Developmental Malformations
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Dec. 12, 2024
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Dandy-Walker syndrome …
- Updated 01.19.2024
- Released 08.13.1998
- Expires For CME 01.19.2027
Dandy-Walker syndrome
Introduction
Overview
Dandy-Walker syndrome involves a constellation of posterior fossa malformations, including cerebellar vermian hypoplasia, elevation, and rotation of the cerebellar vermis and cyst-like dilatation of the fourth ventricle. Posterior fossa enlargement and hydrocephalus are variably present. Associated symptoms include learning and motor disabilities. Although the pathogenesis of Dandy-Walker syndrome is poorly understood and multifactorial, several genes implicate abnormal mesenchymal development. MRI diagnostic signs include the unpaired caudal lobule, or “tail-sign,” and increased tegmentovermian angle and fastigial recess. The differential diagnosis includes acquired cerebellar lesions as a complication of extreme prematurity and other posterior fossa abnormalities.
Key points
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• Dandy-Walker syndrome is a posterior fossa malformation involving hypoplasia of the cerebellar vermis, which is elevated and upwardly rotated, and cyst-like dilatation of the fourth ventricle. Other malformations are variably associated. | |
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• Dandy-Walker syndrome can be associated with normal intellect and development. | |
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• Developmental prognosis hinges on associated malformations, extent of vermian abnormalities, and the presence of an underlying genetic condition. | |
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• The pathogenesis of Dandy-Walker syndrome is thought to be related to abnormal mesenchymal development due to genetic abnormalities. Several loci have been investigated, but a specific genetic cause is often not found. |
Historical note and terminology
Sutton was the first to describe the association of hydrocephalus, hypoplasia of the cerebellar vermis, and posterior fossa cyst (73). The triad was later confirmed by Dandy and Blackfan, who added four cases (20). The primary defect was thought to be atresia of the foramina of Luschka and Magendie. In 1942 Taggart and Walker added three case reports (74). Benda introduced the eponym "Dandy-Walker syndrome" (07). 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 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 (75; 04). 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 (05). Many cases of Dandy Walker variant correspond to inferior vermian hypoplasia.
In this article, the term Dandy-Walker syndrome is used in reference to Dandy-Walker malformation, which consists of cerebellar vermian hypoplasia, elevation, and rotation of the cerebellar vermis and cyst-like dilatation of the fourth ventricle (52). From a didactic point of view, one can distinguish between the following:
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• Dandy-Walker syndrome proper (isolated) |
Table 1. Defined Syndromes that Include Dandy-Walker Syndrome
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• Aase-Smith | |
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Modified from: (46; 12; 52; 50; 45; 37). | |
Neurocutaneous melanosis has been repeatedly found associated with cystic posterior fossa lesions including Dandy-Walker syndrome (41).
Clinical manifestations
Presentation and course
Although discrepancies are present among authors concerning the definition of Dandy-Walker syndrome, the following features are not generally contested:
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Core features | |
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- hypoplasia of the cerebellar vermis, which is elevated and upwardly rotated | |
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Other features often, but variably, present | |
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- Hydrocephalus | |
At birth, most infants are asymptomatic or mildly symptomatic. Macrocephaly is the most common presenting sign, and there may be evidence of increased intracranial pressure. In about 80% of cases the diagnosis is made during the first year (33; 51; 52); however, some patients first come to clinical attention as adults (49; 64). Unusual presentations in the neonatal period are occipital encephalocele and apnea. Although all patients have cerebellar vermian hypoplasia, cerebellar dysfunction evolves in only about one half of children (28). Nystagmus may be present, but cranial nerve signs are exceptional. Intellectual impairment is found in at least one half of patients. In the series reported by Gerszten and Albright (n=20), 45% of patients had moderate to severe cognitive impairment. There was no relationship between volumetric measurements of the posterior fossa structures and the degree of cerebellar dysfunction and mental retardation. In the series reported by Boddaert and colleagues in 2003 (n=20), all children with normal vermian lobulation and without supratentorial anomalies had normal intellectual outcome. Cognitive impairment is not due to increased intracranial pressure but to impaired cerebellar function. Increasing evidence provides that the cerebellum is important for motor and cognitive learning (65). Agenesis or hypogenesis of the corpus callosum is found in about one sixth of Dandy-Walker syndrome patients. Various cardiovascular anomalies (eg, septal defects, tetralogy of Fallot, dextrocardia, and coarctation of aorta) have been noted (48; 33; 49). Other associated neuropathologic and neuroimaging findings and systemic manifestations are listed in Table 2.
Table 2. Reported Associated Findings in Dandy-Walker Syndrome
Central nervous system
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• Hypogenesis and agenesis of corpus callosum |
Systemic
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• Facial hemangioma | |
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| |
A retrospective review of 329 patients with Dandy Walker syndrome found 73 with brainstem abnormalities, the most common of which was pontine hypoplasia. More severe brainstem malformations, characterized as tegmental dysplasia, had a greater association with massive ventriculomegaly, additional malformations of the corpus callosum and gray matter, and interhemispheric cysts. These patients had increased rates of bulbar dysfunction, seizures, and mortality (03).
Clinical descriptions of patients and comorbidities must be interpreted cautiously as many different posterior fossa malformations may be grouped together inappropriately, eg, Dandy Walker, mega cisterna magna, and Joubert syndrome (69).
Prognosis and complications
The overall prognosis mainly depends on possible associated findings (eg, cardiac malformations, additional CNS malformations, and chromosomal aberrations). The type and number of associated anomalies have impacts on survival and outcome (59; 63). Intellectual prognosis is considered favorable if vermian lobulation is preserved and supratentorial anomalies (in particular callosal dysgenesis) are absent (09).
