Dandy Walker Complex

Course

The Dandy-Walker complex consists of the classic Dandy-Walker malformation (DWM), Dandy-Walker variants, and a mega cisterna magna.

The characteristic findings with a Dandy-Walker malformation (Fig. 1) consists of an enlarged cisterna magna, an absent cerebellar vermis, and superior displacement of the tentorium (Fig. 2)¹. Although ventriculomegaly is present in the majority of cases of DWM, it is not required for the diagnosis². Ventriculomegaly often develops postnatally³.

Figure 1. Dandy-Walker malformation.

Figure 2. Normal cerebellum. Normal insertion of the tentorium (arrow).

The Dandy-Walker variant has a variable degree of cerebellar vermian hypoplasia with or without enlargement of the posterior fossa. Inferior vermian defects are more common than classic DWM, occurring in 57% - 75% of cases^4,5.MRI studies have shown that a clear distinction between a DWM and a Dandy-Walker variant is not consistently possible².

A mega cisterna magna (Fig. 3) has been defined as a posterior fossa ? 10 mm with a normal cerebellar vermis and 4^th ventricle.

Figure 3. Mega cisterna magna (arrow).

The continuum from classic DWM to mega cisterna magna relates to the timing and severity of the insult on the developing brain. With a DWM, the roof of the 4^th ventricle and the cerebellar vermis are affected (Fig. 4). A Dandy-Walker variant may be due to a more localized cerebellar insult. If only the roof of the 4th ventricle is affected a mega cisterna magna with a normal cerebellum will result^2,6,7.

Figure 4. Dandy-Walker malformation.

The prevalence of Dandy-Walker malformation has been estimated at 1/30,000 births⁸. The recurrence risk for isolated DWM is 1% to 5%⁹.

Associated malformations occur in 50 to 70% of cases with DWM (Table I)⁸. As the number of associated anomalies increases, so does the neonatal mortality rate and the likelihood of a karyotypic abnormality³. Neonates with two or more other anomalies are six times more likely to die than neonates with an isolated DWM¹⁰. Agenesis of the corpus callosum (Fig. 5) is a frequently associated central nervous system malformation. Cardiac anomalies are also commonly associated with DWM.

Table I. Congenital Anomalies Associated with Dandy-Walker Malformation^34,45,46

• Agenesis of the corpus callosum
• Holoprosencephaly
• Microcephaly
• Encephalocele
• Ventriculomegaly
• Congenital diaphragmatic hernia
• Cystic hygromas
• Cleft lip and palate
• Schizencephaly
• Meningomyelocele
• Polydactyly/syndactyly
• Polycystic kidneys

Figure 5. Dandy-Walker malformation and agenesis of the corpus callosum (arrow).

Karyotypic abnormalities are present in 40% of fetuses with DWM⁴. A DWM is, therefore, a significant sonographic marker for a chromosomal abnormality. The most common karyotypic abnormalities associated with DWM are trisomy 13, 18 and 21^3,4.In a fetus with DWM, a transverse cerebellar diameter < 5^th centile suggests cerebellar hypoplasia and a possible karyotypic abnormality¹¹.

There are a number of syndromes that may have a DWM as one component (Table II).

Table II. Syndromes Associated with Dandy-Walker Malformations

• Aicardi
• Fryns
• Meckel-Gruber
• Smith-Lemli-Opitz
• Walker-Warburg

Aicardi Syndrome

The Aicardi syndrome characteristically consists of callosal agenesis, ocular abnormalities and infantile spasms¹². Additional features include vertebral anomalies, mental delay and Dandy Walker malformation¹³. Early embryologic over distension of the neural tube is the cause for both the congenital absence of the corpus callosum, as well as the Dandy Walker malformation¹⁴.

This disorder is lethal in males and is, therefore, only detected in karyotypically normal females.

Fryns Syndrome

Fryns syndrome is an autosomal recessive disorder with multiple congenital anomalies (Table III)¹⁵.

