Background

The brain and spinal cord are covered by three membranes, collectively known as the meninges. ⁸ There is a space between the first membrane that covers the nervous tissue and the second membrane. This is known as the subarachnoid space. It is filled with a fluid known as cerebrospinal fluid (CSF). CSF acts as a support structure for the brain and spinal cord, and normally allows a uniform pressure to be maintained on the nervous tissue structure. The same fluid is found in hollow cavities or ventricles within each side of the brain and the part of the brain that joins the base to the spinal cord (brain stem).

There are four ventricles,⁸ the two in the hemispheres are termed the lateral ventricles, the two in the mid brain, extending down through the brain stem into the central channel running through the middle of the spinal cord, are termed the third and fourth ventricles.

CSF is secreted by cells in all the ventricles.⁸ All four ventricles are in communication with one another and also communicate with the subarachnoid space (the compartment within the spinal column, which contains the cerebrospinal fluid and the large blood vessels that supply the brain and spinal cord) via passageways out of the fourth ventricle.

What is Dandy-Walker syndrome?

Dandy-Walker syndrome is a congenital brain malformation involving the cerebellum (an area at the back of the brain that controls movement) and the fluid-filled spaces around it. ¹ The main features of this syndrome are: ^{1, 4, 6}

• an enlargement of the fourth ventricle (a small channel that allows fluid to flow freely between the upper and lower areas of the brain and spinal cord)
• a partial or complete absence of the area of the brain between the two cerebellar hemispheres (cerebellar vermis) and
• cyst formation near the internal base of the skull.

An increase in the size of the fluid spaces surrounding the brain, as well as an increase in pressure may also be present.

Excessive production of CSF, or failure of reabsorption due to obstruction of the passageways out of the fourth ventricle, leads to an accumulation of fluid in the brain ventricles. ^2,8 This results in the failure of parts of the cerebellum to develop correctly. A large cyst is then visible on scans of the back of the brain.

Cause

In the majority of cases of Dandy-Walker syndrome the cause is not known, although there are a few known cases resulting from autosomal recessive genes. ⁸ Autosomal recessive means an abnormal gene on one of the autosomal chromosomes (one of the first 22 ‘non-sex’ chromosomes) from each parent. The syndrome is most often congenital (present from birth) but it can be acquired due to infection, chemical agents and other prebirth factors. ⁵ Dandy-Walker syndrome may result from chromosomal anomalies or environmental factors.³ Associated environmental factors include first trimester exposure to:

• rubella,
• cytomegalovirus (a type of herpes virus which can pass through the placenta and infect the unborn baby ¹⁰)
• toxoplasmosis (a common disease that occurs worldwide in most birds and warm-blooded mammals, including humans. It is caused by infection with toxoplasma gondii, one of the world’s most common parasites, which is contained in undercooked meat, raw meat, cat faeces and any soil or cat litter contaminated with infected cat faeces ¹¹) or
• Warfarin (an anticoagulant ¹²).

The incidence of Dandy-Walker malformation is approximately 1 in every 25,000-35,000 live births. ^{8, 13}

Hydrocephalus

Hydrocephalus is present in approximately 90% of cases of this syndrome.^2,4 Dandy-Walker syndrome causes 2-4% of all hydrocephalus cases. Cyst formation in Dandy-Walker syndrome may interfere with the body’s ability to drain CSF from the brain, resulting in hydrocephalus. The classic clinical signs of hydrocephalus in infancy result from an increase in the pressure within the skull. ⁹ The child’s head increases in circumference and becomes larger than normal for its age, with an abnormal shape, prominent veins on the forehead and a wide soft spot or fontanelle on top.

Associated brain abnormalities

There are often many associated brain abnormalities including ² :

• agenesis of the corpus callosum (a birth defect in which the structure that connects the two hemispheres of the brain, known as the the corpus callosum, is partially or completely absent) is present in 17% of cases
• occipital encephalocoele (failure of fusion of the bones at the back of the head) is present in 7% of cases
• spina bifida
• syringomyelia (cysts in the spinal cord)
• small heads and bone abnormalities of the neck (Klippel-Feil syndrome)
• other associated abnormalities including facial, ocular (eye) and cardiac.

Symptoms

The syndrome can differ greatly in its level of severity. Neurological symptoms are caused by intracranial hypertension and include headache, vomiting, fainting spells and disequilibrium. ⁵

Symptoms, which often occur in early infancy, include ^{1, 6} :

• slow motor development
• progressive enlargement of the skull.

In older children, symptoms of increased intracranial pressure include ^{1, 13} :

• irritability
• vomiting
• convulsions
• signs of cerebellar dysfunction, such as unsteadiness, lack of muscle co-ordination, or jerky movements of the eyes
• increased head circumference
• bulging at the back of the skull
• problems with the nerves that control the eyes, face and neck
• abnormal breathing patterns
• seizures (up to 15%).

Dandy-Walker syndrome can affect vision in a variety of ways. Common vision problems may include ¹³ :

• nystagmus (involuntary back and forth movement of eyes)
• cataracts
• retinal dysgenesis (abnormal formation of the retina)
• choroid coloboma (abnormal formation of the eye between the sclera, the white part of the eye, and the retina)
• vision problems due to hydrocephalus (these can include visual field defects, faulty depth perception, trouble with shape recognition, and cortical visual impairment)
• occipital encephalocele (a defect in the closure of the neural tube near the base of the skull).

