Dandy Walker Complex

Under this term are included a group of conditions that share in common
one sonographic findings: the impression that the fourth ventricle
communicates with the cisterna magna. These conditions include: Dandy-
Walker malformation, Blake’s pouch cyst, vermian hypoplasia/agenesis.
They have a similar sonographic appearance, particularly in early
gestation, and differentiation requires a multiplanar approach.

Abstract: Under this term are included a group of conditions that share in
common one sonographic findings: the impression that the fourth ventricle
communicates with the cisterna magna. These conditions include: Dandy-
Walker malformation, Blake’s pouch cyst, vermian hypoplasia/agenesis. They
have a similar sonographic appearance, particularly in early gestation, and
differentiation requires a multiplanar apparoach. Magnetic resonance mey also
be useful. The prognosis is variable, and depends mostly upon the frequent
occurrence of associated anomalies. Blake’s pouch cyst, the most common
entity, when isolated is probably a normal variant.

Key words: Blake’s pouch cys, Dandy-Walker malformation, Joubert syndrome ,

vermian agenesis, vermian hypoplasia, COACH syndrome, CORS syndrome,
oral-facial-digital syndrome type VI, Senior–Løken syndrome

Authors: Gianluigi Pilu1, Gustavo Malinger2, Selim Buyukkurt3

1. Department of Obstetrics and Gynecology of the University of Bologna, Italy

2. Fetal Neurology Clinic, Department of Obstetrics and Gynecology, Wolfson
Medical Center, Holon, Israel
3. Departmet of Obstetrics and Gynecology, University of Cukurova, Adana,
Turkey

Includes:
Dandy Walker malformation, vermian hypoplasia, vermian agenesis, Blake’s
pouch cyst, Joubert syndrome and related entities (vermian agenesis/hypoplasia
with ‘molar tooth’ sign)

Excludes:

Megacisterna magna, cerebellar hypoplasia

Definition
Dandy-Walker malformation defines the combination of an enlarged cisterna
with superior displacement (rotation) of the cerebellar vermis.1-5 The
term Dandy-Walker complex (or continuum) indicates a spectrum of anomalies
with anatomic similarities to Dandy-Walker malformation. There is no general
consensus in the categorization of posterior fossa anomalies and the interested
reader is referred to specific works on this subjects.1-5 In this section we include
a group of anomalies that share in common one sonographic finding: the
impression that in a axial plane of the head the fourth ventricle is open
posteriorly and communicates with the cisterna magna. This finding will be
referred to in the following as the ‘open fourth ventricle’. The most frequent
anomalies that demonstrate this sign include: Blake’s pouch cyst, vermian
agenesis/hypoplasia, Dandy-Walker malformation; Joubert syndrome and
related entities (vermian agenesis/hypoplasia with ‘molar tooth’ sign) The
rational for grouping them together is that they are often difficult to differentiate
and they tend to overlap clinically.

Incidence
Dandy-Walker malformation is found in 4-12% of all cases of infantile
hydrocephalus and has an estimated prevalence of about 1:30,000 births.6-8
The incidence of the other varieties of the Dandy-Walker complex is unknown.

Embryology and Pathogenesis

In the late first trimester, the fourth ventricle is large and a relatively small
cerebellum is found on top of it. In the following weeks the cerebellum grows to
enfold completely the fourth ventricle. However, a small finger-like appendage
of the fourth ventricle, the Blake’s pouch, is frequently seen protruding into the
cisterna magna, caudally to the cerebellum. It has been suggested that there is
a continuum of anatomic anomalies involving the fourth ventricle-Blake’s pouch
complex.9 The mildest of these anomalies is the Blake’s pouch cyst, a persistence
of the Blake’s pouch that results in an isolated superior displacement of the
cerebellar vermis.10, 11 At the other end of the spectrum stands the Dandy-Walker
malformation, where the upward displacement of a normal to hypoplastic
vermis is associated with an enlargement of the cisterna magna.1-4 In vermian
hypoplasia (previously referred to as Dandy-Walker variant) the cisterna magna
is of normal size and the vermis is small and frequently (although not always)
rotated upward.1-4, 12, 13 Many cases of the mildest anomaly in this group, the
Blake’s pouch cyst, resolve spontaneously throughout gestation and therefore
probably represent a delay in normal anatomic development. 10 In the other
entities of the Dandy-Walker complex, the expansion of the fourth ventricle is
concomitant with aberrant development of the cerebellum and of the vermis in
particular, and these cases are more likely to be associated with neurologic
compromise. The Dandy-Walker malformation was originally described in
individuals with obstructive hydrocephalus and was postulated to arise from a
primary atresia of the foramina of Luschka and Magendie.6, 8 A similar
explanation was proposed for the Blake’s pouch cyst.14 It is now clear that most
patients with the Dandy Walker complex do not develop hydrocephalus
suggesting that the pathogenesis is more complex and is not merely the
consequence of obstruction and overdistension of the fourth ventricle. Several
hypotheses have been formulated but there is no clear evidence supporting any
of them.

