Joubert syndrome

Joubert syndrome is predominantly inherited in an autosomal recessive manner.^[1] This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. Affected people inherit one mutated copy of the gene from each parent, who is referred to as a carrier. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When 2 carriers of an autosomal recessive condition have children, each child has a:

• 25% chance to be affected
• 50% chance to be an unaffected carrier like each parent
• 25% chance to be unaffected and not a carrier.

In rare cases, when Joubert syndrome is caused by mutations in the OFD1 gene on the X chromosome, it is inherited in an X-linked recessive manner.^[2] X-linked recessive conditions usually occur in males, who only have one X chromosome (and one Y chromosome). Females have two X chromosomes, so if they have a mutation on one X chromosome, they still have a working copy of the gene on their other X chromosome and are typically unaffected. While females can have an X-linked recessive condition, it is very rare.

If a mother is a carrier of an X-linked recessive condition and the father is not, the risk to children depends on each child's sex.

• Each male child has a 50% chance to be unaffected, and a 50% chance to be affected
• Each daughter has a 50% chance to be unaffected, and a 50% chance to be an unaffected carrier

If a father has the X-linked recessive condition and the mother is not a carrier, all sons will be unaffected, and all daughters will be unaffected carriers.

People with specific questions about the inheritance of Joubert syndrome for themselves or family members are encouraged to speak with a genetic counselor or other genetics professional. A genetics professional can help by:

• thoroughly evaluating the family history
• addressing questions and concerns
• assessing recurrence risks
• facilitating genetic testing if desired
• discussing reproductive options

Yes. There is a relatively high prevalence of Joubert syndrome and related disorders (JSRD) in the French Canadian population, with several founder effects noted.^[3] A founder effect is the effect on a gene pool that occurs when a new population is formed (founded) by a small number of individuals from a larger population, with limited genetic variation. Founder effects are typically associated with an increase in the frequency of a specific autosomal recessive allele (version of a gene).^[4]

The family first described by Joubert et al in 1969 has been traced to a founder who immigrated to Quebec from France in the 1600s. However, it reportedly appears that there are other founder groups in the French Canadian population.^[3] We are not aware of reports stating the prevalence or carrier frequency of Joubert syndrome in this population.

The exact incidence or prevalence of Joubert syndrome and related disorders in the general population has not been determined, but many authors use a range between 1 in 80,000 and 1 in 100,000. This may be an underestimate.^[3][5]

The diagnosis of Joubert syndrome is based on the presence of characteristic clinical features as well as the MRI finding of the molar tooth sign.^[3]

The diagnosis of "classic" or “pure” Joubert syndrome is based on the presence of the following three primary criteria:

• the molar tooth sign on MRI
• hypotonia (weak muscle tone) in infancy with later development of ataxia
• developmental delays / intellectual disability

Additional features often identified in people with Joubert syndrome include an abnormal breathing pattern (alternating tachypnea and/or apnea) and abnormal eye movements.

The term “Joubert syndrome and related disorders” (JSRD) refers to those with Joubert syndrome who have additional findings such as retinal dystrophy, renal (kidney) disease, ocular colobomas, occipital encephalocele (protruding tissue at the back of the skull), fibrosis of the liver, polydactyly, and/or other abnormalities. A significant proportion of people diagnosed with classic Joubert syndrome in infancy or early childhood will eventually have additional findings that represent JSRD.^[3]

While mutations in many genes are known to be associated with Joubert syndrome, they are only identified in about 50% of affected people who have genetic testing. Therefore, genetic testing is not required for a diagnosis of Joubert syndrome or JSRD.^[3]

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.