Última actualización:
2/26/2026
Años publicados: 1987, 1988, 1989, 1993, 2000, 2003, 2009, 2012, 2015, 2026
NORD gratefully acknowledges Paula Vega, Stacey Afriyie and Manny Uzobuife, Editorial Interns from the University of Notre Dame and Jeff Milunsky, MD, FCMG, Co-Director, Center for Human Genetics, Inc., Director of Clinical Genetics, and Senior Director of Molecular Genetics, for their assistance in the preparation of this report.
Waardenburg syndrome (WS) is a group of genetic disorders present at birth that affect hair, skin, and eye color and may cause hearing loss. Common features include a white patch of hair on the forehead (white forelock), differences in eye color (heterochromia), patchy light-colored skin (leukoderma), and, in some types, a wide nasal bridge due to lateral (outward) displacement of the inner corners of the eyelids (dystopia canthorum).
There are four main types of WS, with some forms also affecting the arms and hands or the large intestine (Hirschsprung disease). Most cases are inherited in an autosomal dominant pattern.
Treatment focuses on managing specific symptoms, such as hearing loss, pigment changes, and limb differences.
Researchers have described different types of Waardenburg syndrome (WS), based on associated symptoms and specific genetic findings. Common features of Waardenburg syndrome may include:
The signs and symptoms of Waardenburg syndrome can vary greatly, even among members of the same family. Some individuals may have only one feature, such as hearing loss or a change in eye color, while others may have several characteristics associated with the condition.
The signs and symptoms of the different subtypes are described as follows:
WS1
WS2
WS3
WS4
Facial differences not associated with subtype1,2:
Waardenburg syndrome (WS) is most commonly caused by changes (variants) in several genes: PAX3, MITF, SOX10, EDN3, and EDNRB.
PAX3 plays an important role in the development of neural crest cells, which give rise to pigment-producing cells (melanocytes) 7, and also to parts of the inner ear, and certain facial structures. Changes in PAX3 are most commonly associated with WS type 1 (WS1) and type 3 (WS3). These changes can disrupt melanocyte development in the inner ear, leading to hearing loss. 7, 8
MITF gene changes are most often linked to WS type 2 (WS2). 5 The MITF gene helps regulate the development and survival of melanocytes. Variants in this gene can reduce the number or function of pigment cells and affect inner ear function, resulting in hearing loss. 9
The SOX10 gene works together with PAX3 to regulate the MITF gene expression and plays a broader role in neural crest cell development. 10-12
EDN3 and EDNRB gene changes are associated with WS4A and WS4B. These can affect neural crest cell development before birth, leading to fewer or nonfunctional pigment and gut nerve cells (sometimes causing Hirschsprung disease).13
Variants in the SOX10 gene are associated with WS type 4C (WS4C). These changes can affect pigment cells and enteric nerve cells (nerve cells of the intestine), sometimes causing Hirschsprung disease. SOX10 gene variants may also contribute to central nervous system (CNS) abnormalities in some people.14
New gene variants are still being discovered, and research continues to understand how all these genes contribute to Waardenburg syndrome.
Inheritance
In most cases, Waardenburg syndrome is inherited as an autosomal dominant trait, although some cases of WS4 appear to have an autosomal recessive pattern of inheritance. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a new variant (de novo) which occurs for the first time in the affected individual without being inherited. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy. The risk is the same for males and females.
Variants in the PAX3 gene are typically inherited in an autosomal dominant pattern. However, rare cases of WS type 3 (WS3) suggest that it may sometimes follow an autosomal recessive pattern. 15 For example, in a large family (kindred) in which several members were affected by WS1, one child was diagnosed with severe WS3. The parents, who were closely related by blood (consanguineous), were both affected by mild WS1. Evidence suggested that siblings with WS1 inherited one altered copy of the PAX3 gene from one parent (heterozygosity), whereas the child with WS3 inherited altered copies of the PAX3 gene from both parents (homozygosity).
Variants in the EDNRB or EDN3 genes are typically inherited in an autosomal recessive pattern.5 Recessive genetic disorders occur when an individual inherits two altered copies of a gene, one from each parent. Individuals who inherit one normal copy and one altered copy are called carriers and usually do not show symptoms. When both parents are carriers, each pregnancy carries a 25% chance of having an affected child, a 50% chance of having a carrier child, and a 25% chance of having a child who inherits two normal copies. The risk is the same for males and females. All individuals carry several recessive gene variants. Parents who are closely related (consanguineous) have a higher likelihood of carrying the same altered gene variant, increasing the risk of having children with a recessive genetic disorder.
