Joubert syndrome and differential diagnosis [133 genes]

Joubert syndrome, classically, is characterized by:

• The characteristic congenital malformation of the cerebellum and a particular brain stem, called the molar tooth sign.
• Hypotonia followed by the development of ataxia.
• Delayed development.

These findings are often accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, respiratory abnormalities improve with age. Cognitive abilities are variable, from severe intellectual disability to normal. Other findings may include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities.

Joubert syndrome: 1 / 100,000 (ORPHA:475)

The benefits derived from a genetic diagnosis in this context can range from family genetic counseling, typical of genetic studies in general, to the early detection of associated comorbidities, thus achieving better symptomatic management.

Service is indicated when clinical and especially radiological findings support the diagnostic suspicion. The service is recommended when there is a high suspicion of the disease.

It is estimated that variants in the nucleotide sequence and CNVs can find the molecular cause in 62%-94% of all patients with a clinical diagnosis. An exome-based approach is the most cost-efficient strategy due to the high number of genes involved.