Table III. Clinical manifestations of Fryns syndrome^15,16

• Facial anomalies
• Micropthalmia
• Anophthalmia
• Microcephaly
• Cerebellar hypoplasia
• Dandy-Walker malformation
• Agenesis of the corpus callosum
• Ventriculomegaly
• Cystic hygroma
• Diaphragmatic hernia
• Pulmonary hypoplasia
• Cardiac defects
• Narrow thorax
• Renal dysplasia
• Small bowel atresia
• Imperforate anus
• Distal limb hypoplasia
• Fetal hydrops
• Polyhydramnios

Phenotypia expression is highly variable. Fryns syndrome is the most common autosomal recessive syndrome with a congenital diaphragmatic hernia¹⁶. However, a diaphragmatic hernia is not necessarily a feature of Fryns syndrome¹⁷. Survival with Fryns syndrome is improved without a diaphragmatic hernia¹⁸. The incidence of FS is 1/14,000¹⁶.

A Dandy Walker malformation occurs from in 10%¹⁶ to 50%¹⁹ of cases.

Approximately 10% of patients with congenital diaphragmatic hernia have Fryns syndrome²⁰.

Meckel-Gruber Syndrome (MGS)

Meckel-Gruber syndrome (MGS) is a lethal autosomal recessive condition. It has been mapped to six different loci on different chromosomes²¹.

The triad of common findings with MGS include: cystic renal dysplasia; occipital encephalocele; and post-axial polydactyly. These specific stamata are found in 100% , 90%, and 83.3% of cases, respectively²². However, there are wide phenotypic variations (Table IV).

Table IV. Congenital Anomalies Associated with Meckel-Gruber Syndrome⁴⁷

• Dandy-Walker malformation
• Occipital encephalocele
• Microcephaly
• Ventriculomegaly
• Cleft lip/palate
• Micrognathia
• Cardiac malformations
• Syndactyly
• Polydactyly
• Club foot
• Renal dysplasia

A Dandy Walker malformation is one of the central nervous system malformations associated with this syndrome²³.

Pulmonary hypoplasia, due to the associated dysplastic kidneys and oligohydramnios, is the leading cause of death.

Prenatal diagnosis in affected families has occurred in the 1st trimester²⁴.

The incidence of MGS is between 1/13,250 and 1/140,000. The incidence in Finland is 1/9,000²³.

Dandy Walker malformation and occipital encephaloceles are due to disturbances in the development of the rhombencephalon²⁵.

MGS is the most common syndromic etiology for neural tube defects; accounting for 5% of neural tube defects.

Approximately half of families with more than one child affected by MGS may have different manifestations of the syndrome²⁶. In one series only 18% of subsequently affected siblings had all three of the classic defects²⁷.

Smith-Lemli-Opitz Syndrome (SLOS)

SLOS is an autosomal recessive disorder with multiple congenital anomalies (Table V), intra-uterine growth restriction and developmental delay.

Table V. Congenital anomalies associated with Smith-Lemli-Opitz^28,29,48

• Dandy-Walker malformation
• Ventriculomegaly
• Microcephaly
• Cataracts
• Micrognathia
• Cleft palate
• Congenital heart defects
• Renal anomalies
• Mesomalic shortening
• Syndactyly of the 2nd and 3rd toes
• Polydactyly
• Genital malformations (phenotypic/karyotypic discordance)
• Intra-uterine growth restriction

The biochemical defect results in a significant reduction in the final enzyme (7-dehydrocholesterol reductase) in the cholesterol pathway. While there have been multiple mutations identified, seven mutations account for almost 70% of the cases²⁸.

SLOS has a wide phenotypic expression that extends from isolated syndactyly to holoprosencephaly. The severity of anomalies in a particular case may relate to the degree that cholesterol production is inhibited by the specific mutation resulting in SLOS²⁹.

Walker-Warburg Syndrome (WWS)

WWS is a severe form of congenital muscular dystrophy. The characteristic features of WWS are outlined in Table VI. Its estimated incidence is 1.7/100,000. Most children die by the age of three³⁰.

