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Disease Profile

Waardenburg syndrome type 1

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)

WS1; Waardenburg's syndrome type 1

Categories

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

Summary

Waardenburg syndrome type 1 is a genetic condition characterized by eyes that appear widely spaced, congenital hearing loss, and patchy pigment disturbances of the iris, hair and skin.[1][2] Mutations in the PAX3 gene cause the symptoms observed in this condition.[1] Treatment is symptomatic and supportive.[2] Waardenburg syndrome type 1 is inherited in an autosomal dominant manner.[1][2]

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
Abnormality of vision
Abnormality of sight
Vision issue

[ more ]

0000504
Congenital sensorineural hearing impairment
0008527
Heterochromia iridis
Different colored eyes
0001100
Hypopigmented skin patches
Patchy loss of skin color
0001053
Lacrimation abnormality
Abnormality of tear production
0000632
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
Short nose
Decreased length of nose
Shortened nose

[ more ]

0003196
Telecanthus
Corners of eye widely separated
0000506
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
White forelock
White part of hair above forehead
0002211
White hair
0011364
30%-79% of people have these symptoms
Premature graying of hair
Early graying
Premature graying
Premature greying
Premature hair graying

[ more ]

0002216
Synophrys
Monobrow
Unibrow

[ more ]

0000664
Tented upper lip vermilion
0010804
Underdeveloped nasal alae
Underdeveloped tissue around nostril
0000430
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
Abnormality of cardiovascular system morphology
0030680
Aganglionic megacolon
Enlarged colon lacking nerve cells
0002251
Cleft palate
Cleft roof of mouth
0000175
Cleft upper lip
Harelip
0000204
Meningocele
0002435
Myelomeningocele
0002475
Ptosis
Drooping upper eyelid
0000508
Scoliosis
0002650
Sprengel anomaly
High shoulder blade
0000912
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

0000486
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
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Hypopigmentation of the fundus
0007894
Hypoplastic iris stroma
0007990
Oral cleft
Cleft of the mouth
0000202
Partial albinism
Partial absent skin pigmentation
0007443
Smooth philtrum
0000319
Spina bifida
0002414
Supernumerary ribs
Extra ribs
0005815
Supernumerary vertebrae
0002946

Cause

Waardenburg syndrome type 1 is caused by mutations in the PAX3 gene. Researchers believe that mutations in the PAX3 gene destroy the ability of the PAX3 protein to bind to DNA and regulate the activity of other genes. As a result, pigment cells (melanocytes) do not develop in certain areas of the skin, hair, eyes, and inner ear, which leads to the hearing loss and patchy loss of pigmentation that are characteristic features of Waardenburg syndrome. In addition, these mutations disrupt the development of certain craniofacial bones, causing the widely spaced eyes that are unique to Waardenburg syndrome type 1.[3]

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

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.

Social Networking Websites

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 1. 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 Institute on Deafness and Other Communication Disorders (NIDCD) conducts and supports biomedical and behavioral research and research training in the normal and disordered processes of hearing, balance, smell, taste, voice, speech, and language. 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.
  • 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.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Waardenburg syndrome type 1. Click on the link to view a sample search on this topic.

References

  1. Waardenburg syndrome. Genetics Home Reference (GHR). April 2006; https://ghr.nlm.nih.gov/condition/waardenburg-syndrome. Accessed 10/20/2011.
  2. Milunsky JM. Waardenburg Syndrome Type I. GeneReviews. August 2009; https://www.ncbi.nlm.nih.gov/books/NBK1531/. Accessed 10/20/2011.
  3. PAX3. Genetics Home Reference (GHR). April 2006; https://ghr.nlm.nih.gov/gene/PAX3. Accessed 10/20/2011.

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