Rare Nephrology News

Disease Profile

Joubert syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Antenatal

ICD-10

Q04.3

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Cerebelloparenchymal disorder 4; Cerebellar vermis agenesis; Joubert-Boltshauser syndrome;

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

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]

Symptoms

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]

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.

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 foot morphology
Abnormal feet structure
Abnormality of the feet
Abnormality of the foot
Foot deformities
Foot deformity

[ more ]

0001760
Abnormal saccadic eye movements
0000570
Abnormality of ocular smooth pursuit
0000617
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

Cause

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]

Diagnosis

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]

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.

    Treatment

    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.

      Organizations

      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

        Learn more

        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.

            References

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

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