Waardenburg Syndrome

Waardenburg syndrome is a rare condition characterized by a combination of hearing loss and changes in pigmentation of the skin, eyes, and hair. It is a genetic condition, which means it is caused by inheriting certain genes. The condition is categorized into four types (I, II, III, and IV) according to their presentation.

The condition is named after Petrus Johannes Waardenburg, a Dutch ophthalmologist who first observed the condition in 1951. Dr. Waardenburg described symptoms now categorized as Waardenburg syndrome type I. The Swiss ophthalmologist and geneticist David Klein also made very important contributions to better understand the condition. Both doctors observed and described cases of deaf and mute children with unusual eye features and partial albinism of the hair and body. Over the years, other forms of the condition have been identified.

A person with Waardenburg syndrome may have whitish locks of hair on the front of their heads, noticeable facial asymmetry, white-colored eyelashes, and wide-set inner eye corners. Cases often present varying symptoms.

Unlike many congenital or genetic conditions, most people with Waardenburg syndrome have no cognitive defects or mental impairment. For reasons still unknown, Waardenburg syndrome also occurs in ferrets.

There are still many things doctors do not understand about Waardenburg syndrome, partly because it is so rare. Recent estimates show that its prevalence is only 1.19–2.08 per 10,000 persons. The condition affects all races and sexes.

Being a heritable condition, Waardenburg syndrome is not contagious. It is not caused by chemicals or infection by viruses or bacteria. There is no cure for the condition, but most patients do not have any mental issues that prevent them from living a normal life.

Waardenburg syndrome can have many symptoms, which often vary among patients. Some publications classify the condition according to its present symptoms. Waardenburg syndrome has the following classic symptoms:

• Distinctive facial abnormalities, such as asymmetry
• Unusual pigmentation of the hair, eyes, or skin
• Deafness at birth

Waardenburg syndrome types and symptoms are as follows:

Type I: Characterized by defects in the eyes and hearing:

• Vision problems
• Reduced hearing or complete hearing loss
• Heterochromia, or different color in the iris
• Patches of lighter skin color (hypopigmentation)
• Frequent lacrimation or tearing
• Widely-spaced eyes
• Thick, white eyebrows
• White eyelashes

Type II: Notable for having problems in the internal organs, such as the kidneys, pulmonary artery, and large intestine:

• Premature appearance of gray hair
• Heterochromia of the iris
• Hypopigmented skin patches
• Mild to total deafness
• White or grayed lock of hair on the forehead
• Kidney problems
• Pulmonary artery abnormalities
• Hirschsprung's disease (aganglionic megacolon), a condition where parts of the large intestine do not function due to a lack of nerve cells
• Ptosis, or drooping eyelid
• Telecanthus, or increased distance between the eyes

Type III: Patients with type III Waardenburg syndrome may have defects in the face and fingers:

• Blepharophimosis, or narrowed eye opening
• Syndactyly of the skin of fingers, i.e., fusion of the skin between the fingers (fortunately, in this case, only the skin is fused and not the internal parts of the fingers)
• Downward-slanted eye openings
• Hearing problems
• Stiffness of the joints
• Microcephaly, or too small head
• Narrowed nose bridge
• Synostosis of the carpal bones, or fusion of joints in the fingers
• Tented upper lip vermillion, or the unusual “tenting” of the upper lip
• Unusually thick eyebrows

Type IV: Type IV may be more serious than the other types of Waardenburg syndrome in terms of symptoms. It is characterized by several problems in the eyes and digestive system:

• Vision issues due to defects in the macula (the area near the retina where vision is sharpest)
• Hirschsprung's disease
• Constipation
• Hearing impairment
• Intestinal obstruction
• Premature gray hair
• White eyebrows and eyelashes
• A white lock of hair on the forehead

Some patients with Waardenburg syndrome also have other health problems. Some have Hirschsprung's disease, a condition that makes babies unable to pass poop, which can lead to life-threatening issues. Some have abnormally-high blood pressure in the pulmonary artery. The pulmonary artery supplies blood from the heart directly to the lungs, and elevated blood pressure readings mean the lungs are becoming congested, which can result in breathing and oxygenation issues.

Many signs and symptoms of Waardenburg syndrome are similar to other conditions. Areas of different skin pigmentation might be mistaken for vitiligo, and deafness could be caused by familial deafness. Symptoms can also be caused by Vogt-Koyanagi-Harada syndrome, which is also characterized by the appearance of white patches in the hair, and whitening of eyelashes and eyebrows.

The cause of Waardenburg syndrome is inheriting certain mutated genes. According to studies, each type of Waardenburg is caused by different mutated genes.

Type I and type III are usually caused by the mutated gene PAX3, and patients with this type often have deletions, shifts, splice sits, and other abnormalities in their chromosomes. Type II is caused by the MITF gene, and patients present abnormalities in their chromosomes. The genes that cause type IV are not completely clear, but experiments show that the genes EDNRB, EDN3, and SOX10 could be the culprits; these genes are also suspected to cause rare cases of Hirschsprung’s disease.

