Dandy-Walker syndrome

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Zehra Malik, M.B.B.S[2]

Synonyms and keywords: Dandy-Walker Malformation, Dandy-Walker Deformity

Dandy-Walker Variant

Overview

Dandy-Walker Syndrome occurs in utero due to disruption in the development of the cerebellar vermis. It is characterized by the presence of hypoplastic cerebellar vermis, hydrocephalus, and cystic dilation of fourth ventricle. It usually presents itself in the first year of life due to symptoms caused by hydrocephalus. MRI is the diagnostic study of choice and surgical placement of shunt is the mainstay of therapy to reduce the hydrocephalus and to minimize brain damage.

Historical Perspective

• The term Dandy-Walker Syndrome was introduced in 1954 by a German psychiatrist Clemens Benda in the light of the following discoveries:,
  • In 1914, American neurosurgeon Walter Dandy and American pediatrician Kenneth Blackfan recognized the association between the partial or complete absence of cerebellar vermis, hydrocephalus, and fourth ventricular enlargement.
  • In 1942, Canadian-American neurosurgeon Arthur Earl Walker and American physician John Taggart contributed by highlighting the possible cause to be the maldevelopment of the foramen of Lushka and Magendie.
• An English surgeon named John Bland Sutton was the first to describe the association of underdeveloped cerebellar vermis, hydrocephalus, and an enlarged posterior fossa in 1887.

Classification

There is no established system for the classification of Dandy-Walker Syndrome. However, Barkovich classified posterior fossa CSF collection into the following:

• Dandy-Walker Complex includes malformation with intact communication between the fourth ventricle and posterior fossa CSF collection. It is further divided into Type A and B depending on the cerebellar vermis visibility. In Type A, cerebellar vermis is hypoplastic and not visible or deformed and Type B cerebellar vermis is visible.
• Posterior fossa arachnoid cyst: The fourth ventricle does not have direct communication with posterior fossa CSF collection.
• Prominent cisterna magna: It is characterized by atrophic vermis and cerebellar vermis with cisterna magna and fourth ventricle enlargement without the enlargement of posterior fossa.

Pathophysiology

• It is thought that Dandy-Walker Syndrome is the result of disruptions that occur during the development of cerebellar vermis leading to a fourth ventricle that is in continuation with the posterior fossa subarachnoid space.
• Embryonic development of cerebellum starts at week 5, it forms from the top part of metencephalon. The cerebellar hemisphere is formed from the forward surface of fourth ventricle. The lack of midline fusion of the cerebellar hemisphere by the 15th week of embryonic development results into underdeveloped cerebellar vermis.
• The exact pathogenesis of hydrocephalus in Dandy-Walker Syndrome is not fully understood. Several factors could play a role in development of hydrocephalus.
  • The initial hypothesis of atresia of the foramen of Luschka and Magendie as a possible cause is not well supported. It was found later that these foramina are patent in a large number of patients with DWM and hydrocephalus is not present at birth in more than 80% of patients diagnosed with DWM. Moreover, the closure of one or two foramina can be compensated by the presence of other foramen preventing the collection of fluid.
  • Another hypothesis was proposed suggesting the outflow impairment to be distal to fourth ventricle outlets, possibly caused by inflammation of arachnoid mater causing outflow obstruction. Excisions of these obstructions have not been able to show whether impaired arachnoid absorption is involved, since the subarachnoid space always takes days to weeks to fill up following excision.
  • Stenosis of aqueduct of Sylvius once suggested, does not seem to be the causing factor in pathogenesis of hydrocephalus. Shunts placed in the posterior fossa cyst almost always drain all above ventricles. Occasionally when it is present, it is functional stenosis caused by herniation of posterior fossa content.
  • Increased pressure in venous sinuses due to compression from the posterior fossa cyst could also contribute to the pathogenesis or worsening of hydrocephalus, no evidence has been found so far.
  • The importance of understanding the pathogenesis of hydrocephalus in Dandy-Walker Syndrome forms the basis of choosing most appropriate treatment.

Causes

• Several etiologic factors can lead to Dandy-Walker Syndrome, it is the time (4th to 7th embryonic week) and duration of insult that has more influence on the occurrence of disease rather than the type of causative factor.
• Mendelian conditions like Walker-Warburg Syndrome, Mohr Syndrome, Meckel-Gruber Syndrome are associated with Dandy-Walker Malformation.
• Genetic factors that are associated with DWM phenotype include:
  • Trisomy 18, triploidy and trisomy 13 most commonly.
  • First molecularly defined cause is the Z1C1 and Z1C4 heterozygous deletion on chromosome 3q24.
  • Second DWM-linked locus is the deletion or duplication of FOXC1 gene on 6p25.3.
  • Deletions on the long arm of chromosome 13.
• Environmental factors include prenatal exposure to rubella, cytomegalovirus, toxoplasmosis, coumadin, alcohol and maternal diabetes.

Differentiating Dandy-Walker Syndrome from other Diseases

• Dandy-Walker Syndrome must be differentiated from Blake's pouch cyst, mega cisterna magna, and posterior fossa arachnoid cyst.

• Blake's pouch cyst occurs if invagination of the fourth ventricle fails to rupture by the fourth month of gestation. The disease differs from Dandy-Walker Syndrome due to the following features:
  • The cerebellum is not hypoplastic, though it may be compressed by the enlarged posterior fossa (mass effect).
  • The cerebellar tentorium/confluence of sinuses is not raised.
  • Hydrocephalus, if present involves all four ventricles.

