Getting to Know Waardenburg Syndrome, a Rare and Miraculous Genetic Disorder

Have you ever seen a child with different colored eyeballs ? Or even a child with a patch of white hair like gray hair? It could be that this magical condition is known by the medical term Waardenburg syndrome.

Waardenburg syndrome affects about 1 in 40,000 people. This condition is classified as a rare genetic disorder. So, can this condition affect a child’s health? Read more information below.

Definition of Waardenburg Syndrome

Quoted from Medline Plus , Waardenburg syndrome (WS) is a group of conditions that are inherited through families.

This syndrome involves deafness and pale skin, hair, and eye color. This genetic disorder is visible at birth (congenital).

The range and severity of symptoms and associated findings can vary greatly from case to case. 

WS syndrome is a group of genetic conditions that can cause hearing loss and changes in color (pigmentation) of the hair, skin, and eyes.

Although most people with this syndrome have normal hearing, moderate to severe hearing loss may occur in one or both ears.

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 patches of white hair or premature graying of hair) is another common sign of the condition.

The characteristics of Waardenburg syndrome vary among affected individuals, even among people in the same family. Key features often include:

• characteristic facial abnormalities; 
• markedly reduced coloring (pigmentation) of the hair, skin, and/or irises of both eyes (irises); 
• congenital deafness. Some affected individuals may also have hearing loss due to abnormalities in the inner ear (sensorineural deafness).
• Some affected individuals may have an unusually wide nasal bridge due to lateral displacement of the inner corners (canthi) of the eyes (dystopia canthorum). 
• the presence of a tuft of white hair growing on the forehead (white crest); 
• premature graying or whitening of hair;
• differences in color in the two irises or in different areas of the same iris (heterochromia irides); and/or patchiness,
• abnormally lightened (depigmented) areas of skin (leukoderma). 

Symptoms of Waardenburg Syndrome According to Type

Common symptoms may include:

• Cleft lip (rare)
• Constipation
• Deafness (more common in type II disease)
• Very pale blue eyes or mismatched eye colors (heterochromia)
• Pale skin, hair, and eyes (partial albinism)
• Difficulty straightening the joint completely
• Possible slight decline in intellectual function
• Wide-set eyes (in type I)
• White patches in hair or early graying of hair.

However, in detail, researchers have described different types of Waardenburg syndrome (WS), based on associated symptoms and specific genetic findings.

According to the National Organization for Rare Disorders page , there are four main types of WS syndrome, namely:

Type I (WS1)

Waardenburg syndrome type I (WS1) is typically associated with a lateral displacement of the inner corner of the eye (i.e., dystopia canthorum). People with WS1 almost always have wide-set eyes.

Type II (WS2)

This type is almost not much different from WS1. In people with WS2, they do not have wide eyes, but hearing loss is more common in people with type II compared to type I.

Type III (WS3)

Another form, known as type III (WS3), has been described in which characteristic facial, eye (ocular), and hearing (auditory) abnormalities may be associated with typical malformations of the arms and hands (upper legs).

This type is often referred to as Klein-Waardenburg syndrome, or Waardenburg syndrome with upper limb anomalies. 

Bilateral deformities may include underdevelopment (hypoplasia) and abnormal shortness of the upper limbs; abnormal bending of certain finger joints in a fixed position (flexion contractures); fusion of the wrist (carpal) bones, and/or webbing or fusion (syndactyly) of certain fingers. In some cases, other skeletal abnormalities may be present, such as abnormal elevation of the shoulder blades (Sprengel deformity).

Type IV (WS4)

Type IV (also known as Waardenburg-Shah syndrome or Waardenburg-Hirschsprung disease) has the signs and symptoms of both Waardenburg syndrome and Hirschsprung disease, an intestinal disorder that causes severe constipation or intestinal obstruction.

This condition is also known as aganglionic megacolon, which is a gastrointestinal (GI) disorder characterized by the absence of certain nerve cell bodies (ganglia) in the smooth muscle walls of the large intestine (i.e., colon).

As a result, there is an absence or disruption of the involuntary rhythmic contractions that propel food through the GI tract (peristalsis). 

Associated symptoms and findings may include abnormal accumulation of stool within the colon, dilation of the colon above the affected segment (megacolon), abdominal distention (distension), vomiting, poor appetite ( anorexia ), failure to grow and gain weight at the expected rate (failure to thrive), and/or other abnormalities.

Rare cases of WS4 have been described in which affected individuals also have neurological symptoms due to abnormalities of the brain and spinal cord (central nervous system).

In such cases, additional findings include growth restriction, abnormally reduced muscle tone (hypotonia), flexion or extension of certain joints in various fixed postures (arthrogryposis), and/or other abnormalities.

Causes of Waardenburg Syndrome

Generally, this syndrome is caused by hereditary factors. However, not a few of them develop new syndromes or mutations.

In most cases, Waardenburg syndrome type I (WS1) and type II (WS2) are inherited as autosomal dominant traits (only one parent must inherit the gene) with variable penetrance and expressivity.

