What is Joubert Syndrome?

Joubert Syndrome is a rare genetic condition where two parts of the brain do not develop properly during pregnancy, causing varying degrees of physical, mental and sometimes visual impairments. 

Joubert Syndrome has a range of different signs and symptoms, most of which are detectable at birth. These children need specific tailored support and lifelong health monitoring.

This article aims to discuss the causes, detection and management of this condition.

Overview

Joubert Syndrome is a genetic disorder that primarily affects balance, coordination and muscle tone due to the abnormal development of the cerebellum and brainstem. It can also cause abnormal breathing, abnormal eye and tongue movement and low muscle tone. The condition is diagnosed by  an MRI scan and managed with medication and supportive therapy.  

Causes of joubert syndrome

Genetic inheritance is passed on via genes, which are grouped together into 23 pairs of chromosomes, in human beings. One chromosome, from each pair, is received from each parent. In the complicated production of genes inevitably some will be faulty. However, this does not usually matter as the other copy (from the other parent) will be correct and  overcome the faulty gene. However if both parents pass on a faulty gene, some rare conditions can arise and we call these conditions ‘autosomal recessive’. Joubert Syndrome is an example of an autosomal recessive condition.   

The genes faulty in Joubert Syndrome cause cilia to develop abnormally. Cilia are tiny projections from the cell surface that helps them understand their environment and aids cell to cell communication. On a larger scale, the cilia  help whole organs to function such as the brain and certain cells in the liver and kidneys. Cilia are also needed for the perception of sensory input, which are interpreted by the brain as sight, hearing and smell. Joubert Syndrome is part of a group of disorders called ‘ciliopathies’.  It is the disruption of these chemical signalling pathways in development that causes most of the features seen in Joubert Syndrome. To date over 40 causative genes have been identified.¹

Joubert Syndrome was first described by a pioneering paediatric neurologist in 1969 called Dr Marie Joubert.  Before her work on this condition, all the features seen in these children were not recognised as being part of a specific syndrome.  

Marie Joubert described this condition in four siblings with underdeveloped cerebellar vermis who had symptoms of abnormal rapid breathing, abnormal eye movements, ataxia (balance, coordination and speech difficulties) and intellectual disability.²  

 It is now known that the brain abnormality present in Joubert syndrome is an absent or underdeveloped cerebellar vermis and abnormal brain stem. The cerebellum is an area at the back of the brain that is involved in coordination and movement related to motor skills, especially involving the hands and feet. It also helps maintain posture, balance and equilibrium. The brainstem is the area at the base of the brain that connects it to the spinal cord. The brainstem is responsible for regulating breathing and heart rate.  Abnormalities in these two  brain areas can be detected on an MRI (magnetic resonance imaging) scan and it is called the ‘molar tooth sign’ as the part of the brain stem that does not form correctly tends to look like a molar tooth. 

Recently, a link between the intellectual disability seen in Joubert Syndrome and an abnormality in the hippocampus has been seen. The hippocampus is known to be involved in learning and memory and abnormalities in the hippocampus can be associated with neurological or psychiatric disorders.³

Signs and symptoms of joubert syndrome

 Common features of  Joubert Syndrome  are: 

• Ataxia  (the inability to control voluntary muscle movements such as walking, picking things up and speaking)
• Fast or abnormal breathing
• Delayed language development
• General learning difficulties - these vary from mild to severe
• Weak muscle tone
• Seizures 

In addition there are some other characteristic features  such as:

• Cleft lip and palate
• Facial features specific to this condition such as broad forehead, droopy eyelids, wide spaced eyes, low set ears and triangular shaped mouth
• Extra fingers or toes
• Tongue abnormalities
• Specific issues kidneys and liver

Due to the involvement of different organ systems, Joubert Syndrome is considered a multi-system condition.  Most of these symptoms are picked up in infancy, especially when the child does not reach the normal developmental physical milestones. 