Pathology
Enlargement of the Blake’s pouch (or of the entire fourth ventricle in the most
severe forms) is responsible for the superior displacement of the vermis that is
encountered in the Dandy-Walker complex. The enlarged Blake’s pouch/fourth
ventricle balloons into the cisterna magna and in the most severe cases
obliterates it and distend the posterior fossa. With most techniques of
diagnostic imaging, whether prenatal or postnatal, the thin walls of the Blake’s
pouch/fourth ventricle are difficult to visualize and the impression is that of a
communication between the fourth ventricle and the cisterna magna.9, 15

The term Blake’s pouch cyst was originally introduced in infantile neuroradiology
to indicate a type of obstructive hydrocephalussecondary to failure of formation
of the foramen of Magendie and Luschka, resulting in a compressive cyst of the
posterior fossa displacing superiorly the cerebellar vermis.14, 16 More recently, the
term has become popular in fetal imaging studies to indicate cases with a
posterior fossa cyst displacing superiorly an intact cerebellar vermis, typically in
association with a normal ventricular system and a normal size of the posterior
fossa.3, 4, 10, 17 This finding has been interpreted as failed or delayed regression of
the Blake’s pouch. The entity described in the original neonatal studies and the
one later described in fetal studies are likely to be different, as the latter has
typically a normal outcome and appears to be rarely associated with
ventriculomegaly.

Vermian agenesis/hypoplasia is characterized by a small vermis with a normal

cisterna magna; it has been suggested that the term hypoplasia should be
limited to cases in which the vermis is small but has a normal morphology (all
the lobules are present); conversely, the term partial agenesis should be used in
those cases in which a part, typically the most inferior portion is absent. In these
patients the cisterna magna has a normal size.4, 5, 10, 18, 19 This condition was
originally defined as Dandy-Walker variant20, 21 a term no longer in use.
Dandy-Walker malformation is characterized by the enlargement of the cisterna
magna. The cerebellar vermis is significantly rotated and may be intact or
incompletely formed.1, 3, 4, 10 Hydrocephalus was classically considered an
essential diagnostic element of this condition, but more recent evidence
suggests that it is not present at birth in most patients, although it may develops
in later life.6, 8

Joubert syndrome and related disorders are a group of conditions that share in
common hypoplasia of the cerebellar vermis in association with the
characteristic neuroradiologic 'molar tooth sign. These features are associated
with extraneural anomalies to constitute different syndromes: classical Joubert
syndrome, Coloboma, Oligophrenia/developmental delay, Ataxia, Cerebellar
vermis hypoplasia, Hepatic fibrosis (COACH), cerebello-oculo-renal syndrome
(CORS), oral-facial-digital syndrome type VI (OFD-VI), Senior–Løken syndrome.
The gene products that are affected in these group of conditions are however
known to take part into the development of the primary cilium and/or basal
body and centrosome apparatus. Essentially, Joubert and related disorders are
now considered to belong to the general group of ciliopathies.22-24

Etiology
Genetic factors have a major role in the etiology of the Dandy-Walker complex.
Dandy-Walker malformation and vermian hypoplasia/agenesis may occur as a
part of Mendelian disorders and chromosomal aberrations.25 In rare cases, the
disease is inherited as an autosomal recessive or dominant trait. Environmental
factors, including viral infections, alcohol and diabetes, have also been
suggested to play a role in the genesis of Dandy-Walker malformation, but the
evidence is uncertain.25 Joubert syndrome and related entities have a genetic
etiology with autosomal recessive or X-linled transmission. The genetics is
however complex with at least 8 genes involved.

