Joubert Syndrome

What Causes Joubert Syndrome?

JS is caused by abnormal changes in genes (mutations) that impair the development of specific cell structures. Scientists have identified mutations in more than 30 different genes that appear to play a role in JS. A combination of multiple gene mutations is likely responsible for the disorder in at least some cases, but some cases have no discernible genetic cause.

The gene mutations associated with JS affect the development of microscopic hair-like structures on the surface of cells called primary cilia. Primary cilia are vital in the function of sensory cells, and they also play a role in communication pathways between nerve cells. Researchers believe that cilia abnormalities are responsible for the brain defects in JS, but they don’t know precisely how the disorder develops.

Is Joubert Syndrome Hereditary?

JS is an inherited disorder. Most cases are inherited in an autosomal recessive pattern, meaning that a child must inherit two copies of the mutated gene, one from each parent, for the disorder to develop. The parents in these cases carry just one copy of the mutation, so they typically do not show any symptoms of JS themselves.

In rare cases, JS is inherited in an X-linked recessive pattern. In these cases, the disorder-causing mutation is on the X chromosome. Females have two copies of the X chromosome in their cells. One copy is inherited from the mother and the other from the father. Males have only one copy of the X chromosome, inherited either from the mother or father. Males develop this type of JS if they have the gene mutation on their only X chromosome. Females only develop the disorder if they have the mutation on both of their X chromosomes. Consequently, this form of the condition is more common in males than females.

How Is Joubert Syndrome Detected?

JS is usually first detected in infancy after a baby has exhibited symptoms characteristic of the disorder. At that point, imaging exams of the baby’s brain can detect the condition’s distinctive malformations.

Diagnosis of JS may be possible using ultrasound before birth, but prenatal detection of the condition is rare. Ultrasound imaging does not always show the relevant features of JS, and some of the developmental features may be similar to those of other disorders, such as Dandy-Walker syndrome.

Parents who have a child with JS have a 25 percent chance of having another affected child with each pregnancy.

How Is Joubert Syndrome Diagnosed?

Doctors can diagnose JS if a child exhibits symptoms of the disorder and imaging scans show the condition’s distinctive malformations. Symptoms that can suggest the presence of JS include:

• Weak muscle tone in infants
• Coordination and movement problems in older children
• Developmental delays
• Intellectual impairment

When doctors suspect JS, they will usually conduct a magnetic resonance imaging (MRI) scan to look for brain malformations. In JS, a structure toward the rear of the brain called the cerebellar vermis is typically underdeveloped or missing entirely. Abnormalities in the brain stem are also common.

Genetic testing can detect the gene mutations responsible for some cases of JS.

PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.

How Is Joubert Syndrome Treated?

JS has no cure. Standard treatment for the disorder includes therapies intended to reduce the impact of developmental delays. Common therapies include:

• Physical therapy
• Occupational therapy
• Speech therapy
• Infant stimulation (providing babies with sensory-stimulating activities and surroundings)

Treatment of JS also includes ongoing monitoring to identify complications such as kidney disease, liver disease, and vision impairments.

How Does Joubert Syndrome Progress?

Children with JS exhibit a wide range of symptoms and complications. Some children have only mild symptoms and experience only slight developmental delays. In other cases, developmental and intellectual impairments are severe. Factors that influence the severity of symptoms include:

• Which gene mutation causes the disorder.
• The degree of malformation in the cerebellar vermis.
• The involvement of other vital organs.

JS can be fatal in childhood. The most common cause of death in young children is respiratory failure. Kidney failure is the most common cause of death in children older than six years.

How Is Joubert Syndrome Prevented?

There is no known way to prevent JS. Parents with a family history of the disorder or who have had another child with JS are advised to consult a genetic counselor to assess their risk if they plan to have another child.

Joubert Syndrome Caregiver Tips

• Learn everything you can about the disorder. JS is rare, and it’s not well known even to some medical professionals. You’ll be able to be an active part of your child’s medical team if you know as much as possible about their condition.
• Be an advocate for your child. It’s likely that teachers and other important people in your child’s life will not know how to best deal with your child’s challenges. Be educated and be prepared to speak up on behalf of your child.
• Find a community. The Joubert Syndrome & Related Disorders Foundation (JSRDF) maintains a directory of resources to help you find local and online support groups for families living with JS.

