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Genetics Home Reference: your guide to understanding genetic conditions
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Joubert syndrome

Reviewed January 2011

What is Joubert syndrome?

Joubert syndrome is a disorder that affects many parts of the body. The signs and symptoms of this condition vary among affected individuals, even among members of the same family.

The hallmark feature of Joubert syndrome is a brain abnormality called the molar tooth sign, which can be seen on brain imaging studies such as magnetic resonance imaging (MRI). This sign results from the abnormal development of regions near the back of the brain called the cerebellar vermis and the brainstem. The molar tooth sign got its name because the characteristic brain abnormalities resemble the cross-section of a molar tooth when seen on an MRI.

Most infants with Joubert syndrome have weak muscle tone (hypotonia) in infancy, which evolves into difficulty coordinating movements (ataxia) in early childhood. Other characteristic features of the condition include episodes of unusually fast or slow breathing in infancy and abnormal eye movements. Most affected individuals have delayed development and intellectual disability, which range from mild to severe. Distinctive facial features are also characteristic of Joubert syndrome; these include a broad forehead, arched eyebrows, droopy eyelids (ptosis), widely spaced eyes, low-set ears, and a triangle-shaped mouth.

Joubert syndrome can include a broad range of additional signs and symptoms. The condition is sometimes associated with other eye abnormalities (such as retinal dystrophy, which can cause vision loss), kidney disease, liver disease, skeletal abnormalities (such as the presence of extra fingers and toes), and hormone (endocrine) problems. When the characteristic features of Joubert syndrome occur in combination with one or more of these additional signs and symptoms, researchers refer to the condition as "Joubert syndrome and related disorders (JSRD)."

How common is Joubert syndrome?

Joubert syndrome is estimated to affect between 1 in 80,000 and 1 in 100,000 newborns. However, this estimate may be too low because Joubert syndrome has such a large range of possible features and is likely underdiagnosed.

What genes are related to Joubert syndrome?

Joubert syndrome and related disorders can be caused by mutations in at least 10 genes. The proteins produced from these genes are known or suspected to play roles in cell structures called cilia. Cilia are microscopic, finger-like projections that stick out from the surface of cells and are involved in chemical signaling. Cilia are important for the structure and function of many types of cells, including brain cells (neurons) and certain cells in the kidneys and liver. Cilia are also necessary for the perception of sensory input (such as sight, hearing, and smell).

Mutations in the genes associated with Joubert syndrome and related disorders lead to problems with the structure and function of cilia. Defects in these cell structures probably disrupt important chemical signaling pathways during development. Although researchers believe that defective cilia are responsible for most of the features of these disorders, it remains unclear how they lead to specific developmental abnormalities.

Mutations in the 10 genes known to be associated with Joubert syndrome and related disorders only account for about half of all cases of these conditions. In the remaining cases, the genetic cause is unknown.

Related Gene(s)

Changes in these genes are associated with Joubert syndrome.

  • AHI1
  • ARL13B
  • CC2D2A
  • CEP290
  • INPP5E
  • NPHP1
  • OFD1
  • RPGRIP1L
  • TMEM216
  • TMEM67

How do people inherit Joubert syndrome?

Joubert syndrome typically has an autosomal recessive pattern of inheritance, which means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they usually do not show signs and symptoms of the condition.

Rare cases of Joubert syndrome are inherited in an X-linked recessive pattern. In these cases, the causative gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Where can I find information about diagnosis or management of Joubert syndrome?

These resources address the diagnosis or management of Joubert syndrome and may include treatment providers.

  • Gene Review: Joubert Syndrome and Related Disorders (http://www.ncbi.nlm.nih.gov/books/NBK1325)
  • Genetic Testing Registry: Familial aplasia of the vermis (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0431399)
  • Genetic Testing Registry: Joubert syndrome 10 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C2749019)
  • Genetic Testing Registry: Joubert syndrome 2 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1842577)
  • Genetic Testing Registry: Joubert syndrome 3 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1837713)
  • Genetic Testing Registry: Joubert syndrome 4 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1846790)
  • Genetic Testing Registry: Joubert syndrome 5 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1857780)
  • Genetic Testing Registry: Joubert syndrome 6 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1853153)
  • Genetic Testing Registry: Joubert syndrome 7 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1969053)
  • Genetic Testing Registry: Joubert syndrome 8 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C2676771)
  • Genetic Testing Registry: Joubert syndrome 9 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C2676788)
  • Joubert Syndrome & Related Disorders Foundation: Diagnosis (http://www.jsrdf.org/diagnostics)

You might also find information on the diagnosis or management of Joubert syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/joubert-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/joubert-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Joubert syndrome?

You may find the following resources about Joubert syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for Joubert syndrome?

  • agenesis of cerebellar vermis
  • cerebello-oculo-renal syndrome
  • cerebellooculorenal syndrome 1
  • CORS
  • familial aplasia of the vermis
  • JBTS
  • Joubert-Bolthauser syndrome

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Joubert syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding Joubert syndrome?

agenesis ; ataxia ; autosomal ; autosomal recessive ; brainstem ; cell ; chromosome ; disability ; dysplasia ; familial ; fibrosis ; gene ; hepatic ; hormone ; hypotonia ; imaging ; inheritance ; inherited ; juvenile ; kidney ; magnetic resonance imaging ; muscle tone ; mutation ; pattern of inheritance ; perception ; ptosis ; recessive ; renal ; sex chromosomes ; sign ; syndrome ; X-linked recessive

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Brancati F, Dallapiccola B, Valente EM. Joubert Syndrome and related disorders. Orphanet J Rare Dis. 2010 Jul 8;5:20. doi: 10.1186/1750-1172-5-20. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20615230?dopt=Abstract)
  • Doherty D. Joubert syndrome: insights into brain development, cilium biology, and complex disease. Semin Pediatr Neurol. 2009 Sep;16(3):143-54. doi: 10.1016/j.spen.2009.06.002. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19778711?dopt=Abstract)
  • Gene Review: Joubert Syndrome and Related Disorders (http://www.ncbi.nlm.nih.gov/books/NBK1325)
  • Maria BL, Quisling RG, Rosainz LC, Yachnis AT, Gitten J, Dede D, Fennell E. Molar tooth sign in Joubert syndrome: clinical, radiologic, and pathologic significance. J Child Neurol. 1999 Jun;14(6):368-76. (http://www.ncbi.nlm.nih.gov/pubmed/10385844?dopt=Abstract)
  • Parisi MA. Clinical and molecular features of Joubert syndrome and related disorders. Am J Med Genet C Semin Med Genet. 2009 Nov 15;151C(4):326-40. doi: 10.1002/ajmg.c.30229. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19876931?dopt=Abstract)
  • Valente EM, Brancati F, Dallapiccola B. Genotypes and phenotypes of Joubert syndrome and related disorders. Eur J Med Genet. 2008 Jan-Feb;51(1):1-23. doi: 10.1016/j.ejmg.2007.11.003. Epub 2007 Nov 23. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18164675?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: January 2011
Published: September 15, 2014