Dandy–Walker syndrome

Dandy–Walker syndrome
Variant DWS with dysplasia of the pons and cerebellum in an 8-year old. T2 weighted sagittal MRI.
Classification and external resources
Specialty medical genetics
ICD-10 Q03.1
ICD-9-CM 742.3
OMIM 220200
DiseasesDB 3449
eMedicine radio/206
MeSH D003616

Dandy–Walker syndrome (DWS) is a rare group of congenital human brain malformations. There are three subtypes which affect multiple organs to varying degrees, but the fundamental abnormalities involve the cerebellum[1] which controls muscle coordination. The adjacent fourth ventricle is often affected, which can alter the flow of cerebrospinal fluid, increase intracranial pressure, and lead to multiple other brain function problems. The degree of disability varies but is typically lifelong. Treatment may involve physical therapy, special education, or surgical placement of a cerebral shunt. It is named for Walter Dandy and Arthur Earl Walker.[2][3] 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.

Presentation

The key features of this syndrome are an enlargement of the fourth ventricle; 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]

The Dandy–Walker complex is a genetically sporadic disorder that occurs one in every 30,000 live births.[4] Prenatal diagnosis and prognosis of outcomes associated with Dandy–Walker can be difficult.[5] 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.[6] 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.[7]

Diagnosis

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 complete agenesis of the cerebellar vermis. There is also cystic dilation of the fourth ventricle, which fills the posterior fossa. This often involves hydrocephalus and complications due to associated genetic conditions, such as Spina Bifida.

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 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 (genotype) despite the widely varying set of medical characteristics (phenotype) 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.[8]

Genetic associations of the condition are being investigated.[9]

Relation to PHACES syndrome

Recent research has found that Dandy–Walker syndrome often occurs in patients with PHACES syndrome.[10]

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.[11] Endoscopic third ventriculostomy is also an option.

Treatment may also consist of various therapies such as occupational therapy, physiotherapy, speech therapy or specialized education. Services of a teacher of students with blindness/visual impairment may be helpful if the eyes are affected.

References

  1. 1 2 "NINDS Dandy–Walker Syndrome Information Page". National Institute of Neurological Disorders and Stroke. September 16, 2008. Retrieved June 26, 2016.
  2. ↑ synd/433 at Who Named It?
  3. ↑ Whonamedit - dictionary of medical eponyms
  4. ↑ Osenbach RK, Menezes AH (1992). "Diagnosis and management of the Dandy–Walker malformation: 30 years of experience.". Pediatr Neurosurg. 18 (4): 179–89. PMID 1472430.
  5. ↑ Guibaud L, Larroque A, Ville D, Sanlaville D, Till M, Gaucherand P, et al. (2012). "Prenatal diagnosis of 'isolated' Dandy–Walker malformation: imaging findings and prenatal counselling.". Prenat Diagn. 32 (2): 185–93. PMID 22418964. doi:10.1002/pd.3828.
  6. ↑ Romero R, Pilu G, Jeanty P, Ghidini A, Hobbins JL. Prenatal diagnosis of congenital anomalies. Appleton & Lange, Norwalk, 1988, pp. 30-33.
  7. ↑ Kaplan LC (Dec 1985). "Congenital Dandy Walker malformation associated with first trimester warfarin: A case report and literature review". Teratology. 32 (3): 333–337. PMID 4082063. doi:10.1002/tera.1420320302.
  8. ↑ 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. PMID 16722803. doi:10.1146/annurev.genom.7.080505.115610. Retrieved 2008-06-15.
  9. ↑ 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. PMID 15338008. doi:10.1038/ng1420.
  10. ↑ Metry DW, Dowd CF, Barkovich AJ, Frieden IJ (July 2001). "The many faces of PHACE syndrome". J. Pediatr. 139 (1): 117–23. PMID 11445804. doi:10.1067/mpd.2001.114880.
  11. ↑ Yüceer N, Mertol T, Arda N (2007). "Surgical treatment of 13 pediatric patients with Dandy–Walker syndrome". Pediatr Neurosurg. 43 (5): 358–63. PMID 17785999. doi:10.1159/000106383.

 This article incorporates public domain material from the United States Government document "Dandy-Walker Syndrome Information Page" by National Institute of Neurological Disorders and Stroke.

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