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Synonyms: Joubert-Boltshauser syndrome, cerebelloparenchymal disorder IV, familial cerebellar vermis agenesis, cerebello-oculo-renal syndrome.
Joubert's 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.
The incidence of Joubert's syndrome has been estimated to range between 1/80,000 and 1/100,000 live births, although this may be an underestimate.
Joubert's syndrome is transmitted as an autosomal recessive trait (genetic heterogeneity - chromosome 9 is a possible candidate). Mutations in five genes have been identified, including AHI1, NPHP1 and RPGRIP1L.[5, 6]
Recurrence risk is 25% in most families, although X-linked inheritance should also be considered.
- 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 meningo-encephalocele, 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's 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, 7]
- Detection of the MTS should be followed by a diagnostic protocol to assess multi-organ involvement.
- MRI findings also include dilated cisterna magna, occipital meningo-encephalocele, 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 of gestation has been shown to be an effective method of antenatal diagnosis.
Leber's amaurosis (blindness with normal optic fundi and brain and kidney abnormalities) may be associated.
- Treatment is symptomatic and supportive and will include physiotherapy, and occupational and speech therapy.
- The parents will need a great deal of support.
- This 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.
Further reading and references
; Clinical and molecular features of Joubert syndrome and related disorders. Am J Med Genet C Semin Med Genet. 2009 Nov 15151C(4):326-40.
; Familial agenesis of the cerebellar vermis. A syndrome of episodic hyperpnea, abnormal eye movements, ataxia, and retardation. Neurology. 1969 Sep
; Genotypes and phenotypes of Joubert syndrome and related disorders. Eur J Med Genet. 2008 Jan-Feb51(1):1-23. Epub 2007 Nov 23.
; Joubert Syndrome and related disorders. Orphanet J Rare Dis. 2010 Jul 85:20.
; Genetic basis of Joubert syndrome and related disorders of cerebellar development. Hum Mol Genet. 2005 Oct 15
; Genetic complexity in Joubert syndrome and related disorders. Kidney Int. 2007 Dec72(12):1421-3.
; Recognition of the clinical signs and symptoms of Joubert syndrome. Adv Neonatal Care. 2003 Aug
; Prenatal diagnosis in pregnancies at risk for Joubert syndrome by ultrasound and MRI. Prenat Diagn. 2005 Jun
; [Autosomal recessive cerebellar ataxias. Their classification, genetic features and pathophysiology] Rev Neurol. 2005 Oct 1-15