Recurrence risk
In the absence of a recognizable syndrome, a recurrence risk of 1-5% is
suggested for Dandy-Walker malformation and vermian
hypoplasia/agenesis.25 Autosomal transmission, both dominant and recessive
has been documented. There are no available information on Blake’s pouch cyst,
and vermian agenesis/hypoplasia include probably a number of heterogeneous
entities. Joubert and related cerebellar disorders are transmitted as an
autosomal or X-linked recessive trait and have therefore a high recurrence
risk. 22-24

Associated anomalies
The Dandy-Walker complex is frequently associated with chromosomal
aberrations, syndromes and other cerebral malformations (mostly
ventriculomegaly, agenesis of the corpus callosum, holoprosencephaly,
cephaloceles), polycystic kidneys, cardiovascular defects and facial clefting. 10, 11,
21 A detailed list of condition found in association with Dandy-Walker
malformation is reported in Table 1.

Diagnosis
The landmark of the Dandy-Walker complex is the open fourth ventricle. This is
demonstrated by sweeping the transducer in the posterior fossa along the axial
plane and visualizing a fluid-filled tract seemingly connecting the cavity of the
fourth ventricle to the cisterna magna. In early gestation this is a normal finding,
as the developing cerebellar vermis has not yet completely enfolded the fourth
ventricle.26-28 It is therefore imprudent to make a diagnosis of the Dandy-
Walker complex at this gestational age, with the possible exception of those
(rare) cases in which there is an obvious cystic enlargement of the cisterna
magna or other abnormal findings. After 20 weeks the vermis has normally
‘closed’ the fourth ventricle and therefore the demonstation an opening is
indicative of the Dandy Walker complex.
The varieties of the Dandy-Walker complex have much different prognostic
implications. Differentiation may be difficult at times, and requires a systematic
approach using multiplanar examinations possibly aided by magnetic
resonance. Assessement includes evaluation of the vermis (absent, hypoplastic,
intact), and of the cisterna magna (normal, enlarged).3, 4, 10 The degree of
vermian rotation is also relevant.29 The evaluation of these findings is difficult
and involves an elements of subjectivity, but an expert examiner using either
sonography or magnetic resonance (or both) is able to make a precise diagnosis
in the majority of cases,4, 10, 13, 19 probably with the remarkable exception of
subtle vermian hypoplasia/partial agenesis.10, 13, 19

To assess the presence of the vermis the best approach is to sweep the
transducer in the posterior fossa along the axial plane. The vermis appears as
an ovalar echogenic structure interposed between the fourth ventricle and the
cisterna magna. When this is not seen and the area of the fourth ventricle is
seen to communicate with the cisterna magna at any level, vermian agenesis
can be inferred.30, 31

To assess the integrity of the vermis and the position of the torcular a median
view is required. This can be obtained directly by multiplanar imaging, scanning
preferably through the posterior fontanel as this allows better visualization of
posterior fossa and brain stem. Three dimensional ultrasound can also been
utilized.32, 33 Indeed, one of the major shortcomings in the median view is the
difficulty to obtain with absolute precision the exact plane of section and to
confuse the cerebellar hemispheres with the vermis. The advantage of three
dimensional ultrasound is to control the sections using as reference the
orthogonal planes. The use of volume contrast imaging may also facilitate
visualization of subtle anatomic details.32, 33 Once the vermis has been
identified in the median plane, both a qualitative and a quantitative evaluation
should be performed. It has been suggested that if the posterior apex (fastigium)
of the fourth ventricle and the two main fissures of the vermis can be identified,
the vermis is presumably intact.10, 19, 32-35 The secondary fissure is at times
difficult to define in early gestation and a semiquantitative approach can be
used alternatively (normally, twice as much vermis is found below than above
the primary fissure.34Measurements of the fetal cerebellar vermis have been
reported.36, 37 Most cases of defective vermis involve agenesis of the caudal
portion and therefore the vertical diameter is probably the most relevant one.
A small vermis with an abnormal configuration (absence of fastigium and/or
fissure) indicates partial agenesis. Conversely, a small vermis with a normal
configuration indicates hypoplasia.5, 10, 19, 35 In practice, the distinction
between these two entities in the fetus is difficult.

