Joubert syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Joubert syndrome is a condition that affects the development of the brain. This condition can also impact many other parts of the body. The signs and symptoms seen in people with Joubert syndrome can vary, even among members of the same family.

The hallmark feature of Joubert syndrome is a combination of brain abnormalities called the molar tooth sign, which can be seen using magnetic resonance imaging (MRI). The molar tooth sign occurs when structures near the back of the brain, including the brainstem and the central part of the cerebellum (vermis), develop abnormally. This sign got its name because these brain abnormalities resemble the shape or outline of a molar tooth when seen on an MRI scan.

Infants with Joubert syndrome often have low muscle tone (hypotonia) and may experience breathing problems, with episodes of unusually fast (hyperpnea) or slow (apnea) breathing. Abnormal eye movements, which can include rapid, involuntary eye movements (nystagmus) or problems with side-to-side movements of the eyes (oculomotor apraxia), are also common.

Most individuals with Joubert syndrome have intellectual disabilities, which can range from mild to severe. Children with Joubert syndrome often have delayed development of speech and motor skills, such as sitting and walking. Problems with coordination and balance (ataxia) are common, but ataxia may become less severe over time. Most children with Joubert syndrome learn to walk on their own, although some affected individuals require walking support or wheelchair assistance.

Additional signs and symptoms that are seen in people with Joubert syndrome can include seizures, difficulty regulating body temperature, and behavioral problems. People with Joubert syndrome may have a broad range of other signs and symptoms. Kidney disease, liver disease, skeletal abnormalities (such as the presence of extra fingers and toes), or hormone (endocrine) problems may occur in affected individuals. Eye abnormalities may also be present and can include the breakdown of the light-sensitive tissue at the back of the eye (retinal dystrophy), which can cause vision loss.

In the past, individuals with the molar tooth sign were separated into different subgroups of Joubert syndrome based on their additional features. The term “Joubert syndrome and related disorders” (JSRD) was used to refer to these subgroups. Today, all people with the molar tooth sign, including those with additional signs and symptoms, are considered to have Joubert syndrome.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Joubert syndrome can be caused by variants (also called mutations) in one of more than 40 genes. The proteins produced from most of these genes are known or suspected to be involved with cell structures called primary cilia. Primary cilia are microscopic, finger-like projections that stick out from the surface of cells. They are part of signaling pathways that transmit information between cells. Primary cilia are important for the structure and function of many types of cells, including brain cells and certain cells in the kidneys and liver.

Variants in many of the genes that are associated with Joubert syndrome lead to problems with the structure and function of primary cilia, which can disrupt important signaling pathways during early development. Researchers believe that defective primary cilia are responsible for most of the features of Joubert syndrome.

Sixty-two to 94 percent of all people with Joubert syndrome have variants in one of the genes that are associated with this condition. In the remaining cases, the genetic cause is unknown.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Joubert syndrome can have different inheritance patterns depending on its genetic cause.

Joubert syndrome is almost always inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

Joubert syndrome can also be inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

In rare cases, the condition is inherited in an X-linked pattern. A condition is considered X-linked if the altered gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In males (who have only one X chromosome), a variant in the only copy of the gene in each cell is sufficient to cause the condition. In females (who have two copies of the X chromosome), one altered copy of the gene may or may not cause the condition. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Joubert syndrome is estimated to affect between 1 in 80,000 and 100,000 newborns. However, this estimate may be low because some affected individuals likely do not receive a diagnosis.

Which doctor should you see?

The suggested department for discussing Joubert syndrome is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Joubert syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.