Hearing loss is not a primary characteristic of Dandy-Walker syndrome, however, there may be sensorineural loss, conductive hearing loss (especially in children who also have a cleft palate), or central loss due to agenesis of the corpus callosum. ¹³

The syndrome can appear dramatically or develop unnoticed. ¹ In some cases the symptoms are occasional. It can also be asymptomatic in some people. ⁵

Treatment

Dandy Walker syndrome is generally discovered before birth, by ultrasound. Ultrasound scans may detect the Dandy-Walker syndrome cysts. ¹ An MRI is usually performed for detailed evaluation of Dandy-Walker malformation lesions, and complications after a diagnosis is suspected, using computed tomography (CT scan) and ultra-sound. MRI evaluation can be used antenatally to confirm the diagnosis and gain more detailed information.³

Treatment for individuals with Dandy-Walker syndrome generally consists of treating the associated problems. ¹ A special tube to drain off excess fluid may be placed inside the skull. This will reduce intracranial pressure and help control swelling¹. Symptoms caused by elevated intracranial pressure can be relieved by shunt drainage of cerebro-spinal fluid. ⁵ The shunt can be used for the cyst (cystoperitoneal), the ventricles (ventriculoperitoneal), or both. In smaller children with moderate hydrocephalus, cyst drainage tends to be successful. ⁵

With treatment, prognosis is generally good with a 75-100% chance of survival, but approximately 50% of cases will develop developmental delay. ²

Parents of children with Dandy-Walker syndrome may benefit from genetic counselling if they intend to have more children. ¹ Most cases are sporadic but there is 1% chance of recurrence in further pregnancies. ²

What is the prognosis?

The effect of this syndrome on intellectual development is variable, with some children having normal cognition and others never achieving normal intellectual development, even when the excess fluid build-up is treated both early and correctly.¹ Life expectancy depends on the severity of the syndrome and associated malformations. The presence of multiple congenital defects may shorten a person’s life span.

Support and information

Support and advice about Dandy-Walker syndrome is available from:

• Association for Spina Bifida and Hydrocephalus (ASBAH) - http://www.asbah.org/
• Dandy-Walker Alliance, Inc. - http://www.dandy-walker.org
• National Organization for Rare Disorders (NORD) - http://www.rarediseases.org
• Dandy Walker Yahoo Support groups http://uk.dir.groups.yahoo.com/dir/1602463485 
• Personal Website on Dandy-Walker Syndrome http://www.geocities.com/murat_yil/dandy.html

References

1. National Institute of Neurological Disorders and Stroke (NINDS) (2008) NINDS Dandy-Walker Syndrome Information Page. [online]. NINDS. Available from: http://www.ninds.nih.gov/disorders/dandywalker/ dandywalker.htm. [Accessed 4 August]
2. Contact a Family (2009) Dandy-Walker Syndrome. [online] Contact a Family. Available from: http://www.cafamily.org.uk/medicalinformation/conditions/azlistings/d13_1.html?print=all. [Accessed 4 August 2009]
3. Zimmerman, R. and Bilaniuk, L. ( 2005) Magnetic resonance evaluation of fetal ventriculomegaly-associated congenital malformations and lesions. Seminars in Fetal Neonatal Medicine,10 (5):429-43
4. Sanders, R. and T, Winter (2006) Clinical Sonography. (4 eds) [ebook] London: Lippincott Williams and Wilkins. Available from: http://books.google.co.uk/books?id=ZBNh49Dn67AC&pg=PA357&dq=dandy+walker+syndrome &lr=#v=onepage&q=dandy%20walker%20syndrome&f=false. [Accessed 5 august 2009]
5. Hynd, G., Morgan, A. And Vaughn, M. (2001) Malformations. In Antunovic, V., Dragutinovic, G., Levic , Z. And Samardzic, M., eds, 2001. Magnetic Resonance in the diagnosis of C.N.S Disorders. CIC Edizioni, pp 27-28
6. Epstein, M. And Johanson, C. (1987) The Dandy Walker Syndrome. In Myrianthopoulos, N., Vinken, P., Bruyn, G. and Klawans, H., eds, 1987. Handbook of Clinical Neurology: Malformations v.50, Elsevier Science Ltd, Chapter 18
7. Imataka G, Yamanouchi H, Arisaka O. (2007) Dandy-Walker syndrome and chromosomal abnormalities. Congenital Anomaly (Kyoto), 47(4):113-8
8. Lavanya T, Cohen M, Gandhi SV, Farrell T, Whitby EH. (2008) A case of a Dandy-Walker variant: the importance of a multidisciplinary team approach using complementary techniques to obtain accurate diagnostic information. British Journal Radiology, 81(970):e242-5
9. Netdoctor (2006) Dandy-Walker Syndrome. [online]. Netdoctor. Available from: http://www.netdoctor.co.uk/ ate/childrenshealth/200255.html. [Accessed 5 August 2009]
10. BBC Health (2008) Cytomegalovirus. [online]. BBC. Available from: http://www.bbc.co.uk/health/conditions/ cmv1.shtml. [Accessed 5 August 2009]
11. NHS (2007) Toxoplasmosis. [online]. NHS. Available from: http://www.nhs.uk/Conditions/Toxoplasmosis/Pages/ Introduction.aspx. [Accessed 5 August 2009]
12. BBC (2008) Warfarin. [online[. BBC. Available from: http://www.bbc.co.uk/health/ask_the_doctor/ warfarin.shtml. [Accessed 5 August 2009]
13. Colorado Department of Education (2009) Fact Sheet: Dandy Walker Syndrome. [online]. Colorado Department of Education. Available from: http://www.cde.state.co.us/cdesped/download/pdf/blv- DandyWalkerSyndrome.pdf. [Accessed 5 August 2009]

This information is not meant to replace the advice of any physician or qualified health professional. The information provided by Cerebra is for information purposes only and is not a substitute for medical advice or treatment for any medical condition. You should promptly seekprofessional medical assistance if you have concerns regarding any health issue.