Dandy-Walker malformation

Dandy-Walker malformation affects brain development, primarily development of the cerebellum, which is the part of the brain that coordinates movement. In individuals with this condition, various parts of the cerebellum develop abnormally, resulting in malformations that can be observed with medical imaging. The central part of the cerebellum (the vermis) is absent or very small and may be abnormally positioned. The right and left sides of the cerebellum may be small as well. In affected individuals, a fluid-filled cavity between the brainstem and the cerebellum (the fourth ventricle) and the part of the skull that contains the cerebellum and the brainstem (the posterior fossa) are abnormally large. These abnormalities often result in problems with movement, coordination, intellect, mood, and other neurological functions.

In the majority of individuals with Dandy-Walker malformation, signs and symptoms caused by abnormal brain development are present at birth or develop within the first year of life. Some children have a buildup of fluid in the brain (hydrocephalus) that may cause increased head size (macrocephaly). Up to half of affected individuals have intellectual disability that ranges from mild to severe, and those with normal intelligence may have learning disabilities. Children with Dandy-Walker malformation often have delayed development, particularly a delay in motor skills such as crawling, walking, and coordinating movements. People with Dandy-Walker malformation may experience muscle stiffness and partial paralysis of the lower limbs (spastic paraplegia), and they may also have seizures. While rare, hearing and vision problems can be features of this condition.

Less commonly, other brain abnormalities have been reported in people with Dandy-Walker malformation. These abnormalities include an underdeveloped or absent tissue connecting the left and right halves of the brain (agenesis of the corpus callosum), a sac-like protrusion of the brain through an opening at the back of the skull (occipital encephalocele), or a failure of some nerve cells (neurons) to migrate to their proper location in the brain during development. These additional brain malformations are associated with more severe signs and symptoms.

Dandy-Walker malformation typically affects only the brain, but problems in other systems can include heart defects, malformations of the urogenital tract, extra fingers or toes (polydactyly) or fused fingers or toes (syndactyly), or abnormal facial features.

In 10 to 20 percent of people with Dandy-Walker malformation, signs and symptoms of the condition do not appear until late childhood or into adulthood. These individuals typically have a different range of features than those affected in infancy, including headaches, an unsteady walking gait, paralysis of facial muscles (facial palsy), increased muscle tone, muscle spasms, and mental and behavioral changes. Rarely, people with Dandy-Walker malformation have no health problems related to the condition.

Problems related to hydrocephalus or complications of its treatment are the most common cause of death in people with Dandy-Walker malformation.

Dandy-Walker malformation is estimated to affect 1 in 10,000 to 30,000 newborns.

Researchers have found mutations in a few genes that are thought to cause Dandy-Walker malformation, but these mutations account for only a small number of cases. Dandy-Walker malformation has also been associated with many chromosomal abnormalities. This condition can be a feature of some conditions in which there is an extra copy of one chromosome in each cell (trisomy). Dandy-Walker malformation most often occurs in people with trisomy 18 (an extra copy of chromosome 18), but can also occur in people with trisomy 13, trisomy 21, or trisomy 9. This condition can also be associated with missing (deletions) or copied (duplications) pieces of certain chromosomes. Dandy-Walker malformation can also be a feature of genetic syndromes that are caused by mutations in specific genes. However, the brain malformations associated with Dandy-Walker malformation often occur as an isolated feature (not associated with other health problems), and in these cases the cause is frequently unknown.

Research suggests that Dandy-Walker malformation could be caused by environmental factors that affect early development before birth. For example, exposure of the fetus to substances that cause birth defects (teratogens) may be involved in the development of this condition. In addition, a mother with diabetes is more likely than a healthy mother to have a child with Dandy-Walker malformation.

Genetic Testing Information

• Genetic Testing Registry: Dandy-Walker syndrome

Genetic and Rare Diseases Information Center

• Isolated Dandy-Walker malformation

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Catalog of Genes and Diseases from OMIM

• DANDY-WALKER SYNDROME; DWS

Scientific Articles on PubMed

• PubMed

• Aldinger KA, Lehmann OJ, Hudgins L, Chizhikov VV, Bassuk AG, Ades LC, Krantz ID, Dobyns WB, Millen KJ. FOXC1 is required for normal cerebellar development and is a major contributor to chromosome 6p25.3 Dandy-Walker malformation. Nat Genet. 2009 Sep;41(9):1037-42. doi: 10.1038/ng.422. Epub 2009 Aug 9. Citation on PubMed or Free article on PubMed Central
• Bokhari I, Rehman L, Hassan S, Hashim MS. Dandy-Walker Malformation: A Clinical and Surgical Outcome Analysis. J Coll Physicians Surg Pak. 2015 Jun;25(6):431-3. Citation on PubMed
• Grinberg I, Northrup H, Ardinger H, Prasad C, Dobyns WB, Millen KJ. Heterozygous deletion of the linked genes ZIC1 and ZIC4 is involved in Dandy-Walker malformation. Nat Genet. 2004 Oct;36(10):1053-5. doi: 10.1038/ng1420. Epub 2004 Aug 29. Citation on PubMed
• Has R, Ermis H, Yuksel A, Ibrahimoglu L, Yildirim A, Sezer HD, Basaran S. Dandy-Walker malformation: a review of 78 cases diagnosed by prenatal sonography. Fetal Diagn Ther. 2004 Jul-Aug;19(4):342-7. doi: 10.1159/000077963. Citation on PubMed
• Imataka G, Yamanouchi H, Arisaka O. Dandy-Walker syndrome and chromosomal abnormalities. Congenit Anom (Kyoto). 2007 Dec;47(4):113-8. doi: 10.1111/j.1741-4520.2007.00158.x. Citation on PubMed
• Reeder MR, Botto LD, Keppler-Noreuil KM, Carey JC, Byrne JL, Feldkamp ML; National Birth Defects Prevention Study. Risk factors for Dandy-Walker malformation: a population-based assessment. Am J Med Genet A. 2015 Sep;167A(9):2009-16. doi: 10.1002/ajmg.a.37124. Epub 2015 May 1. Citation on PubMed
• Sasaki-Adams D, Elbabaa SK, Jewells V, Carter L, Campbell JW, Ritter AM. The Dandy-Walker variant: a case series of 24 pediatric patients and evaluation of associated anomalies, incidence of hydrocephalus, and developmental outcomes. J Neurosurg Pediatr. 2008 Sep;2(3):194-9. doi: 10.3171/PED/2008/2/9/194. Citation on PubMed
• Spennato P, Mirone G, Nastro A, Buonocore MC, Ruggiero C, Trischitta V, Aliberti F, Cinalli G. Hydrocephalus in Dandy-Walker malformation. Childs Nerv Syst. 2011 Oct;27(10):1665-81. doi: 10.1007/s00381-011-1544-4. Epub 2011 Sep 17. Citation on PubMed
• Tohyama J, Kato M, Kawasaki S, Harada N, Kawara H, Matsui T, Akasaka N, Ohashi T, Kobayashi Y, Matsumoto N. Dandy-Walker malformation associated with heterozygous ZIC1 and ZIC4 deletion: Report of a new patient. Am J Med Genet A. 2011 Jan;155A(1):130-3. doi: 10.1002/ajmg.a.33652. Epub 2010 Dec 10. Citation on PubMed
• Zaki MS, Masri A, Gregor A, Gleeson JG, Rosti RO. Dandy-Walker malformation, genitourinary abnormalities, and intellectual disability in two families. Am J Med Genet A. 2015 Nov;167A(11):2503-2507. doi: 10.1002/ajmg.a.37225. Epub 2015 Jun 24. Citation on PubMed