PICTORIAL ESSAY

Brain Stem and Cerebellar Findings in Joubert Syndrome

Ibrahim A. Alorainy, MD,* Sohail Sabir, FRCR,* Mohammed Z. Seidahmed, MD,‡

Hamid A. Farooqu, FRCR,§ and Mustafa A. Salih, MD†

Summary: Joubert syndrome is often missed clinically and radio-

logically if not enough attention is paid to its subtle and variable

clinical presentation and the imaging findings in the posterior fossa.

The purpose of this paper is to illustrate the brain stem and cerebellar

imaging findings in Joubert syndrome. Awareness of the clinical and

neuroimaging findings in Joubert syndrome and maintenance of a

high index of suspicion are essential to correctly diagnose this rare con-

genital malformation.

Key Words: Joubert syndrome, congenital brain malformation,

cerebellum, brain stem

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Joubert syndrome is an autosomal recessive disorderwith familial vermian hypoplasia/aplasia and other less

well-defined brain stem malformations in which the patientmanifests episodic hyperpnea and apnea in the neonatalperiod, abnormal eye movements, hypotonia, ataxia, andmental retardation.1–6 Though this syndrome is essentiallya clinical diagnosis, posterior fossa and brain stem malforma-tions such as cerebellar vermian dysgenesis, dilatation of thefourth ventricle, and thickened stretched superior cerebellarpeduncles are the main morphologic features; these are wellappreciated by the use of modern imaging modalities such asCT and MRI.

Joubert syndrome is a relatively rare disorder and fewcases have been described in the literature, especially withreference to its radiologic manifestations on MR imaging. Thepurpose of this paper is to illustrate the brain stem andcerebellar findings in Joubert syndrome on CT and MRI inview of its clinical presentation. After reviewing this article,the reader should be able to clearly recognize the posteriorfossa features essential for the diagnosis of Joubert syndrome.

METHODSClinical and radiologic data were obtained for 12 Saudi

children (6 boys and 6 girls). The age range was 2 to 35 months

(mean 20months). Two patients were siblings. The clinical symp-toms included neonatal breathing abnormalities of episodictachypnea and apnea, jerky eye movements, developmentaldelay, retinal atrophy, and ataxia. MRI was obtained for all sixpatients; CT scans were obtained for only two. One of thepatients underwent MRI on two occasions to determine whetherany significant interval change had occurred. MRI was per-formed using 1.5-Tesla equipment and included axial, sagittal,and coronal short TR and TE (500/10) (T1-weighted) and longTR and TE (400/110) (T2-weighted) spin-echo imaging se-quences. Routine axial CT scans were performed in two cases.The imaging components of Joubert syndrome were studieswith special attention to the brain stem and cerebellum.

RESULTSCT and MRI showed a constellation of abnormalities

of the central nervous system in our patients with Joubertsyndrome. We will focus on the brain stem and cerebellumfeatures.

In 1969, Joubert et al described for the first time a groupof children with hypoplasia of the cerebellar vermis, episodictachypnea and apnea, abnormal eye movements, and globaldevelopmental delay.1 Besides the clinical presentation, CTand MRI can provide useful tools for the detection of mor-phologic changes and can help establish the diagnosis.7–9

Radiologic findings and signs are summarized in Tables1 and 2.

CerebellumAwareness of the normal topography of the cerebellar

vermis is essential to detect the degree of abnormal vermiandevelopment in cases of Joubert syndrome. In normal subjects,separate vermian lobules and folia are reasonably delineatedby MRI at birth, penetrating deep into the vermis (Fig. 1A). InJoubert syndrome the vermian lobules are generally dysplastic,ranging from hypoplasia to complete agenesis (see Figs. 1B,C). A central cleft or deep groove is seen between the right andleft portions of the inferior vermis due to failure of fusion.Vermian folia are inadequately formed, they do not extenddeep enough within the vermis, and there is incomplete divisioninto separate vermian lobules.

Cerebellar hemispheres are usually less affected and arenearly normal, occupying most of the posterior fossa. The hemi-spheres bulge under the fourth ventricle to come in contact inthe midline due to absence or hypoplasia of the vermis. Onaxial images the cerebellar hemispheres are separated only bya thin cleft or groove. In the midline sagittal images there isvisualization of cerebellar hemisphere for the same reason (seeFigs. 1B, C), whereas in normal subjects it is not expected to

Received for publication August 1, 2005; accepted October 11, 2005.From the *Department of Radiology & Medical Imaging, King Khalid

University Hospital, King Saud University, Riyadh, Saudi Arabia;†Department of Pediatrics, King Khalid University Hospital, King SaudUniversity, Riyadh, Saudi Arabia; ‡Department of Pediatrics, SecurityForces Hospital, Riyadh, Saudi Arabia; and §Department of Radiology,Security Forces Hospital Riyadh, Saudi Arabia.

