Joubert syndrome

What causes Joubert syndrome?

Joubert syndrome and related disorders may be caused by changes (mutations) in any of many genes (some of which are unknown). The proteins made from these genes are either known or thought to affect cell structures called cilia. Cilia are projections on the cell surface that play a role in signaling. They are important for many cell types, including neurons, liver cells and kidney cells. Cilia also play a role in the senses such as sight, hearing, and smell.

Mutations in the genes responsible for Joubert syndrome and related disorders cause problems with the structure and function of cilia, likely disrupting important signaling pathways during development. However, it is still unclear how specific developmental abnormalities result from these problems.

Last updated on 05-01-20

How is Joubert syndrome diagnosed?

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.

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.

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.

Last updated on 05-01-20

How is Joubert syndrome inherited?

Joubert syndrome is predominantly inherited in an autosomal recessive manner. 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. 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 agenetic 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

Last updated on 05-01-20

Is there a connection between Joubert syndrome and autism?

There is a connection, but it remains somewhat unclear. Autism is a relatively common condition, occurring in 1 in 500 children, and is more likely in boys with a 4:1 male:female ratio. There are likely many different causes for this increasingly common diagnosis. Features of classical autism include poor eye contact and limited communication skills as well as repetitive or self- stimulatory behaviors. Autism has been reported in a number of children with Joubert syndrome in several publications. However, more recent surveys suggest that these behavioral disturbances do not represent classic autism, but are more likely to be related to the underlying cerebellar disorder, eye movement problems, and associated developmental disabilities. You can read more about the question of whether there is a connection between Joubert syndrome and autism on the University of Washington School of Medicine's Joubert Research Program's Web site. Click on the link to view their frequently asked questions.

Last updated on 05-01-20

What is Joubert syndrome?

Joubert syndrome is disorder of brain development that may affect many parts of the body. It is characterized by the absence or underdevelopment of the cerebellar vermis (a part of the brain that controls balance and coordination) and a malformed brain stem (connection between the brain and spinal cord). Together, these cause the characteristic appearance of a molar tooth sign on MRI. Signs and symptoms can vary but commonly include weak muscle tone (hypotonia); abnormal breathing patterns; abnormal eye movements; ataxia; distinctive facial features; and intellectual disability. Various other abnormalities may also be present. Joubert syndrome may be caused by mutations in any of many genes. Inheritance is usually autosomal recessive, but rarely it may be X-linked recessive. Treatment is supportive and depends on the symptoms in each person.

Last updated on 05-01-20

Should I have carrier testing if my male partner has a child with Joubert syndrome?

Joubert syndrome is predominantly inherited in an autosomal recessive manner, in which case both parents must be carriers to have an affected child. In rare cases, Joubert syndrome is inherited in an X-linked recessive manner.

  • If a male child has autosomal recessive Joubert syndrome, it is assumed his father is a carrier. To have another affected child with a different partner, the partner must also be a carrier of autosomal recessive Joubert syndrome. Many genes can be responsible for Joubert syndrome (some of which are unknown), and digenic inheritance is possible. This means that children may be at risk if one parent carries a mutation in one responsible gene, and the other parent carries a mutation in a different responsible gene.

  • If a male child has X-linked recessive Joubert syndrome, the most likely reason is that his mother is a carrier of X-linked Joubert syndrome, and the father is not a carrier. Males cannot be "carriers" of X-linked recessive conditions; if they have a mutation in the responsible X-linked gene, they will be affected.

Because the genetics of Joubert syndrome can be complex, people with questions about carrier testing are strongly encouraged to speak with a genetic counselor or other genetics professional. Whether to have genetic testing is a personal decision. A genetic counselor can provide more detailed information about the genetic risks to specific family members. They also discuss the risks, benefits, and limitations of genetic testing, and can facilitate the testing process for people who decide to have testing.

Last updated on 05-01-20

Can steroid use increase the chance to have a child with Joubert syndrome?

No. A person with a history of steroid use does not have a higher chance to have a child with Joubert syndrome. Joubert syndrome is a genetic condition caused by changes (mutations) in genes that can be passed from parent to child. These mutations are present from birth and are not acquired during a person's lifetime.

Last updated on 05-01-20

Is Joubert syndrome more common in people of French Canadian descent?

Yes. There is a relatively high prevalence of Joubert syndrome and related disorders (JSRD) in the French Canadian population, with several founder effects noted. 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).

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. 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.

Last updated on 05-01-20

Name: Joubert Syndrome & Related Disorders Foundation JSRDF 9 Dorenfeld CT
Petaluma, CA, 94952, United States
Phone: +1-614-864-1362 Email: info@jsrdf.org Url: https://jsrdf.org/

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