In a retrospective study of 19 patients who were identified with Dandy Walker syndrome based on prenatal imaging that was confirmed postnatally, the presence of CNS anomalies outside of the posterior fossa and size of interhemispheric cyst, if present, were associated with worse developmental outcomes. However, non-CNS anomalies and hydrocephalus were not (77). From an imaging standpoint, prognosis depends on the degree of ventriculomegaly, which should be serially measured (18). In the absence of chromosomal alterations related to increasing maternal age, isolated Dandy Walker syndrome on prenatal ultrasound has an improved prognosis (72). In addition, prognosis of normal intellectual outcome is related to normal lobulated cerebellum in the absence of other abnormalities, such as corpus callosum dysgenesis (18).
Along the line of the importance of clear diagnostic criteria, one has to be careful to imply prognostic implications from article titles: this point is exemplified quoting two articles on “schizophrenia” and “psychosis,” respectively, in patients with inferior vermian hypoplasia, not Dandy-Walker malformation (22; 68).
Bolduc and Limperopoulos drew attention to limited methodology in many neurodevelopmental outcome studies in children with cerebellar malformations, including Dandy-Walker malformation (11). Outcome is less favorable in series with prenatal diagnosis due to higher frequency of associated findings including chromosomal aberrations (24; 35). Despite this observation, normal neurologic outcome is possible after prenatal diagnosis is confirmed postnatally, even among patients who require CSF shunt (79). A study from Montreal, Canada, on outcomes in children with congenital cerebellar malformations includes data on 10 patients with Dandy malformation (54). At a median age of 13.5 years, seven children had global developmental delay; for eight of 10 patients, no exact information about cognitive abilities is available (too young for reliable testing, information not known). Six of 10 children had associated cerebral malformations. A selection bias towards more severely affected patients in this report is possible.
Complications related to shunt dysfunction. Even in centers with considerable expertise, the mortality of nontumoral infantile hydrocephalus during childhood is in the range of 10%. Sudden unexpected death in patients with Dandy-Walker syndrome not related to shunt problems has been observed (25).
An occasional late complication is the development of syringomyelia, resulting from a herniation of the Dandy-Walker cyst through the foramen magnum (32).
Clinical vignette
Case 1. The proband was the first child of healthy nonconsanguineous young parents. The pregnancy was uneventful. Prenatal ultrasound investigation at 32 weeks' gestation revealed a posterior fossa malformation. Dandy-Walker syndrome was diagnosed. Spontaneous delivery at 38 weeks was uneventful. Clinical examination was normal, as was renal ultrasound. Head circumference was 33 cm (50th to 90th percentile). Dandy-Walker syndrome was confirmed by MRI.
Follow-up examination at 10 months disclosed marked developmental delay with milestones corresponding to 4 to 5 months. Head circumference was 43 cm (10th percentile). There was a convergent squint. Clinical examination was otherwise normal.
Case 2. The diagnosis of Dandy-Walker syndrome was made 4 weeks before delivery. Head circumference at term birth was 40 cm, rapidly increasing postnatally. A ventriculoperitoneal shunt was inserted at 5 weeks. At 2 years of age, an additional cyst drainage was installed due to further increase of head size and a history of occasional vomiting. Subsequently, the patient did well, having only minor truncal cerebellar ataxia. When last seen at 7 years of age, cognitive abilities were normal for her age. She has a capillary nevus of her right frontal region.
Biological basis
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• The pathogenesis of Dandy Walker syndrome is thought to be related to abnormal mesenchymal development due to genetic abnormalities. Several loci have been investigated, but often a specific genetic cause is not found. |
Etiology and pathogenesis
Table 3. Developmental and Diagnostic Differences Between Dandy-Walker Syndrome and Selected Mimickers
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Defined syndrome |
Key developmental abnormalities |
Key differentiating features of Dandy-Walker syndrome (DWS) |
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Dandy-Walker syndrome |
Development anomaly of roof of rhombencephalon via two embryologically abnormal pathways: (1) Vermian developmental stoppage, cannot anatomically cover fourth ventricle; (2) Altered permeation of fourth ventricular CSF outflow foramina |
Key imaging features distinguish conditions (Table 5). |
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Vermian hypoplasia (isolated, inferior, and more) |
Embryologically, may represent a continuum of paradigm outlined for Dandy-Walker syndrome affecting vermian development |
Key imaging features distinguish conditions (Table 5). |
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Blake pouch cyst |
Abnormal fenestration / permeabilization of Blake pouch (normally becomes foramen of Magendie) AND foramina of Luschka |
Key imaging features distinguish conditions (Table 5). |
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Mega cisterna magna |
Abnormal fenestration / permeabilization of Blake pouch (normally becomes foramen of Magendie) |
Normal vermis |
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Joubert syndrome |
Abnormal decussation of superior peduncular tracts |
Molar tooth sign |
The etiology of Dandy-Walker syndrome is poorly understood and probably multifactorial. A developmental and imaging-based conceptualization of Dandy-Walker syndrome and mimics leads to the most clear understanding and differentiation (Tables 3 and 5). Dandy-Walker syndrome can be part of defined Mendelian disorders and other syndromes (Table 3). Dandy-Walker syndrome can also be found in association with various chromosomal aberrations (46; 12; 76; 24). However, in the majority of patients diagnosed postnatally, Dandy-Walker syndrome is not associated with other syndromes and chromosomal aberrations; it is an isolated finding.
In a broad sense, the pathophysiology of Dandy-Walker syndrome appears to result from a developmental hindbrain disturbance occurring in early embryonic life, perhaps in the sixth to the seventh week. The initial theory relating Dandy-Walker syndrome causally to impairment of the fourth ventricle outlets has been questioned in light of demonstrated foraminal patencies in a considerable proportion of patients. The dilatation of the fourth ventricle is most likely due to persistence of the anterior membranous area that forms the roof of the early fourth ventricle without the normal regression and disappearance as the choroid plexus and vermis develop (13).