Table VI. Congenital defects associated with Walker-Warburg syndrome³¹

Congenital Defect Frequency
Lissencephaly21/21
Cerebellar malformation 20/20
Retinal abnormality18/18
Muscular dystrophy14/14
Ventriculomegaly20/21
Dandy-Walker10/19
Microphthalmia8/21
Congenital cataracts7/20
Posterior encephalocele 5/21

*Data obtained from 21 patients.

WWS is an autosomal recessive disorder. 10-20% of cases can be confirmed by DNA analysis of mutations in the protein O-mannosyltransferase 1 (POMT 1) gene^31,32. The genetic basis for the majority of cases are not known. In families with a known family member, antenatal ultrasound has detected ventriculomegaly, as early as 13 weeks’ gestation³³ and an occipital encephalocele was detected in another case at 18 weeks’ gestation³⁴.

1st Trimester Associaton with Dandy-Walker Malformations

First trimester congenital infections, and warfarin or alcohol exposure have been associated with DWM^35,36.

Sonographic Findings

The 1996 guidelines for the performance of a standard 2^nd trimester ultrasound examination included an assessment of the cerebellum and cisterna magna (Fig 6)³⁷.

Figure 6. . Normal transaxial image of the cerebellum and vermis.

The sonographic detection of DWM has been reported as early as 14 weeks' gestation³⁸.

The cerebellar vermis forms beginning superiorly at a gestational age of 9 weeks and progresses inferiorly until the process is complete at around 15 weeks' gestation⁴. By 18 weeks' gestation the cerebellum and vermis have their customary appearance⁴⁰. A diagnosis should not, therefore, be made until ? 18 weeks’ gestation^39,40.

False positive diagnoses of a DWM or Dandy-Walker variant result when only axial images are obtained or the cerebellum is scanned in an angled semi-coronal plane (Fig. 7)^41,42.

Figure 7. Semi-coronal angle through a normal 4^th ventricle (arrow).

An elevation of a normal vermis towards the tentorium (Fig. 8) can suggest the presence of vermian defect when one is not present^1,4,41. With two-dimensional sonography the suggestion of a small vermian defect is usually a false positive. The characteristic gap between the cerebellar hemispheres with Dandy-Walker malformation has a trapezoid (Fig. 9), rather than a "key-hole", appearance⁴³. To improve the diagnostic accuracy of antenatal sonography in the detection of Dandy-Walker malformation, at least two scanning planes should be used⁴⁴. A three-dimensional coronal view provides the best evaluation of the vermis (Figs. 10 a,b).

Figure 8. Elevation of normal vermis (arrow).

Figure 9. Trapezoid gap between cerebellar hemisphere (arrow).

Figure 10a. 3D Parasagittal view of vermis (v).

Figure 10b. Vermian hypoplasia (markers).

Because of the subtleties involved in the antenatal sonographic detection of either cerebellar vermian hypoplasia or cerebellar dysplasia, antenatal sonography permits the diagnosis of only a classic DWM with any degree of certainty. Neuropathologic examination fails to corroborate a diagnosis of DWM in 59% of cases. A similar, or higher, false positive rate occurs with Dandy-Walker variant, i.e. agenesis of the inferior cerebellar vermis⁴³.

Neonatal Outcome

Developmental delay has been reported in approximately 50% of cases with isolated DWM³. It has been suggested that developmental delay is due to associated central nervous system anomalies rather than to vermian absence³⁵. The overall prognosis, i.e. normal development to severe disability, appears to be similar with a complete absence of the vermis and inferior vermian agenesis^4,11. The liveborn mortality rate among fetuses with DWM is approximately 40%⁴.

The outcome of fetuses with DWM is worse than for neonates with a similar condition. This discrepancy is due to severe associated anomalies or karyotypic abnormalities found in the fetuses diagnosed with DWM³⁵.

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References

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