Waardenburg Syndrome – Pictures, Symptoms, Diagnosis, Treatment

What is Waardenburg Syndrome?

First discovered in 1948, Waardenburg syndrome is a rare autosomal dominant condition characterized by craniofacial or interocular anomalies (facial and head structure deformities), bilateral deafness (deafness in both ears), and hypopigmentation of the skin, eyes and hair.

Epidemiology of Waardenburg Syndrome (WS)

Waardenburg syndrome affects both males and females of all races. Since this is an autosomal dominant condition, a parent possessing the WS gene will pass on the condition to the child 50% of the time. it is estimated that this syndrome affects 1 out of 42,000 births, with 2-62% of them presenting deafness.

Waardenburg Syndrome Characteristics and Clinical Features

This syndrome has the following characteristics and clinical features:
Craniofacial anomalies – Abnormalities in the structure of the skull and face can be seen. Individuals with this condition can have wide set eyes due to a broad nasal root, a condition called dystopia canthorum.
Hypopigmented eyes, hair and skin – White pigmentations can be present in the skin, a lock of gray or white hair growing prematurely can be seen, and a pale color of eyes is noted and the color can be different in both eyes. One iris can be strikingly blue, while the other brown or gray.

• Deafness that occurs unilaterally or bilaterally
• Musculoskeletal anomalies may be present
• Aganglionic megacolon may also be noted in some forms of the condition.

Causes

Gene mutation is the primary cause of this syndrome. Mutation in the PAX gene is seen in most common forms. Mutations in the PAX gene causes changes in the neural crest. The mutation in the PAX gene causes impaired activity of the neural crest, which is supposedly responsible for the melanocytes, craniofacial bone and cartilage, and smooth muscles.
Affectation of the PAX gene explains the involvement of symptoms we commonly see in Waardenburg syndrome; which are hypopigmentation, craniofacial anomalies and muscle deformities.

Signs and Symptoms

• Deafness (bilateral or unilateral)
• White patches in the skin
• Premature graying of the hair
• Presence of white locks of hair
• Heterochromia- the color of the eyes do not match
• Wide set eyes (hypertelorism)
• A prominent square jaw
• Eyebrows are bushy and seem to merge as one
• Displacement of the inner canthus (inner part of the eye) laterally
• Abnormalities in the eyelid
• Striking blue sapphire eyes in non-Caucasian individuals
• Defects in the muscles, bones and joints
• Presence of a cleft lip (happens rarely)
• Constipation
• Abdominal pain or swelling

Waardenburg Gene Mutations

Mutation of the PAX gene is seen in most cases of Waardenburg syndrome; however, other forms of this syndrome also signify a particular gene mutation. With the advent of medical technology and genetics, tracing the particular gene causing the subtype of Waardenbrug syndrome is now possible.

Diagnosis

Waardenburg syndrome (WS) is diagnosed through the following procedures:

Clinical assessment of the physical features

WS can be diagnosed through the presence of the clinical features. Although not all cases of Waardenburg syndrome presents all the clinical features, there are signs and symptoms that are present in all types. Any of these would signal the clinician that the condition might be Waardenburg syndrome.

Family history

A review of the family history is also used in diagnosing the condition. The review usually covers three generations.  Example: a grandparent may exhibit a white forelock of hair while young or a parent might have eyes of different colors. Family review is very important in diagnosing Waardenburg syndrome; this helps the clinician rule out other disease conditions.

Gene isolation

This is a procedure that confirms the presence of the syndrome.  Genetic studies and gene isolation identify the gene affected and the location of the mutation.

Radiologic examination

This is done to evaluate the hearing impairment in some forms of Waardenburg syndrome. Tomography can be used to describe the hearing impairment and help the clinician rule out any other anomalies.

Treatment

As of now, there is no known cure or treatment of Waardenburg syndrome. The goal of management for this syndrome is to treat or manage some of its symptoms. Treatment is usually focused on deafness, if severe. Other abnormalities associated with the condition are managed symptomatically.

Management of Deafness or Hearing Impairment

Once diagnosed with Waardenburg syndrome, the child or infant must begin with programs to manage the hearing impairment. These include:

• Use of hearing aids to amplify sounds, making them clearer and defined. This may be recommended to individuals with hearing impairments that are partial.
• Cochlear implants that can be surgically implanted to aid in hearing, but the probability and success of this procedure must be carefully discussed with a physician.
• Sign language can be taught to individuals with Waardenburg syndrome. Sign language helps them communicate with the hearing and non-hearing community.

Management of Aganglionic Megacolon

In some types of Waardenburg syndrome (type IV particularly), aganglionic megacolon is present. This condition can pose significant problems for the child. Agaglionic megacolon can be managed through the following:

• Creation of a colostomy, where the large intestine is cut and an opening is sutured to the abdomen
• Pull through procedure when the child grows older
• Laxatives to manage constipation
• High fiber diet to cleanse the colon and to prevent constipation

Physical therapy for Musculoskeletal Abnormalities

Physical therapy can somewhat manage the musculoskeletal abnormalities present with the disease, it can improve the child’s gait, walking and mobility, but it does not treat the abnormalities or the disease per se. Some individuals with Waardenburg syndrome present themselves with joint problems; this can be managed with physical therapy exercises and the use of supportive devices.

Other supportive measures

Waardenburg syndrome is a difficult condition to deal with. Aside from the fact that no treatment or cure is available, the condition itself can present difficult impacts for both the patient and the family. Supportive measures are made available to aid this problem.

Enhance Parental Coping

A pressing issue in the management of this condition is its impact on parents. Parents play a key role in the management of Waardenburg syndrome. Since this condition has no cure, living a quality life is crucial. To enhance parental coping, the following measures can be employed.

• Verbalization of one’s feelings about the condition to reduce stress or anxiety.
• Relaxation techniques.
• Use of journals or diaries if verbalization is not possible.
• Setting or rearranging priorities.
• Collection of useful information or notes about the disease.

Finding support systems or organizations

Other support systems can also help both the patient and the parents deal with the condition. Support systems or organization whose members have the same condition can be therapeutic. This way, both parents and child do not feel left out.

Life Expectancy

Individuals affected with Waardenburg syndrome have a normal life expectancy. Meaning they can live up to 60 to 70 years old. However their life expectancy can be affected by the underlying disease conditions that come with Waardenburg syndrome.

Complications

Complications may include:

• Joint and muscle deformities
• Immobility
• Mental retardation
• Inability to speak or muteness
• Depression
• Social isolation
• Seizures (if the nervous system is affected)
• Cataracts
• Possible psychiatric disorders
• Absorption problems and malnutrition

Prevention

Genetic Counseling

Waardenburg syndrome can be prevented by genetic counseling. In genetic counseling, a rigorous history of the familial diseases are taken. This helps the clinician identify signs and symptoms of an inherited disease (like Waardenburg syndrome) in the family.

To confirm if such risk is present in the family, genetic tests can identify the members who possess the mutated gene and are at risk of passing it to a child.

The diagnosis of Waardenburg syndrome can be devastating to both child and his/her parents, but proper knowledge about the disease and the different options available to manage it, gives a sense of empowerment to face the condition head on.

Pictures

Source – Adam, inc

Hypopigmented patches on hair

Pale color eyes in Waardenburg Syndrome

Proofreaded for correctness on 15/10/2015 by Minna