Dandy–Walker syndrome

Dandy–Walker syndrome
Classification and external resources
ICD-10	Q03.1
ICD-9	742.3
OMIM	220200
DiseasesDB	3449
eMedicine	radio/206
MeSH	D003616

Dandy–Walker syndrome (DWS), or Dandy–Walker complex, is a congenital brain malformation involving the cerebellum and the fluid filled spaces around it. A key feature of this syndrome is the partial or even complete absence of the part of the brain located between the two cerebellar hemispheres (cerebellar vermis).^[1] The Dandy–Walker complex is a genetically sporadic disorder that occurs one in every 25,000 live births, mostly in females.^[2]

Presentation

The key features of this syndrome are an enlargement of the fourth ventricle; a partial or complete absence of the cerebellar vermis, the posterior midline area of cerebellar cortex responsible for coordination of the axial musculature; 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. The syndrome can appear dramatically or develop unnoticed.

Symptoms, which often occur in early infancy, include slower motor development and progressive enlargement of the skull. In older children, symptoms of increased intracranial pressure such as irritability, vomiting and convulsions and signs of cerebellar dysfunction such as unsteadiness and lack of muscle coordination or jerky movements of the eyes may occur. Other symptoms include increased head circumference, bulging at the back of the skull, problems with the nerves that control the eyes, face and neck, and abnormal breathing patterns.

Dandy–Walker syndrome is frequently associated with disorders of other areas of the central nervous system including absence of the corpus callosum, the bundle of axons connecting the two cerebral hemispheres, and malformations of the heart, face, limbs, fingers and toes.^[1]

Prenatal diagnosis is possible with ultrasound. Because the syndrome is associated with an increased risk for fetal karyotype abnormalities, amniocentesis can be offered after prenatal diagnosis.^[3] There is a relative contraindication of taking Warfarin during pregnancy, as it is associated with an increased risk of Dandy–Walker syndrome if taken during the first trimester.^[4]

Classification

The term Dandy–Walker represents not a single entity, but several abnormalities of brain development which coexist. There are, at present, three identified types of Dandy–Walker complexes. These represent closely associated forms of the disorder: DWS malformation, DWS mega cisterna magna and DWS variant.

Malformation

The DWS malformation is the most severe presentation of the syndrome. The posterior fossa is enlarged and the tentorium is in high position. There is partial or complete agenesis of the cerebellar vermis. There is also cystic dilation of the fourth ventricle, which fills the posterior fossa. This often involves hydrocephaly and complications due to associated genetic conditions, such as Spina Bifida.

Mega cisterna magna

The second type is a mega cisterna magna. The posterior fossa is enlarged but it is secondary to an enlarged cisterna. This form is represented by a large accumulation of CSF in the cisterna magna in the posterior fossa. The cerebellar vermis and the fourth ventricle are normal.

Variant

The third type is the variant, which is less severe than the malformation. This form (or forms) represents the most wide-ranging set of symptoms and outcomes of DWS. Many patients who do not fit into the two other categories of DWS are often labeled as variant. The fourth ventricle is only mildly enlarged and there is mild enlargement of the posterior fossa. The cerebellar vermis is hypoplastic and has a variably sized cyst space. This is caused by open communication of the posteroinferior fourth ventricle and the cisterna magna through the enlarged vallecula. Patients exhibit hydrocephalus in 25% of cases and supratentorial CNS variances are uncommon, only present in 20% of cases. There is no torcular-lambdoid inversion, as usually seen in patients with the malformation. The third and lateral ventricles as well as the brain stem are normal.

Relation to other rare disorders: genetic ciliopathy

Until recently, the medical literature did not indicate a connection among many genetic disorders, both genetic syndromes and genetic diseases, that are now being found to be related. As a result of new genetic research, some of these are, in fact, highly related in their root cause despite the widely-varying set of medical symptoms that are clinically visible in the disorders. Dandy–Walker syndrome is one such disease, part of an emerging class of diseases called ciliopathies. The underlying cause may be a dysfunctional molecular mechanism in the primary cilia structures of the cell, organelles which are present in many cellular types throughout the human body. The cilia defects adversely affect "numerous critical developmental signaling pathways" essential to cellular development and thus offer a plausible hypothesis for the often multi-symptom nature of a large set of syndromes and diseases. Known ciliopathies include primary ciliary dyskinesia, Bardet-Biedl syndrome, polycystic kidney and liver disease, nephronophthisis, Alstrom syndrome, Meckel-Gruber syndrome and some forms of retinal degeneration.^[5]

Genetic associations of the condition are being investigated.^[6]

Relation to PHACES syndrome

Recent research has found that Dandy–Walker syndrome often occurs in patients with PHACES syndrome.^[7]

Treatment

Treatment for individuals with Dandy–Walker Syndrome generally consists of treating the associated problems, if needed.