Gene mutations that cause type I, II, and III Waardenburg syndrome are autosomal dominant, which means that the odds of having the condition is one in four if one of the parents possesses the carrier gene. However, there is some evidence that these mutations occur sporadically.

Waardenburg syndrome can be diagnosed shortly after birth or in early childhood, and some are diagnosed at a later age. Doctors diagnose it after a physical examination and assessment of family history. This may mean that you have to make several visits to the doctor’s clinic.

The diagnosis for the condition often starts when parents seek treatment for vision, hearing, and speech problems in their babies. The doctor will assess the signs and symptoms. Doctors often give particular focus to the eyes. The doctor may measure the dimensions of the eye using a caliper and use an ophthalmoscope to examine the iris, cornea, and retina to confirm heterochromia. The doctor may measure hearing abilities using audiometry.

In addition, your doctor may recommend a genetic test to determine if you or your child carries the genes associated with Waardenburg syndrome. In a genetic test, you will have to give a sample of your blood, hair, skin, or other tissue, which will be examined for mutations or other abnormal genes.

To check for problems in the bowels or intestines, the doctor may perform a test called bowel transit time. In this procedure, the doctor will measure how long food travels through the bowels. Slow bowel transit times may indicate a stricture or blockage in the intestines, which is indicative of Hirschsprung’s disease. It is often performed in young children.

If Hirschsprung’s disease is present or other suspected problems in the intestines, the doctor may recommend a colon biopsy. This procedure involves gathering a tissue sample from the intestines, usually through the use of an endoscope inserted into the rectum. A doctor called a pathologist will examine the extracted tissue for abnormalities, such as a lack of nerve cells.

There is no set procedure to diagnose Waardenburg syndrome. The condition is diagnosed by examining the signs and symptoms.

There is no standard treatment for Waardenburg syndrome. Intervention is focused on addressing the signs and symptoms.

For children, the goal is to preserve hearing and treat any conditions in the intestines and kidneys. Hearing is given primary importance because of its involvement in speech and learning development. The doctor will assess hearing and will continue to monitor it throughout treatment. Hearing is essential for language, communication, and cognitive development in a child. If there is any hearing impairment, the doctor will prescribe a hearing aid.

In addition, the doctor may prescribe a special diet and a number of medicines to prevent constipation. For children, diet is centered on fresh, whole fruits and veggies, plus lots of water. Hypopigmented skin has less protection against ultraviolet rays from the sun, so you must protect these areas by wearing black clothing or using an umbrella outdoors.

In case of kidney problems, the doctor may recommend surgery. If pulmonary hypertension is present, the doctor will assess the possible cause and prescribe treatments to avoid damage to the lungs. For example, the patient may be given oxygen to ensure proper oxygenation of the blood, and blood thinners so blood flows easily in the lungs.

If the patient presents syndactyly, the doctor may prescribe surgery to correct the condition. The procedure is simple and uncomplicated. If there is fusion of the joints in the fingers, the doctor may prescribe physical therapy.

There is no evidence that Waardenburg syndrome causes severe deficits in mental function or cognition. If there are any, the doctor may refer the child to a speech pathologist or therapist. Note that school-age children with Waardenburg syndrome usually do not have severe mental deficits and are capable of going to and performing well in conventional schools.

Some children may have speech and learning difficulties because they grew up deaf or with some degree of hearing loss. If hearing issues are addressed early in childhood, patients with Waardenburg syndrome are able to live a normal life.

If you have a close relative with Waardenburg syndrome, you can go to your doctor for genetic counseling. In genetic counseling, a doctor will give you information about genetic disorders; the doctor will explain what genes play a role in the condition and the likelihood of passing it to your children, or having children that are carriers of the gene.

The main reason for genetic counseling is to understand the nature, inheritance, and implications of heritable disorders. This way, you have information you can use to make choices.

If you have Waardenburg syndrome and would like to start a family, you need to have genetic counseling first. The important thing is to receive information from a genetics professional that will give you sound medical advice.

Some people with Waardenburg syndrome have hearing difficulties. Fortunately, the availability of hearing aids enables deaf individuals to have normal hearing and live a normal life.

For hypopigmentation, you can use makeup to hide the off-colored skin. Choose makeups that are gentle and have UV-blocking properties. In addition, you can use hair colorants to hide white or graying hair. If you have brittle hair, choose non-permanent hair colors that are applied before going out of the house and rinsed at the end of the day. Such colors are gentle on the hair and scalp and are less likely to cause irritation.

For facial asymmetry, you can try using glasses. In addition, wearing dark-colored eyeglasses may help hide excess tearing of the eyes.

If you have eye issues, make sure to adopt proper eye-care practices. This includes not staring at a fixed spot for too long, which often happens when you use a computer or smart phone. Do not rub your eyes. Make sure to dab excess tears from the eye so secretions do not build up and cause irritation.

For children, the doctor may recommend a speech pathologist or therapist so the child’s learning and development are kept on track as treatment progresses. Lastly, plan and stick to regular checkups to monitor hearing and vision, as well as check for any developing problems in the lungs, intestines, or kidneys. On a general note, Waardenburg syndrome symptoms do not cause severe disability or mental impairment, especially when symptoms are addressed early.