On this page
Joubert syndrome
This condition is characterised by a distinctive brain malformation and can lead to developmental delays, breathing abnormalities, and issues affecting the eyes, kidneys, and liver. It is present from birth and affects individuals across all populations.
Available at Jeen Health
Clinical tests that include this
Overview
Joubert syndrome is a rare inherited condition that affects the development and function of the brain, particularly the cerebellum (which helps coordinate movement) and the brainstem (which controls vital functions like breathing). It is often classified as a ciliopathy, a group of disorders caused by problems with cilia, which are tiny, hair-like structures on the surface of many cells in the body [PMID:24072978].
The hallmark brain feature of Joubert syndrome is called the 'molar tooth sign,' which can be seen on brain imaging. This sign is due to an abnormal formation of the cerebellar vermis and the brainstem. The condition can impact various organ systems, leading to a range of symptoms that vary in severity among affected individuals. Joubert syndrome is typically identified in infancy or early childhood.
Symptoms & clinical features
The symptoms of Joubert syndrome can be wide-ranging but often include early developmental delays, affecting milestones such as sitting, crawling, and walking. Many individuals experience hypotonia (reduced muscle tone) in infancy, which can make them appear 'floppy'.
Characteristic features often include unusual eye movements, such as oculomotor apraxia, where moving the eyes quickly can be difficult. Breathing abnormalities, such as rapid breathing followed by pauses, especially in infancy, are also common. Other potential symptoms can include kidney disease, liver fibrosis, retinal degeneration leading to vision problems, and structural abnormalities of the tongue or extra fingers/toes (polydactyly) [PMID:23568774].
Video: Genetics 101
Affected organs
Joubert syndrome primarily affects the brain, specifically the cerebellum and brainstem, leading to the distinctive 'molar tooth sign'. However, its impact extends beyond the brain. Other organs commonly affected include the kidneys, which can develop cysts or scarring (fibrosis). The liver may also be affected by fibrosis, potentially leading to impaired function over time. The eyes can be impacted, sometimes with retinal degeneration that can affect vision. Additionally, the condition can affect the skeleton, leading to polydactyly (extra digits), and in some cases, the endocrine system [PMID:24072978].
Risks & severity
The severity of Joubert syndrome is highly variable, even among individuals with the same genetic cause. Some individuals may experience mild developmental delays and learning difficulties, while others may have more significant intellectual disability and profound motor impairment. The breathing irregularities often improve with age, but kidney and liver issues can progress over time.
Life expectancy can depend on the severity of organ involvement, particularly the kidneys and liver, as well as the extent of neurological issues. The exact prevalence of Joubert syndrome is estimated to be between 1 in 80,000 to 1 in 100,000 live births, but this might be an underestimate due to its varied presentation and diagnostic challenges.
Genetic causes
Joubert syndrome is a genetically heterogeneous condition, meaning it can be caused by pathogenic changes in a number of different genes. These genes are involved in the structure and function of cilia, which are microscopic, hair-like projections on the surface of many cells. Examples of genes associated with Joubert syndrome include CC2D2A, CEP290, and TMEM67.
The CEP290 gene, for instance, provides instructions for a protein that is vital for the proper assembly and function of cilia. When there are pathogenic variants in CEP290, the cilia do not function correctly, which disrupts cellular processes, particularly in brain development. These gene changes lead to the characteristic brain malformations and other systemic symptoms seen in Joubert syndrome.
Inheritance pattern
Joubert syndrome is typically inherited in an autosomal recessive pattern. This means that a person must inherit two copies of a pathogenic gene variant - one from each parent - to develop the condition. Individuals who inherit only one copy of a pathogenic variant are called carriers; they usually do not show symptoms of the condition themselves but can pass the variant on to their children.
If both parents are carriers of a pathogenic variant in the same gene associated with Joubert syndrome, there is a 25% (1 in 4) chance with each pregnancy that their child will inherit two copies of the variant and be affected by the condition. There is also a 50% (2 in 4) chance that their child will be a carrier, and a 25% (1 in 4) chance that their child will inherit two normal copies of the gene.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
Diagnosis & testing
Diagnosis of Joubert syndrome is usually suspected based on characteristic clinical features and confirmed through brain imaging, such as an MRI, which reveals the 'molar tooth sign.' This distinctive appearance is caused by the abnormal development of the cerebellar vermis and brainstem structures [PMID:23568774].
