Joubert syndrome: symptoms, causes and possible treatments.

We explain what this congenital neurological disease consists of.

Joubert syndrome is a rare neurological disease that causes malformations in several brain structures that 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's syndrome is, what are its symptoms and the causes that originate it, and also how to diagnose and treat this disease.

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What is Joubert's syndrome?

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 by agenesis (defective development) or hypoplasia (incomplete development).

This syndrome was first described in 1969 and owes its name to Marie JoubertMarie Joubert, a neurologist and pediatrician who investigated 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 have other disorders such as Leber congenital amaurosis (retinal disease), nephronophthisis (diseases affecting the kidney) and/or cystic medullary kidney disease.

It is estimated that this syndrome may affect 1 in 80,000 to 100,000 newborns.. However, this estimate seems to be too low, as this syndrome has a wide range of clinical features and signs, so it may be underdiagnosed.

Moreover, 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 distinguishing features of Joubert syndrome is what is known as the "molar tooth sign", detectable on neuroimaging studies, such as magnetic resonance imaging: the enlarged and horizontally positioned superior cerebellar peduncles, together with the elongated pons-mesencephalon junction, produce this molar tooth image.

During the course of the neonatal period, Joubert's syndrome is often manifested by irregular breathing (episodic tachypnea and/or apnea) and nystagmus. Later, in infancy, hypotonia (decreased Muscle tone) may appear and later, the patient may develop cerebellar ataxia (unsteady gait and imbalance).

Delayed motor development is also common. The intellectual faculties of persons with this rare disease may vary from severe intellectual deficit to normal or standard intelligence. Occasionally, the presence of oculomotor apraxia may be detected by neuro-ophthalmological examination.

These patients usually present with a characteristic face: large head, prominent forehead, high and rounded eyebrows rounded eyebrows, epicanthal folds, ptosis, upturned nose, open mouth, rhythmic tongue protrusion movements (spontaneous tongue protrusion) and sometimes low-set ears.

Other clinical manifestations present in Joubert syndrome involve retinal dystrophy, polydactyly and seizures (more infrequent).

Causes

Joubert syndrome may be caused by mutations in more than 30 different genes.. Studies suggest that proteins produced from these genes 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 of 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 cell types, including neurons and certain cells of 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's syndrome would account for 60-90% of all cases of this disease. In the remaining cases, the specific cause is still unknown.

Diagnosis

The diagnosis of Joubert's syndrome is based on clinical and radiological data.. We have already reviewed the clinical signs and symptoms, and as far as the radiological classification of the syndrome is concerned, it could be divided into mild, moderate and severe vermis dysgenesis.

Some investigators have also suggested the existence of two other groups: one with additional abnormalities of the cerebrum, cerebellum (excluding vermis) or brainstem; and one in which the radiological features of the syndrome are absent.

Magnetic resonance imaging shows partial or complete absence of the cerebellar vermis, normal or diminished posterior fossa 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 have elongation 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 medial region of the vermis.

In some cases, the so-called molar tooth sign, discussed above, is for some practitioners a pathognomonic sign of the syndrome; that is, a clinical manifestation that is found only in a given morbid state and is sufficient by itself to characterize the disease and to establish the diagnosis.

Treatment

There is neither a cure nor a specific treatment for Joubert's syndrome.. The usual treatment is to treat the symptoms and underlying pathologies of the disease. The management of this disorder requires a multidisciplinary approach, with special attention to respiratory and feeding problems in neonates and children, sometimes requiring monitoring of respiratory function.

Pharmacological intervention is usually required to attenuate the most disabling physical symptoms, as well as early physical and cognitive stimulation. It is also advisable to perform a neuropsychological, cognitive and behavioral evaluation, with the aim of providing younger patients with the necessary tools to be able to carry out a comprehensive rehabilitation.

On the other hand, identifying and monitoring aspects inherent to the disease itself, such as ocular degeneration, renal complications and other disorders associated with the syndrome, should be a priority and should be performed as soon as possible, in order to adjust therapeutic measures to the specific needs of the patient.