HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by van Beek, E. J. R. Articles by Majoie, C. B. L. M. Search for Related Content PubMed PubMed Citation Articles by van Beek, E. J. R. Articles by Majoie, C. B. L. M.

Case 25: Joubert Syndrome¹

¹ From the Department of Radiology, Academic Medical Center, G1-242, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. Received December 9, 1998; revision requested February 15, 1999; revision received April 20; accepted June 28. Address correspondence toC.B.L.M.M.

Index terms: Brain, abnormalities, 15.142, 15.15 • Brain, MR, 15.121411, 15.121413 • Brain, ventricles, 164.92 • Diagnosis Please • Joubert syndrome, 15.142

	HISTORY

TOP HISTORY IMAGING FINDINGS DISCUSSION REFERENCES

 
A 4-month-old full-term male infant was referred for magnetic resonance (MR) imaging because he had an increased head circumference (greater than 97th percentile), developmental delay, abnormal eye movements with suspected blindness, and episodes of abnormal breathing.

	IMAGING FINDINGS

TOP HISTORY IMAGING FINDINGS DISCUSSION REFERENCES

 
The transverse T1-weighted (Fig 1) and T2-weighted (Fig 2a) MR images both showed dysplasia of the superior cerebellar peduncles that resulted in a molar tooth configuration. The more caudal T2-weighted transverse MR image (Fig 2b) showed the fourth ventricle shaped like a bat wing. Furthermore, both the T1-weighted and T2-weighted transverse MR images showed that the cerebellar hemispheres were in contact in the midline as a result of severe hypoplasia of the vermis. The off-midline inversion-recovery MR image (Fig 3b) showed that especially the middle cerebellar peduncle was reduced in size. Furthermore, there was evidence of severe vermian hypoplasia that involved the superior and inferior vermes, with an open communication between the fourth ventricle and the extracerebellar subarachnoid space (Fig 3a), but without evidence of a posterior fossa cyst.

View larger version (126K): [in this window] [in a new window] [Download PPT slide]   Figure 1. Transverse T1-weighted spin-echo MR image at the level of the mesencephalon; 570/14 (repetition time msec/echo time msec); field of view, 135 x 180; matrix, 192 x 256; section thickness, 5 mm. Note the slenderness of the cerebellar peduncles (arrows) that results in the molar tooth configuration. The cerebellar hemispheres are in direct contact in the midline (arrowheads) due to severe hypoplasia of the vermis.

View larger version (120K): [in this window] [in a new window] [Download PPT slide]   Figure 2a. (a, b) Two contiguous transverse T2-weighted fast spin-echo MR images at the level of (a) the mesencephalon and (b) the pontomedullary junction; 3,800/120; field of view, 135 x 180; matrix, 190 x 256; section thickness, 5 mm. (a) Image demonstrates the slender cerebellar peduncles (arrows) that result in the molar tooth configuration. The direct contact of the cerebellar hemispheres in the midline (arrowheads) is also visible. (b) Image obtained 5 mm caudad to adepicts the fourth ventricle (IV) that is shaped like a bat wing.

View larger version (122K): [in this window] [in a new window] [Download PPT slide]   Figure 2b. (a, b) Two contiguous transverse T2-weighted fast spin-echo MR images at the level of (a) the mesencephalon and (b) the pontomedullary junction; 3,800/120; field of view, 135 x 180; matrix, 190 x 256; section thickness, 5 mm. (a) Image demonstrates the slender cerebellar peduncles (arrows) that result in the molar tooth configuration. The direct contact of the cerebellar hemispheres in the midline (arrowheads) is also visible. (b) Image obtained 5 mm caudad to adepicts the fourth ventricle (IV) that is shaped like a bat wing.