A special tube (shunt) to reduce intracranial pressure may be placed inside the skull to control swelling.^[8]

Treatment may also consist of various therapies such as occupational therapy, physical therapy, speech therapy or specialized education. Services of a vision teacher may be helpful if the eyes are affected.

Parents of children with Dandy–Walker syndrome may benefit from genetic counseling if they intend to have more children.

Prognosis

The spectrum of outcomes for Dandy–Walker syndrome is diverse. Mortality statistics are often compiled by neurologists who deal with worst-case outcomes, which thus reflect a high mortality rate, or grim prognosis – both pre- and postnatal – in DWS infants.

Children with less severe symptoms may have normal intellectual development; children with severe malformation may have mental retardation. Longevity depends on the severity of the syndrome and associated malformations. The presence of multiple congenital defects may shorten life span.

Eponym

It is named for Walter Dandy and Arthur Earl Walker.^[9][10]

References

1. ^ ^{a b} National Institute of Neurological Disorders and Stroke, "NINDS Dandy–Walker Syndrome Information Page," http://www.ninds.nih.gov/disorders/dandywalker/dandywalker.htm. Last updated September 16, 2008. Last accessed July 6, 2009.
2. ^ "Report: Man with Almost No Brain Has Led Normal Life," July 25, 2007. Accessed at http://www.foxnews.com/story/0,2933,290610,00.html on July 6, 2009
3. ^ Romero R, Pilu G, Jeanty P, Ghidini A, Hobbins JL. Prenatal diagnosis of congenital anomalies. Appleton & Lange, Norwalk, 1988, pp. 30-33.
4. ^ Kaplan LC (Dec 1985). "Congenital Dandy Walker malformation associated with first trimester warfarin: A case report and literature review". Teratology 32 (3): 333–337. doi:10.1002/tera.1420320302. PMID 4082063. 
5. ^ Badano, Jose L.; Norimasa Mitsuma, Phil L. Beales, Nicholas Katsanis (September 2006). "The Ciliopathies : An Emerging Class of Human Genetic Disorders". Annual Review of Genomics and Human Genetics 7: 125–148. doi:10.1146/annurev.genom.7.080505.115610. PMID 16722803. http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.genom.7.080505.115610. Retrieved 2008-06-15. 
6. ^ Grinberg I, Northrup H, Ardinger H, Prasad C, Dobyns WB, Millen KJ (October 2004). "Heterozygous deletion of the linked genes ZIC1 and ZIC4 is involved in Dandy–Walker malformation". Nat. Genet. 36 (10): 1053–5. doi:10.1038/ng1420. PMID 15338008. 
7. ^ Metry DW, Dowd CF, Barkovich AJ, Frieden IJ (July 2001). "The many faces of PHACE syndrome". J. Pediatr. 139 (1): 117–23. doi:10.1067/mpd.2001.114880. PMID 11445804. http://linkinghub.elsevier.com/retrieve/pii/S0022-3476(01)25968-X. 
8. ^ Yüceer N, Mertol T, Arda N (2007). "Surgical treatment of 13 pediatric patients with Dandy–Walker syndrome". Pediatr Neurosurg 43 (5): 358–63. doi:10.1159/000106383. PMID 17785999. http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=000106383. 
9. ^ synd/433 at Who Named It?
10. ^ http://www.whonamedit.com/doctor.cfm/418.html

External links

• Dandy–Walker Alliance, a non-profit organization of individuals directly and indirectly affected by Dandy–Walker
• Metry Phaces article in the Journal of Pediatrics, July 2001
• E-medicine webpage definition
• Hydrocephalus Association
• Dandy–Walker Malformation article from Pan Arab Journal of Neurosurgery
• Dandy–Walker Syndrome page at Medical College of Wisconsin website