Joubert syndrome affects several parts of the body. The symptoms of this condition vary among the affected population. One of the features of this syndrome includes the brain malformation that presents the absence or the underdevelopment of the cerebellar vermis and malformed brain stem. The part of the brain involved controls the coordination and balance. This condition is estimated to affect around 1 out of 258,000 although the true prevalence could be 1 out of 100,000 individuals.
Causes
This syndrome occurs as the result of a mutation in at least 10 different genes including NPHP1, AHI1 and CEP290. These genes are considered to play important roles in the cell structures known as cilia which are necessary for the chemical signaling. The cilia are important for several types of cells such as the neurons, cells in the kidneys and the liver. The genetic mutation results in the problems of the function and the structure of cilia which disrupt the chemical signaling pathways. Typically, these cases are inherited in an autosomal recessive pattern meaning both the copies of the gene in each cell are defective. Some of the cases can also be inherited in an X-linked recessive pattern meaning the defective gene is located on the X-chromosome, which is one of the sex chromosomes.
Symptoms
In several of the cases, the symptoms are evident in the infancy and the children exhibit delays in gross motor milestones. Most of the infants present weak muscle tone (hypotonia) that presents difficulty with coordinating movements. They may also have episodes of abnormally fast or slow breathing that can occur after the birth but can improve with age. Oculomotor apraxia occurs that can the cause problem with the movement of the eyes from one side to another and they may also exhibit mild to severe intellectual disability. The facial features include droopy eyelids, wide spaced eyes, triangular shaped mouth and broad forehead. Some of the additional symptoms include eye problems such as retinal dystrophy that can result in vision loss, hormone problems, kidney disease, liver disease and the skeletal abnormalities like the presence of an extra digit. When individuals present the additional symptoms, it is referred to as ‘Joubert syndrome and related disorders’ (JSRD).
Diagnosis
The diagnosis of this condition is based on the identification of the physical features characteristic of this syndrome such as the ‘molar tooth sign’ that is evident on an MRI. In around 40% of the cases, the diagnosis can be confirmed with the genetic molecular testing that detects the genetic mutation causing this condition. If the syndrome is prevalent in the family, a carrier testing and prenatal diagnosis are possible.
Treatment
There is no cure for this syndrome and the treatment is supportive and symptomatic. Some of the children may benefit from the physical, speech and occupational therapy. The children presenting abnormal breathing should be monitored to prevent developing complications. They should also have a regular screening for kidney, liver and retinal complications associated with this condition. Some of the affected individuals and their families may also benefit from the genetic counseling.
References
https://rarediseases.info.nih.gov/diseases/6802/joubert-syndrome
https://ghr.nlm.nih.gov/condition/joubert-syndrome#inheritance
http://my.clevelandclinic.org/health/articles/joubert-syndrome
https://rarediseases.org/rare-diseases/joubert-syndrome/