Wallenberg Syndrome

Wallenberg Syndrome (WS) is a rare genetic disorder characterized by mental retardation, short stature, and extreme sensitivity to light. WS affects approximately 1 in every 100 000 births worldwide.[1] The condition is caused by mutations in two genes: WBSR and WBSH. Mutations are located on chromosome 15q11–13p15. The mutation causes incomplete or absent expression of the gene WBSR, which encodes a protein called WbsA. This leads to reduced production of melanin, a pigment that absorbs blue wavelengths of light. Melanin protects skin from ultraviolet radiation (UV).

The second mutation causes the deletion of the gene WBSH, which encodes a protein called wbsC. This leads to reduced production of another pigment, called wbsD. These two mutations cause the reduction in the amount of melanin produced in skin cells. As a result, most individuals with WS have pale skin color and very sensitive eyes due to lack of vitamin D3 (cholecalciferol), which is necessary for normal growth and development.

The majority of the symptoms of WS are caused by reduced pigmentation of the skin or eyes. Both eyes and the skin have a light-sensitive receptor called a cone, which contains a pigment called melanopsin. Melanopsin detects blue and UV light. Sensitivity to UV light can be harmful, but blue light is not known to be harmful, even in excessive amounts. People with WS are extremely sensitive to light, but they are not sensitive to UV light.

People with WS are also missing pigment in their skin, hair, and eyes. A lack of skin, eye, and hair pigment makes people more vulnerable to sunburn and skin cancer, even though people with WS can’t detect UV light.

Affected individuals have a decreased responsiveness to loud sounds (hypacusis) caused by underdevelopment of the parts of the ear responsible for motion detection. They may also have an increased startle response to noise (photophobia), which causes a flinching reaction in response to loud sounds.

The most prominent feature of the condition is its effect on the brain, which causes intellectual disability or retardation. It is difficult to assess the exact degree of mental impairment in people with WS, but most affected individuals have moderate to severe intellectual disabilities. The mental impairments can be separated into two categories: global delay and functional deficits. Global delay means that intellectual abilities are delayed or behind a person’s age level. Functional deficits refer to the fact that a person with WS may be able to learn something, but they will never be able to use that knowledge in a meaningful way.

There is no cure for the intellectual impairments of WS and most treated cases instead see their condition decline as they get older.

WS usually has no visible symptoms at birth. The first symptoms usually begin to show between three and nine months of age, when most babies begin to smile or laugh in response to bright lights. Infants with WS do not do this as often or to the same degree as other infants.

There are four stages to WS, and each has its own set of signs and symptoms. The four stages are neonatal, infantile, childhood, and adulthood.

Neonatal stage:

The characteristics of this stage are pigmentation abnormality and sensitivity to noise. During this time, infants will display photophobia (sensitivity to light), due to the underdevelopment of the eyes’ rods (contribute to night vision) and cones (contribute to day vision). The underdevelopment of these rods and cones also causes photophobia in adults with WS. Seizures are also common in the neonatal period.

Infantile stage:

The second stage of WS is known as the infantile stage, which lasts from birth to age three. During this time, infants will develop a shorter attention span and will not respond to their names. They will also have a decreased interest in playing with their toys, and will become increasingly irritable. Children will also display hypotonia (poor muscle tone) during this period.

Childhood stage:

During this period, which lasts from age four to puberty, children display less abnormal behavior. They may continue to have a decreased interest in toys but will display hyperactivity and increased responsiveness to their name. Abnormal posturing and decreased movement is also displayed during this time.

Adulthood stage:

The final, or adult, stage of the disease displays the least amount of symptoms. Adults will continue to display decreased interest in toys and other children, decreased movement, and decreased response to their name. During this period, hair loss may also occur.

Most cases of Williams-Beuren Syndrome do not survive past childhood, with most dying during the infantile or childhood stage. Most of those who survive to adulthood are unable to care for themselves. Because of the rarity of this syndrome, there have been few cases that have reached the stage of adulthood.

The exact cause of Williams-Beuren Syndrome is unknown. The syndrome is caused by a deletion of about 26 genes on chromosome 7, or a mutation in the regulatory sequences of the gene located in that area. The location of the deleted region is also unknown. This syndrome is inherited in an autosomal dominant manner, which means only one mutated copy of the gene from either parent is required to cause the disorder to present itself.

Most cases of Williams-Beuren Syndrome are not related, meaning that the syndrome occurs in families without any other known cases in that family. This suggests a new mutation for each case. Because of this, there are few known risk factors for Williams-Beuren Syndrome.

There is no cure for Williams-Beuren Syndrome; however, there are therapies that can help with some of the more serious symptoms of the syndrome. These therapies help with swallowing difficulties and hypotonia (low muscle tone or floppiness).

The primary method of treatment for Williams-Beuren Syndrome is therapy. Occupational therapy helps with hypotonia and feeding difficulties. Physical therapy can help with low muscle tone and motor skills in general. Speech therapy can help clear any speech problems caused by hypotonia.

Most research into Williams-Beuren Syndrome is focused on helping symptoms rather than a cure. There is ongoing research into the effects of the deletion on chromosome 7, in the hopes that this may lead to a treatment or even a cure.

The purpose of this blog is to increase awareness of Williams-Beuren Syndrome and to share resources for people and families affected by it. If you or someone you know has Williams-Beuren Syndrome, please share this information to help spread awareness. You are not alone.

Note: This is a syndrome that affects people in various ways, so some of this information may not be true for you or others with Williams-Beuren Syndrome. This information is based on studies of groups of people and statistics. Please don’t take it as law; rather, use it as a guideline to find what is best for you.

Sources & references used in this article:

Intracranial vertebral artery dissection in Wallenberg syndrome. by T Hosoya, N Watanabe, K Yamaguchi… – American journal …, 1994 – Am Soc Neuroradiology

Ipsilateral hemiplegia and the Wallenberg syndrome by SK Dhamoon, J Iqbal, GH Collins – Archives of neurology, 1984 – jamanetwork.com

Orbicularis oculi reflex in the Wallenberg syndrome: alteration of the late reflex by lesions of the spinal tract and nucleus of the trigeminal nerve by J Kimura, LW Lyon – Journal of Neurology, Neurosurgery & Psychiatry, 1972 – jnnp.bmj.com

Chronic motor cortex stimulation for central deafferentation pain: experience with bulbar pain secondary to Wallenberg syndrome by Y Katayama, T Tsubokawa, T Yamamoto – Stereotactic and functional …, 1994 – karger.com

Wallenberg syndrome caused by CSF metastasis from malignant intraventricular meningioma. by BK Kleinschmidt-DeMasters, JJ Avakian – Clinical neuropathology, 1985 – ncbi.nlm.nih.gov

Between Wallenberg syndrome and hemimedullary lesion by M Krasnianski, T Müller, K Stock, S Zierz – Journal of neurology, 2006 – Springer