View larger version (147K): [in this window] [in a new window] [Download PPT slide]   Figure 3a. (a, b) Two contiguous sagittal inversion-recovery MR images of the brain; 10,944/60; inversion time, 400 msec; field of view, 173 x 230; matrix, 154 x 256; section thickness, 5 mm. (a) Image obtained in the midline shows the severe hypoplasia of the vermis (small arrow), with direct communication (large arrow) between the fourth ventricle and the extracerebellar subarachnoid space. (b) Image obtained 5 mm to the left off midline shows the hypoplastic cerebellar peduncle (arrows).

View larger version (144K): [in this window] [in a new window] [Download PPT slide]   Figure 3b. (a, b) Two contiguous sagittal inversion-recovery MR images of the brain; 10,944/60; inversion time, 400 msec; field of view, 173 x 230; matrix, 154 x 256; section thickness, 5 mm. (a) Image obtained in the midline shows the severe hypoplasia of the vermis (small arrow), with direct communication (large arrow) between the fourth ventricle and the extracerebellar subarachnoid space. (b) Image obtained 5 mm to the left off midline shows the hypoplastic cerebellar peduncle (arrows).

	DISCUSSION

TOP HISTORY IMAGING FINDINGS DISCUSSION REFERENCES

A classification into two groups has been proposed on the basis of the presence or absence of retinal dystrophy (3). In the group with retinal dystrophy, there is a high prevalence of multicystic renal disease, and there appears to be a worse prognosis in terms of survival than in the group without retinal dystrophy (3). The exact location of the defective gene has not been established, although both the X chromosome and the nephronophthisis 1 region on chromosome 2 have been excluded (3,10).

The main imaging findings, which are present almost uniformly, are partial or complete absence of the vermis, hypoplastic cerebellar peduncles, and fourth ventricular deformity (6,11). The cerebellar hemispheres are usually normal. The cerebrum is not affected, although moderate lateral ventricular enlargement due to atrophy was described in 6%–20% of cases, with corpus callosum dysgenesis present in 6%–10% (6,11). In the presented case, no supratentorial abnormalities were present, and no explanation for the increased head circumference could be found.

Partial or complete absence of the cerebellar vermis has been described as an isolated anomaly or as part of Dandy-Walker syndrome, Down syndrome, or Joubert syndrome (12,13). In patients with Dandy-Walker syndrome, there is a posterior fossa cyst that leads to expansion of the posterior fossa. Down syndrome is diagnosed clinically or by karyotype (trisomy 21). The absence of vermis leads to a midline cleft between the cerebellar hemispheres, which are both normal. The combination of hypoplasia of the cerebellar peduncles that results in the molar tooth sign (4) and severe hypoplasia of the vermis that gives a bat-wing appearance to the fourth ventricle (13) is highly suggestive of Joubert syndrome.

The importance of recognizing Joubert syndrome is related to the outcome, its autosomal recessive trait, and the potential complications that may develop. A follow-up study in 19 children with Joubert syndrome showed that three children died before 3 years of age, whereas the remaining children showed neuromotor developmental retardation and various levels of reduced cognitive development (7). Retinal dysplasia is correlated highly with renal cystic disease and seems to carry a worse prognosis in terms of survival (3,7). Retinal dysplasia is often difficult to diagnose early; hence, regular ocular screening should be performed. In patients with retinal anomalies, it also is advisable to monitor renal function and perform ultrasonography (US) of the kidneys to detect cystic renal disease (3).

The disorder is an autosomal recessive trait, as shown by the results of two studies (3,7) in which 48 siblings in 22 families and four pairs of siblings in 19 children, respectively, were described. These numbers illustrate the importance of genetic counseling. Furthermore, once a diagnosis of Joubert syndrome is made in one neonate, the diagnosis of Joubert syndrome can be made antenatally by looking for the imaging findings at US during a subsequent pregnancy (13).

Finally, the diagnosis is important for future procedures that require anesthesia (14). Patients with Joubert syndrome are extremely sensitive to the respiratory depressant effects of anesthetic agents, such as opioids, and nitrous oxide. Therefore, these agents should be avoided, and close perioperative respiratory monitoring is essential.