Reprints: Dr. Ibrahim Alorainy, P.O. Box 9047, Riyadh 11413, Saudi Arabia(e-mail: alorainy@ksu.edu.sa).

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see the cerebellar hemispheres in the midline sagittal plane.Similarly, due to absence of the posterior vermian lobe, thecerebellar hemispheres can be appreciated on the coronalimages, being separated only by a midline cleft and thusproducing the ‘‘buttock sign’’ (Figs. 2B, C).10

Other cerebellar anomalies that have been less com-monly reported include prominent cerebellar folia and somedegree of hypoplasia or cerebellar heterotopias.

Fourth VentricleThe fastigium of the fourth ventricle in normal subjects

is located approximately midway between the obex andcolliculocentral point (see Fig. 1A). In Joubert syndrome,there is variable dysplasia of the vermis, resulting in distortionand dilatation of the fourth ventricle, which also shows con-vexity of its roof posterosuperiorly and that of its floor towardthe brain stem. The fastigium is shifted rostrally (see Figs. 1B,C), and the fourth ventricle assumes a rectangular instead ofa normal triangular shape as seen on midline sagittal images.Inferiorly, the foramen of Magendie is larger and there is widecommunication between the fourth ventricle and cisterna magna(see Figs. 1B, C). On axial images just below the pontome-sencephalic junction, the dilated or distorted fourth ventricle takesthe shape of a batwing or umbrella (Figs. 3B–D).

TABLE 1. Brain Stem and Cerebellar Imaging Findings inJoubert Syndrome

Superior cerebellar peduncles

Thick and horizontal 12/12 100%

Asymmetric 2/12 17%

‘‘Molar tooth’’ sign 12/12 100%

Fastigium

Rostral deviation 12/12 100%

Fourth ventricle

Distorted Batwing/umbrella shape 12/12 100%

Vermis

Hypoplasia 9/12 75%

Absent 3/12 25%

Midbrain

Absence of decussation 12/12 100%

Shallow isthmus 12/12 100%

Cerebrospinal fluid spaces

Lateral ventricular dilatation 8/12 67%

Prepontine cistern dilatation 7/12 58%

Posterior fossa cyst 3/12 25%

TABLE 2. Signs in Joubert Syndrome

Molar Tooth Sign

Batwing sign

Umbrella sign

Buttock sign

FIGURE 1. A, T1-weighted midline sagittal MR image. Normal appearance of key anatomic reference points. Triangular shape offourth ventricle (white asterisk) with fastigium (thick white arrow) lying roughly equidistant between the colliculocentral point (cp)and the obex (open black arrow). Note the size of the interpeduncular fossa and the isthmus of the brain stem (solid black arrow).Also note clear definition of primary (pr) and prepyramidal (pre) fissures of the vermis. B and C, T1-weighted midline sagittal MRimages from two different patients with Joubert syndrome. Fastigium of fourth ventricle (thick white arrow) is shifted rostrally inrelation to the obex (open black arrow). Fourth ventricle (white asterisk) is dilated with rounding of the roof due to a dysplasticvermis (black asterisk). The foramen of Magendie is wide (open white arrow) due to inferior vermian hypoplasia and opens into thelarge cisterna magna (open asterisk) in B. Pontomesencephalic junction/isthmus (short black arrow) is narrow. Cerebellarhemispheres (H) are visualized in the midline images due to a hypoplastic/dysgenetic vermis.

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FIGURE 2. A, T2-weighted coronalMR image of a normal subject show-ing cerebellar hemispheres (H), whichare separated by vermis with itsanterior (A) and posterior lobes (as-terisk). T1-weighted (B) and T2-weighted (C) coronal MR images ofa patient with Joubert syndrome. Thecerebellar hemispheres are seen tocome together in the midline (pairedarrows), being separated only bya sagittal cleft containing cerebrospi-nal fluid, due to dysgenesis/agenesisof the vermis. This appearance isknown as the ‘‘buttock sign.’’

