes disrupt the normal development of melanocytes, leading to abnormal pigmentation of the skin, hair, and eyes and problems with hearing.
Types I and III Waardenburg syndrome are caused by mutations in the PAX3 gene. Mutations in the MITF and SNAI2 genes are responsible for type II Waardenburg syndrome.
Mutations in the SOX10, EDN3, or EDNRB genes cause type IV Waardenburg syndrome. In addition to melanocyte development, these genes are important for the development of nerve cells in the large intestine. Mutations in any of these genes result in hearing loss, changes in pigmentation, and intestinal problems related to Hirschsprung disease.
How do people inherit Waardenburg syndrome?
Waardenburg syndrome is usually inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition. A small percentage of cases result from new mutations in the gene; these cases occur in people with no history of the disorder in their family.
Some cases of type II and type IV Waardenburg syndrome appear to have an autosomal recessive pattern of inheritance, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.
Where can I find information about treatment for Waardenburg syndrome?
You may find information on treatment or management of Waardenburg syndrome or some of its symptoms in the links below, particularly the links for
Gene Reviews, MedlinePlus Encyclopedia, Educational resources, and Patient support.
Where can I find additional information about Waardenburg syndrome?
You may find the following resources about Waardenburg syndrome helpful. These materials are written for the general public.
- MedlinePlus - Health information
- Encyclopedia: Waardenburg Syndrome (http://www.nlm.nih.gov/medlineplus/ency/article/001428.htm)
- Health Topic: Hearing Disorders and Deafness (http://www.nlm.nih.gov/medlineplus/hearingdisordersanddeafness.html)
- Health Topic: Skin Pigmentation Disorders (http://www.nlm.nih.gov/medlineplus/skinpigmentationdisorders.html)
- Genetic and Rare Diseases Information Center - Information about genetic conditions and rare diseases (http://rarediseases.info.nih.gov/GARD/Disease.aspx?PageID=4&DiseaseID=5520)
- Additional NIH Resources - National Institutes of Health
- National Center for Biotechnology Information: Genes and Disease (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowSection&rid=gnd.section.187)
- National Institute on Deafness and Other Communication Disorders (http://www.nidcd.nih.gov/health/hearing/waard.asp)
- Educational resources - Information pages
- Center for Craniofacial Development and Disorders, Johns Hopkins University (http://www.hopkinsmedicine.org/craniofacial/Education/DefinedArticle.cfm?MUArticleID=84&Source=Family)
- Madisons Foundation (http://www.madisonsfoundation.org/index.php/component/option,com_mpower/diseaseID,226/)
- Orphanet: Waardenburg syndrome type 1 (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=894)
- Orphanet: Waardenburg syndrome type 2 (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=895)
- Orphanet: Waardenburg syndrome type 3 (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=896)
- Orphanet: Waardenburg syndrome type 4 (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=897)
- Patient support - For patients and families
- Alexander Graham Bell Association for the Deaf and Hard of Hearing (http://www.agbell.org/)
- American Society for Deaf Children (http://www.deafchildren.org)
- Boys Town National Research Hospital (http://www.boystownhospital.org/Hearing/info/genetics/syndromes/waardenburg.asp)
- National Organization for Rare Disorders (http://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Waardenburg+Syndrome)
- Resource list from the University of Kansas Medical Center (http://www.kumc.edu/gec/support/waardenb.html)
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
- Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=ws1)
- Gene Tests - DNA tests ordered by healthcare professionals
- DNA Test: Waardenburg syndrome, type III (http://www.genetests.org/query?testid=239852)
- DNA Test: Waardenburg syndrome type I (http://www.genetests.org/query?testid=2176)
- DNA Test: Waardenburg syndrome type IIA (http://www.genetests.org/query?testid=225096)
- ACTion Sheets - Newborn screening follow up
- ACTion sheet: Congenital hearing loss >~30db (http://www.acmg.net/resources/policies/ACT/Act_Sheet-Hearing-Loss_4-17-06.pdf)
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=PubMed&term=(Waardenburg's+Syndrome[MAJR])+AND+(Waardenburg[TIAB])+AND+english[la]+AND+human[mh]&orig_db=PubMed&filters=ON&pmfilter_EDatLimit=1800+Days)
- OMIM - Genetic disorder catalog
- OMIM: Waardenburg syndrome, type I (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=193500)
- OMIM: Waardenburg syndrome, type IIA (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=193510)
- OMIM: Waardenburg syndrome, type III (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=148820)
- OMIM: Waardenburg syndrome type IIB (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600193)
- OMIM: Waardenburg syndrome type IIC (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606662)
- OMIM: Waardenburg syndrome type IID (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=608890)
- OMIM: Waardenburg syndrome type IV (Waardenburg-Shah syndrome) (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=277580)
What other names do people use for Waardenburg syndrome?
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What if I still have specific questions about Waardenburg syndrome?
- See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
- Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
- Submit your question to Ask the Geneticist (http://www.askthegen.org/).
What glossary definitions help with understanding Waardenburg syndrome?
autosomal ;
autosomal dominant ;
autosomal recessive ;
cell ;
constipation ;
gene ;
inheritance ;
intestine ;
melanin ;
melanocytes ;
mutation ;
nerve cell ;
new mutation ;
pattern of inheritance ;
pigment ;
pigmentation ;
recessive ;
sign ;
symptom ;
syndrome
You may find definitions for these and many other terms in the Genetics Home Reference
Glossary (http://ghr.nlm.nih.gov/glossary).
References
- Gene Review: Waardenburg syndrome type I (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=ws1)
- Newton VE. Clinical features of the Waardenburg syndromes. Adv Otorhinolaryngol. 2002;61:201-8. Review. No abstract available. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12408085)
- Pardono E, van Bever Y, van den Ende J, Havrenne PC, Iughetti P, Maestrelli SR, Costa F O, Richieri-Costa A, Frota-Pessoa O, Otto PA. Waardenburg syndrome: clinical differentiation between types I and II. Am J Med Genet. 2003 Mar 15;117A(3):223-35. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12599185)
- Read AP. Waardenburg syndrome. Adv Otorhinolaryngol. 2000;56:32-8. Review. No abstract available. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=10868211)
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
healthcare professional.
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
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