Management and treatment for joubert syndrome

Joubert Syndrome can have a spectrum of severity in terms of presentation so to find the best management for a child is to do a baseline set of tests to determine the exact nature and extent of the Syndrome. The Joubert Syndrome and Related Disorders Foundation Website recommends to:⁴

• Perform a MRI scan-  to diagnose and assess for neurological disorders especially tone, respiratory pattern, eye movements and development
• Check sleep history and assess for sleep apnoea (when breathing starts and stops when you sleep)
• Assess oral motor function through a speech therapist
• Assess intellectual development with age related tools
• Perform a thorough paediatric ophthalmologist assessment 
• Perform an abdominal ultrasound scan to evaluate for liver or kidney changes with blood tests for kidney and liver function too
• Measure blood pressure
• Perform an endocrine evaluation for pituitary abnormalities
• Consult  a clinical geneticist

There is no cure for the brain abnormality seen in Joubert Syndrome. However, after the above evaluations a multidisciplinary approach can be taken to reduce symptoms and increase the quality of life. 

• Respiratory issues - If breathing patterns are significant in their abnormality, sleep apnoea should be monitored for and treated.  In addition, supplementary oxygen, mechanical support or, in rare cases, tracheostomy can be used
• Poor muscle tone - Speech therapist needs to manage poor oromotor function and in severe cases nasogastric or gastrostomy tubes can be used
• Individual educational assessments can be performed to maximise school performance
• Other neurological Issues - surgery of any hydrocephalus (fluid on the brain) and medication for any seizures
• Professional medical support with medication for any behavioural issues
• Ophthalmological - Surgery for any correctable eye issues, such as squint or droopy eyelids (ptosis). Corrective lenses for vision
• Kidney and Liver disease - regular monitoring and treatment if kidney performance compromised or liver fibrosis is noted
• Surgical treatment for polydactyly
• Cleft Lip/palate - standard surgical treatment
• Endocrinologist review for menstrual irregularities or pituitary hormone deficiency Genetic counselling for families with a familial risk for the condition and especially for parents with an affected child, who may wish to have further children

FAQs

How is joubert syndrome diagnosed?

Joubert Syndrome is diagnosed from considering the child’s signs and symptoms and performing an MRI scan. There are characteristic signs on this scan which are specific for Joubert Syndrome, including the ‘molar-tooth’ sign which indicates the underdevelopment of the cerebellar vermis and the brain stem. 

Therefore the diagnosis is made on the presence of  

• The molar tooth sign on MRI scan
• Weak muscle tone (hypotonia) in infancy with the development of difficulty with coordination, balance and speech in childhood (ataxia)
• Developmental delay and learning difficulties

It is possible now to further confirm the diagnosis genetically, in most children, as we have a much greater understanding of the genes involved.  

How can I prevent joubert syndrome?

There is no way to prevent Joubert Syndrome but genetic counsellors and geneticists can be consulted if you are concerned that you have a familial risk. If one child is born with Joubert Syndrome, you will be offered genetic counselling with regard to risk in future pregnancies.

Who is  at risk of joubert syndrome?

Joubert Syndrome can run in families. Also those of Ashkenazi Jewish, French-Canadian or Hutterite background have a higher risk of the condition occurring. 

How common is joubert syndrome?

Joubert Syndrome is rare and estimated to affect one in 80,000 to one in 100,000 newborns.⁵

When should I see a doctor?

If you are concerned over your child's development or health please see your doctor.  You should see a genetic counsellor  if you have an increased familial risk of Joubert Syndrome and you wish to try for a baby.  

Summary

Joubert Syndrome is a rare, genetically inherited syndrome which is present in about 1 in 80,000 to  100,000 births. It is usually picked up in infancy, when weak muscle tone and developmental delay is investigated. This will likely lead to a brain MRI scan which can show a characteristic pattern indicative of Joubert Syndrome. This syndrome can also cause varying degrees of mental and physical disability as well as kidney, liver and eye complications.

There is unfortunately no cure, so a specifically tailored management plan should be developed for each child to support the detected health issues and help the child develop and grow to their full potential.