FIGURE 3. T2-weighted axial MRimage of a normal subject throughthe level of the pons (A). Note thethin size and orientation of thesuperior cerebellar peduncles (whitearrows). B–D, T2-weighted axial MRimages at the level of the pons indifferent patients with Joubert syn-drome. There is dilatation of thefourth ventricle (asterisk) with a de-formed roof and an anteriorly convexfloor, taking the shape of a batwingor umbrella. C shows a midlinesagittal cleft separating the twocerebellar hemispheres (black ar-row). An enlarged cisterna magna isalso noted (open arrow) in B.

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FIGURE 4. T2-weighted axial MR image ofa normal subject at the level of the lowermidbrain (A). The anterior posterior thick-ness of the midbrain—the isthmus (double-headed arrow)—is greater than the anteriorposterior thickness of the interpeduncularfossa (curved arrow). B, T2-weighted axialMR image from a patient with Joubertsyndrome. The interpeduncular cistern isdeeper and wider than normal (curvedarrow), with a resultant narrow isthmus.Thick vertical superior cerebellar peduncles(paired black arrows) represent the roots ofthe tooth for the ‘‘molar tooth’’ appear-ance diagnostic of Joubert syndrome. Thesuperior aspect of the fourth ventricle isseen at this level (asterisk) due to rostraldeviation of the fourth ventricle. C, T1-weighted sagittal MR images from a normalsubject (left) and another with Joubertsyndrome (right) showing the referenceplane (black line) for the axial image atlower midbrain level. The reference linepasses through the rostrally deviated fourthventricle in the case of Joubert syndrome.D, T2-weighted axial MR image showingthat sometimes the cerebral/cerebellarpeduncles may be unequally affected,giving the appearance of a decaying tooth(arrow).

FIGURE 5. Paramidline sagittal T1-weighted MR image of a normal subject (A). It is difficult to identify the superior cerebellarpeduncles (downward-pointing white arrow), partly because of their smaller size (normal 1–2 mm) and partly because of partialvolume averaging. They are normally oriented obliquely downward relative to the dorsal mesencephalon. B and C, T1-weightedparamidline sagittal MR images from two different patients with Joubert syndrome showing thick superior cerebellar peduncles(paired white arrows), oriented almost at right angles to the posterior surface of the brain stem. Note the wide prepontinecerebrospinal fluid space (white asterisk).

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Brain StemThe abnormalities involving the isthmus (ie, junction of

midbrain and pons, the pontomesencephalic junction) aremore consistent in Joubert syndrome. The normal isthmusincludes the area just below the inferior colliculi and above thepons. It receives the superior cerebellar peduncles and is thesite for their decussation. Normally, the anterior-posteriordimension of the isthmus of the midbrain is greater than theanteroposterior dimension of the interpeduncular fossa (Fig. 4A).In Joubert syndrome, there is lack of decussation of the superiorcerebellar peduncles, and subsequently the interpeduncular

fossa is deep and the isthmus is variably thinner than normal(see Fig. 4B). A slight sagittal elongation of the isthmus is alsonoticed (see Figs. 1B, C). The myelinated rounded area in thelower midbrain that is seen on midline sagittal imagesrepresenting the decussation of the superior cerebellar pedun-cles is absent in Joubert syndrome.

Normally the superior cerebellar peduncles are thin (about1–2 mm) and are oriented obliquely downward (Fig. 5A). InJoubert syndrome, the superior cerebellar peduncles aredysplastic, and instead of having a slight downward coursethey are orientated almost horizontally and perpendicular to

FIGURE 6. A, T2-weighted coronalMR image of a normal subject. Notethe thin superior cerebellar pe-duncles (black arrows) and normalconfiguration of the fourth ventricle(black asterisk) on coronal plane. B,T2-weighted coronal MR image ofa patient with Joubert syndromeshowing thick superior cerebellarpeduncles (black arrows). The fourthventricle is dilated and distorted(black asterisk). The cerebellar hemi-spheres are separated in the midlineby a wide cleft of cerebrospinal fluiddue to hypoplastic vermis.

FIGURE 7. Key features of Joubertsyndrome on an axial image at lowermidbrain level (A) and on a midlinesagittal image (B): 1, deep interpe-duncular fossa; 2, narrow isthmus; 3,lack of decussation of superior cere-bellar peduncles; 4, dilated, dis-torted, and rostrally deviated fourthventricle; 5, thick vertical superiorcerebellar peduncles; 6, rostral de-viation of fastigium of fourth ventri-cle; 7, normal position of obex; 8,wide foramen of Magendie; 9, cer-ebellar hemispheres visualized onmidline image; 10, dysplastic vermis.

