Joubert Syndrome

Joubert Syndrome

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Joubert Syndrome is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • cerebellooculorenal syndrome 1; CORS1
  • cerebelloparenchchymal disorder IV familial
  • Joubert-Bolthauser syndrome

Disorder Subdivisions

  • None

General Discussion

Joubert syndrome is an autosomal recessive genetic disorder that affects the area of the brain that controls balance and coordination. This condition is characterized by a specific finding on an MRI called a "molar tooth sign" in which the cerebellar vermis of the brain is absent or underdeveloped and the brain stem is abnormal. The most common features of Joubert syndrome are lack of muscle control (ataxia), abnormal breathing patterns (hyperpnea), sleep apnea, abnormal eye and tongue movements and low muscle tone.

Symptoms

Many of the clinical symptoms of Joubert syndrome are apparent in infancy and most affected children have delays in gross motor milestones. The most common features are lack of muscle control (ataxia), abnormal breathing patterns (hyperapnea), sleep apnea, abnormal eye and tongue movements and low muscle tone. Intellect ranges from normal to severe mental retardation. Joubert syndrome is characterized by a specific finding on an MRI called a "molar tooth sign" in which the cerebellar vermis of the brain is absent or underdeveloped and the brain stem is abnormal.



Joubert syndrome is a very variable condition and the full spectrum of symptoms has not yet been determined. Several conditions have been described in which the "molar tooth sign" and characteristics of Joubert syndrome are present in addition to other findings. It is not yet clear if these conditions are variants of Joubert syndrome or separate syndromes. These conditions have been termed "Joubert syndrome and related disorders". Some of the other problems that may be associated with Joubert syndrome include eye abnormalities such as abnormal development of the retina, abnormality in the iris (coloboma), abnormal eye movements (nystagmus), crossed eyes (strabismus), and drooping eyelids (ptosis). Other problems sometimes associated with Joubert syndrome include kidney and/or liver abnormalities, extra fingers and toes (polydactyly), a gap in the skull with protrusion of the membranes that cover the brain (encephalocele) and hormone abnormalities.

Causes

Joubert syndrome is inherited as an autosomal recessive genetic disorder.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.



All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.



Ten genes have been identified that cause Joubert syndrome. A mutation in the AHI1 (JBTS3) gene is responsible for this condition in approximately 11% of families. Affected individuals with this gene mutation often have impaired vision due to retinal dystrophy. A mutation in the NPHP1 (JBTS4) gene causes approximately 1-2% of Joubert syndrome. Affected individuals with this gene mutation often develop a progressive kidney disease called nephronophthisis. A mutation in the CEP290 (JBTS5) gene causes about 4-10% of Joubert syndrome. Mutations in the TMEM67 (JBTS6), JBTS1, JBTS2, JBTS7, JBTS8 and JBTS9 genes are also associated with Joubert syndrome. Other genes responsible for this condition are currently unknown.

Affected Populations

The prevalence of Joubert syndrome has been estimated to be 1/258,000 but is probably an underestimate of the true prevalence, which may be closer to 1/100,000.

Standard Therapies

Diagnosis

The diagnosis of Joubert syndrome is based on physical symptoms and the "molar tooth sign" as seen on an MRI. Molecular genetic testing is available for the four genes that have been shown to cause Joubert syndrome in about 40% of cases. Carrier testing and prenatal diagnosis are available if one of these gene mutations has been identified in an affected family member.



Treatment

The treatment for Joubert syndrome is symptomatic and supportive. Developmental delays are usually treated with physical therapy, occupational therapy, speech therapy and infant stimulation. Individuals with Joubert syndrome should be evaluated by appropriate specialists including nephrologists, ophthalmologists, geneticists and neurologists. Annual screening is recommended for liver, kidney and retinal abnormalities.



Genetic counseling is recommended for individuals with Joubert syndrome and their families.

Investigational Therapies

Dr. Joseph Gleeson and his team at the University of California, San Diego

Department of Neuroscience, Howard Hughes Medical Institute are interested in identifying new genes responsible for Joubert syndrome using a combination of approaches. Research is then carried out to further understand the functional role of these genes during development.



For more information please visit:

http://cbd.ucsd.edu/

Contact: Adrienne Collazo or Kiley Hill

Phone: (858) 822-3786

Fax: (858) 246-0436



Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.



For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com

References

TEXTBOOKS

Acosta MT, Pearl PL. Joubert syndrome. In: The NORD Guide to Rare Disorders, Philadelphia: Lippincott, Williams and Wilkins, 2003:542.



JOURNAL ARTICLES

Bennett C, Parisi M, Eckert M, et al. Joubert syndrome: A haplotype segregation strategy and exclusion of the zinc finger protein of cerebellum 1 (ZIC1) gene. American Journal of Medical Genetics 2004;125A:117-124.



Satran D, Pierpont M, Dobyns W. Cerebello-oculo-renal syndromes including Arima, Senior-L?ken and COACH syndromes: More than just variants of Joubert syndrome. American Journal of Medical Genetics 1999;86;459-469.



Gitten J, Dede D, Fennel E, et al. Neurobehavioral Development in Joubert Syndrome. Journal of Child Neurology 1998;13: 391-397.



Boltshauser E, Steinlin M, Landau K, et al. Follow Up in Children with Joubert Syndrome. Neuropediatrics 1997;28: 204-211.



Pellegrino J, ensch M, Muenke M, et al. Clinical and Molecular Analysis in Joubert Syndrome. American Journal of Medical Genetics 1997;72: 59-62.



Maria B, et al. Joubert Syndrome Revisited: Key Ocular Motor Signs

With Magnetic Resonance Imaging Correlation. Journal of Child Neurology 1997;12:423-430.



Joubert Syndrome: Are Kidneys Involved?

Boltshauser E, Forster I, Deonna T, et al. Neuropediatrics 1995;26: 320-321.



Yachnis A, Rorke L, Trojanowski J. Cerebellar Dysplasias in Humans: Developmental and Possible Relationship to Glial and Primitive Neuroectodermal Tumors of the Cerebellar Vermis. Journal of Neuropathology and Experimental Neurology 1994;53;61-71.



Boltshauser E Friede RL. Uncommon Syndromes of Cerebellar Vermis Aplasia I: Joubert Syndrome. Develop Med Child Neurol 1978; 20: 758-763.



FROM THE INTERNET

Parisi M, Glass I. Updated 3/8/07. Joubert Syndrome. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1993-2011. Available at http://www.genetests.org. Accessed 3/23/11.



Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Joubert Syndrome; JBTS. Entry No: 213300. Last Edited December 6, 2010. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed March 23, 2011.

Resources

Joubert Syndrome and Related Disorders Foundation

414 Hungerford Drive

Suite 252

Rockville, MD 20850

Tel: (614)864-1362

Email: info@jsrdf.org

Internet: http://www.joubertfoundation.com/



The Arc

1825 K Street NW, Suite 1200

Washington, DC 20006

Tel: (202)534-3700

Fax: (202)534-3731

Tel: (800)433-5255

TDD: (817)277-0553

Email: info@thearc.org

Internet: http://www.thearc.org



NIH/National Institute of Neurological Disorders and Stroke

P.O. Box 5801

Bethesda, MD 20824

Tel: (301)496-5751

Fax: (301)402-2186

Tel: (800)352-9424

TDD: (301)468-5981

Internet: http://www.ninds.nih.gov/



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



Madisons Foundation

PO Box 241956

Los Angeles, CA 90024

Tel: (310)264-0826

Fax: (310)264-4766

Email: getinfo@madisonsfoundation.org

Internet: http://www.madisonsfoundation.org



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

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