Waardenburg syndrome type 2

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Disease Profile

Unknown

US Estimated

Europe Estimated

Age of onset

Neonatal

ICD-10

E70.3

Inheritance

Waardenburg syndrome type 2 (WS2) is usually inherited in an autosomal dominant manner.^[1] 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.^[4] 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

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

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.

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.

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

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.

Not applicable

Other names (AKA)

WS 2; WS type 2

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

Do you have updated information on this disease? We want to hear from you.

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]

Related diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnosis includes Waardenburg syndrome type 1 and 4, piebaldism, Tietz syndrome, oculocutaneous albinism (see these terms) and other forms of congenital non-progressive sensorineural hearing loss. Visit the Orphanet disease page for more information.

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

American Society for Deaf Children (ASDC)
PO Box 23
Woodbine, MD 21797
Toll-free: 1-800-942-2732
E-mail: info@deafchildren.org
Website: https://deafchildren.org/
National Association of the Deaf
8630 Fenton Street Suite 820
Silver Spring, MD 20910
Telephone: +1-301-587-1788
TTY: +1-301-587-1789
Fax: +1-301-587-1791
E-mail: NADinfo@nad.org
Website: https://www.nad.org/
The National Organization of Albinism and Hypopigmentation (NOAH)
PO Box 959
East Hampstead, NH 03826-0959
Toll-free: 800-473-2310;
Telephone: 603-887-2310
E-mail: noah@albinism.org
Website: https://www.albinism.org

Social Networking Websites

Visit the Adults & Children with Waardenburg syndrome group on Facebook.

Organizations Providing General Support

The Vision of Children Foundation (VOC)
12555 High Bluff Drive, Suite 330
San Diego, CA 92130
Telephone: +1-858-314-7916
E-mail: info@visionofchildren.org
Website: https://www.visionofchildren.org/

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

Véronique Pingault. Waardenburg syndrome type 2. Orphanet. October, 2015; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=895.
Jeff Mark Milunsky. Waardenburg Syndrome Type I. GeneReviews. August 7, 2014; https://www.ncbi.nlm.nih.gov/books/NBK1531/.
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/.
Carol A. Bocchini. WAARDENBURG SYNDROME, TYPE 2D; WS2D. OMIM. January 21, 2015; https://omim.org/entry/608890.
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.
Cassandra L. Kniffin. WAARDENBURG SYNDROME, TYPE 2A; WS2A. OMIM. May 24, 2016; https://omim.org/entry/193510.
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.
Cassandra L. Kniffin. WAARDENBURG SYNDROME, TYPE 2C; WS2C. OMIM. March 15, 2010; https://omim.org/entry/606662.
Cassandra L. Kniffin. WAARDENBURG SYNDROME, TYPE 2E; WS2E. OMIM. May 24, 2016; https://omim.org/entry/611584.

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Neonatal

E70.3

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

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.

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.

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

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.

Not applicable

Other names (AKA)

Categories

Summary

Symptoms

Diagnosis

Organizations

Organizations Supporting this Disease

Social Networking Websites

Organizations Providing General Support

Learn more

Where to Start

In-Depth Information

References

Rare Nephrology & Urology News

Rare Nephrology & Urology News

Neonatal

E70.3

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

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.

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.

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

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.

Not applicable

Other names (AKA)

Categories

Summary

Symptoms

Diagnosis

Related diseases

Organizations

Organizations Supporting this Disease

Social Networking Websites

Organizations Providing General Support

Learn more

Where to Start

In-Depth Information

References

Rare Nephrology
& Urology News

Rare Nephrology
& Urology News

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.

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