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the posterior surface of the brain stem. This can be seen on allplanes but is best appreciated on paramidline sagittal images(see Figs. 5B, C). They are also thicker than normal (Fig. 6B).Sometimes the superior cerebellar peduncles are unequallyaffected with an asymmetric appearance, one side being thinneror thicker than the other (see Fig. 4D).

Together, these findings of prominent and thicker hori-zontal superior cerebellar peduncles, deeper-than-normal in-terpeduncular fossa and a thin isthmus, and variable vermiandysgenesis give the shape of a molar tooth on MR axialimages; this is one of the most consistent imaging finding inJoubert syndrome.11 The roots of this ‘‘tooth’’ are representedby thick and perpendicular nondecussated superior cerebellarpeduncles, while the crus cerebri (cerebral peduncles) of thebrain stem, with the deep interpeduncular fossa in between,represent the body of the ‘‘tooth’’ (see Fig. 4B).

The brain stem—more particularly the medulla and uppercervical spinal cord—tends to be small.8 Less commonly thereis elongation of the medulla with a low position of obex.12 Onautopsy examination, the medulla lacks the usual bulgescorresponding to the medullary pyramids and inferior olives.11

Cerebrospinal Fluid SpacesThe foramen of Magendie of the fourth ventricle is wide,

with a broad inferior communication with the foramenmagnum (see Figs. 1B, C). Dilatation of the posterior fossacisterns (eg, wide prepontine cistern) was noted in almost allthe patients (see Figs. 5B, C) with a giant cisterna magna (seeFigs. 1B, C).

Supratentorial AbnormalitiesMost patients are found to have normal cerebral

hemispheres. Among other findings, however, mild tomoderate cerebral atrophy with prominent ventricles, dysgen-esis of the corpus callosum, absent septum pellucidum, andmyelination delay can be noticed.

Associated AbnormalitiesSome of the inconstantly associated features include

retinal coloboma and retinal dystrophy, cystic disease of thekidneys, and polydactyly.13–15 Their presence should alert theclinician to arrange for appropriate imaging examination tolook for the above-mentioned neuroimaging features. On theother hand, retinal and renal function should be monitored inpatients with imaging findings of Joubert syndrome because ofevidence that such dysfunction can be progressive.

DISCUSSIONThe prognosis of patients with Joubert syndrome is poor,

with severe mental and motor retardation16 and a 5-yearsurvival rate of 50%. Death is due to feeding difficulties and

respiratory infections. The recurrence risk is 25%; therefore, ina given set of clinical information, it is important to recognizeradiologic features (Fig. 7) that can help to establish thediagnosis and to plan genetic counseling17 and prenatalscreening for future pregnancies.

The diagnosis of Joubert syndrome relies largely onclinical features and radiologic findings. Therefore, in the settingof suspicious clinical findings, a high index of suspicion anda search for the characteristic neuroimaging findings of thebrain stem and cerebellum are essential in the diagnosis,management, and genetic counseling of this rare congenitalmalformation.

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2. Boltshauser E, Isler W. Joubert syndrome: episodic hyperpnea, abnormaleye movement, retardation and ataxia, associated with dysplasia of thecerebellar vermis. Neuropediatrie. 1997;8:57–66.

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11. Maria BL, Quisling RG, Rosainz LC, et al. Molar tooth sign in Joubertsyndrome: clinical, radiological, and pathological significance. J ChildNeurol. 1999;14:368–376.

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13. King MD, Dudgeon J, Stephenson JB. Joubert’s syndrome with retinaldysplasia: neonatal tachypnea as the clue to a genetic brain-eyemalformation. Arch Dis Child. 1984;59:709–718.

14. Steimlin M, Schmid M, Landau K, et al. Follow-up in children withJoubert’s syndrome. Neuropediatrics. 1997;28:204–211.

15. Lindhout D, Barth PG, Valk J, et al. The Joubert’s syndrome associatedwith bilateral chorioretinal coloboma. Eur J Pediatr. 1980;134:173–176.

16. Campbell S, Tsannatos C, Pearce JM. The prenatal diagnosis of Joubert’ssyndrome of familial agenesis of the cerebellar vermis. Prenat Diagn.1984;4:391–395.

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