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Disease Profile

Waardenburg syndrome type 3

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)

Klein-Waardenburg syndrome; Waardenburg syndrome, type 3; Waardenburg syndrome with upper limb anomalies;

Categories

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

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 896

Definition
A very rare subtype of Waardenburg syndrome (WS) that is characterized by limb anomalies in association with congenital hearing loss, minor defects in structures arising from neural crest, resulting in pigmentation anomalies of eyes, hair, and skin.

Epidemiology
Incidence is unknown, but WS3 is the rarest form of all Waardenburg syndrome types.

Clinical description
WS3 is characterized by the association of limb anomalies (predominantly involving upper limbs, with hypoplasia of the musculoskeletal system, flexion contractures, fusion of the carpal bones, syndactylia) with features of Waardenburg syndrome (see this term), which include congenital sensorineural hearing loss, hypopigmentation abnormalities of irides, hair and skin and minor facial dysmorphism in combination with dystopia canthorum.

Etiology
WS3 is caused by heterozygous or homozygous mutations in the PAX3 (2q36.1) gene.

Diagnostic methods
Diagnosis is made through criteria of the association of WS1 manifestations with limb anomalies. PAX3 gene analysis confirms diagnosis resulting in an abnormality of melanocytes of skin, ears and hair.

Antenatal diagnosis
Antenatal diagnosis is possible for affected parents.

Genetic counseling
The defects are more severe in homozygous than heterozygous forms. Genetic counseling is recommended.

Management and treatment
Hearing aids to counter hearing loss, effective therapy to improve language, communication, and cognitive skill and limbs physiotherapy are recommended. Associated manifestations are treated as appropriate (e.g. skin and eyes protection from the sun).

Prognosis
Due to the very few number of cases described so far, information on prognosis and quality of life is limited. Disease progression is variable, with symptoms being more severe in homozygous than in heterozygous forms.

Visit the Orphanet disease page for more resources.

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
Blepharophimosis
Narrow opening between the eyelids
0000581
Cutaneous finger syndactyly
Webbed fingers
Webbed skin of fingers

[ more ]

0010554
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Joint stiffness
Stiff joint
Stiff joints

[ more ]

0001387
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Narrow nasal bridge
Narrow bridge of nose
Nasal Bridge, Narrow
Nasal bridge, thin

[ more ]

0000446
Synostosis of carpal bones
Fusion of wrist bones
0005048
Tented upper lip vermilion
0010804
Thick eyebrow
Bushy eyebrows
Dense eyebrow
Heavy eyebrows
Prominent eyebrows
Thick eyebrows

[ more ]

0000574
30%-79% of people have these symptoms
Atelectasis
Partial or complete collapse of part or entire lung
0100750
Telecanthus
Corners of eye widely separated
0000506
White hair
0011364
5%-29% of people have these symptoms
Acrocyanosis
Persistent blue color of hands, feet, or parts of face
0001063
Atrial septal defect
An opening in the wall separating the top two chambers of the heart
Hole in heart wall separating two upper heart chambers

[ more ]

0001631
Camptodactyly of finger
Permanent flexion of the finger
0100490
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Spastic paraplegia
0001258
Tracheomalacia
Floppy windpipe
0002779
Percent of people who have these symptoms is not available through HPO
Aganglionic megacolon
Enlarged colon lacking nerve cells
0002251
Autosomal dominant contiguous gene syndrome
0001452
Autosomal dominant inheritance
0000006
Autosomal recessive inheritance
0000007
Blue irides
Blue eyes
0000635
Brachydactyly
Short fingers or toes
0001156
Carpal synostosis
0009702
Clinodactyly
Permanent curving of the finger
0030084
Heterochromia iridis
Different colored eyes
0001100
Hypopigmented skin patches
Patchy loss of skin color
0001053
Joint contracture of the hand
0009473
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
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
Scapular winging
Winged shoulder blade
0003691
Sensorineural hearing impairment
0000407
Synophrys
Monobrow
Unibrow

[ more ]

0000664
Variable expressivity
0003828
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

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

  • Genetics Home Reference (GHR) contains information on Waardenburg syndrome type 3. This website is maintained by the National Library of Medicine.

In-Depth Information

  • 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 3. Click on the link to view a sample search on this topic.