National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Joubert syndrome


Other Names:
Cerebelloparenchymal disorder 4; Cerebellar vermis agenesis; Joubert-Boltshauser syndrome; Cerebelloparenchymal disorder 4; Cerebellar vermis agenesis; Joubert-Boltshauser syndrome; JBTS1; CPD4; Cerebellooculorenal syndrome 1; CORS1; Joubert syndrome 1 See More
Categories:
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.[1][2][3] 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.[1][4][5] Treatment is supportive and depends on the symptoms in each person.[1]
Last updated: 11/29/2016
Most infants with Joubert syndrome have weak muscle tone (hypotonia), which evolves into difficulty coordinating movements (ataxia) in early childhood.[3] Affected children may have episodes of unusually fast or slow breathing (hyperpnea), which tends to occur shortly after birth. This may intensify with emotional stress, but progressively improves with age and usually disappears around 6 months of age.[3][6]

Abnormal eye movements are also common. Oculomotor apraxia occurs frequently and causes difficulty moving the eyes from side to side. People with oculomotor apraxia have to turn their heads to see things in their peripheral vision.[6]

Developmental abilities, in particular language and motor skills, are delayed with variable severity. Mild to severe intellectual disability is common, but some people with Joubert syndrome have normal intellectual abilities.[6]

Distinctive facial features are also characteristic. These include a broad forehead, arched eyebrows, droopy eyelids (ptosis), widely spaced eyes, low-set ears, and a triangular-shaped mouth.[3]

Joubert syndrome can cause a wide range of additional signs and symptoms. The condition is sometimes associated with other eye abnormalities (such as retinal dystrophy, which can cause vision loss); kidney disease; liver disease; skeletal abnormalities (such as extra fingers and toes); and hormone (endocrine) problems. When the characteristic features of Joubert syndrome occur with one or more of these additional features, researchers refer to the condition as "Joubert syndrome and related disorders (JSRD)"[3] or as a subtype of Joubert syndrome.[6]
Last updated: 11/29/2016

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 67 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Apnea 0002104
Ataxia 0001251
Cerebellar vermis hypoplasia 0001320
Episodic tachypnea 0002876
Global developmental delay 0001263
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Muscular hypotonia
Low or weak muscle tone
0001252
Oculomotor apraxia 0000657
30%-79% of people have these symptoms
Biparietal narrowing 0004422
Feeding difficulties in infancy 0008872
Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait
[ more ] 		0001288
Long face
Elongation of face
Increased height of face
Increased length of face
Vertical elongation of face
Vertical enlargement of face
Vertical overgrowth of face
[ more ] 		0000276
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
5%-29% of people have these symptoms
Abnormal form of the vertebral bodies 0003312
Abnormality of the hypothalamus-pituitary axis 0000864
Aganglionic megacolon
Enlarged colon lacking nerve cells
0002251
Anteverted nares
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils
[ more ] 		0000463
Aplasia/Hypoplasia of the corpus callosum 0007370
Encephalocele 0002084
Foot polydactyly
Duplication of bones of the toes
0001829
Hand polydactyly
Extra finger
0001161
Highly arched eyebrow
Arched eyebrows
Broad, arched eyebrows
High, rounded eyebrows
High-arched eyebrows
Thick, flared eyebrows
[ more ] 		0002553
Hydrocephalus
Too much cerebrospinal fluid in the brain
0000238
Iris coloboma
Cat eye
0000612
Low-set ears
Low set ears
Lowset ears
[ more ] 		0000369
Occipital myelomeningocele 0007271
Oral cleft
Cleft of the mouth
0000202
Polymicrogyria
More grooves in brain
0002126
Prominent nasal bridge
Elevated nasal bridge
High nasal bridge
Prominent bridge of nose
Prominent nasal root
Protruding bridge of nose
Protruding nasal bridge
[ more ] 		0000426
Ptosis
Drooping upper eyelid
0000508
Renal cyst
Kidney cyst
0000107
Retinal dysplasia 0007973
Scoliosis 0002650
Seizure 0001250
Situs inversus totalis
All organs on wrong side of body
0001696
Strabismus
Cross-eyed
Squint
Squint eyes
[ more ] 		0000486
Tremor 0001337
Percent of people who have these symptoms is not available through HPO
Abnormal saccadic eye movements 0000570
Abnormality of ocular smooth pursuit 0000617
Abnormality of the foot
Abnormal feet morphology
Abnormality of the feet
Foot deformities
Foot deformity
[ more ] 		0001760
Agenesis of cerebellar vermis 0002335
Aggressive behavior
Aggression
Aggressive behaviour
Aggressiveness
[ more ] 		0000718
Autosomal recessive inheritance 0000007
Brainstem dysplasia 0002508
Central apnea 0002871
Chorioretinal coloboma
Birth defect that causes a hole in the innermost layer at the back of the eye
0000567
Dysgenesis of the cerebellar vermis 0002195
Elongated superior cerebellar peduncle 0011933
Enlarged fossa interpeduncularis 0100951
Epicanthus
Eye folds
Prominent eye folds
[ more ] 		0000286
Generalized hypotonia
Decreased muscle tone
Low muscle tone
[ more ] 		0001290
Hemifacial spasm
Spasms on one side of the face
0010828
Hepatic fibrosis 0001395
Hyperactivity
More active than typical
0000752
Hypoplasia of the brainstem
Small brainstem
Underdeveloped brainstem
[ more ] 		0002365
Impaired smooth pursuit 0007772
Macrocephaly
Increased size of skull
Large head
Large head circumference
[ more ] 		0000256
Macroglossia
Abnormally large tongue
Increased size of tongue
Large tongue
[ more ] 		0000158
Molar tooth sign on MRI 0002419
Neonatal breathing dysregulation
Impaired breathing in newborn
0002790
Optic nerve coloboma 0000588
Postaxial hand polydactyly
Extra little finger
Extra pinkie finger
Extra pinky finger
[ more ] 		0001162
Prominent forehead
Pronounced forehead
Protruding forehead
[ more ] 		0011220
Protruding tongue
Prominent tongue
Tongue sticking out of mouth
[ more ] 		0010808
Retinal dystrophy
Breakdown of light-sensitive cells in back of eye
0000556
Self-mutilation
Deliberate self-harm
Self mutilation
[ more ] 		0000742
Triangular-shaped open mouth 0200096
Showing of 67 |
Last updated: 7/1/2020
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.[7]
Last updated: 11/29/2016
Joubert syndrome is predominantly inherited in an autosomal recessive manner.[4] 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.[5] 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
Last updated: 11/29/2016
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.[8]

