The disorder is characterized by absence or underdevelopment of the cerebellar vermis and a malformed brain stem (molar tooth sign). The most common features include ataxia (lack of muscle control), hyperpnea (abnormal breathing patterns), sleep apnea, abnormal eye and tongue movements, and hypotonia. Other malformations such as extra fingers and toes, cleft lip or palate, tongue abnormalities, and seizures may also occur. There may be mild or moderate retardation. Joubert syndrome is one of the many genetic syndromes associated with syndromic retinitis pigmentosa. The syndrome was first identified by pioneering pediatric neurologist Marie Joubert in Montreal, Canada, while working at the Montreal Neurological Institute and McGill University.
Treatment for Joubert syndrome is symptomatic and supportive. Infant stimulation and physical, occupational, and speech therapy may benefit some patients. Infants with abnormal breathing patterns should be monitored.
The prognosis for individuals with Joubert syndrome varies. Some patients have a mild form with minimal motor disability and good mental development, while others may have severe motor disability and moderate mental retardation.
- JBTS3: Mutations in a gene of unknown function called AHI1 is associated with a subset of Joubert syndrome cases.
- JBTS4: In some rare cases of Joubert syndrome, mutations have been found in NPHP1 which is also associated with nephronophthisis, a cystic kidney disorder.
- JBTS5: The gene CEP290 has been associated with both Joubert syndrome and Leber’s congenital amaurosis, type 10.
Research has revealed that a number of genetic disorders, not previously thought to be related, may indeed be related as to their root cause. Joubert syndrome is one such disease. It is a member of an emerging class of diseases called cilopathies.
The underlying cause of the ciliopathies may be a dysfunctional molecular mechanism in the primary cilia structures of the cell, organelles which are present in many cellular types throughout the human body. The cilia defects adversely affect “numerous critical developmental signaling pathways” essential to cellular development and thus offer a plausible hypothesis for the often multi-symptom nature of a large set of syndromes and diseases.
Currently recognized ciliopathies include Joubert syndrome, primary ciliary dyskinesia, Bardet-Biedl syndrome, polycystic kidney disease and polycystic liver disease, nephronophthisis,Alstrom syndrome, Meckel-Gruber syndrome and some forms of retinal degeneration.
- ^ Saraiva, JM, Baraitser M (1992) Joubert syndrome: a review. Am. J. Med. Genet. 43: 726-731
- ^ Joubert M, Eisenring JJ, Robb JP, Andermann F (September 1969). “Familial agenesis of the cerebellar vermis. A syndrome of episodic hyperpnea, abnormal eye movements, ataxia, and retardation”. Neurology 19 (9): 813–25. PMID 5816874.
- ^ Ferland R. J. et al. Abnormal cerebellar development and axonal decussation due to mutations in AHI1 in Joubert syndrome. Nature Genetics, September 2004, 36:1008-1013.
- ^ Dixon-Salazar T. et al. Mutations in the AHI1 gene, encoding jouberin, cause Joubert syndrome with cortical polymicrogyria. “American Journal of Human Genetics”, December 2004, 75(6):979-87.
- ^ Parisi M. A. et al. The NPHP1 gene deletion associated with juvenile nephronophthisis is present in a subset of individuals with Joubert syndrome. American Journal of Human Genetics, July 2004, 75:82-91.
- ^ Traboulsi EI, Koenekoop R, Stone EM (2006). “Lumpers or splitters? The role of molecular diagnosis in Leber congenital amaurosis”. Ophthalmic Genet. 27 (4): 113–5.doi:10.1080/13816810601013146. PMID 17148037.
- ^ Badano, Jose L.; Norimasa Mitsuma, Phil L. Beales, Nicholas Katsanis (September 2006). “The Ciliopathies : An Emerging Class of Human Genetic Disorders”. Annual Review of Genomics and Human Genetics 7: 125–148.doi:10.1146/annurev.genom.7.080505.115610. PMID 16722803. Retrieved 2008-06-15.