Signs and Symptoms
The symptoms of Joubert syndrome, a rare genetic disorder, are the result of the abnormal development of the brain–notably the cerebellar vermis, the brain structure responsible for proprioception (knowing how your body is oriented in space) and the brain stem, which integrates all sorts of sensory input.
These malformations give rise to a wide array of symptoms that characterize the syndrome. The most common symptoms of Joubert syndrome include:
- Hyperpnea, or abnormally rapid breathing
- Hypotonia, or decreased muscle tone
- Ataxia, or the inability to coordinate voluntary muscle movements
- Jerky eye movements
- Mental retardation, ranging from severe retardation to normal cognitive functioning
- Physical deformities, for example a cleft palate, or extra fingers or toes (polydactyly)
- Possible kidney and liver abnormalities
Genetics of Joubert Syndrome
Mostly sporadic, or occurring in families without a prior apparition of the syndrome, some cases of Joubert syndrome show an autosomal recessive inheritance where both parents have to carry a copy of the mutation. This means that each sibling of an affected individual has a 25 percent chance of being affected, a 50 percent chance of being an asymptomatic carrier and a 25 percent chance of being unaffected and not a carrier.
A number of genes have been identified as carriers of a possible mutation causing Joubert syndrome. These genes are known under the names AHI1, CEP290, TMEM67 and NPHP1. However, there are suggestions that there are other genes involved. In total, it is estimated that at least ten genes are involved in causing this rare genetic disorder.
Diagnosis is often based upon the symptoms of the disorder. Furthermore, prenatal diagnosis by DNA testing is available for families in which disease-causing gene mutations have been identified. For other at-risk pregnancies with no mutations identified, prenatal imaging is the best practical diagnostic option. This is, however, quite challenging before the early third trimester since most symptoms cannot be accurately assessed earlier.
Prevalence and Prognosis
Being a rare genetic condition, the prevalence of Joubert syndrome can only be estimated. The estimates range from 1 in every 100,000 to roughly 250,000 births.
The prognosis for affected individuals depends largely on the severity of the disorder, which in turn depends on whether the cerebellar vermis is completely or only partially absent. Children with a mild form of the disorder will have minimal motor disability and a good mental development, while those suffering from a more severe form may have serious motor disability and moderate mental retardation. This has an influence on the life expectancy, where those suffering from mild forms of the syndrome can live lives of conventional length, individuals with severe forms of the disorder may die early in life.
At present, there is no known cure for Joubert syndrome. Treatment is symptomatic and supportive. Some children may benefit from physical, occupational and speech therapy. If abnormal breathing patterns occur, these should be monitored and screening for complications associated with Joubert syndrome (liver and kidney problems) should be performed on a regular basis.
- GeneReviews: https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=joubert
- Joubert Syndrome & Relates Disorders Foundation: https://www.joubertfoundation.com/
- National Institute of Neurological Disorders and Stroke: https://www.ninds.nih.gov/disorders/joubert/joubert.htm
- Parisi, M.A.; Doherty, D.; Chance, P.F. & Glass, I.A. (2007). Joubert syndrome (and related disorders). European Journal of Human Genetics. 15, 511 – 521.