Joubert syndrome

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.^[1] The syndrome was first identified by pioneering pediatric neurologist Marie Joubert in Montreal, Canada, while working at the Montreal Neurological Institute and McGill University.^[2]

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.^[3][4]

• JBTS4: In some rare cases of Joubert syndrome, mutations have been found in NPHP1 which is also associated with nephronophthisis, a cystic kidney disorder.^[5]

• JBTS5: The gene CEP290 has been associated with both Joubert syndrome and Leber’s congenital amaurosis, type 10.^[6]

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 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.^[7]

References