A word of caution is needed regarding the possibility to obtain` a truly,

apparently normal, median plane by 2D or 3D ultrasound in a fetus with
complete vermian agenesis due to the fact that the cerebellar hemispheres may
be displaced into the midline and in contact with each other.30, 31 In these
patients the coronal plane may be useful to demonstrate that the vermis is
absent and the folia abnormally oriented.30, 31, 38

The degree of rotation of the cerebellar vermis is also relevant. It has been
recently demonstrated that the Blake’s pouch cyst has usually a rotation of less
than 30°, while a value in excess of 45° favors the diagnosis of a Dandy-Walker
malformation.29

Postnatally, the expansion of the cisterna magna is evaluated by observing the

torcular Herophilii. Normally the torcular Herophilii is implanted in the inner skull
at the same level of neck muscles. When the cisterna magna is expanded the
torcular is displaced upward. This evaluation is difficult with antenatal
ultrasound, and magnetic resonance is usually more effective. 4, 10

The Blake’s pouch cyst, which is by far the most frequent variety encountered
prenatally is featured by a slight (< 30°) rotation of an intact cerebellar vermis
with a normal cisterna magna.17, 29 Vermian hypoplasia/partial agenesis is
featured by an upward displacement of a small vermis, while the cisterna magna
and torcula are normal (Figure 7).5, 13 The landmark of the Dandy-Walker
malformation is the large cisterna magna and the consequent superior
displacement of the torcular. The vermis is always significantly rotated
superiorly (>45°)29 and may be either normal or defective.35, 39 It has been
suggested that the shape of the opening of the fourth ventricle in the axial plane
is relevant for the differential diagnosis of the different varieties of the Dandy-
Walker complex.40 Also in our experience, an hourglass opening (buttock sign)
is typical of the Blake’s pouch. A triangular or square shaped opening is
indicative of either vermian hypoplasia or Dandy-Walker malformation).

Postnatally, the predominant finding of Joubert syndrome and related entities

the typical appearance of the mesencephalon in the axial plane commonly
referred to as 'molar tooth sign,' that is the consequence of a deep posterior
interpeduncular fossa with thick and elongated superior cerebellar peduncles,
associated with variable degree of hypoplasia or agenesis of the cerebellar
vermis. In pregnancies at risk, the demonstration of an open fourth ventricle in
the axial plane has been described as the most important finding. The authors
of the original report have not found sagittal planes to be of value.30 Indeed the
absence of the vermis results in apposition of the two cerebellar hemispheres
in the midline that mimicks the presence of a normal vermis. In low risk
pregnancies, this condition can be easily missed. A handful of cases has been
recently reported in which the ‘molar tooth’ sign could be identified prenatally
with both ultrasound and magnetic resonance,a and it is lickely that the
increased resolution of current ultrasound as well as increased experience allow
now more confident diagnosis.38

Differential diagnosis
The Dandy-Walker complex should be differentiated by other cystic anomalies
of the posterior fossa. In case of megacisterna magna, the cisterna magna is
large but the cerebellum is intact and the fourth ventricle is triangular and
closed.10, 31, 34 Cerebellar hypoplasia results in ex-vacuo large cisterna magna41 but
the main feature of the condition is a global reduction in the size of an otherwise
normally shaped cerebellum.4, 10, 31 Arachnoid cysts growing in the posterior fossa
have a mass effect and cause asymmetrical distortion of the cerebellum.10, 31 The
greatest difficulty is probably encountered by posterior fossa hemorrhage that
results at times in destruction of the cerebellar vermis and enlargement of the
cisterna magna mimicking very closely a Dandy-Walker malformation or
vermian hypoplasia.10, 42 Thrombosis of the torcular Herophilii may result in
massive dilatation of the superior sagittal sinus mimicking a posterior fossa fluid
collection. A specific diagnosis is however relatively easy, considering that the
blood contained in the enlarged dural sinuses has on sonography a
corpuscolated appearance, usually with a large echogenci blood clot at the level
of the torcular, and that the fluid accumulation is found cranial to the posterior
fossa.43, 44