Genetic investigations and animal studies on mouse embryos have drifted the “mechanical” hypothesis towards the interplay of the developing cerebellum and the posterior fossa mesenchyme, at least in a subset of patients. Several genomic regions and genes have been implicated in patients or mouse models.
For example, chromosome 6p25.3 was linked to Dandy-Walker malformation was identified by Aldinger and colleagues. They showed that deletions or duplications encompassing FOXC1 are associated with cerebellar and posterior fossa malformations, including cerebellar vermis hypoplasia, mega cisterna magna, and Dandy-Walker malformation (01). In six individuals (three fetuses) with 6p25 deletions, including FOXC1, various combinations of cerebellar and ocular (anterior chamber defects consistently, and others) malformations were confirmed (23). Studies on mouse embryos have further elucidated the interaction of the developing cerebellum and the posterior fossa mesenchyme, “communicating” with each other as they develop. Foxc1 is widely expressed in the extracellular matrix surrounding the cerebellar anlage. Foxc1-deficient mice have a lower number of cerebellar radial glial cells, disrupting cerebellar development (31).
Haldipur and colleagues have expanded their studies on mice models and comparisons with observations in humans with Dandy-Walker malformation (30). They have demonstrated that hypomorphic Foxc1 mutant mice have granule and Purkinje cell abnormalities causing subsequent disruptions in postnatal cerebellar foliation and lamination. A partially formed posterior lobule echoes the posterior vermis “tail sign” observed in human neuroimaging. In a large exome sequencing study of 100 families with either cerebellar hypoplasia or Dandy-Walker malformation, remarkable differences were found between the two cohorts and between the subgroups of Dandy-Walker malformations with or without an unpaired caudal lobule or “tail sign” (02). Among 36 individuals with sufficiently detailed neuroimaging, 30 patients had a “tail sign.” The rate of a genetic diagnosis was lowest in this group. This observation underscores the potential diagnostic significance of the “tail sign.”
The OMIM (Online Mendelian Inheritance in Man catalogue) lists "Dandy-Walker malformation with encephalocele, autosomal dominant" (%609222) based on previous publications. Darbro and coworkers reexamined two previously reported pedigrees (21). They found a nonsense mutation in the NID1 gene in the Vietnamese family, but not in the Indian family. However, further analyses of genes interacting with NID1 led to identification of a heterozygous missense mutation in LAMC1 in the second family. Remarkably both genes are "players" involved in the extracellular matrix, which is considered essential in the developing posterior fossa mesenchyma and its derivatives. It is worth mentioning that the Vietnamese kindred were reported as "autosomal dominant occipital cephalocele" (06). Imaging revealed occipital skull defects and variable retrocerebellar fluid accumulation, but no cerebellar vermis anomalies as seen in Dandy-Walker malformation proper. The same heterozygous ND1 variant (c.1162 C> T) reported by Dabro and coworkers was later confirmed in four members of a 3-generation family by McNiven and coworkers (43).
AP1S2 mutations were reported in "X-linked Dandy-Walker malformation with intellectual disability" in a family previously reported as Pettigrew syndrome (15). This is another X-linked mental retardation syndrome, rather than a Dandy-Walker malformation proper, as imaging revealed inferior vermis hypoplasia and mega cisterna magna, respectively.
Exact phenotyping varies by study, making generalization of specific genes to Dandy-Walker syndrome challenging.
Epidemiology
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• Dandy-Walker syndrome is a common congenital brain malformation. |
The prevalence of isolated (ie, not associated with another defined syndrome) Dandy-Walker syndrome was estimated to be about 1 per every 30,000 live births (49). It accounts for about 2% to 4% of infantile hydrocephalus (33). In some, but not all, larger series, a mild preponderance toward females is seen (33; 49); this is particularly evident in patients with facial hemangioma (61; 56). A population-based survey of fetal posterior fossa anomalies from the northern region of England found an incidence of Dandy-Walker malformation of approximately 1 per 11,000 (39).
A comprehensive epidemiological study was reported using data from the European population-based registries of congenital anomalies in the European Surveillance of Congenital Anomalies network (EUROCAT) (60). Data were collected from 28 registries in 17 countries in the observation period from 2002 to 2015. Results are presented for Dandy-Walker malformation and Dandy-Walker variant, diagnosed using the International Classification of Diseases. Although the individual diagnostic allocation and the large regional variability may be questioned, the overall study results are of interest. A total of 734 cases were registered: 562 Dandy-Walker malformation and 172 Dandy-Walker variant cases. About 90% were diagnosed prenatally. The overall prevalence of Dandy-Walker malformation was 6.79 per 100,000 births, with 39.2% livebirths, 56.5% termination of pregnancy, and 4.3% late fetal deaths. The livebirth prevalence was 2.74 per 100,000 births. About 40% had an isolated Dandy-Walker malformation. A substantial proportion had multiple congenital anomalies, chromosomal aberrations, and genetic syndromes.
Prevention
Primary prevention of Dandy-Walker syndrome is not possible. According to Murray and colleagues, in isolated Dandy-Walker syndrome, the recurrence risk for parents of an affected proband is in the order of 1% to 5% (46). Bordarier and Aicardi reported that the risk is "practically negligible" (12). Prenatal diagnosis is possible (see Diagnostic workup).