Our congratulations to the 178 individuals who submitted the most likely diagnosis (Joubert syndrome) for Diagnosis Please, Case 25. The names and locations of the individuals, as submitted, are as follows:

• Hisashi Abe, Osaka-city, Japan
  
• Gholamali Afshang, MD, Tinley Park, Ill
  
• Nabil Ammouri, MD, Zahle, Lebanon
  
• Dr Richard J. Archer, Launceston, Australia
  
• Juan Arenas, Spain
  
• Andrew E. Auber, MD, San Antonio, Tex
  
• Fco J. Ayala Lopez, Los Mochis, Sin, Mexico
  
• Gabriela Baade, Buenos Aires, Argentina
  
• Yasutaka Baba, Kagoshima, Japan
  
• Peter Bach, MD, Hemer, Germany
  
• Dean Baird, MD, Arlington, Va
  
• Edward L. Baker, MD, San Francisco, Calif
  
• Ken Baliga, Rockford, Ill
  
• A. James Barkovich, MD, San Francisco, Calif
  
• Carlos E. Bauni, MD, Bahia Blanca, Argentina
  
• Alexander Baxter, Seattle, Wash
  
• Catherine Beal, MD, St Louis, Mo
  
• Corning Benton, MD, FACR, Cincinnati, Ohio
  
• Grazia Bitti, Cagliari, Italy
  
• Frank S. Bonelli, MD, PhD, Rockford, Ill
  
• Giuseppe Brancatelli, MD, Palermo, Italy
  
• Eric L. Bressler, MD, Minnetonka, Minn
  
• Michael P. Buetow, MD, Okemos, Mich
  
• Tirso Cascajares Murillo, MD, Los Mochis, Sin, Mexico
  
• Dr Sew-Kee Chang, Singapore
  
• Maria Valeria Cherchi, MD, Cagliari, Italy
  
• Lui Chun-Chung, MD, Kaohsiung, Taiwan
  
• Pablo Cikman, MD, Córdoba, Argentina
  
• Deniz Ciliz, MD, Ankara, Turkey
  
• Antônio José da Rocha, São Paulo, Brazil
  
• Heike E. Daldrup-Link, MD, Munich, Germany
  
• Federico Dalla Torre, Cipolletti, Argentina
  
• Xavier De La Barrera, MD, Mexicali, Mexico
  
• Jose Luiz F. De Mendonca, MD, Brasília, D.F., Brazil
  
• J. F. K. de Villiers, Gisborne, New Zealand
  
• Jean Claude Decarie, Montreal, Quebec, Canada
  
• Gautam Dehadrai, MD, Chicago, Ill
  
• Mark C. DeLano, MD, East Lansing, Mich
  
• Jaime H. Delgado, MD, Rancho Palos Verdes, Calif
  
• David DeLone, MD, San Antonio, Tex
  
• Kemal Demir, MD, Istanbul, Turkey
  
• Dra. Estela Di Nella, Buenos Aires, Argentina
  
• Dr Uwe Dietrich, Bielefeld, Germany
  
• Olivier Dourthe, MD, Sophia Antipolis, France
  
• Allen D. Elster, MD, Winston-Salem, NC
  
• Seyed A. Emamian, MD, PhD, Washington, DC
  
• Volkher Engelbrecht, MD, PhD, Dusseldorf, Germany
  
• Keith D. Epperson, MD, Milwaukee, Wis
  
• Bilge (Bozkurt) Ergen, B.evler-Ankara, Turkey
  
• Laura Z. Fenton, MD, Denver, Colo
  
• Sandra K. Fernbach, Chicago, Ill
  
• Eric W. Flint, MD, Pittsburgh, Pa
  
• Richard Friedland, MD, Poughkeepsie, NY
  
• Stephen Fry, MD, Minneapolis, Minn
  
• Milton Fuentealba, MD, Rio Negro, Argentina
  
