The Joubert syndrome (JS) is a rare autosomal recessive disorder whose main clinical signs are muscular hypotonia, ataxia, mental retardation, abnormal eye movements and a respiratory pattern of alternating hyperpnea-apnea.
First described in 1969, the prevalence is estimated to be 1 in 100,000.
JS is characterized by partial or complete agenesis of the cerebellar vermis – the structure connecting both parts of the cerebellum. Furthermore, other bordering parts of the cerebellum can be involved, too.
Clinical course shows abnormal breathing pattern (episodic tachypnea and/or apnea) and nystagmus with onset during the neonatal period. The breathing pattern is characterized by effortless hyperventilation, which is more conspicuous in the awake state and intensifies after stimulation. Paroxysmal hyperventilation is often punctuated by intermittent central apnea. However, abnormal respiratory pattern is not a consistent finding, and respiratory distress in the proper sense is not a feature. During infancy, muscular hypotonia can be observed, and later cerebellar ataxia (staggering gait and imbalance) may develop. Delayed motor function development is common, and cognitive function ranges from normal intelligence to severe deficits. Oculomotor apraxia and seizures may occur. Additional findings can include renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, oral hamartomas, and endocrine abnormalities.
Physical characteristic are: Large head, prominent forehead, high rounded eyebrows, epicanthal folds, an upturned nose with prominent nostrils, palate malformations, laryngomalacia, micrognathia, an open mouth (with oval, 'rhomboid' and finally triangular shape), tongue protrusion and rhythmic tongue motions, and occasionally low-set and tilted ears. Other features sometimes present in Joubert syndrome include retinal dystrophy, and polydactyly.
Diagnosis is based on the main clinical features. These must be accompanied by the presence of a neuroradiological hallmark, designated as the “molar tooth sign'' (MTS) on magnetic resonance imaging (MRI). In view of the complex genetic heterogeneity, mutations are only found in about 50% of patients at present.
Management is symptomatic and should be multidisciplinary, prognosis for mild or moderate forms is favourable, and therapy of severe forms should be carried out at a specialized reference centre.