Joubert's syndrome: what is it, symptoms, treatment, prognosis

What is Joubert Syndrome?

Joubert's syndrome Is an autosomal recessive genetic disorder that affects the areas of the brain that control balance and coordination. This condition is characterized by a specific MRI picture, called the sign of a "molar", when in which the cerebellar worms (bundles of nerve fibers) are absent or underdeveloped, and the brain stem has anomalies. The most common signs of Joubert syndrome are lack of muscle control (ataxia), abnormal breathing (hyperpnea), sleep apnea, abnormal eye and tongue movements, and low muscle tone.

Signs and symptoms

Many of the clinical symptoms of Joubert syndrome appear in infancy, and most affected children have delays in major motor milestones. The most common signs are insufficient muscle control (ataxia), abnormal breathing (hyperapnea), sleep apnea, abnormal eye and tongue movements, and low muscle tone. Intelligence ranges from normal to severe mental retardation. Joubert's syndrome is characterized by a specific MRI scan called the molar sign, in which the cerebellar worms are absent or underdeveloped and the brain stem is abnormal.

Joubert's syndrome is a highly variable condition and the full spectrum of symptoms is not yet fully understood. Several conditions have been described in which a complement of the condition was present in addition to the “molar” symptom and the main symptoms of Joubert's syndrome. It is not yet clear whether these conditions are variants of Joubert's syndrome or separate syndromes. These conditions have been termed "Joubert-related disorders." Some of the problems that may be associated with Joubert syndrome include eye abnormalities, such as abnormal development of the retina, abnormalities in the iris (coloboma), rapid eye movement (nystagmus), slanting eyes (strabismus) and drooping eyelids (ptosis). Other problems sometimes associated with Joubert syndrome include kidney and / or liver abnormalities, extra fingers and toes (polydactyly), a gap in the skull with protrusions of membranes covering the brain (encephalocele) and hormonal abnormalities.

Causes

Joubert's syndrome is inherited as an autosomal recessive genetic disorder.

Recessive genetic disorders occur when a person inherits the same abnormal gene for one trait from each parent. If a person receives one normal gene and one gene for the disease, the person will be a carrier of the disease, but usually asymptomatic. The risk that two carrier parents will both pass on the defective gene and therefore infect the baby is 25% with each pregnancy. The risk of having a child who will be a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for this particular trait is 25%. The risk is the same for men and women.

All humans carry 4-5 abnormal genes. Parents who are close relatives (brother and sister) have a higher chance than unrelated parents who have the same abnormal gene, which increases the risk of having children with a recessive genetic disorder.

Ten genes have been identified that cause the disorder. Gene mutation AHI1 (JBTS3) is responsible for this condition in about 11% of families. Affected people with this gene mutation often have visual impairment due to retinal dystrophy. Gene mutation NPHP1 (JBTS4) causes approximately 1-2% of Joubert's syndrome. People with this gene mutation often develop progressive kidney diseasecalled nephronophthisis. Gene mutation CEP290 (JBTS5) causes about 4-10% of Joubert's syndrome. Gene mutations TMEM67 (JBTS6), JBTS1, JBTS2, JBTS7, JBTS8 and JBTS9 are also associated with the syndrome. The other genes responsible for this condition are currently unknown.

Affected populations

The prevalence of the disease is estimated at 1 / 258,000, but this is likely an underestimate of the true prevalence, which could be closer to 1 / 100,000.

Related disorders

Several conditions have been described in which a complement of the condition was present in addition to the “molar” symptom and the main symptoms of Joubert's syndrome. It is not yet clear whether these conditions are variants of Joubert's syndrome or separate syndromes.

• Dekaban-Arim syndrome is characterized by visual impairment and renal dysfunction.
• Severe retinal dysplasia is characterized by blindness.
• COACH syndrome is characterized by mental retardation, retinal coloboma malformations, and liver abnormalities.
• Senior-Loken syndrome is characterized by visual impairment and a type of renal dysfunction called nephronophthisis.
• Varadi-Pappa syndrome is also known as type VI oral-facial-digital syndrome. This condition is characterized by cleft lip or palate, tongue abnormalities, extra tissue between the gums, tongue and mouth, dental abnormalities, facial abnormalities, extra fingers and toes, poor growth.
• Nephronophthisis is a specific type of kidney dysfunction.
• Oculomotor apraxia is characterized by an abnormality of eye movement.

Symptoms of the following disorders may be similar to those of Joubert's Syndrome. Comparisons can be useful for differential diagnosis:

• Dandy Walker Syndrome - This is a rare malformation of the brain that is present at birth (congenital). It is characterized by an abnormally enlarged space in the back of the brain (cystic 4th ventricle), which interferes with the normal flow of cerebrospinal fluid through the openings between the ventricle and other parts brain. Excess fluid builds up around the brain and causes abnormally high pressure in the skull, swelling of the head (congenital hydrocephalus) and neurological disorders. Delays in motor skills and learning difficulties can also occur. Dandy-Walker syndrome is a form of obstructive or internal non-communicating hydrocephalus that means that the normal flow of cerebrospinal fluid is blocked, resulting in expansion ventricles.
• Oral Facial Digital Syndrome (OLCS) is a generic term for at least 10 distinctly different genetic disorders that characterized by defects and deficiencies in the development of the structure of the oral cavity, including the mouth, tongue, teeth and jaw; the development of facial structures, including the head, eyes and nose; fingers and toes; along with varying degrees of mental retardation. Signs and symptoms of OLCS are extremely diverse, which makes diagnosis difficult. Type I OLCS is the most common of all types of this disorder, and is quite rare. Each of the following types is even rarer.
• Meckel's syndrome Is a rare hereditary disease characterized by disorders affecting several body systems (multisystem). Three classic symptoms are commonly associated with Meckel syndrome: a protrusion of a part of the brain and the membranes surrounding it (meningia) through a defect in the back or front of the skull (occipital encephalocele), multiple cysts in the kidneys (polycystic kidney disease), and extra fingers and / or toes (polydactyly). Affected children may also have disorders affecting the head and face (craniofacial), liver, lungs, and urinary tract. Meckel's syndrome is inherited as an autosomal recessive trait.

Diagnostics

The diagnosis of the disease is based on physical symptoms and the sign of a "molar" on MRI. Molecular genetic testing is also available for four genes that have been shown to cause disease in about 40% of cases.

Standard treatments

Treatment of Joubert's syndrome is symptomatic and supportive. Developmental delays are usually treated with physical therapy, occupational therapy, speech therapy, and infant stimulation. Individuals with the disease should be treated by appropriate professionals, including nephrologists, ophthalmologists, geneticists, and neurologists. For liver, kidney and retinal diseases, annual examinations are recommended.

Forecast

The prognosis of Joubert's syndrome varies from person to person and largely depends on whether the cerebellar worm is partially developed or completely absent. Some patients may have a shorter life expectancy due to complications of the disease, including kidney or liver disease.

Some children with the syndrome have a mild form of the disorder and have minimal motor impairment and good mental health. development, while others may have severe motor impairment, moderate developmental impairment, and multiple organ impairment.