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Disease Profile

Waardenburg syndrome

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.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Infancy

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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)

Van der Hoeve Halbertsma Waardenburg Gualdi Syndrome; Mende Syndrome

Summary

Waardenburg syndrome (WS) is a group of genetic conditions characterized by varying degrees of hearing loss and differences in the coloring (pigmentation) of the eyes, hair, and skin. Signs and symptoms can vary both within and between families. Common features include congenital sensorineural deafness; pale blue eyes, different colored eyes, or two colors within one eye; a white forelock (hair just above the forehead); or early graying of scalp hair before age 30. Various other features may also be present. WS is classified into 4 subtypes (types 1, 2, 3 and 4) based on whether certain features are present and the genetic cause. Mutations in at least 6 different genes are known to cause WS, and it may be inherited in an autosomal dominant (most commonly) or autosomal recessive manner. Treatment depends on the specific symptoms present.[1]

Symptoms

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
Abnormal facial shape
Unusual facial appearance
0001999
Abnormality of vision
Abnormality of sight
Vision issue

[ more ]

0000504
Conductive hearing impairment
Conductive deafness
Conductive hearing loss

[ more ]

0000405
Heterochromia iridis
Different colored eyes
0001100
Hypopigmented skin patches
Patchy loss of skin color
0001053
Premature graying of hair
Early graying
Premature graying
Premature greying
Premature hair graying

[ more ]

0002216
Prominent nasal bridge
Elevated nasal bridge
High nasal bridge
Prominent bridge of nose
Prominent nasal root
Protruding bridge of nose
Protruding nasal bridge

[ more ]

0000426
Synophrys
Monobrow
Unibrow

[ more ]

0000664
30%-79% of people have these symptoms
Abnormal lip morphology
Abnormal lip
Abnormality of the lip
Lip abnormality

[ more ]

0000159
Lacrimation abnormality
Abnormality of tear production
0000632
Telecanthus
Corners of eye widely separated
0000506
Underdeveloped nasal alae
Underdeveloped tissue around nostril
0000430
White forelock
White part of hair above forehead
0002211
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
5%-29% of people have these symptoms
Abnormal vagina morphology
0000142
Abnormality of the uterus
Uterine abnormalities
Uterine malformations

[ more ]

0000130
Aganglionic megacolon
Enlarged colon lacking nerve cells
0002251
Aplasia/Hypoplasia of the colon
Absent/small colon
Absent/underdeveloped colon

[ more ]

0100811
Intestinal obstruction
Bowel obstruction
Intestinal blockage

[ more ]

0005214
Myelomeningocele
0002475
Oral cleft
Cleft of the mouth
0000202
Ptosis
Drooping upper eyelid
0000508
Percent of people who have these symptoms is not available through HPO
Aplasia of the vagina
Absent vagina
0003250
Autosomal dominant inheritance
0000006
Blepharophimosis
Narrow opening between the eyelids
0000581
Blue irides
Blue eyes
0000635
Congenital sensorineural hearing impairment
0008527
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Hypopigmentation of the fundus
0007894
Hypoplastic iris stroma
0007990
Mandibular prognathia
Big lower jaw
Increased projection of lower jaw
Increased size of lower jaw
Large lower jaw
Prominent chin
Prominent lower jaw

[ more ]

0000303
Partial albinism
Partial absent skin pigmentation
0007443
Smooth philtrum
0000319
Spina bifida
0002414
Sprengel anomaly
High shoulder blade
0000912
Supernumerary ribs
Extra ribs
0005815
Supernumerary vertebrae
0002946
Thick eyebrow
Bushy eyebrows
Dense eyebrow
Heavy eyebrows
Prominent eyebrows
Thick eyebrows

[ more ]

0000574
White eyebrow
Pale eyebrow
0002226
White eyelashes
Blonde eyelashes
Pale eyelashes

[ more ]

0002227

Diagnosis

A diagnosis of Waardenburg syndrome (WS) is made based on the presence of signs and symptoms. In 1992, the Waardenburg Consortium proposed diagnostic criteria, which includes both major and minor criteria. A diagnosis of WS type 1 (the most common type) needs 2 major, or 1 major and 2 minor of the following criteria:[2][3]

Major criteria:

  • Congenital sensorineural hearing loss (present from birth)
  • Iris pigmentary (coloration) abnormality, such as heterochromia iridis (complete, partial, or segmental); pale blue eyes (isohypochromia iridis); or pigmentary abnormalities of the fundus (part of the eye opposite the pupil)
  • Abnormalities of hair pigmentation, such as white forelock (lock of hair above the forehead), or loss of hair color
  • Dystopia canthorum – lateral displacement of inner angles (canthi) of the eyes (in WS types 1 and 3 only)
  • Having a 1st degree relative with Waardenburg syndrome

Minor criteria:

  • Leukoderma (white patches of skin) present from birth
  • Synophrys (connected eyebrows, or "unibrow") or medial eyebrow flare
  • Broad or high nasal bridge (uppermost part of the nose)
  • Hypoplasia (incomplete development) of the nostrils
  • Premature gray hair (under age 30)

WS type 2 has features similar to type 1, but the inner canthi of the eyes are normal (no dystopia canthorum present).

WS type 3 also has similar features to WS type 1, but is additionally characterized by musculoskeletal abnormalities such as muscle hypoplasia; flexion contractures (inability to straighten joints); or syndactyly (webbed or fused fingers or toes).

WS type 4 has similar features to WS type 2, but with Hirschsprung disease (a condition resulting from missing nerve cells in the muscles of part or all of the large intestine).[3]

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

  • DermNet NZ is an online resource about skin diseases developed by the New Zealand Dermatological Society Incorporated. DermNet NZ provides information about this condition.
  • 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. This website is maintained by the National Library of Medicine.
  • The National Center for Biotechnology Information (NCBI) was established in 1988 as a national resource for molecular biology information. Click on the link to view information on this topic.
  • 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

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • 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) lists the subtypes and associated genes for Waardenburg syndrome in a table called Phenotypic Series. Each entry in OMIM includes 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.
  • 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.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Waardenburg syndrome. Click on the link to view a sample search on this topic.

References

  1. Véronique Pingault. Waardenburg syndrome. Orphanet. November, 2015; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=3440.
  2. Jeff Mark Milunsky. Waardenburg Syndrome Type I. GeneReviews. August 7, 2014; https://www.ncbi.nlm.nih.gov/books/NBK1531/.
  3. Dominic Tabor. Waardenburg syndrome. DermNet NZ. October, 2015; https://www.dermnetnz.org/colour/waardenburg.html.

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