Differential diagnosis
Associated or underlying disorders
Differentiation of isolated Dandy-Walker syndrome from other conditions with Dandy-Walker syndrome as a possible association is mainly based on clinical evidence of additional features (eg, dysmorphic signs, cleft palate, growth retardation, joint contractures, skeletal abnormalities, ocular findings). Differentiation from other posterior fossa cystic lesions (ie, mega cisterna magna and retrocerebellar arachnoid cyst) should not be problematic in the postnatal situation if standard neuroimaging criteria are followed (36; 75; 04). The position of the choroid plexus in the fourth ventricle gives important clues to the nature of a posterior fossa cyst: normal in arachnoid cyst, absent in Dandy-Walker, displaced into the superior cyst wall in Blake pouch (47). In difficult situations CSF flow MRI can improve the diagnostic certainty (83). Some authors consider Blake pouch cyst consisting of posterior ballooning of the superior medullary velum into the cisterna magna as an entity within the Dandy-Walker continuum (16). The delineation of Ritscher-Schinzel syndrome from Dandy-Walker syndrome may not be clear-cut; although the older sister of the index patient of our initial report had marked shunt dependent hydrocephalus, the proband did not have ventriculomegaly (57; 37). Joubert syndrome is characterized by near total absence of cerebellar vermis, normal cerebellar hemispheres, a "bat-wing" shaped fourth ventricle, and a "molar-tooth" shaped midbrain; a large posterior fossa cyst is not a feature (71; 04). Exceptionally, a Dandy-Walker malformation may mask recognition of the molar tooth sign (62). A similar exceptional case was included in an article reporting a further gene (ARMC9) associated with Joubert syndrome (78). Unfortunately, patients with clear-cut evidence of a molar tooth sign are still published as having Dandy-Walker malformation rather than Joubert syndrome and related disorders (67). For review of vermian agenesis see Bordarier and Aicardi (12). PHACE(S) association (MIM 606519) is often associated with a facial hemangioma, but the posterior fossa anomalies are distinct from Dandy-Walker syndrome. In a cohort of 55 patients with PHACE syndrome, a classical-type Dandy-Walker malformation was described in a single individual, whereas unilateral cerebellar hypoplasia was the predominant finding (70). Attention has been drawn to acquired cerebellar lesions as a potential complication of extreme prematurity (44) and posthermorrhagic cerebellar disruption respectively (38). These changes may mimic Dandy-Walker syndrome and may erroneously be called Dandy-Walker variant (17). These dynamic changes have been impressively illustrated by Pichiecchio and colleagues in a patient with prenatal cerebellar hemorrhage and postnatal progressive upward displacement of a hypoplastic vermis and enlargement of the posterior fossa mimicking perfectly a “classical” Dandy Walker syndrome (53).
Diagnostic workup
The diagnosis of Dandy-Walker syndrome, both prenatally and postnatally, is based on neuroimaging (ultrasound and gold standard MRI), along with genetic testing (Table 4). Great care is required not to overlook a molar tooth sign in rare instances of Joubert syndrome mimicking Dandy-Walker syndrome. Updated 2022 MRI guidelines have added increased diagnostic certainty in differentiating mimickers (Tables 3 and 5). Careful clinical investigation is mandatory to assess if Dandy-Walker syndrome is isolated or an associated finding in the context of other defined syndromes as isolated cases may have better prognoses (72).
Table 4. Pre- and Postnatal Diagnostic Approach to Dandy-Walker Syndrome
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Step 1. Prenatal ultrasound, (72) criteria Note: Cerebellar vermis does not completely form until 18 weeks’ gestation, prohibiting a sooner diagnosis of Dandy-Walker syndrome (18). |
Incomplete cerebellar separation, varying absence of cerebellar vermis, dilated fourth ventricle, enlarged posterior fossa cistern, width of lateral ventricle body posterior foot more than 10 mm (72)* |
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Step 2. Choose prenatal MRI and/or genetic testing, or both, to aid in delivery planning and prognosis (18). |
See Table 5 for prenatal MRI diagnostic guidelines. |
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Step 3. Choose postnatal MRI and/or genetic testing to aid in prognostic counseling. |
See Table 5 for postnatal MRI diagnostic guidelines.*** Genetic testing, including karyotype analysis and SNP array |
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* Prognosis depends on degree of ventriculomegaly, which should be serially measured (18). | |
Table 5. 2022 Diagnostic MRI Guidelines for Differentiating Dandy-Walker Syndrome from Mimics
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Revised criteria |
Dandy-Walker syndrome |
Blake pouch cyst |
Hypoplasia of vermian with or without Blake pouch cyst |
Hypoplasia solely of vermian |
Hypoplasia of inferior vermian |
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Angle of fastigial recess |
Obtuse* |
Acute/Varies |
Acute/Varies |
Acute |
Acute |
|
Angle of tegmentovermian |
Increased more than 45 degrees* |
Increased 18 to 45 degrees |
Increased 18 to 45 degrees |
Near 0 |
Near 0 |
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Vermis |
Hypoplasia of inferior vermian |
Normal anatomy |
Hypoplasia of vermian |
Widespread hypoplasia of vermian |
Hypoplasia of inferior vermian |
|
Unpaired caudal lobule (tail sign) |
Yes |
No/Varies |
Widespread hypoplasia of vermian |
No |
No |
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Location of taenia-tela choroidea complex and choroid plexus |
Inferolateral displacement |
Superomedial placement/varies |
Hypoplasia of inferior vermian |
Superomedial placement |
Superomedial placement |
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* Measures most significant for Dandy-Walker syndrome | |||||
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Modified from (66; 82) | |||||
MRI can be used to diagnose Dandy-Walker syndrome pre- and postnatally with features described in Table 5. In addition to the features described in Table 5, other specific postnatal findings include the superior fossa angle, location of torcular, and height of the vermis (82). Regarding characteristics to consider for prenatal diagnosis, it is important to be aware that an enlarged fourth ventricle may be found at 14 to 16 weeks’ gestation as a transient phenomenon (14); thus, prenatal diagnosis is usually possible toward 20 weeks' gestation (24; 35). For experienced investigators, the diagnosis is usually possible by ultrasound. In some instances, however, differentiation of Dandy-Walker syndrome, mega cisterna magna, and retrocerebellar arachnoid cyst can be problematic (26). This difficulty has been largely mastered with increasing experience and technical advances (19). Pinto and colleagues have raised an alert regarding an important potential pitfall in early second trimester fetal MRI (55). They illustrate two fetuses with upward anti-clockwise rotation of the vermis at 21 and 20 weeks’ gestation, respectively, followed by complete normalization on follow-up imaging. They conclude that follow-up imaging is crucial in order not to misinterpret this anatomic situation and to avoid the potential risk of unnecessary pregnancy termination. Authors of another study suggest that the “tail sign” could be helpful in the differential diagnosis between Dandy Walker syndrome, vermian malrotation, and vermian hypoplasia (08). The “tail sign” appears as a “dysmorphic” and elongated end of the posterior vermis on the sagittal plane.