Genetic testing is crucial for confirming the diagnosis and identifying the specific gene responsible. This can involve a gene panel test that looks at many genes associated with Joubert syndrome. In the UK, genetic testing for suspected Joubert syndrome falls under the NHS Genomic Medicine Service (GMS) pathways, and referrals for testing are typically made by a paediatrician or clinical geneticist. Relevant R-codes for genetic testing can be found in the NHS National Genomic Test Directory.
Management & lifestyle
Management of Joubert syndrome focuses on addressing individual symptoms and providing supportive care, as there is currently no cure for the underlying genetic cause. This often involves a multidisciplinary team, including paediatricians, neurologists, nephrologists (kidney specialists), ophthalmologists (eye specialists), and therapists.
Early intervention therapies, such as physiotherapy, occupational therapy, and speech therapy, are important to support development and manage motor difficulties. Regular monitoring for potential kidney and liver complications is also crucial. For example, kidney function may be monitored to manage chronic kidney disease, and regular eye examinations can help detect and manage retinal issues. Genetic counselling is an important part of supporting families with Joubert syndrome, providing information on inheritance, recurrence risks, and family planning options.
UK care pathway
In the UK, individuals suspected of having Joubert syndrome would typically be referred to a clinical genetics service within the NHS Genomic Medicine Service. These services can coordinate the necessary diagnostic tests, including genetic testing through the NHS National Genomic Test Directory (using relevant R-codes from PanelApp), and provide genetic counselling. Genetic counsellors offer support and information about the condition, its inheritance, and implications for families.
Frequently asked questions
What is the 'molar tooth sign'?
The 'molar tooth sign' is a distinctive brain malformation seen on MRI scans of individuals with Joubert syndrome. It refers to the abnormal shape of the superior cerebellar peduncles and an underdeveloped cerebellar vermis, which together resemble a molar tooth.
Can Joubert syndrome be detected before birth?
In some cases, severe brain abnormalities or other physical features associated with Joubert syndrome might be identified during prenatal ultrasound scans or foetal MRI. If there's a family history, prenatal genetic testing could also be considered.
Will my child with Joubert syndrome have learning difficulties?
Developmental delays and learning difficulties are common in individuals with Joubert syndrome, but the severity varies widely. Some individuals may have mild challenges, while others experience more significant intellectual disability. Early intervention therapies can help support development.
Is there a cure for Joubert syndrome?
Currently, there is no cure for Joubert syndrome. Management focuses on treating the symptoms and providing supportive care tailored to each individual's specific needs, including therapies and monitoring for potential complications like kidney or liver problems.
How common is Joubert syndrome?
Joubert syndrome is considered a rare condition, with an estimated prevalence of approximately 1 in 80,000 to 1 in 100,000 live births. However, due to its varied presentation, the exact number might be slightly higher.
References
- Spahiu L, Behluli E, Grajçevci-Uka V. Joubert syndrome: Molecular basis and treatment. Journal of mother and child. 2022. PMID: 36803942
- Bachmann-Gagescu R, Dempsey JC, Bulgheroni S. Healthcare recommendations for Joubert syndrome. American journal of medical genetics. Part A. 2020. PMID: 31710777
- Bachmann-Gagescu R, Dempsey JC, Phelps IG. Joubert syndrome: a model for untangling recessive disorders with extreme genetic heterogeneity. Journal of medical genetics. 2015. PMID: 26092869
- Adam MP, Bick S, Mirzaa GM. Joubert Syndrome. 1993. PMID: 20301500
- Gana S, Serpieri V, Valente EM. Genotype-phenotype correlates in Joubert syndrome: A review. American journal of medical genetics. Part C, Seminars in medical genetics. 2022. PMID: 35238134
- Devlin LA, Dewhurst RM, Sudhindar PD. Renal ciliopathies. Current topics in developmental biology. 2025. PMID: 40254346
- Tran AM, Jnah AJ, De Castro Pretelt MJ. Genetics Review: Joubert Syndrome. Neonatal network : NN. 2025. PMID: 40537162
- Aksu Uzunhan T, Ertürk B, Aydın K. Clinical and genetic spectrum from a prototype of ciliopathy: Joubert syndrome. Clinical neurology and neurosurgery. 2023. PMID: 36580738