Implications for targeted examination

The Dandy-Walker complex has genetic implications, and sonography is usually
offered to couples at risk. Although the most severe forms of this condition can
be recognized as early as 14 weeks,45 caution is necessary because of the
ambiguous images caused by the incomplete development of the cerebellum at
this gestational age.26, 27 We recommend to limit the diagnosis of Dandy-Walker
complex to those cases in which either a very large cisterna magna or other
abnormal findings are encountered. In the midtrimester, it is stressed that the
transcerebellar view only demonstrate the superior part of the vermis and
therefore is not sufficient to rule out the Dandy-Walker complex. A lower scan is
required to demonstrate the ‘closure’ of the inferior vermis. Couples at risk
should be informed that false negatives and false positives cases have been
reported, and that an antenatal diagnosis is not possible in all cases, particularly
with minor anatomic alterations.
In pregnancies at incraesed risk of Joubert syndrome and related entities
because of a previous affected child neurosonography should be performed to
assess the presence and integrity of the vermis. An open fourth ventricle after
20 weelks’ gestation and/or failure to visualize the main landmarks of the
cerebellar vermis are strongly suggestive of a recurrence. On the basis of the
available evidence, MR should also be performed in that it allows a better
demonstration of the abnormalities of the mesencephalon (molar tooth sign).
In the absence of a familial history the diagnosis of Joubert and related
syndromes is a major challenge even for an expert using either ultrasound or
MR.

Implications for sonographic screening

In the midtrimester, a cisterna magna measuring more than 10 mm 46 and/or
an ‘open’ fourth ventricle} alert to the possibility of Dandy-Walker complex.4, 10,
17 The transcerebellar view, that is recommended as a part of the standard
sonographic examination of the fetal brain47will not detect all cases of the
Dandy-Walker complex. The available experience suggest that a standard exam
may not reveal even severe forms of the Dandy Walker complex.

Prognosis
Neurosurgical series that report the combination of Dandy-Walker
malformation with hydrocephalus describe abnormal neurologic development
in 40-70% of survivors.6-8 Dandy-Walker malformation is also a part of many
genetic syndromes, with a wide spectrum of outcomes. The clinical significance
of Dandy-Wallker malformation without ventriculomegaly is debated.48 It has
been suggested that the neurologic outcome is mainly related to the
appearance of the cerebellar vermis. When this is of normal size and
morphology a normal development has been reported in 85% of cases.
Conversely, when the vermis is abnormally lobulated and/or there are
associated cerebral anomalies, the prognosis is poor.35, 39 In reality this
evaluation is difficult prior to birth.4, 10 Most of the antenatal series thus far
reported demonstrated a poor outcome in a large proportion of cases. In a
recent antenatal stuidiy about 50% of isolated cases had a normal
outcome.10 The association with other complex anomalies and/or syndrome was
the main risk factor for an abnormal outcome.10

Vermian hypoplasia/agenesis is also frequently a part of muiltiple anomalies

and genetic syndromes. When isolated may be asymptomatic but precise risk
figures are not available.10, 12, 13, 48, 49

About one third of Blake’s pouch cysts detected antenatally are associated with
other anomalies, including chromosomal aberrations (in most cases trisomy
21).10, 11When the Blake’s pouch cyst is an isolated finding and the karyotype
is normal, however, the outcome is usually good. Intrauterine remission occurs
in about 50% of cases, and a normal developmental outcome is registered in
96% of cases.10, 11 Despite small case series in the pediatric literature in which
Blake’s pouch cyst is associated with obstructive hydrocephalus this occurred
only in 1/51 cases diagnosed antenatally.10, 11 Blake’s pouch cyst does appear
to represent a risk factor for other anomalies, but when isolated is probably a
normal variant.10, 11

Most infants with Joubert syndrome and related disorders have severe
intellectual impairment and early death is common. Neurologic dysfunction
typically includes ataxia, abnormal breathing patterns (hyperpnea intermixed
with central apnea in the neonatal period) and abnormal behaviour
(temperament, hyperactivity, aggressiveness, and dependency)22-24

Obstetric management
The diagnostic workup must include a detailed search for associated anomalies
including karyotyping. Genetic consultation is reccomended. When Joubert
syndrome is suspected, a search for the specific mutations may be considered.
In counselling couples, it is stressed that with the exception of Joubert sydrome,
the Dandy-Walker complex may have a good outcome when there are no
associated anomalies. Blake’s pouch cyst, the most common abnormal finding
of the posterior fossa, is most frequently a normal variant. Serial scans are
suggested because of the potential for cerebral maldevelopment including
ventriculomegaly. With the exception of those cases associated with
hydrocephalus and macrocrania, that may require cesarean delivery, no
modification of the standard obstetric management is indicated.