Some people with JS also suffer from other brain and mental health-related issues, a condition called co-morbidity. Here are a few of the disorders commonly associated with JS:

• Some studies have linked JS with autism.
• Epilepsy is sometimes associated with JS.
• Brain-related disorders such as hydrocephalus and problems with the corpus callosum may be associated with JS.
• People with JS sometimes suffer from oculomotor apraxia.

Joubert Syndrome Brain Science

JS is most commonly diagnosed when an MRI scan shows abnormal development in specific parts of the brain. The distinctive features of the disorder include:

• An underdeveloped (hypoplastic) or completely missing cerebellar vermis, a structure that divides the two halves of the cerebellum
• Thickened and incorrectly oriented superior cerebellar peduncles, structures that connect the cerebellum to the midbrain
• Malformation of the brainstem

These malformations show up on an MRI scan as an easily recognizable pattern referred to as a “molar tooth sign,” so-called because it looks like the cross-section of a tooth.

Although a molar tooth sign can indicate JS, it can also be present in the case of other disorders such as COACH syndrome, Senior-Loken syndrome, Varadi-Papp syndrome, Cogan’s syndrome, and Malta syndrome.

Joubert Syndrome Research

Title:  UAB HRFD Core Center: Core A: The Hepato/Renal Fibrocystic Diseases Translational Resource

Stage: Recruiting

Principal Investigator: Lisa Guay-Woodford, MD

Children’s National Health System

Washington, DC

In 2005, The University of Alabama at Birmingham established a NIDDK-funded, interdisciplinary center of excellence in PKD-related research, with specific emphasis on recessive PKD. In the previous Core Center award period, a Core Resource to capture clinical and mutational data for ARPKD patients (“Core A: ARPKD Clinical and Genetic Resource,” NCT00575705) was developed. However, studies in the last several years have demonstrated that ARPKD and other single-gene disorders characterized by renal cystic disease and extra-renal phenotypes share numerous pathogenic features. In the current competitively- renewed Center, this Core resource has been expanded to include other hepato/renal fibrocystic diseases.

Title: The Effect of a Dietary Supplement Rich in Nitric Oxide in Patients Diagnosed With Primary Ciliary Dyskinesia

Stage: Recruiting

Principal investigator:  Ricardo A. Mosquera, MD

The University of Texas Health Science Center, Houston

Houston, TX

The purpose of this study is to determine the effect of a dietary supplement rich in nitric oxide (NO) on nasal nitric oxide and fractional exhaled nitric oxide (FeNO), on ciliary beat frequency assessed by high-speed digital video microscopy, and on lung function assessed by spirometry in normal patients and patients with primary ciliary dyskinesia (PCD).

Title: Inherited Retinal Degenerative Disease Registry (MRTR)

Stage: Recruiting

Principal investigator:  Todd Durham, PhD

Foundation Fighting Blindness

Columbia, MD

The My Retina Tracker® Registry is sponsored by the Foundation Fighting Blindness and is for people affected by one of the rare inherited retinal degenerative diseases studied by the Foundation. It is a patient-initiated registry accessible via a secure online portal at www.MyRetinaTracker.org. Affected individuals who register are guided to create a profile that captures their perspective on their retinal disease and its progress; family history; genetic testing results; preventive measures; general health and interest in participation in research studies. The participants may also ask their clinician to add clinical measurements and results at each clinical visit. Participants are urged to update the information regularly to create longitudinal records of their disease, from their own perspective, and their clinical progress. The overall goals of the Registry are: to better understand the diversity within the inherited retinal degenerative diseases; to understand the prevalence of the different diseases and gene variants; to assist in the establishment of genotype-phenotype relationships; to help understand the natural history of the diseases; to help accelerate research and development of clinical trials for treatments; to provide a tool to investigators that can assist with recruitment for research studies and clinical trials.