Boemer and colleagues observed (antenatally) a Dandy-Walker malformation in siblings with carnitine palmitoyltransferase II (CPT2) deficiency, a potential diagnostic pitfall (10).
Chromosomal aberrations are more frequent in prenatally diagnosed Dandy-Walker syndrome (76; 24). Microarray is recommended. Specific gene sequencing or phenotype-based gene panels can be used if other features suggest a genetic syndrome and chromosomal testing is normal.
Management
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• Treatment of Dandy-Walker syndrome involves monitoring for a treating hydrocephalus and providing developmental therapies, as needed. |
The treatment of Dandy-Walker syndrome is surgical. Direct surgery on the posterior cranial fossa and membrane excision, which was attempted previously, has been abandoned (33). Aggressive cyst fenestration has been re-recommended (80). Currently, the treatment of choice if progressive hydrocephalus is evident is some form of shunting. Controversy exists concerning the optimal proximal shunt placement. Some specialists initially prefer a standard ventriculoperitoneal shunt (34), whereas others first attempt a cystoperitoneal derivation (33). Combined shunting of the cyst and lateral ventricles is recommended by Osenbach and Menezes (49). In this subgroup of pediatric hydrocephalus, the possible role of third ventriculostomy versus cerebrospinal fluid shunt is not yet clear. Upward herniation of the posterior compartment through the tentorial incisura is uncommon but should be carefully monitored by follow-up neuroimaging.
In light of the frequently observed delayed milestones and cognitive impairment, evaluation of psychomotor development is essential for provision of supportive measures, including physiotherapy or special education.
Special considerations
Pregnancy
Prenatal diagnosis is possible after formation of the cerebellar vermis at 18 weeks’ gestation along with genetic testing for isolated versus non-isolated Dandy-Walker syndrome (Table 4) (18; 72).
Media
References
- 01
- Aldinger KA, Lehmann OJ, Hudgins L, et al. FOXC1 is required for normal cerebellar development and is a major contributor to chromosome 6p25.3 Dandy-Walker malformation. Nat Genet 2009;41(9):1037-42. PMID 19668217
- 02
- Aldinger KA, Timms AE, Thomson Z, et al. Redefining the etiologic landscape of cerebellar malformations. Am J Med Genet 2019;105(3):606-15. PMID 31474318
- 03
- Alves CAPF, Sidpra J, Manteghinejad A, et al. Dandy-Walker phenotype with brainstem involvement: 2 distinct subgroups with different prognosis. AJNR Am J Neuroradiol 2023;44(10):1201-7. PMID 37591769
- 04
- Barkovich AJ. Pediatric neuroimaging. 3rd ed. New York: Raven Press, 2000.
- 05
- Barkovich A, Dobyns W. Cerebellar Development: Bench to Bedside 2006 International Conference; November 9-12, 2006; Washington, DC.