• Akira Fujikawa, Tokyo, Japan
  
• Teresa Adriana Garcia, MD, Buenos Aires, Argentina
  
• Anne Geoffray, MD, Nice, France
  
• Dietrich Gerhardt, MD, Waterloo, Iowa
  
• Lawrence E. Ginsberg, Houston, Tex
  
• Christine M. Glastonbury, Salt Lake City, Utah
  
• Brad Gluck, MD, Southampton, NY
  
• W. Zev Goldstein, MD, Poughkeepsie, NY
  
• Prof Dr Wolfgang Grodd, Tuebingen, Germany
  
• Dr Francois Gudinchet, MD, Lausanne, Switzerland
  
• Michael S. Hamar, MD, Luenen, Germany
  
• Alvand Hassankhani, MD, Durham, NC
  
• Alberto Iaia, MD, Wilmington, Del
  
• Dr Kartik Jhaveri, Mumbai, India
  
• Philip L. Johnson, MD, Kan
  
• Yun Ju Jung, Kyunggi-do, South Korea
  
• Hirotsugu Kado, Fukui, Japan
  
• Peter Kalina, MD, Lloyd Harbor, NY
  
• Albert Kaminsky, Melbourne, Victoria, Australia
  
• Douglas S. Katz, MD, Mineola, NY
  
• Yasushi Kawata, Akita, Japan
  
• Min-Yeong Kim, MD, Seoul, Korea
  
• Osman Kizilkilic, MD, Istanbul, Turkey
  
• Jennifer J. Kottra, MD, Flagstaff, Ariz
  
• Josef Kramer, MD, PhD, Linz, Austria
  
• Dr Mahesh Kumar, Bolton, United Kingdom
  
• Jeffrey Kuo, San Francisco, Calif
  
• Dr Stephanos Lachanis, Athens, Greece
  
• Sergio M. Lagman, MD, Jacksonville, Fla
  
• Barton Lane, MD, Stanford, Calif
  
• Jong Chan Lee, Seoul, Korea
  
• Steven Lev, Great Neck, NY
  
• Richard A. Levy, MD, Saginaw, Mich
  
• Han Lixin, MD, Guangzhou, China
  
• Julio Loureiro, MD, Buenos Aires, Argentina
  
• Cheemun Lum, MD, Toronto, Ontario, Canada
  
• Franklin Marden, MD, St Louis, Mo
  
• Laura Marini, MD, Rio Negro, Argentina
  
• Dr. Juan Carlos Martínez, Valencia, Spain
  
• Marcel Maya, MD, Los Angeles, Calif
  
• Andrew J. McDonnell, MD, Corning, NY
  
• Barry C. McNulty, MD, Canton, Ohio
  
• Edward Menges, MD, Aptos, Calif
  
• Dr. Francois Mesmin, Reims, France
  
• Manabu Minami, MD, Tokyo, Japan
  
• Hidetoshi Miyake, MD, Oita, Japan
  
• Sergio J. Moguillansky, MD, Rio Negro, Argentina
  
• Eduardo Mondello, Buenos Aires, Argentina
  
• Toshio Moritani, Japan
  
• Suresh K. Mukherji, MD, Chapel Hill, NC
  
• Miguel E. Nazar, MD, Capital Federal, Argentina
  
• Donald T. Nicell, MD, Jonesboro, Ark
  
• Ioannis Nikas, Athens, Greece
  
• Ralph E. Norton, MD, Houston, Tex
  
• James Okoh, MD, Columbia, Md
  
• Laura Oleaga, Bilbao, Spain
  
• Perihan Özkan, Istanbul, Turkey
  
• Serefnur Ozturk, MD, Ankara, Turkey
  
• M. Pajewski, MD, Tel-Aviv, Israel
  
• Harish Panicker, Pontiac, Mich
  
• Sophia Pantazi, MD, Toronto, Ontario, Canada
  
• Sung-Tae Park, MD, Pohang Kyung-buk, Korea
  
• Teresa Peltz, MD, Cagliari, Italy
  
