Dandy-Walker syndrome

Eugen J Boltshauser MD (Dr. Boltshauser of the University of Zurich has no relevant financial relationships to disclose.)
Peter G Barth MD PhD, editor. (Dr. Barth of the University of Amsterdam has no relevant financial relationships to disclose.)
Originally released August 13, 1998; last updated November 5, 2016; expires November 5, 2019

Overview

The core features of Dandy-Walker syndrome are hypoplasia, elevation, and rotation of the cerebellar vermis and cyst-like dilatation of the fourth ventricle, whereas posterior fossa enlargement and hydrocephalus are not invariably present. In view of the now well-documented nonmotor cerebellar functions, it is not surprising that a considerable proportion of children with Dandy-Walker syndrome have learning problems. The pathogenesis of Dandy-Walker syndrome is poorly understood and is likely to be heterogeneous. Evidence suggests that at least part of Dandy-Walker syndrome may be due to heterozygous loss of Zinc finger genes and mutations affecting FOXC1 and FGF17 genes. Mutations in NID1 and LAMC1 genes, which are involved in and interact with the extracellular matrix, suggest that abnormal mesenchymal development in the posterior fossa results in malformations of both the cerebellum and the overlying leptomeninges, and that the mesenchyme interacts with the developing cerebellum. Acquired cerebellar lesions as a complication of extreme prematurity potentially mimicking neuroimaging in Dandy-Walker syndrome and sometimes erroneously referred to as Dandy-Walker variant should be considered in the differential diagnosis. Potential pitfalls in prenatal diagnosis are indicated.

Historical note and terminology

The association of hydrocephalus, hypoplasia of the cerebellar vermis, and posterior fossa cyst was first described by Sutton in 1887 (Sutton 1887). The triad was later confirmed by Dandy and Blackfan, who added 4 cases (Dandy and Blackfan 1914). The primary defect was thought to be atresia of the foramina of Luschka and Magendie. In 1942 Taggart and Walker added 3 case reports (Taggart and Walker 1942). Benda introduced the eponym "Dandy-Walker syndrome" (Benda 1954). He considered it a developmental anomaly not necessarily due to foraminal atresia, because some autopsy cases had patent foramina. In 1959 based on a murine model of hydrocephalus, Brodal and Hauglie-Hanssen postulated that an abnormal distension of the fourth ventricle leads to a maldevelopment of the cerebellar vermis. The definition of the syndrome, the diagnostic criteria, and the nomenclature remain a perpetual subject of debate between authors. In light of the variability of developmental posterior fossa abnormalities, some authors consider these to be part of a spectrum, "lumping" diverse conditions into a Dandy-Walker complex or Dandy-Walker continuum. In the neuroradiological literature a distinction is often made between Dandy-Walker malformation and Dandy-Walker variant; the latter term is applied if the posterior fossa is not enlarged, the hypoplasia of the cerebellar vermis is less pronounced, or both (Tan et al 1995; Barkovich 2000). In view of its variable definition and lack of specificity the terms Dandy-Walker variant and Dandy-Walker complex are best avoided.

This view has been explicitly supported by experts in the field (Barkovich and Dobyns 2006). Many cases of Dandy Walker variant correspond to inferior vermis hypoplasia.

In this article, the term Dandy-Walker syndrome is used in reference to Dandy-Walker malformation, a term used by several authors (Pellock and Johnson 1993). From a didactic point of view, one can distinguish between the following:

• Dandy-Walker syndrome proper (isolated)
• Dandy-Walker syndrome as part of another defined syndrome (see Table 1).

Table 1. Defined Syndromes that Include Dandy-Walker syndrome

• Aase-Smith
• Coffin-Siris
• Ellis-van Creveld
• Fraser cryptophthalmus
• Goldenhar
• Hydrolethalus
• Meckel-Gruber
• Marden-Walker
• Mohr (oro-facio-digital II)
• Ritscher-Schinzel (3C)
• Walker-Warburg
• Wyburn-Mason

Note: Syndromes with vermian agenesis but without posterior fossa cyst are not included.

Modified from: (Murray et al 1985; Bordarier and Aicardi 1990; Pellock and Johnson 1993; Ozkinay et al 1995; Morava et al 1996; Kosaki et al 1997).

Neurocutaneous melanosis has been repeatedly found associated with cystic posterior fossa lesions including Dandy-Walker syndrome (Marnet et al 2009).

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