Joubert Syndrome

Synonyms: Joubert-Boltshauser syndrome, cerebelloparenchymal disorder IV, familial cerebellar vermis agenesis, cerebellooculorenal syndrome.¹

Joubert syndrome is a rare autosomal recessive condition characterised by partial or complete absence of the cerebellar vermis leading to neonatal breathing abnormalities, jerky eye movements, hypotonia, ataxia, impaired equilibrium, and mental handicap.²

Joubert syndrome is transmitted as an autosomal recessive trait (genetic heterogeneity - chromosome 9 is a possible candidate³). Mutations in five genes have been identified, including AHI1, NPHP1 and RPGRIP1L.^4,5

Onset is in early infancy with abnormally rapid breathing, jerky eye movements, mental retardation, hemifacial spasms, seizures and ataxia.

• Eyes; abnormal eye movements, chorioretinal coloboma, ptosis, and retinal dysplasia.
• Mouth; tongue tumours and protrusion.
• Hand and foot; polydactyly.
• Neurological: hypotonia, hypoplasia or aplasia of the cerebellar vermis, occasional occipital meningoencephalocoele, hemifacial spasms and ataxia.
• Gastrointestinal; duodenal atresia or fibrosis.
• Renal; cystic kidneys.
• Mental and motor retardation.
• Behavioural problems; self-mutilation.
• Neonatal apnoea followed by episodic hyperpnoea which may improve and subsequently disappear.

• The diagnosis of Joubert syndrome is confirmed with MRI, which shows classic neuroradiological finding of a complex midbrain-hindbrain malformation known as the "molar tooth sign" (MTS), originating from the association of cerebellar vermis hypoplasia, horizontally-oriented and thickened superior cerebellar peduncles and a deepened interpeduncular fossa ('molar tooth sign').^2,6
• MRI findings also include dilated cisterna magna, occipital meningoencephalocoele, Dandy-Walker malformation, hypoplasia of the corpus callosum, retrobulbar cystic mass.
• Abdominal ultrasound may show cystic kidneys.
• Genetic testing is not currently available but the physical abnormalities may be detected at antenatal ultrasound. A fetal MRI scan at between 20 and 22 weeks gestation has been shown to be an effective method of antenatal diagnosis.⁷

• Other autosomal recessive ataxias, e.g. Friedreich's Ataxia, ataxia-telangiectasia.⁸

• Leber amaurosis (blindness with normal optic fundi and brain and kidney abnormalities) may be associated.

• Treatment is symptomatic and supportive and will include physiotherapy, occupational and speech therapy.
• The parents will need a great deal of support.

• Depends on the degree of malformation or agenesis of the cerebellar vermis.
• Some will have a mild form with mild physical disability and good mental development.
• In others, there may be severe physical disability, moderate mental retardation and death in infancy or early childhood.