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

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.^[3]

• 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.^[3] 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.

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.

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.^[4]

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.