• Mega cisterna magna occurs due to delay in rupture of the fourth ventricle invagination. The disease differs from Dandy-Walker Syndrome due to the following features
  • The cerebellum is not usually hypoplastic.
  • The fourth ventricle is of relatively normal shape.
  • Hydrocephalus is uncommon.

• Posterior fossa arachnoid cyst is a collection of cerebrospinal fluid in the arachnoid mater. The disease differs from Dandy-Walker Syndrome due to the following features:
  • The cyst is clearly localized in a specific location separate from the fourth ventricle outlets.
  • The cerebellum is not hypoplastic, though it may be compressed by the cyst (mass effect).
  • The CSF flow in the cyst is not continuous with that of the fourth ventricle.
  • Hydrocephalus, if it occurs, is due to the cyst pressing on the cerebellum and compressing the cerebral aqueduct or fourth ventricle outlets.

Epidemiology and Demographics

• The prevalence of Dandy-Walker Syndrome is approximately 1 in 25,000 to 1 in 30,000 live births.
• Slight female predominance is observed.
• Dandy-Walker Syndrome is the underlying cause of 1% to 4% of cases of hydrocephalus.
• There is no established racial predilection to Dandy-Walker Syndrome.

Risk Factors

• There are no established risk factors for Dandy-Walker Syndrome. However, non-Hispanic black ethnicity and history of infertility were seen to increase the risk of DWM, further research is required.

Screening

• There is insufficient evidence to recommend routine screening for Dandy-Walker syndrome.

Natural History, Complications, and Prognosis

• If left untreated, patients with Dandy-Walker Syndrome may progress to develop severe neurologic deficits. Fifty percent of patients affected die before reaching the third year of life. The 20-23% of patients that reach adult life will have auditory, visual, and motor deficits.
• Other possible complications include malformations of gastrointestinal, face, limb, heart, and genitourinary system.
• Prognosis is generally poor if hydrocephalus is left untreated.

Diagnosis

Diagnostic Study of Choice

• MRI is the diagnostic study of choice.

History and Symptoms

• The majority of the patients (up to 85%) present in the first year of life with signs and symptoms of increased intracranial pressure such as irritability, increased head circumference, vomiting, convulsions.

Physical Examination

• Signs of hydrocephalus in infants include increasing head size, vomiting, excessive sleepiness, irritability, downward deviation of the eyes (known as "sunsetting eyes"), and seizures.

Laboratory Findings

• There are no diagnostic laboratory findings associated with Dandy-Walker Syndrome.

Electrocardiogram

• There are no ECG findings associated with Dandy-Walker Syndrome.

X-ray

• There are no x-ray findings associated with Dandy-Walker Syndrome.

Echocardiography or Ultrasound

• There are no echocardiography findings associated with Dandy-Walker Syndrome.
• Fetal 3D ultrasound can suspect posterior fossa malformation as early as 14 weeks of gestation. However, it should be confirmed by a fetal MRI.

CT scan

• If MRI is unavailable then CT may be used, but it is less detailed.
• It is suggested that a suspected diagnosis based on CT should be confirmed by performing an MRI.

MRI

• An MRI is the most important imaging modality in diagnosing Dandy-Walker Syndrome due to its superior anatomic resolution and multiplanar imaging.

Other Imaging Findings

• There are no other imaging findings associated with Dandy-Walker Syndrome.

Other Diagnostic Studies

• There are no other diagnostic studies associated with Dandy-Walker Syndrome.

Treatment

Medical Therapy

• There is no available medical therapy for Dandy-Walker Syndrome.

Surgery

• The mainstay of treatment is to reduce the hydrocephalus and posterior fossa enlargement.
• Shunt placement is the treatment of choice at the moment to achieve this goal.
• Superiority of the type of shunt over the other is not well established. Types of shunts in question are,
  • Ventriculoperitoneal (VP): Supratentorial shunt
    • Drains lateral ventricles. It is a supratentorial shunt.
    • Easier to place.
    • Low incidence of migration/malposition.
    • Early decompression of supratentorial compartment, therefore preferred by some authors.
    • Lower rate of complications overall.
    • Less effective in DWM due to the infratentorial collection of fluid.
  • Cystoperitoneal (CP):
    • Drains both, lateral ventricles and fourth ventricle provided the aqueduct is patent, which can be determined by pre-procedural imaging. It is an infratentorial shunt.
    • Higher incidence of migration/malposition and overdrainage. Overdrainage can cause cerebral herniation, it is recommended to use flow regulating or anti-syphon valve.
    • Other complications include brain stem tethering and subdural hematoma. and subdural hematoma
  • Combined VP/CP shunt: Some authors prefer this procedure as it equalizes supratentorial and infratentorial pressure, especially in cases with functional aqueductal stenosis.

• Supratentotial shunts are overall more successful in the long term than infratentorial.

• Other procedure includes endoscopic third ventriculostomy (ETV).

Primary Prevention

• There are no established measures for the primary prevention of Dandy-Walker Syndrome.

Secondary Prevention

• Reducing the hydrocephalus and posterior fossa enlargement decreases the progression of brain damage and slows the progression of complications.