- 06
- Bassuk AG, McLone D, Bowman R, Kessler JA. Autosomal dominant occipital cephalocele. Neurology 2004;62(10):1888-90. PMID 15159504
- 07
- Benda CE. The Dandy-Walker syndrome or the so-called atresia of the foramen of Magendie. J Neuropathol Exp Neurol 1954;13:14-29. PMID 13118372
- 08
- Bernardo S, Vinci V, Saldari M, et al. Dandy-Walker malformation: is the “tail sign” the key sign? Prenat Diagn 2015;35(13):1358-64. PMID 26448595
- 09
- Boddaert N, Klein O, Ferguson N, et al. Intellectual prognosis of the Dandy-Walker malformation in children: the importance of vermian lobulation. Neuroradiology 2003;45(5):320-4. PMID 12682795
- 10
- Boemer F, Deberg M, Schoos R, et al. Diagnostic pitfall in antenatal manifestations of CPT II deficiency. Clin Genet 2016;89(2):193-7. PMID 25827434
- 11
- Bolduc MR, Limperopoulos C. Neurodevelopmental outcomes in children with cerebellar malformations: a systematic review. Dev Med Child Neurol 2009;51(4):256-67. PMID 19191827
- 12
- Bordarier C, Aicardi J. Dandy-Walker syndrome and agenesis of the cerebellar vermis: diagnostic problems and genetic counseling. Dev Med Child Neurol 1990;32(4):285-94. PMID 2185113
- 13
- Brodal A, Hauglie-Hanssen E. Congenital hydrocephalus with defective development of the cerebellar vermis (Dandy-Walker syndrome). Clinical and anatomic findings in two cases with particular reference to the so-called atresia of the foramina of Magendie and Lluschka. J Neurol Neurosurg Psychiatry 1959;22:99-108. PMID 13655097
- 14
- Bronshtein M, Zimmer EZ, Blazer S. Isolated large fourth ventricle in early pregnancy—a possible benign transient phenomenon. Prenat Diagn 1998;18(10):997-1000. PMID 9826889
- 15
- Cacciagli P, Desvignes JP, Girard N, et al. AP1S2 is mutated in X-linked Dandy-Walker malformation with intellectual disability, basal ganglia disease and seizures (Pettigrew syndrome). Eur J Hum Genet 2014;22(3):363-8. PMID 23756445
- 16
- Calabro F, Arcuri T, Jinkins JR. Blake's pouch cyst: an entity within the Dandy-Walker continuum. Neuroradiology 2000;42(4):290-5. PMID 10872175
- 17
- Castro Conde JR, Martinez ED, Rodriguez RC, Rodriguez De Hoyos AL. CNS siderosis and Dandy-Walker variant after neonatal alloimmune thrombocytopenia. Pediatr Neurol 2005;32:346-9. PMID 15866436
- 18
- Cater SW, Boyd BK, Ghate SV. Abnormalities of the fetal central nervous system: prenatal US diagnosis with postnatal correlation. Radiographics 2020;40(5):1458-72. PMID 32706613
- 19
- Chapman T, Mahalingam S, Ishak GE, Nixon JN, Sibert J, Dighe MK. Diagnostic imaging of posterior fossa anomalies in the fetus and neonate: part 2, posterior fossa disorders. Clin Imaging 2015;39(2):167-75. PMID 25457569
- 20
- Dandy WE, Blackfan KD. Internal hydrocephalus: an experimental, clinical and pathological study. Am J Dis Child 1914;8:406-82.
- 21
- Darbro BW, Mahajan VB, Gakhar L, et al. Mutations in extracellular matrix genes NID1 and LAMC1 cause autosomal dominant Dandy-Walker malformation and occipital cephaloceles. Hum Mutat 2013;34(8):1075-9. PMID 23674478
- 22
- Dawra RD, Karia S, Shah N, Desousa A. Psychosis in a case of Dandy-Walker Syndrome: a case report. J Clin Diagn Res 2017;11(5):VD03-4. PMID 28658885
- 23
- Delahaye A, Khung-Savatovsky S, Aboura A, et al. Pre- and postnatal phenotype of 6p25 deletions involving the FOXc1 gene. Am J Med Genet Part A 2012;158A(10):2430-8. PMID 22903608
- 24
- Ecker JL, Shipp TD, Bromley B, Benacerraf B. The sonographic diagnosis of Dandy-Walker and Dandy-Walker variant: associated findings and outcomes. Prenat Diagn 2000;20(4):328-32. PMID 10740206
- 25
- Elterman RD, Bodensteiner JB, Barnard JJ. Sudden unexpected death in patients with Dandy-Walker malformation. J Child Neurol 1995;10(5):382-4. PMID 7499758
- 26
- Estroff JA, Parad RB, Barnes PD, Madsen JP, Benacerraf BR. Posterior fossa arachnoid cyst: an in utero mimicker of Dandy-Walker malformation. J Ultrasound Med 1995;14(10):787-90. PMID 8544249
- 27
- Friede RL. Developmental neuropathology. 2nd ed. Berlin: Springer-Verlag, 1989.
- 28
- Gerszten PC, Albright AL. Relationship between cerebellar appearance and function in children with Dandy-Walker syndrome. Pediatr Neurosurg 1995;23(2):86-92. PMID 8555101
- 29
- Hailu Z. Radiopedia: Dandy-Walker malformation. Available at: https://radiopaedia.org/articles/dandy-walker-malformation-1?lang=us. Accessed 2023.
- 30
- Haldipur P, Dang D, Aldinger KA, et al. Phenotypic outcomes in mouse and human Foxc1 dependent Dandy-Walker cerebellar malformation suggest shared mechanisms. Elife 2017;6. PMID 28092268
- 31
- Haldipur P, Gillies GS, Janson OK, et al. Foxc1 dependent mesenchymal signaling drives embryonic cerebellar growth. ELife 2014;3. PMID 25513817
- 32
- Hammond CH, Chitnavis B, Penny CC, Strong AJ. Dandy-Walker complex and syringomyelia in an adult: case report and discussion. Neurosurgery 2002;50(1);191-4. PMID 11844250
- 33
- Hirsch JF, Pierre-Kahn A, Renier D, Sainte-Rose C, Hoppe-Hirsch E. The Dandy-Walker malformation. A review of 40 cases. J Neurosurg 1984;61:515-22. PMID 6747688
- 34
- Kalidasan V, Carroll T, Allcutt D, Fitzgerald RJ. The Dandy-Walker syndrome--a 10-year experience of its management and outcome. Eur J Pediatr Surg 1995;5(Suppl 1):16-8. PMID 8770571
- 35
- Kolble N, Wisser J, Kurmanavicius J, et al. Dandy-Walker malformation: prenatal diagnosis and outcome. Prenat Diagn 2000;20(4):318-27. PMID 10740205
