Joubert Syndrome and Related Disorders

Background and History: 

Dr. Marie Joubert is a Canadian neurologist who first reported this syndrome in 1969.  Actually, many types of Joubert syndrome are now recognized and it is no longer considered to be a single disorder, hence the title.   Related disorders are those in which the classic neurologic signs of Joubert syndrome are accompanied by other features.

Clinical Correlations: 

The clinical features are highly variable both within and among families.  Multiple systems are involved including the brain, liver, eyes, and kidneys.  Infants are floppy at birth and are slow to reach developmental milestones.  The most serious problem from birth is breathing irregularity, sometimes requiring urgent ventilator assistance.  Breathing may be abnormally rapid but at other times breathing simply stops.  Most but not all individuals have some cognitive impairment.  Behavior problems such as hyperactivity and aggressiveness are common.  Most patients have difficulty following targets with their eyes and use head turns instead.  Others have abnormalities in the eye leading to severe visual impairment.   Older patients are said to have a distinctive facial appearance with a long narrow face, prominent brow and jaw, with a large nasal bridge and nose.  The eyebrows are often highly arched.

Older patients also have a certain amount of unsteadiness (ataxia).  Liver and kidney disease is common.

Genetics: 

Most conditions in this group of disorders are inherited in an autosomal recessive pattern in which two abnormal (mutated) copies of a gene are required.  The parents with one such copy are usually normal but they can expect that one in four of their children will inherit this condition.

Mutations in at least 18 genes have been identified in this disorder.

Diagnosis and Prognosis: 

This multisystem condition(s) requires a multispecialty team for diagnosis and care, including pediatricians, neuroradiologists, pulmunologists, ophthalmologists, kidney and liver specialists, and neurologists.  The most useful diagnostic sign is a characteristic malformation of the midbrain known as the ‘molar tooth sign’ as visualized on an MRI.  Respiratory difficulties require vigilant care, especially during the newborn period, and are sometimes fatal.  A certain number of children fail to survive early childhood but others survive to young adulthood.

Additional Information
Inheritance/Pedigree: 
Autosomal recessive