Joubert syndrome is a rare neurological disease which causes deformities in various brain structures, such as the cerebellum, and causes problems with respiratory, muscle and motor coordination in the person who has it.
In this article, we explain what Joubert syndrome is, what are its symptoms and the causes that provoke it, as well as how to diagnose and treat this condition.
What is Joubert syndrome?
Joubert syndrome is a rare congenital neurological disease characterized by malformation of the midbrain and cerebellum, in particular with varying degrees of dysgenesis of cerebellar worms, either by agenesis (defective development) or by hypoplasia (incomplete development).
This syndrome was first described in 1969 and owes its name to Marie Joubert, A neurologist and pediatrician who investigated the disease in Quebec, Canada.
The disease is an autosomal recessive disorder (two copies of the abnormal gene must be present for the disease to develop) and is clinically heterogeneous, as some patients may have other disorders such as congenital Leber’s amaurosis (retinal disease). kidney) and / or cystic medullary renal disease.
It is estimated that this syndrome may affect 1 in 80,000 or 100,000 newborns. However, this estimate appears to be too low, as this syndrome has a wide range of clinical features and signs, so it may not be sufficiently diagnosed.
On the other hand, the genetic mutations at the origin of this disease are more frequent in certain ethnic groups, such as the Jewish Ashkenazi, Franco-Canadian and Hutterite populations.
Clinical signs and symptoms
One of the distinguishing features of Joubert syndrome is the so-called “molar sign”, detectable in neuroimaging studies, such as in magnetic resonance imaging: the upper cerebellar peduncles, enlarged in size and position horizontal, next to the elongated bridge-midbrain junction, they produce this image of a molar or tooth.
During the neonatal period, Joubert syndrome frequently manifests as irregular breathing (episodic tachypnea and / or apnea) and nystagmus. Then, in childhood, hypotonia (decreased muscle tone) may appear and later the patient may develop cerebellar ataxia (unsteady gait and imbalance).
A delay in motor development is also common. The intellectual faculties of people with this rare disease can range from severe intellectual disability to normal or standard intelligence. Sometimes, by means of the neuroophthalmologic examination, the presence of oculomotor apraxia may be detected.
These patients usually present a characteristic face: large head, prominent forehead, high eyebrows. and rounded, epicanthus folds, ptosis, curved nose, open mouth, rhythmic protruding movements of the tongue (withdrawing the tongue spontaneously), and sometimes low implantation ears.
Other clinical manifestations present in Joubert syndrome involve retinal dystrophy, polydactyly and seizures (rarer).
Joubert syndrome it can be caused by mutations in over 30 different genes. Studies show that proteins produced from these genes play an important role in cellular structures called primary cilia. Cilia are microscopic cerebellar worm villi that protrude from the surface of cells and participate in sensing the physical environment and chemical signaling.
The alterations of this disease are thought to result from the absence or the low degree of development of the middle part of the cerebellum, the vermis and the cilia located in the plasma membrane of the cells of this structure of the brain, which displace the cerebrospinal fluid. .
Primary cilia are important for the structure and function of many types of cells, including neurons and some kidney and liver cells. These tiny villi are also necessary for the perception of sensory information, which the brain interprets for the senses of sight, hearing and smell.
However, genetic mutations known to be associated with Joubert syndrome are believed to account for 60 to 90% of all cases of this disease. In the rest of the cases, the specific cause is still unknown.
The diagnosis of Joubert syndrome is based on clinical and radiological data. We have already reviewed the clinical signs and symptoms, and with regard to the radiological classification of the syndrome, it could be divided into: mild, moderate and severe vermal dysgenesis.
Some researchers have also suggested that there are two groups: one with additional abnormalities of the brain, cerebellum (excluding vermis) or brainstem; and another, in which the radiological features of the syndrome are absent.
Nuclear magnetic resonance imaging images show the partial or complete absence of cerebellar worms, the posterior fossa normal or diminished, and an absence of pyramidal decussation (crossing of pyramidal fibers, which travel from the cortex to the spinal cord).
Patients diagnosed with Joubert syndrome also present with an elongation and narrowing of the junction between the bridge and the midbrain, a deep interpeduncular fossa with thickening of the upper cerebellar peduncles, and hypoplasia and incomplete fusion of the midline region of the vermis.
In some cases, the so-called molar sign, which we talked about earlier, is for some professionals a pathognomonic sign of the syndrome; that is to say, a clinical manifestation which is only found in a given morbid state and which in itself is sufficient to characterize the disease and to establish the diagnosis.
There is no cure or specific treatment for Joubert syndrome. The most common is to treat the symptoms and conditions underlying the disease. The management of this disorder requires a multidisciplinary approach, with particular attention to the respiratory and feeding problems of the newborn and the child, and it is sometimes necessary to monitor the respiratory function.
Pharmacologic intervention is usually needed to relieve the most debilitating physical symptoms, as well as early stimulation, both physically and cognitively. It is also advisable to carry out a neuropsychological, cognitive and behavioral assessment, with the aim of providing younger patients with the necessary tools to be able to carry out a complete rehabilitation.
On the other hand, the identification and control of aspects inherent in the disease itself, such as ocular degeneration, renal complications and other disorders associated with the syndrome, must be a priority and must be carried out as soon as possible, in order to to adjust the therapeutic measures to the specific needs of the patient.
Angemi, J., and Zuccotti, J. (2012). Updates on Joubert Syndrome. Alcmeó.
Bibas, H., Coronel, AM, Fauze, R., and Sialle, M. (2005). Joubert syndrome and “molar sign” in the cerebellar-oculo-renal malformation group in two patients. Chilean Journal of Pediatrics, 76 (6), 605-611.
Yachnis, AT and Rorke, LB (1999). Neuropathology of Joubert syndrome. Journal of Child Neurology, 14 (10), 655-659.