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Disease Profile

Waardenburg syndrome type 2

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Neonatal

ICD-10

E70.3

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

WS 2; WS type 2

Categories

Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Eye diseases;

Summary

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).[1][2] Sensorineural hearing loss occurs in the majority of people with WS2, and heterochromia iridis (differences in eye coloring) occurs in about half.[1] Progressive hearing loss has also been reported in some people with WS2.[3]

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.[1]

Waardenburg syndrome type 2 can be further divided into subtypes based on the genetic cause, when the responsible gene can be identified.

Symptoms

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.[1] Progressive hearing loss has also been reported in some people with WS2.[3] In some people, particularly those with WS type 2E, signs of Kallmann syndrome are present.[1]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Premature graying of hair
Early graying
Premature graying
Premature greying
Premature hair graying

[ more ]

0002216
30%-79% of people have these symptoms
Heterochromia iridis
Different colored eyes
0001100
Hypopigmented skin patches
Patchy loss of skin color
0001053
Sensorineural hearing impairment
0000407
White forelock
White part of hair above forehead
0002211
5%-29% of people have these symptoms
Abnormality of the kidney
Abnormal kidney
0000077
Abnormality of the pulmonary artery
Abnormality of lung artery
0004414
Aganglionic megacolon
Enlarged colon lacking nerve cells
0002251
Ptosis
Drooping upper eyelid
0000508
Telecanthus
Corners of eye widely separated
0000506
Percent of people who have these symptoms is not available through HPO
Albinism
0001022
Autosomal dominant inheritance
0000006
Congenital sensorineural hearing impairment
0008527
Hypoplastic iris stroma
0007990
Partial albinism
Partial absent skin pigmentation
0007443
Synophrys
Monobrow
Unibrow

[ more ]

0000664
Underdeveloped nasal alae
Underdeveloped tissue around nostril
0000430
Variable expressivity
0003828
White eyebrow
Pale eyebrow
0002226
White eyelashes
Blonde eyelashes
Pale eyelashes

[ more ]

0002227
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge

[ more ]

0000431

Diagnosis

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).[5]

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[6]
  • Type 2B is associated with a locus on chromosome 1[7]
  • Type 2C is associated with a locus on chromosome 8[8]
  • Type 2D is caused by mutations is the SNAI2 gene on chromosome 8[4]
  • Type 2E is caused by mutations in the SOX10 gene on chromosome 22[9]

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Social Networking Websites

      Organizations Providing General Support

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

        • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
        • Genetics Home Reference (GHR) contains information on Waardenburg syndrome type 2. This website is maintained by the National Library of Medicine.
        • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

          In-Depth Information

          • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
            Orphanet
            Orphanet
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Waardenburg syndrome type 2. Click on the link to view a sample search on this topic.

            References

            1. Véronique Pingault. Waardenburg syndrome type 2. Orphanet. October, 2015; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=895.
            2. Jeff Mark Milunsky. Waardenburg Syndrome Type I. GeneReviews. August 7, 2014; https://www.ncbi.nlm.nih.gov/books/NBK1531/.
            3. Koyama H, Kashio A, Sakata A, et al. The Hearing Outcomes of Cochlear Implantation in Waardenburg Syndrome. BioMed Research International. 2016; 2016:https://www.hindawi.com/journals/bmri/2016/2854736/.
            4. Carol A. Bocchini. WAARDENBURG SYNDROME, TYPE 2D; WS2D. OMIM. January 21, 2015; https://omim.org/entry/608890.
            5. Chen Y, Yang F, Zheng H, Zhou J, Zhu G, Hu P4, Wu W. Clinical and genetic investigation of families with type II Waardenburg syndrome. Mol Med Rep. March, 2016; 13(3):1983-1988.
            6. Cassandra L. Kniffin. WAARDENBURG SYNDROME, TYPE 2A; WS2A. OMIM. May 24, 2016; https://omim.org/entry/193510.
            7. Cassandra L. Kniffin. WAARDENBURG SYNDROME, TYPE 2B; WS2B. OMIM. March 15, 2010; https://www.omim.org/entry/600193?search=waardenburg%20type%202b&highlight=type%202b%20waardenburg.
            8. Cassandra L. Kniffin. WAARDENBURG SYNDROME, TYPE 2C; WS2C. OMIM. March 15, 2010; https://omim.org/entry/606662.
            9. Cassandra L. Kniffin. WAARDENBURG SYNDROME, TYPE 2E; WS2E. OMIM. May 24, 2016; https://omim.org/entry/611584.

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