Joubert syndrome
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. 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. Treatment is supportive and depends on the symptoms in each person.
Symptoms
Most infants with Joubert syndrome have weak muscle tone (hypotonia), which evolves into difficulty coordinating movements (ataxia) in early childhood. 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.
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.
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.
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.
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)” or as a subtype of Joubert syndrome.
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.
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.
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.
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.
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.
Management
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.