- 36
- Kollias SS, Ball WS, Prenger EC. Cystic malformations of the posterior fossa: differential diagnosis clarified through embryologic analysis. Radiographics 1993;13(6):1211-31. PMID 8031352
- 37
- Kosaki K, Curry CJ, Roeder E, Jones KL. Ritscher-Schinzel (3C) syndrome: documentation of the phenotype. Am J Med Genet 1997;68(4):421-7. PMID 9021015
- 38
- Limperopoulos C, Folkerth R, Barnewolt CE, Connolly S, Du Plessis AJ. Posthemorrhagic cerebellar disruption mimicking Dandy-Walker malformation: fetal imaging and neuropathology findings. Semin Pediatr Neurol 2010;17(1):75-81. PMID 20434704
- 39
- Long A, Moran P, Robson S. Outcome of fetal cerebral posterior fossa anomalies. Prenat Diagn 2006;26:707-10. PMID 16764010
- 40
- Maria BL, Bozorgmanesh A, Kimmel KN, Theriaque D, Quisling RG. Quantitative assessment of brainstem development in Joubert syndrome and Dandy-Walker syndrome. J Child Neurol 2001;16(10):751-8. PMID 11669349
- 41
- Marnet D, Vinchon M, Mostofi K, Catteau B, Kerdraon O, Dhellemmes P. Neurocutaneous melanosis and the Dandy-Walker complex: an uncommon but not so insignificant association. Childs Nerv Syst 2009;2:1533-9. PMID 19711088
- 42
- McGraw P. The molar tooth sign. Radiology 2003;229(3):671-2. PMID 14657304
- 43
- McNiven V, Ito YA, Hartley T, at al. NID1 variant associated with occipital cephaloceles in a family expressing a spectrum of phenotypes. Am J Med Genet A 2019;179(5):837-41. PMID 30773799
- 44
- Messerschmidt A, Brugger PC, Boltshauser E, et al. Disruption of cerebellar development: potential complication of extreme prematurity. AJNR 2005;26:1659-67. PMID 16091510
- 45
- Morava E, Adamovich K, Czeizel AE. Dandy-Walker malformation and polydactyly: a possible expression of hydrolethalus syndrome. Clin Genet 1996;49(4):211-5. PMID 8828988
- 46
- Murray JC, Johnson JA, Bird TD. Dandy-Walker malformation: etiologic heterogeneity and empiric recurrence risks. Clin Genet 1985;28(4):272-83. PMID 4064366
- 47
- Nelson MD Jr, Maher K, Gilles FH. A different approach to cysts of the posterior fossa. Pediatr Radiol 2004;34(9):720-32. PMID 15316692
- 48
- Olson GS, Halpe DC, Kaplan AM, Spataro J. Dandy-Walker malformation and associated cardiac anomalies. Childs Brain 1981;8(3):173-80. PMID 7238134
- 49
- Osenbach RK, Menezes AH. Diagnosis and management of the Dandy-Walker malformation: 30 years of experience. Pediatr Neurosurg 1992;18(4):179-89. PMID 1472430
- 50
- Ozkinay F, Ozyurek AF, Bakiler AR, et al. A case of Marden-Walker syndrome with Dandy-Walker malformation. Clin Genet 1995;47(4):221-3. PMID 7543036
- 51
- Pascual-Castroviejo I, Velez A, Pascual-Pascual SI, Roche MG, Villarejo F. Dandy-Walker malformation: analysis of 38 cases. Childs Nerv Syst 1991;7(2):88-97. PMID 1863935
- 52
- Pellock JM, Johnson MH. Dandy-Walker malformation. In: Lechtenberg R, editor. Handbook of cerebellar diseases. New York: Marcel Dekker Inc, 1993:147-62.
- 53
- Pichiecchio A, Decio A, Di Perri C, Parazzini C, Rossi A, Signorini S. “Acquired” Dandy-Walker malformation and cerebellar hemorrhage: usefulness of serial MRI. Eur J Paediatr Neurol 2016;20(1):188-91. PMID 26507178
- 54
- Pinchefsky EF, Accogli A, Shevell M, Saint-Martin C, Srour M. Developmental outcomes in children with congenital cerebellar malformations. Dev Med Child Neurol 2019;61(3):350-8. PMID 30320441
- 55
- Pinto J, Paladini D, Severino M, et al. Delayed rotation of the cerebellar vermis: an important pitfall in early second trimester fetal MR imaging studies. Ultrasound Obstet Gynecol 2016;48(1):121-4. PMID 26482947
- 56
- Reese V, Frieden IJ, Paller AS, et al. Association of facial hemangiomas with Dandy-Walker and other posterior fossa malformations. J Pediatr 1993;122(3):379-84. PMID 8441091
- 57
- Ritscher D, Schinzel A, Boltshauser E, Briner J, Arbenz U, Sigg P. Dandy-Walker (like) malformation, atrio-ventricular septal defect and a similar pattern of minor anomalies in 2 sisters: a new syndrome. Am J Med Genet 1987;26(2):481-91. PMID 3812597
- 58
- Robinson AJ. Inferior vermian hypoplasia—preconception, misconception. Ultrasound Obstet Gynecol 2014;43(2):123-36. PMID 24497418
- 59
- Salihu HM, Kornosky JL, Druschl CM. Dandy-Walker syndrome, associated anomalies and survival through infancy: a population-based study. Fetal Diagn Ther 2008;24:155-60. PMID 18648217
- 60
- Santoro M, Coi A, Barisic I, et al. Epidemiology of Dandy-Walker malformation in Europe: a EUROCAT population-based registry study. Neuroepidemiology 2019;53(3-4):169-79. PMID 31302658
- 61
- Sarnat HB. Cerebral dysgenesis: embryology and clinical expression. New York: Oxford University Press, 1992.
- 62
- Sartori S, Ludwig K, Fortuna M, et al. Dandy-Walker malformation masking the molar tooth sign: an illustrative case with magnetic resonance imaging follow-up. J Child Neurol 2010;25(11):1419-22. PMID 20823032
- 63
- 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;2:194-9. PMID 18759601
- 64
- Sato K, Kubota T, Nakamura Y. Adult onset of the Dandy-Walker syndrome. Br J Neurosurg 1996;10(1):109-12. PMID 8672253
- 65
- Schmahmann JD, Sherman JC. The cerebellar cognitive affective syndrome. Brain 1998;121(Pt 4):561-79. PMID 9577385
- 66
- Sharma R. Radiopedia: Tegmentovermian angle. Available at: https://radiopaedia.org/articles/tegmentovermian-angle?lang=us. Accessed 2022.
