Dandy-Walker Syndrome
A brain malformation which can present either in isolation or in combination with a number of associated defects, Dandy Walker Syndrome (DWS) is a condition primarily affecting the cerebellum which offers a very variable outlook.
Main features
The brain and spine is cushioned by the cerebrospinal fluid (CSF) which flows around the whole nervous system. Ventricles are particularly important to the movement of CSF, providing space around the brain for the fluid to flow.
In DWS the cerebellum contains a malformation along with the spaces which are filled with the CSF around it. This involves an enlargement of the fourth ventricle. This channel is responsible for the flow of CSF between the spinal cord and the upper and lower areas of the brain. There is also either a total or partial absence of the cerebellar vermis and there may be the formation of cysts, typically close to the base of the skull. These manifest internally.
Cause
DWS is mostly idiopathic. Although is is primarily a congenital condition it can be acquired as a result of exposure to chemical agents, infections or other environmental factors. During pregnancy, gestational diabetes, toxoplasmosis, cytomegalovirus, rubella or Warfarin medication could be the cause for the diagnosis.
Research has indicated that in some cases there may be a familial genetic component. De novo interstitial deletions of the 3q have been noted as being a significant risk factor, and single gene malformations such as Walker-Warburg Syndrome and Meckel’s Syndrome denote a high incidence rate in sibling recurrence. Chromosomal abnormalities connected with DWS include triploidy and trisomies (more specifically, trisomies 9, 18, 13 or 21).
Despite this, the majority of cases seem to suggest DWS appears without any incidences within the family history. For couples who have had a child with DWS, the chances of recurrence in future pregnancies has been calculated as 1%, providing there is no chromosomal or Mendelian disorder. Genetic advice and counselling can be offered to those affected.
DWS can present as an isolated condition, and often does, but it can also be part of a larger collection of malformations known as PHACES:
- P = Posterior fossa defects such as Dandy Walker Malformation
- H = Haemangioma
- A = Arterial lesions of the neck and head
- C = Cardiac abnormalities (including such conditions as aortic coarctation)
- E = Eye and visual defects
- S = Sternal malformations
- ongoing skull enlargement
- poor development of motor skills such as crawling or walking
- vomiting
- irritability
- seizures and/or convulsions
- large head circumference
- abnormal breathing patterns
- features of dysfunction of the cerebellum including unsteady gait, poor muscular co-ordination and jerky eye movements
- bulge at rear of skull
- difficulty controlling nerves responsible for the neck, face and eyes
The incidence rate of all types of DWS is approximately 1:25,000-35,000 live births with a slight predisposition towards females.
More research is required to establish the cause in the majority of cases.
Signs and symptoms
In DWS, the abnormal flow or accumulation of CSF can cause very significant problems, in particular an excess of fluid in the brain ventricles. This can be the result of either the failure of the reabsorption of CSF, due to the ventricular obstruction, or excessive production of the fluid. Whatever the cause, raised intracranial pressure can result and in around 90% of individuals with DWS, hydrocephalus. This often develops postnatally rather than in utero.
All of these factors combine to prevent the cerebellum from developing as it should, which leads to a large and noticeable cyst forming at the rear of the brain.
The raised intracranial pressure (ICP) can produce a number of different symptoms which in infants present as:
In slightly older children, ICP can be identified by:
Children of any age diagnosed with DWS may suffer from spastic paraplegia or seizures.
Diagnosis
The condition is typically diagnosed antenatally when an ultrasound scan may be able to identify the cysts which are characteristic of DWS. Where a suspicion of DWS has arisen, an MRI scan may be arranged in order to understand the extent to which the developing brain has been affected. An alternative to the MRI may be a CT scan.
For those cases where the diagnosis is not confirmed antenatally, symptoms typically present within the first 12 months, leading to the identification of DWS.
However, in a small percentage, 10-20%, DWS does not present until either late childhood or adulthood. In these cases, the features may be different with ICP symptoms dominating the presentation. Cerebellar dysfunction may also be more evident with greater unsteadiness, abnormal eye movements and poor co-ordination present.
DWS is not always symptomatic; some individual may have no presenting features and may remain that way. In these cases, a diagnosis is typically only reached because imaging of the brain is being carried out for an unrelated condition where DWS is identified incidentally.
Associated conditions and treatment
Although the condition means a congenital defect is present which cannot be corrected, treatment is focussed on managing the complications and any associated problems.
Where excess fluid is an issue, a shunt may be inserted to aid drainage. This has the effect of reducing the ICP and helping to minimise swelling. This shunt can be used in either the ventricles (ventriculoperitoneal) or on the cyst (cystoperitoneal) or alternatively, on both. Endoscopic procedures may be considered as an alternative.
Other treatments offered depend on the extent of the complications or associated conditions or the severity of the abnormalities within the central nervous system. Some of the concurrent issues seen within the CNS could include ectopic brain tissue, dysgenesis of the corps callosum, neural tube defects and holoprosencephaly.
Elsewhere in the body, some of the issues which can arise include urogenital defects, syndactyly, polydactyly, heart malformations and abnormal features on the face.
Prognosis
Providing the necessary treatment is provided as and when required, the outlook for children affected by DWS can be good.
Approximately half will go on to be affected by a developmental delay while many will have an entirely normal cognitive development. The potential impairment of intellectual function can be difficult to predict as even in those cases where the hydrocephalus is treated early and effectively, there may not be a full recovery.
The overall prognosis of those affected by DWS ultimately depends on any co-morbid conditions and the severity of the syndrome itself.
Mortality is substantially higher amongst children with DWS, approximately ten times higher. However, the use of shunt and drainage procedures has had a significant impact, slashing mortality rates by half.