Joubert syndrome

Joubert syndrome
Classification and external resources
ICD-10	Q04.3
ICD-9	742.2
OMIM	213300
DiseasesDB	30688

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

Diagnosis

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

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:

• 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.

• TCTN2 and ATXN10 have been associated with Joubert syndrome.

• TMEM138 has been associated with Joubert syndrome.

• TMEM237 is mutated in individuals with a Joubert syndrome related disorder and expands the role of the TMEM family at the ciliary transition zone.

• CEP41 is mutated in Joubert syndrome and is required for tubulin glutamylation at the cilium.

• Mutations in the OFD1 gene can also cause several other disorders with features that overlap with those of oral-facial-digital syndrome. At least two mutations have been identified in people with Joubert syndrome.

Type	OMIM	Gene	Test Available
JBTS1	213300	INPP5E	Yes
JBTS2	608091	TMEM216	Yes
JBTS3	608629	AHI1	Yes
JBTS4	609583	NPHP1	Yes
JBTS5	610188	CEP290/NPHP6	Yes
JBTS6	610688	TMEM67	Yes
JBTS7	611560	RPGRIP1L	Yes
JBTS8	612291	ARL13B	Yes
JBTS9	612285	CC2D2A	Yes
JBTS10	300170	OFD1	Yes
??????	??????	TCTN2	I haven't found one - Davin
??????	??????	ATXN10	I haven't found one - Davin
JBTS15	610523	CEP41	I haven't found one - Davin
JBTS16	614459	TMEM138	I haven't found one - Davin

Ciliopathy

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 ciliopathies.

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.

External links

• The Joubert Syndrome Foundation Home Page
• NINDS Joubert Syndrome Information Page
• Researchers Identify Joubert Syndrome Genes
• GeneReviews: Joubert syndrome
• University of Washington Joubert Research Program
• NCBI Joubert Syndrome
• Joubert Research Program - Seattle Research Hospital Children's Foundation