• David M. Pelz, MD, FRCPC, London, Ontario, Canada
  
• Amir Belisario Perez Lanz, MD, Villahermosa, Tab., Mexico
  
• Victor Pérez-Candela, MD, Las Palmas, Spain
  
• Javier Perich, MD, Barcelona, Spain
  
• Alex Petersen, MD, Newcastle, Australia
  
• John M. Plotke, Naperville, Ill
  
• Jordan Prager, Evanston, Ill
  
• Anita Price, MD, Mineola, NY
  
• George Puskar, MD, Vero Beach, Fla
  
• Swee-Tian Quek, Singapore
  
• Shawn P. Quillin, MD, Charlotte, NC
  
• Carl Andrew Raboi, Tiffin, Iowa
  
• John F. Rice, MD, Louisville, Ky
  
• Javier Rodriguez Lucero, MD, Rosario, Argentina
  
• Francisco J. Romero-Vidal, Barcelona, Spain
  
• Mourad Said, MD, Monastir, Tunisia
  
• Maria J. Sanz-Continenete, MD, Madrid, Spain
  
• Pierre-Jean Sauvage, MD, Mâcon, France
  
• Dr. Recep Savas, Izmir, Turkey
  
• Dr. Yildiray Savas, Istanbul, Turkey
  
• C. Christian Schlaepfer, MD, Chicago, Ill
  
• Hanna Schulman, MD, Beer-Sheva, Israel
  
• Steven M. Schultz, MD, Fort Worth, Tex
  
• Anthony J. Scuderi, MD, Johnstown, Pa
  
• Carlos Antonio Serrano, Olavarria, Argentina
  
• Matt Shapiro, MD, Lowell, Mass
  
• Yoshihisa Shimanuki, MD, Sendai, Japan
  
• Taro Shimono, MD, Kyoto, Japan
  
• Ji-Yeol Shin, MD, PhD, Kyungpook, South Korea
  
• Alexander B. Simonetta, MD, Temple, Tex
  
• Sanjay K. Singh, MD, Friendswood, Texas
  
• R. Sinha, Walsall, United Kingdom
  
• Paolo Siotto, MD, Cagliari, Italy
  
• Eric D. Smith, MD, San Diego, Calif
  
• David Sobel, MD, La Jolla, Calif
  
• Juan Carlos Spina Ramos, Argentina
  
• Juan Carlos Spina, MD, Buenos Aires, Argentina
  
• David C. Stepanek, MD, Yakima, Wash
  
• Stacy Stevens, San Antonio, Tex
  
• Peter M. Stroz, MD, Toronto, Ontario, Canada
  
• Franz Sulzer, Kapfenberg, Austria
  
• J. Takasugi, Mercer Island, Wash
  
• Douglas L. Teich, MD, Brookline, Mass
  
• Mehmet Teksam, MD, Minneapolis, Minn
  
• Alejandro Tempra, MD, Buenos Aires, Argentina
  
• Tapani Tikkakoski, MD, Kokkola, Finland
  
• John To, MD, Iron Mountain, Mich
  
• Sunil Trasi, MD, Metuchen, NJ
  
• Glenn Tsukada, MD, Stanford, Calif
  
• J. Valk, MD, PhD, Wilnis, Netherlands
  
• Juan Vielma, MD, Chile
  
• Kay Vilanova, MD, Girona, Spain
  
• Christopher Vittore, MD, Rockford, Ill
  
• Andrew L. Wagner, MD, Harrisonburg, Va
  
• Hsu-Huei Weng, MD, MPH, Kaohsiung, Taiwan
  
• Jeff West, MD, Jacksonville, Fla
  
• Kay Yan, MD, Long Beach, Calif
  
• Sevim Yildiz, Antalya, Turkey
  
• David M. Yousem, MD, Baltimore, Md
  
• Estban Raul Zirulnik, Mendoza, Argentina
  

	FOOTNOTES

 
Part 1 of this case appears 4 months previously and may contain larger images.

