Waardenburg syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Waardenburg syndrome is a group of genetic conditions that can cause hearing loss and changes in coloring (pigmentation) of the hair, skin, and eyes. Although most people with Waardenburg syndrome have normal hearing, moderate to profound hearing loss can occur in one or both ears. The hearing loss is present from birth (congenital). People with this condition often have very pale blue eyes or different colored eyes, such as one blue eye and one brown eye. Sometimes one eye has segments of two different colors. Distinctive hair coloring (such as a patch of white hair or hair that prematurely turns gray) is another common sign of the condition. The features of Waardenburg syndrome vary among affected individuals, even among people in the same family.

There are four recognized types of Waardenburg syndrome, which are distinguished by their physical characteristics and sometimes by their genetic cause. Types I and II have very similar features, although people with type I almost always have eyes that appear widely spaced and people with type II do not. In addition, hearing loss occurs more often in people with type II than in those with type I. Type III (sometimes called Klein-Waardenburg syndrome) includes abnormalities of the arms and hands in addition to hearing loss and changes in pigmentation. Type IV (also known as Waardenburg-Hirschsprung disease or Waardenburg-Shah syndrome) has signs and symptoms of both Waardenburg syndrome and Hirschsprung disease, an intestinal disorder that causes severe constipation or blockage of the intestine.

ORPHANET DEFINITION A rare genetic multiple congenital anomalies characterized by deafness and defects in neural crest-derived structures, including pigmentation anomalies of the eyes, hair, and skin. Four clinical phenotypes are associated with the term ''Waardenburg syndrome'' (WS).

Inheritance

From: MedlinePlus Genetics, National Library of Medicine

Autosomal dominant

Frequency in the source

From: MedlinePlus Genetics, National Library of Medicine

Prevalence at birth: 1-9 / 1 000 000; Europe; Value and class. Prevalence at birth: 1-9 / 100 000; Netherlands; Value and class.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal facial shape · Very frequent (99-80%)

An abnormal morphology (form) of the face or its components.

Abnormality of skin pigmentation · Very frequent (99-80%)

An abnormality of the pigmentation of the skin.

Hearing impairment · Very frequent (99-80%)

A decreased magnitude of the sensory perception of sound.

Heterochromia iridis · Very frequent (99-80%)

Heterochromia iridis is a difference in the color of the iris in the two eyes.

Premature graying of hair · Very frequent (99-80%)

Development of gray hair at a younger than normal age.

Prominent nasal bridge · Very frequent (99-80%)

Anterior positioning of the nasal root in comparison to the usual positioning for age.

Synophrys · Very frequent (99-80%)

Meeting of the medial eyebrows in the midline.

Hypopigmentation of hair · Very frequent (99-80%)

Hypopigmented skin patches · Very frequent (99-80%)

Abnormal eyebrow morphology · Frequent (79-30%)

An abnormality of the eyebrow.

Abnormality of the eye · Frequent (79-30%)

Any abnormality of the eye, including location, spacing, and intraocular abnormalities.

Congenital sensorineural hearing impairment · Frequent (79-30%)

A type of hearing impairment caused by an abnormal functionality of the cochlear nerve with congenital onset.

Sensorineural hearing impairment · Frequent (79-30%)

A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.

Telecanthus · Frequent (79-30%)

Distance between the inner canthi more than two standard deviations above the mean (objective); or, apparently increased distance between the inner canthi.

Other findings in the same source

From: Orphanet

Additional reported features include Underdeveloped nasal alae (Frequent (79-30%)); White forelock (Frequent (79-30%)); Wide nasal bridge (Frequent (79-30%)); Abnormality of the gastrointestinal tract (Occasional (29-5%)); Aganglionic megacolon (Occasional (29-5%)); Aplasia/Hypoplasia of the colon (Occasional (29-5%)); Blue irides (Occasional (29-5%)); Camptodactyly (Occasional (29-5%)); Elbow contracture (Occasional (29-5%)); Intestinal obstruction (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: MedlinePlus Genetics, National Library of Medicine

Infancy; Neonatal

Inheritance in the source

From: MedlinePlus Genetics, National Library of Medicine

Autosomal dominant

Frequency and the population described

From: MedlinePlus Genetics, National Library of Medicine

Prevalence at birth: 1-9 / 1 000 000; Europe; Value and class. Prevalence at birth: 1-9 / 100 000; Netherlands; Value and class.

Understanding the inheritance label

From: MedlinePlus Genetics

An autosomal dominant pattern means that one altered copy of a relevant gene can be sufficient for the condition. Some affected people inherit the change; others have a new change without an affected parent. The precise finding, family history and condition determine what this means for relatives.

Which doctor should you see?

The suggested department for discussing Waardenburg syndrome is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Waardenburg syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.