Some cases of Waardenburg syndrome type III (WS3) and type IV (WS4) appear to have an autosomal recessive inheritance pattern. Mutations in the EDN3, EDNRB, MITF, PAX3 and SOX10 genes cause Waardenburg syndrome.

In dominant disorders, one copy of the disease gene (received from the mother or father) will be expressed over other normal genes, potentially resulting in the disease.

The risk of transmitting the disease gene from parent to child is 50 percent for each pregnancy regardless of the sex of the resulting child.

In autosomal dominant disorders with variable penetrance and expressivity, manifestations of the disorder may not be present in all persons who inherit the altered (mutated) gene for the disease.

In those who develop symptoms, the specific characteristics manifested can vary greatly in extent and severity from case to case.

How Often Does It Happen?

Waardenburg syndrome is said to affect about 1 in 40,000 people. It accounts for 2 to 5 percent of all cases of congenital hearing loss. Types I and II are the most common forms, while types III and IV are rare.

Diagnosis

WS syndrome can be diagnosed at birth. It can also be diagnosed in early childhood (or, in some cases, later in life) based on a thorough clinical evaluation, identification of characteristic physical findings, a complete patient and family history, and various specialized studies.

For example, in those suspected of WS, the diagnostic evaluation may include the use of calipers to measure the distance between the inner corner of the eye (inner canthi), the outer corner of the eye (outer canthi), and the pupil (interpupillary distance).

A caliper is an instrument with two hinged, movable, curved arms used to measure thickness or diameter.

The researchers suggest that obtaining and evaluating a combination of these measurements, namely using a pre-determined biometric index known as the “W-index,” can sometimes be helpful in confirming the presence or absence of dystopia canthorum, a finding that may suggest WS1.

Additional diagnostic studies may be performed to help detect or characterize specific abnormalities potentially associated with WS. These studies may include:

• examination with an illuminated microscope to visualize the internal structures of the eye (slit-lamp examination), 
• special hearing (hearing) tests, 
• advanced imaging techniques, such as to evaluate inner ear abnormalities, bone defects (eg, seen in WS3), Hirschsprung disease (eg, seen in WS4), etc.

Treatment or Medication for Waardenburg Syndrome

There is no specific treatment. Symptoms are treated as needed. Treatment for WS is directed at the specific symptoms present in each individual.

Such treatment may require a coordinated effort from a team of medical professionals, such as:

• a doctor who specializes in skin disorders (dermatologist)
• eye specialist (ophthalmologist)
• hearing specialist (ENT doctor)
• a doctor who diagnoses and treats disorders of the skeleton, joints, muscles, and related tissues (orthopedist)
• a doctor who specializes in diseases of the digestive tract (Internal Medicine specialist subspecializing in Gastroenterology), speech-language pathologist, physical therapist, and/or other health care professional.

Early recognition of sensorineural hearing loss may play a critical role in ensuring prompt intervention and appropriate supportive management.

In some cases, a doctor may recommend treatment with a cochlear implant, a device in which electrodes implanted in the inner ear stimulate the auditory nerve to send impulses to the brain.

In addition, early, special instruction may be recommended to assist in speech development and certain methods (e.g., sign language, lip reading, use of communication devices, etc.) that may assist communication.

Because individuals with skin pigmentation disorders may be susceptible to sunburn and skin cancer, doctors may recommend avoiding direct sunlight, using sunscreen with a high sun protection factor (SPF), wearing sunglasses and a visor or wide-brimmed hat that helps protect from the sun.

In addition, patients may be advised to follow other appropriate measures. 

For those with reduced pigmentation of the iris, lateral displacement of the inner corner of the eye (dystopia canthorum), and/or other associated eye abnormalities, an ophthalmologist may also recommend certain supportive measures.

This may include the use of special tinted glasses or contact lenses (for example, to help reduce possible sensitivity to light), measures to help prevent or treat infections, or other preventive or therapeutic steps.

In individuals with upper extremity disorders, treatment may include physical therapy and various orthopedic techniques, potentially including surgery.

Additionally, surgery is sometimes recommended to help treat other disorders that may be associated with the disorder.

The specific surgical procedure performed will depend on the severity and location of the anatomic abnormality, associated symptoms, and other factors.

For example, for individuals affected by Hirschsprung disease, treatment may require removal of the affected area of ​​bowel and surgical “rejoining” of the healthy area of ​​bowel.

In some cases, prior to surgical correction of the condition, treatment may require creating an artificial outlet for the colon through an opening in the abdominal wall (i.e., a temporary colostomy).

Additional support services that may be beneficial to some affected individuals include special education and/or other medical, social, or employment services.

Genetic counseling will also be beneficial for affected individuals and their families. Other treatments for this disorder are symptomatic and supportive.

Special diets and medications to maintain bowel movements are also prescribed for people suffering from constipation.

That’s some information about Waardenburg syndrome. Hopefully it can be useful, Parents !

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Republished with permission from theAsianParent Indonesia