Joubert Syndrome: Symptoms, Causes And Possible Treatments
Joubert syndrome is a rare neurological disease which causes malformations in several brain structures, such as the cerebellum, and generates respiratory, muscular and motor coordination problems in the person who suffers from it.
In this article we explain what Joubert syndrome consists of, what its symptoms are and the causes that cause it, and also how to diagnose and treat this disease.
Joubert syndrome is a rare congenital neurological disease characterized by a malformation of the midbrain and cerebellum, specifically with a variable degree of dysgenesis of the cerebellar vermis, either due to agenesis (defective development) or hypoplasia (incomplete development).
This syndrome was first described in 1969 and owes its name to Marie Joubert a neurologist and pediatrician who researched the disease in Quebec, Canada.
The disease is an autosomal recessive condition (two copies of the abnormal gene must be present for the disease to develop) and is clinically heterogeneous, as some patients may present with other disorders such as Leber congenital amaurosis (retinal disease), nephronophthisis (diseases that affect the kidney) and/or cystic medullary kidney disease.
It is estimated that this syndrome can affect 1 in every 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 be underdiagnosed.
Furthermore, the genetic mutations that cause this condition are more common in certain ethnic groups, such as Ashkenazi Jewish populations, French Canadians, and Hutterites.
Clinical signs and symptoms
One of the distinctive features of Joubert syndrome is what is known as the “molar tooth sign,” detectable in neuroimaging studies, such as magnetic resonance imaging: the superior cerebellar peduncles, enlarged and in a horizontal position, together with the elongated bridge-midbrain junction, they produce that image of a molar tooth or molar.
During the neonatal period, Joubert syndrome is frequently manifested by irregular breathing (episodic tachypnea and/or apnea) and nystagmus. Later, in childhood, hypotonia (decreased muscle tone) may appear and later, the patient may develop cerebellar ataxia (unstable gait and imbalance).
The appearance of delay in motor development is also common. The intellectual faculties of people who suffer from this rare disease can vary, from severe intellectual deficit to normal or standard intelligence. Sometimes, through neuro-ophthalmological examination, the presence of oculomotor apraxia may be detected.
These patients usually have a characteristic face: large head, prominent forehead, high eyebrows and rounded, epicanthal folds, ptosis, upturned nose, open mouth, rhythmic tongue protrusion movements (spontaneous sticking out of the tongue) and, sometimes, low-set ears.
Other clinical manifestations present in Joubert syndrome involve retinal dystrophy, polydactyly and seizures (more rare).
Causes
Joubert syndrome It can be caused by mutations in more than 30 different genes The studies carried out suggest that the proteins produced from these genes would play an important role in cellular structures called primary cilia. Cilia are microscopic villi of the cerebellar vermis that protrude from the surface of cells and are involved in sensing the physical environment and chemical signaling.
The alterations of this disease would come from the absence or 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 brain structure, which move the cerebrospinal fluid.
Primary cilia are important for the structure and function of many types of cells, including neurons and certain cells in the kidneys and liver. These tiny villi are also necessary for the perception of sensory information, which the brain interprets for the senses of sight, hearing, and smell.
All in all, the genetic mutations known to be associated with Joubert syndrome would represent 60-90% of all cases of this disease. In the rest of the cases, the specific cause is still unknown.
Diagnosis
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 vermis dysgenesis.
Some researchers have also suggested the existence of two other groups: one that presents additional anomalies of the brain, cerebellum (excluding vermis) or brainstem; and another, in which the radiological characteristics of the syndrome are absent.
Images performed using nuclear magnetic resonance show the partial or complete absence of the cerebellar vermis, the normal or decreased posterior fossa and an absence of pyramidal decussation (crossing of the pyramidal fibers, which travel from the cortex to the spinal cord).
Patients diagnosed with Joubert syndrome also present with lengthening and narrowing of the junction between the pons and midbrain, a deep interpeduncular fossa with thickening of the superior cerebellar peduncles, and hypoplasia and incomplete fusion of the middle region of the vermis.
In some cases, the so-called molar tooth sign, which we have talked about previously, is for some professionals a pathognomonic sign of the syndrome; that is, a clinical manifestation that is only found in a specific morbid state and that is sufficient in itself to characterize the disease and to establish the diagnosis.
Treatment
There is no cure or specific treatment for Joubert syndrome The usual thing is to treat the symptoms and pathologies underlying the disease. The management of this disorder requires a multidisciplinary approach, with special attention to respiratory and nutritional problems in neonates and children, and it is sometimes necessary to monitor respiratory function.
Normally, pharmacological intervention is usually required to mitigate the most disabling physical symptoms, as well as early stimulation, both physically and cognitively. It is also advisable to perform a neuropsychological, cognitive and behavioral evaluation, with the aim of providing younger patients with the necessary tools to carry out comprehensive rehabilitation.
On the other hand, identifying and controlling aspects inherent to the disease itself, such as ocular degeneration, kidney complications and the rest of the disorders associated with the syndrome, must be a priority and must be carried out as soon as possible, to be able to adjust the therapeutic measures to suit. the specific needs of the patient.