References
1. Barkovich AJ, Millen KJ, Dobyns WB. A developmental and genetic classification
for midbrain-hindbrain malformations. Brain. 2009;132(Pt 12):3199-230. Epub
2009/11/26.

2. Garel C, Fallet-Bianco C, Guibaud L. The fetal cerebellum: development and

common malformations. J Child Neurol. 2011;26(12):1483-92. Epub 2011/09/29.

3. Guibaud L. Practical approach to prenatal posterior fossa abnormalities using

MRI. Pediatr Radiol. 2004;34(9):700-11. Epub 2004/08/05.

4. Guibaud L, des Portes V. Plea for an anatomical approach to abnormalities of

the posterior fossa in prenatal diagnosis. Ultrasound Obstet Gynecol.
2006;27(5):477-81.

5. Malinger G, Lev D, Lerman-Sagie T. The fetal cerebellum. Pitfalls in diagnosis

and management. Prenat Diagn. 2009;29(4):372-80. Epub 2009/02/06.

6. 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(3):515-22.
Epub 1984/09/01.

7. Osenbach RK, Menezes AH. Diagnosis and management of the Dandy-Walker

malformation: 30 years of experience. Pediatr Neurosurg. 1992;18(4):179-89.
Epub 1992/01/01.
8. Sawaya R, McLaurin RL. Dandy-Walker syndrome. Clinical analysis of 23 cases.
J Neurosurg. 1981;55(1):89-98. Epub 1981/07/01.

9. Robinson AJ, Goldstein R. The cisterna magna septa: vestigial remnants of

Blake's pouch and a potential new marker for normal development of the
rhombencephalon. J Ultrasound Med. 2007;26(1):83-95. Epub 2006/12/22.

10. Gandolfi Colleoni G, Contro E, Carletti A, Ghi T, Campobasso G, Rembouskos

G, Volpe G, Pilu G, Volpe P. Prenatal diagnosis and outcome of fetal posterior
fossa fluid collections. Ultrasound Obstet Gynecol. 2012, in press. Epub
2011/12/17.

11. Paladini D, Volpe P. Posterior fossa and vermian morphometry in the

characterization of fetal cerebellar abnormalities: a prospective three-
dimensional ultrasound study. Ultrasound Obstet Gynecol. 2006;27(5):482-9.
Epub 2006/04/19.

12. Limperopoulos C, du Plessis AJ. Disorders of cerebellar growth and

development. Curr Opin Pediatr. 2006;18(6):621-7. Epub 2006/11/14.

13. Limperopoulos C, Robertson RL, Estroff JA, Barnewolt C, Levine D, Bassan H,

du Plessis AJ. Diagnosis of inferior vermian hypoplasia by fetal magnetic
resonance imaging: potential pitfalls and neurodevelopmental outcome. Am J
Obstet Gynecol. 2006;194(4):1070-6. Epub 2006/04/04.

14. Calabro F, Arcuri T, Jinkins JR. Blake's pouch cyst: an entity within the Dandy-
Walker continuum. Neuroradiology. 2000;42(4):290-5.

15. Zalel Y, Gilboa Y, Gabis L, Ben-Sira L, Hoffman C, Wiener Y, Achiron R. Rotation

of the vermis as a cause of enlarged cisterna magna on prenatal imaging.
Ultrasound Obstet Gynecol. 2006;27(5):490-3.
16. Cornips EM, Overvliet GM, Weber JW, Postma AA, Hoeberigs CM, Baldewijns
MM, Vles JS. The clinical spectrum of Blake's pouch cyst: report of six illustrative
cases. Childs Nerv Syst. 2010;26(8):1057-64. Epub 2010/03/04.

17. Paladini D, Quarantelli M, Pastore G, Sorrentino M, Sglavo G, Nappi C.

Abnormal or delayed development of the Area Membranacea Posterior of the
brain: the Blake's pouch cyst. Anatomy, ultrasound diagnosis, natural history
and outcome in the fetus. Ultrasound Obstet Gynecol. 2012, in press. Epub
2011/11/15.

18. Gunay-Aygun M, Parisi MA, Doherty D, Tuchman M, Tsilou E, Kleiner DE,

Huizing M, Turkbey B, Choyke P, Guay-Woodford L, Heller T, Szymanska K,
Johnson CA, Glass I, Gahl WA. MKS3-related ciliopathy with features of
autosomal recessive polycystic kidney disease, nephronophthisis, and Joubert
Syndrome. J Pediatr. 2009;155(3):386-92 e1. Epub 2009/06/23.