In contrast, the SOX10 gene can be inherited as an autosomal dominant trait or may occur due to a new spontaneous change (de novo).
At least 1,400 cases have since been recorded in medical literature. Evidence suggests that WS may have a frequency of approximately one in 40,000 births and accounts for about two to five percent of cases of congenital deafness.16 The disorder appears to affect males and females relatively equally. Individuals with WS have a normal life expectancy although their quality of life can be affected by the symptoms they express.
Waardenburg syndrome is a genetic disorder that can be diagnosed early at birth, with symptoms and severity varying significantly among individuals. Primary features often include distinctive facial characteristics, especially dystopia canthorum, and heterochromia iridis, reduced pigmentation of the hair, skin, and eyes, as well as congenital deafness.
In addition to physical features, Waardenburg syndrome can be diagnosed by reviewing the patient’s and family’s medical history and performing tests that help confirm the condition. These tests may include: eye exams using a slit-lamp to look at internal eye structures and measuring distances between the inner corners of the eyes, outer corners, and pupils. Tissue samples (biopsies) from the rectum are used to help confirm related conditions like Hirschsprung disease.
Diagnosis can be confirmed with genetic testing by identifying the specific gene variants related to the syndrome.
The treatment of WS is directed at the specific symptoms that are apparent in each individual. Such treatment may require the coordinated efforts of a team of medical professionals, such as physicians who specialize in skin disorders (dermatologists); eye specialists (ophthalmologists); hearing specialists; physicians who diagnose and treat disorders of the skeleton, joints, muscles, and related tissues (orthopedists); physicians who specialize in diseases of the digestive tract (gastroenterologists); speech-language pathologists; physical therapists; and/or other health care professionals. Early recognition of sensorineural deafness may play an important role in ensuring prompt intervention and appropriate supportive management.18
These treatments include: 18-20
Hearing restoration significantly improves quality of life for children with congenital hearing loss, which can otherwise impair language development and social integration. Successful cochlear implantation supports age-appropriate speech and language development, facilitates participation in mainstream education, enhances social communication, and expands future educational and vocational opportunities. Reported outcomes show sustained device use and high satisfaction among recipients, with the best results achieved through early diagnosis, timely intervention, and comprehensive auditory rehabilitation. 19
Folic acid supplementation in pregnancy is recommended for women at increased risk of having a child with WS1 because of the possibly increased risk for neural tube defects associated with this condition. 20
Although there is currently no cure for WS, major progress has been achieved in preclinical studies of genetic hearing loss in animal models, including gene delivery and stem cell replacement therapies. These approaches remain investigational but represent promising future directions for treatment. 21
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
Contact for additional information about Waardenburg syndrome:
Jeff Milunsky, MD
Co-Director, Center for Human Genetics, Inc.,
Director of Clinical Genetics
Senior Director of Molecular Genetics
Cambridge, MA USA
https://www.chginc.org/
[email protected]
Adults & Children with Waardenburg Syndrome
Website: Adults & Children with Waardenburg Syndrome Facebook
Waardenburg Syndrome Support and Awareness
Website: Waardenburg Syndrome Support and Awareness Facebook
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Aprende más https://rarediseases.org/patient-assistance-programs/caregiver-respite/The information provided on this page is for informational purposes only. The National Organization for Rare Disorders (NORD) does not endorse the information presented. The content has been gathered in partnership with the MONDO Disease Ontology. Please consult with a healthcare professional for medical advice and treatment.
The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).
View reportOrphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the information and resources are available in languages other than English. The summary may include medical terms, so we encourage you to share and discuss this information with your doctor. Orphanet is the French National Institute for Health and Medical Research and the Health Programme of the European Union.
View reportOnline Mendelian Inheritance In Man (OMIM) has a summary of published research about this condition and includes references from the medical literature. The summary contains medical and scientific terms, so we encourage you to share and discuss this information with your doctor. OMIM is authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine.
View reportGeneReviews has an article on this condition covering diagnosis, management, and inheritance. Each article is written by one or more experts on the specific disease and is reviewed by other specialists. The article contains medical and scientific terms, so we encourage you to share and discuss this information with your doctor. The GeneReviews database is managed by the University of Washington.
View report