NORD gratefully acknowledges Joseph G. Gleeson, MD, Professor, Neurogenetics Laboratory, Department of Neurosciences and Pediatrics; Investigator, Howard Hughes Medical Institute, University of California, San Diego, for assistance in the preparation of this report.
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.
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.
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.
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.
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.
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.
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.
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Joubert Syndrome: Are Kidneys Involved?
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FROM THE INTERNET
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