19. Tilea B, Delezoide AL, Khung-Savatovski S, Guimiot F, Vuillard E, Oury JF, Garel
C. Comparison between magnetic resonance imaging and fetopathology in the
evaluation of fetal posterior fossa non-cystic abnormalities. Ultrasound Obstet
Gynecol. 2007;29(6):651-9. Epub 2007/05/04.

20. 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.

21. Has R, Ermis H, Yuksel A, Ibrahimoglu L, Yildirim A, Sezer HD, Basaran S.

Dandy-Walker malformation: a review of 78 cases diagnosed by prenatal
sonography. Fetal Diagn Ther. 2004;19(4):342-7. Epub 2004/06/12.

22. Doherty D. Joubert syndrome: insights into brain development, cilium

biology, and complex disease. Semin Pediatr Neurol. 2009;16(3):143-54. Epub
2009/09/26.
23. Parisi M, Glass I. Joubert Syndrome. In: Pagon RA, Bird TD, Dolan CR,
Stephens K, editors. GeneReviews [Internet]. 2010/03/20 ed. Seattle (WA)::
University of Washington; 2003.

24. Parisi MA. Clinical and molecular features of Joubert syndrome and related
disorders. Am J Med Genet C Semin Med Genet. 2009;151C(4):326-40. Epub
2009/10/31.

25. Murray JC, Johnson JA, Bird TD. Dandy-Walker malformation: etiologic
heterogeneity and empiric recurrence risks. Clin Genet. 1985;28(4):272-83. Epub
1985/10/01.

26. Babcook CJ, Chong BW, Salamat MS, Ellis WG, Goldstein RB. Sonographic
anatomy of the developing cerebellum: normal embryology can resemble
pathology. AJR Am J Roentgenol. 1996;166(2):427-33. Epub 1996/02/01.

27. Bromley B, Nadel AS, Pauker S, Estroff JA, Benacerraf BR. Closure of the
cerebellar vermis: evaluation with second trimester US. Radiology.
1994;193(3):761-3.

28. Laing FC, Frates MC, Brown DL, Benson CB, Di Salvo DN, Doubilet PM.
Sonography of the fetal posterior fossa: false appearance of mega-cisterna
magna and Dandy-Walker variant. Radiology. 1994;192(1):247-51. Epub
1994/07/01.

29. Volpe P, Contro E, De Musso F, Ghi T, Farina A, Tempesta A, Volpe G, Rizzo N,

Pilu G. The brainstem-vermis and brainstem-tentorium angles allow accurate
categorization of fetal upward rotation of the cerebellar vermis. Ultrasound
Obstet Gynecol. 2012, in press.
30. Doherty D, Glass IA, Siebert JR, Strouse PJ, Parisi MA, Shaw DW, Chance PF,
Barr M, Jr., Nyberg D. Prenatal diagnosis in pregnancies at risk for Joubert
syndrome by ultrasound and MRI. Prenat Diagn. 2005;25(6):442-7.

31. Malinger G, Ginath S, Lerman-Sagie T, Watemberg N, Lev D, Glezerman M.

The fetal cerebellar vermis: normal development as shown by transvaginal
ultrasound. Prenat Diagn. 2001;21(8):687-92.

32. Pilu G, Ghi T, Carletti A, Segata M, Perolo A, Rizzo N. Three-dimensional

ultrasound examination of the fetal central nervous system. Ultrasound Obstet
Gynecol. 2007;30(2):233-45. Epub 2007/07/31.

33. Pilu G, Segata M, Ghi T, Carletti A, Perolo A, Santini D, Bonasoni P, Tani G,

Rizzo N. Diagnosis of midline anomalies of the fetal brain with the three-
dimensional median view. Ultrasound Obstet Gynecol. 2006;27(5):522-9.

34. Adamsbaum C, Moutard ML, Andre C, Merzoug V, Ferey S, Quere MP, Lewin
F, Fallet-Bianco C. MRI of the fetal posterior fossa. Pediatr Radiol. 2005;35(2):124-
40.

35. Klein O, Pierre-Kahn A, Boddaert N, Parisot D, Brunelle F. Dandy-Walker

malformation: prenatal diagnosis and prognosis. Childs Nerv Syst. 2003;19(7-
8):484-9.

