Joubert syndrome

Infobox_Disease
Name = Joubert syndrome


Caption =
DiseasesDB = 30688
ICD10 = ICD10|Q|04|3|q|00
ICD9 = ICD9|742.2
ICDO =
OMIM = 213300
MedlinePlus =
eMedicineSubj =
eMedicineTopic =

Joubert syndrome is a rare genetic disorder that affects the area of the brain that controls balance and coordination.

Presentation

The disorder is characterized by absence or underdevelopment of a part of the brain called the cerebellar vermis and a malformed brain stem (molar tooth sign). The most common features include ataxia (lack of muscle control), an abnormal breathing pattern called hyperpnea, 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. The syndrome was first identified by pioneering pediatric neurologist Dr. Marie Joubert in Montreal Canada, while working at the McGill Neurological Institute.Fact|date=July 2008

Treatment

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.

Prognosis

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.

Genetics

Multiple genes that are mutated in individuals with Joubert syndrome have been identified:

* Mutations in a gene of unknown function called AHI1 is associated with a subset of Joubert syndrome cases. [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.]

* In some rare cases of Joubert syndrome, mutations have been found in NPHP1 which is also associated with nephronophthisis, a cystic kidney disorder. [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.]

* The gene CEP290 has been associated with both Joubert syndrome and Leber's congenital amaurosis, type 10.cite journal |author=Traboulsi EI, Koenekoop R, Stone EM |title=Lumpers or splitters? The role of molecular diagnosis in Leber congenital amaurosis |journal=Ophthalmic Genet. |volume=27 |issue=4 |pages=113–5 |year=2006 |pmid=17148037 |doi=10.1080/13816810601013146]

Relation to other rare disorders: genetic ciliopathy

Recent findings in genetic research have suggested that a large number of genetic disorders, both genetic syndromes and genetic diseases, that were not previously related in the medical literature, may be, in fact, highly related in the root cause of the widely-varying set of medical symptoms that are clinically visible in the disorder. Joubert syndrome is one such disease, part of an emerging class of diseases called cilopathies. The underlying cause may be a dysfunctional molecular mechanism in the primary cilia structures of the cell, organelles which are present in many cellular types througout 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. Known ciliopathies include primary ciliary dyskinesia, Bardet-Biedl syndrome, polycystic kidney and liver disease, nephronophthisis, Alstrom syndrome, Meckel-Gruber syndrome and some forms of retinal degeneration. [cite journal
last = Badano
first = Jose L.
authorlink =
coauthors = Norimasa Mitsuma, Phil L. Beales, Nicholas Katsanis
title = The Ciliopathies : An Emerging Class of Human Genetic Disorders
journal = Annual Review of Genomics and Human Genetics
volume = 7
issue =
pages = 125-148
publisher =
location =
date = September 2006
url = http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.genom.7.080505.115610
doi = 10.1146/annurev.genom.7.080505.115610
id =
accessdate = 2008-06-15] .

References

External links

* [http://www.joubertsyndrome.org The Joubert Syndrome Foundation Home Page]
* [http://www.ninds.nih.gov/health_and_medical/disorders/joubert.htm NINDS Joubert Syndrome Information Page]
* [http://www.ninds.nih.gov/news_and_events/news_articles/news_article_Joubert_genes.htm#_ftnref2 Researchers Identify Joubert Syndrome Genes]
* [http://www.genetests.org/query?dz=joubert GeneReviews: Joubert syndrome]