- 67
- Shenoy RD, Kamath N. Dandy-Walker malformation, occipital menginoencephalocele, meso-axial polydactyly and bifid hallux. Clin Dysmorphol 2010;19(3):166-8. PMID 20436349
- 68
- Sinha P, Tarwani J, Kumar P, Garg A. Dandy-Walker variant with schizophrenia: comorbidity or cerebellar cognitive affective syndrome? Indian J Psychol Med 2017;39(2):188-90. PMID 28515557
- 69
- Stambolliu E, Ioakeim-Ioannidou M, Kontokostas K, Dakoutrou M, Kousoulis AA. The most common comorbidities in Dandy-Walker Syndrome patients: a systematic Review of case reports. J Child Neurol 2017;32(10):886-902. PMID 28635420
- 70
- Steiner JE, McCoy GN, Hess CP, et al. Structural malformations of the brain, eye, and pituitary gland in PHACE syndrome. Am J Med Genet A 2018;176(1):48-55. PMID 29171184
- 71
- Steinlin M, Schmid M, Landau K, Boltshauser E. Follow-up in children with Joubert syndrome. Neuropediatrics 1997;28(4):204-11. PMID 9309710
- 72
- Sun Y, Wang T, Zhang N, Zhang P, Li Y. Clinical features and genetic analysis of Dandy-Walker syndrome. BMC Pregnancy Childbirth 2023;23(1):40. PMID 36653756
- 73
- Sutton JB. The lateral recesses of the fourth ventricle: their relation to certain cysts and tumors of the cerebellum, and to occipital meningocele. Brain 1887;9:352.
- 74
- Taggart JK, Walker AE. Congenital atresia of the foramens of Luschka and Magendie. Arch Neurol Psychiatry 1942;48:583-612.
- 75
- Tan EC, Takagi T, Karasawa K. Posterior fossa cystic lesions - magnetic resonance imaging manifestations. Brain Dev 1995;17(6):418-24. PMID 8747420
- 76
- Ulm B, Ulm MR, Deutinger J, Bernaschek G. Dandy-Walker malformation diagnosed before 21 weeks of gestation: associated malformations and chromosomal abnormalities. Ultrasound Obstet Gynecol 1997;10(3):167-70. PMID 9339523
- 77
- Ulrich J, Caird J, Crimmins D. Predicting outcomes in Dandy-Walker malformation: a retrospective cohort study. J Neurosurg Pediatr 2021;28(6):710-5. PMID 34507295
- 78
- Van De Weghe JC, Rusterholz TDS, Latour B, et al. Mutations in ARMC9, which encodes a basal body protein, cause Joubert Syndrome in humans and ciliopathy phenotypes in zebrafish. Am J Hum Genet 2017;101(1):23-36. PMID 28625504
- 79
- Venkatesan C, Kline-Fath B, Horn PS, Poisson KE, Hopkin R, Nagaraj UD. Short- and long-term outcomes of prenatally diagnosed Dandy-Walker malformation, vermian hypoplasia, and Blake pouch cyst. J Child Neurol 2021;36(12):1111-9. PMID 34757866
- 80
- Villavicencio AT, Wellons JC 3rd, George TM. Avoiding complicated shunt systems by open fenestration of symptomatic fourth ventricular cysts associated with hydrocephalus. Pediatr Neurosurg 1998;29(6):314-9. PMID 9973679
- 81
- Weisbrod LJ, Thorell W. Mega cisterna magna. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2023. PMID 35881738
- 82
- Whitehead MT, Barkovich MJ, Sidpra J, et al. Refining the neuroimaging definition of the Dandy-Walker phenotype. AJNR Am J Neuroradiol 2022;43(10):1488-93. PMID 36137655
- 83
- Yildiz H, Yazici Z, Hakyemez B, et al. Evaluation of CSF flow patterns of posterior fossa cystic malformations using CSF flow MR imaging. Neuroradiology 2006;48:595-605. PMID 16752134
- 84
- Zamora EA, Das JM, Ahmad T. Dandy-Walker malformation. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2023. PMID 30855785
Contributors
All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.
Authors
-
Margie A Ream MD PhD
Dr. Ream of Ohio State University College of Medicine received consulting fees from Ionis Pharmaceuticals, INC.
See Profile -
John Barba
Mr. Barba of Ohio State University College of Public Health has no relevant financial relationships to disclose.
See Profile
Editor
-
Ganeshwaran H Mochida MD
Dr. Mochida of Boston Children's Hospital and Harvard Medical School has no relevant financial relationships to disclose.
See Profile
Former Authors
- Eugen J Boltshauser MD
- Joseph R Siebert PhD
Patient Profile
- Age range of presentation
-
- 0 month to 44 years
- Sex preponderance
-
- female>male,>1:1
- Heredity
-
- heredity may be a factor, if part of a defined syndrome (Table 1)
- Population groups selectively affected
-
- none selectively affected
- Occupation groups selectively affected
-
- none selectively affected
ICD & OMIM codes
- ICD-9
-
- Dandy-walker syndrome: 742.3
- ICD-10
-
- Dandy-walker syndrome: Q03.1
- OMIM
-
- Dandy-Walker syndrome: %220200
- Dandy-Walker malformation with occipital cephalocele, autosomal dominant: %609222 (Note: reports associated posterior fossa anomalies, but not Dandy-Walker syndrome according to our definition)
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