36. Achiron R, Kivilevitch Z, Lipitz S, Gamzu R, Almog B, Zalel Y. Development of

the human fetal pons: in utero ultrasonographic study. Ultrasound Obstet
Gynecol. 2004;24(5):506-10. Epub 2004/10/02.

37. Tilea B, Alberti C, Adamsbaum C, Armoogum P, Oury JF, Cabrol D, Sebag G,

Kalifa G, Garel C. Cerebral biometry in fetal magnetic resonance imaging: new
reference data. Ultrasound Obstet Gynecol. 2009;33(2):173-81. Epub
2009/01/28.
38. Pugash D, Oh T, Godwin K, Robinson AJ, Byrne A, Van Allen MI, Osiovich H.
Sonographic 'molar tooth' sign in the diagnosis of Joubert syndrome. Ultrasound
Obstet Gynecol. 2011;38(5):598-602. Epub 2011/03/04.

39. Boddaert N, Klein O, Ferguson N, Sonigo P, Parisot D, Hertz-Pannier L,

Baraton J, Emond S, Simon I, Chigot V, Schmit P, Pierre-Kahn A, Brunelle F.
Intellectual prognosis of the Dandy-Walker malformation in children: the
importance of vermian lobulation. Neuroradiology. 2003;45(5):320-4.

40. Phillips JJ, Mahony BS, Siebert JR, Lalani T, Fligner CL, Kapur RP. Dandy-Walker
Malformation Complex: Correlation Between Ultrasonographic Diagnosis and
Postmortem Neuropathology. Obstet Gynecol. 2006;107(3):685-93.

41. Ghidini A, Fromberg RA, Tiernan J, Wieneke JA, Manz HJ, Sherer DM. Dilated
subarachnoid cisterna ambiens: a potential sonographic sign predicting
cerebellar hypoplasia. J Ultrasound Med. 1996;15(5):413-5. Epub 1996/05/01.

42. Yuksel A, Batukan C. Fetal cerebellar hemorrhage in a severely growth-

restricted fetus: natural history and differential diagnosis from Dandy-Walker
malformation. Ultrasound Obstet Gynecol. 2003;22(2):178-81. Epub 2003/08/09.

43. Laurichesse Delmas H, Winer N, Gallot D, Lopes K, Perrotin F, Fluncker S,

Geissler F, Beaufrere AM, Vendittelli F, Couture C, Lemery D. Prenatal diagnosis
of thrombosis of the dural sinuses: report of six cases, review of the literature
and suggested management. Ultrasound Obstet Gynecol. 2008;32(2):188-98.
Epub 2008/06/03.

44. Visentin A, Falco P, Pilu G, Perolo A, Valeri B, Santini D, Bovicelli L. Prenatal

diagnosis of thrombosis of the dural sinuses with real-time and color Doppler
ultrasound. Ultrasound Obstet Gynecol. 2001;17(4):322-5. Epub 2001/05/08.
45. Achiron R, Achiron A. Transvaginal ultrasonic assessment of the early fetal
brain. Ultrasound Obstet Gynecol. 1991;1(5):336-44. Epub 1991/09/01.

46. Mahony BS, Callen PW, Filly RA, Hoddick WK. The fetal cisterna magna.
Radiology. 1984;153(3):773-6.

47. ISUOG. Sonographic examination of the fetal central nervous system:

guidelines for performing the 'basic examination' and the 'fetal
neurosonogram'. Ultrasound Obstet Gynecol. 2007;29(1):109-16.

48. Bolduc ME, Limperopoulos C. Neurodevelopmental outcomes in children

with cerebellar malformations: a systematic review. Dev Med Child Neurol.
2009;51(4):256-67. Epub 2009/02/05.

49. Limperopoulos C, Robertson RL, Jr., Khwaja OS, Robson CD, Estroff JA,
Barnewolt C, Levine D, Morash D, Nemes L, Zaccagnini L, du Plessis AJ. How
accurately does current fetal imaging identify posterior fossa anomalies? AJR Am
J Roentgenol. 2008;190(6):1637-43. Epub 2008/05/22.

Pilu G, Malinger G, Buyukkurt S: Dandy-Walker complex. Visual Encyclopedia of

Ultrasound in Obstetrics and Gynecology,www.isuog.org, (December 2012).