February 12, 2008
Years published: 1986, 1989, 1991, 1994, 1995, 1999, 2007, 2008
NORD gratefully acknowledges William B. Dobyns, MD, Professor of Human Genetics, Neurology and Pediatrics at the Department of Human Genetics of the University of Chicago, for assistance in the preparation of this report.
Dandy-Walker malformation (DWM) is a brain malformation that occurs during embryonic development of the cerebellum and 4th ventricle. The cerebellum is the area of the brain that helps coordinate movement, and is also involved with cognition and behavior. The 4th ventricle is a space around the cerebellum that channels fluid from inside to around the outside of the brain. DWM is characterized by underdevelopment (small size and abnormal position) of the middle part of the cerebellum known as the cerebellar vermis, cystic enlargement of the 4th ventricle and enlargement of the base of the skull (posterior fossa). DWM is sometimes (20-80%) associated with hydrocephalus, in which blockage of the normal flow of spinal fluid leads to excessive amounts of fluid accumulating in and around the brain. This leads to abnormally high pressure within the skull and swelling of the head, and can lead to neurological impairment.
The symptoms of Dandy Walker syndrome typically include developmental delay, low tone (hypotonia) or later high tone (spasticity), poor coordination and balance (ataxia), and sometimes enlarged head circumference and increased pressure within the skull due to hydrocephalus. Mental retardation occurs in fewer than half, most often in those with severe hydrocephalus, chromosome abnormalities or other birth defects. Seizures occur in 15-30% of those affected. Respiratory control centers in the brainstem are sometimes affected and can lead to respiratory failure, again most likely with severe hydrocephalus. The age at diagnosis varies depending on the onset and severity of hydrocephalus, and presence of other birth defects or medical problems.
The clinical presentation and imaging features of DWM overlap with isolated cerebellar vermis hypoplasia (CVH) and mega-cisterna magna (MCM), and these have been classified together as a spectrum of anomalies known as the Dandy-Walker complex. But emerging experience suggests that this is an oversimplification that may contribute to inaccurate information about both outcome and genetic risks. CVH consists of a small vermis without the striking upward rotation of the vermis, cystic enlargement of the 4th ventricle or enlarged posterior fossa that characterize typical DWM. This malformation has also been called the “Dandy-Walker variant”, a potentially confusing term. The available data regarding outcome is limited, but this is often more severe than in typical DWM. MCM is characterized by an enlarged posterior fossa despite normal or very nearly normal size of the cerebellum. The increased size is associated with an enlarged fluid collection beneath and often behind the cerebellum. This has been reported as a normal variant, but emerging experience suggests that it may be associated with developmental disabilities although these are usually less severe than seen in DWM or CVH. The uncertainty in prognosis for these three overlapping conditions is accounted for by both natural variability and difficulty in distinguishing them.
DWM results from defects in early embryonic development of the cerebellum and surrounding structures. A few patients have chromosome abnormalities including deletion of chromosome 3q24.3 (the location of the first DWM genes, known as ZIC1 and ZIC4), 6p25 or 13q32.2-q33.2, or duplication of 9p. In the remainder, it is probably due to other more complex genetic and perhaps environmental factors (teratogens) as the recurrence risk in siblings less than 5%. A few examples of affected siblings with isolated Dandy-Walker malformation have been reported, suggesting autosomal recessive or X-linked inheritance, but most of these are probably CVH and not typical DWM. In these families, the recurrence risk is higher, up to 25%. DWM may also occur as part of a genetic syndrome that includes multiple birth defects, such as the PHACES syndrome of facial hemangioma, heart and sternal defects and DWM. Many other syndromes and chromosome abnormalities have been reported with DWM, but most of these appear to have CVH rather than typical DWM.
The frequency of Dandy Walker malformation in the US is approximately 1 per 25,000 -35,000 live births and affects more females than males.
Dandy Walker malformation is diagnosed with the use of ultrasound, CT and MRI. Prenatal diagnosis of Dandy-Walker malformation is sometimes made by ultrasound or fetal MRI.
Hydrocephalus associated with Dandy Walker syndrome is treated with surgery to insert a tube to redirect the fluid that surrounds the brain and to assist fluid drainage into other parts of the body that can absorb the fluid.
A supportive team approach for children with Dandy-Waller malformation is often warranted and may include special education, physical therapy and other medical, social or vocational services.
Genetic counseling is recommended for families that have a child with Dandy Walker malformation.
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FROM THE INTERNET
Incesu L and Khosia A. Dandy-Walker Malformation. eMedicine; last updated 10/31/03.
McKusick VA ed. Online Mendelian Inheritance in Man (OMIM). Baltimore, MD: The Johns Hopkins University; Entry No. 220200; Last updated 2/22/05.
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