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.[8]

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.[8]
Last updated: 11/29/2016

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

Management Guidelines

  • Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include Joubert syndrome-related disorders (JSRD), cerebellar vermis malformations without the MTS (which include Dandy-Walker malformation), X-linked cerebellar hypoplasia, ataxia with oculomotor apraxia types 1 and 2 (AOA1, AOA2), congenital disorders of glycosylation (CDG), 3-C syndrome, pontocerebellar hypoplasias/atrophies, orofaciodigital syndromes II and III, and Meckel-Gruber syndrome (see these terms).
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Joubert syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.
  • The University of Washington's Hindbrain Malformation Research Program invites individuals with this condition to participate in their research program. Click on the link for more information on how to participate in their research study.

Patient Registry

  • A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with Joubert syndrome. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

    Registries for Joubert syndrome:
    JS-LIFE (Joubert Syndrome Link to Information & Family Exchange)
     

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Financial Resources

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Joubert syndrome. Click on the link to view a sample search on this topic.

News

Other Conferences

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • I suspect my 32 year old daughter may have Joubert syndrome. Do both my husband and I have to be carriers? Her father's relatives were French Canadians who lived near Quebec, and I have read that there is a large incidence from this area. See answer

  • I am trying for a baby with my partner. From a previous relationship my partner has a son with Joubert syndrome. Is there a risk I could have a baby with Joubert syndrome too? Should I get tested? Also, my partner has previously taken steroids. Do these cause risks of having a Joubert syndrome child? See answer

  • My grandson has Joubert syndrome, autism, and ADHD.  Is autism related to Joubert syndrome? See answer


  1. NINDS Joubert Syndrome Information Page. NINDS. January 21, 2016; http://www.ninds.nih.gov/disorders/joubert/joubert.htm.
  2. Overview. Joubert Syndrome & Related Disorders Foundation. 2016; http://jsrdf.org/what-is-js/.
  3. Joubert syndrome. Genetics Home Reference. January 2011; http://ghr.nlm.nih.gov/condition/joubert-syndrome.
  4. What is Joubert Syndrome?. Hindbrain Malformation Research Program. 2016; http://depts.washington.edu/joubert/joubertsyndrome.php.
  5. Cassandra L. Kniffin. JOUBERT SYNDROME 10; JBTS10. OMIM. December 2, 2015; http://www.omim.org/entry/300804.
  6. Brancati, Francesco, et.al.. Joubert Syndrome and related disorders. Orphanet Journal of Rare Diseases. July 2010; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913941/pdf/1750-1172-5-20.pdf.
  7. Joubert syndrome. Genetics Home Reference. January, 2011; http://ghr.nlm.nih.gov/condition/joubert-syndrome.
  8. Melissa Parisi and Ian Glass. Joubert Syndrome and Related Disorders. GeneReviews. April 11, 2013; http://www.ncbi.nlm.nih.gov/books/NBK1325/.