	REFERENCES

TOP HISTORY IMAGING FINDINGS DISCUSSION REFERENCES

 

1. Joubert M, Eisenring JJ, Robb JP, Andermann F. Familial agenesis of the vermis: a syndrome of episodic hyperpnea, abnormal eye movements, ataxia, and retardation. Neurology 1969; 19:813-825.[Free Full Text]
2. Boltshauser E, Isler W. Joubert syndrome: episodic hyperpnea, abnormal eye movements, retardation and ataxia, associated with dysplasia of the cerebellar vermis. Neuropaediatrie 1977; 8:57-66.
3. Saraiva JM, Baraitser M. Joubert syndrome: a review. Am J Med Genet 1992; 43:726-731.[Medline]
4. Maria BL, Hoang KB, Tusa RJ, et al. "Joubert syndrome" revisited: key ocular motor signs with magnetic resonance imaging correlation. J Child Neurol 1997; 12:423-430.[Medline]
5. King MD, Dudgeon J, Stephenson JB. Joubert’s syndrome with retinal dysplasia: neonatal tachypnoea as the clue to a genetic brain-eye malformation. Arch Dis Child 1984; 59:709-718.[Abstract]
6. Kendall B, Kingsley D, Lambert SR, Taylor D, Finn P. Joubert syndrome: a clinico-radiological study. Neuroradiology 1990; 31:502-506.[Medline]
7. Steinlin M, Schmid M, Landau K, Boltshauser E. Follow-up in children with Joubert’s syndrome. Neuropediatrics 1997; 28:204-211.[Medline]
8. Lindhout D, Barth PG, Valk J, Boen-Tan TN. The Joubert syndrome associated with bilateral chorioretinal coloboma. Eur J Pediatr 1980; 134:173-176.[Medline]
9. Ivarsson SA, Bjerre I, Brun A, Ljungberg O, Maly E, Taylor I. Joubert syndrome associated with Leber amaurosis and multicystic kidneys. Am J Med Genet 1993; 45:542-547.[Medline]
10. Hildebrandt F, Nothwang HG, Vossmerbaumer U, et al. Lack of large, homozygous deletions of the nephronophthisis 1 region in Joubert syndrome type B. Pediatr Nephrol 1998; 12:16-19.[Medline]
11. Adamsbaum C, Moreau V, Bulteau C, Burstyn J, Lair Milan F, Kalifa G. Vermian agenesis without posterior fossa cyst. Pediatr Radiol 1994; 24:543-546.[Medline]
12. Keogan MT, DeAtkine AB, Hertzberg BS. Cerebellar vermian defects: antenatal sonographic appearance and clinical significance. J Ultrasound Med 1994; 13:607-611.[Abstract]
13. Barkovich AJ. Pediatric neuroimaging 2nd ed. New York, NY: Raven, 1995; 249-257.
14. Habre W, Sims C, D’Souze M. Anaesthetic management of children with Joubert syndrome. Paediatric Anaesth 1997; 7:251-253.[Medline]

This article has been cited by other articles:

				J Tynan and P Szkup A 7-year-old female with hypotonia and atakia Br. J. Radiol., September 1, 2005; 78(933): 869 - 870. [Full Text] [PDF]

				P. McGraw The Molar Tooth Sign Radiology, December 1, 2003; 229(3): 671 - 672. [Full Text] [PDF]

This Article Figures Only Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by van Beek, E. J. R. Articles by Majoie, C. B. L. M. Search for Related Content PubMed PubMed Citation Articles by van Beek, E. J. R. Articles by Majoie, C. B. L. M.