Joubert syndrome is a genetic ciliopathy defined by a distinctive brainstem and cerebellar malformation, and its ocular motor apraxia, an inability to generate normal horizontal saccades, is often one of the earliest clues that leads a clinician to look for the underlying molar tooth sign on MRI.
The Molar Tooth Sign
Joubert syndrome is defined by hypoplasia of the cerebellar vermis together with abnormalities of the brainstem, producing an axial MRI appearance at the level of the midbrain that resembles a molar tooth, with thickened, elongated superior cerebellar peduncles and a deepened interpeduncular fossa.
This imaging finding is the defining diagnostic feature of the syndrome, and its presence in a child with hypotonia and abnormal breathing or eye movement patterns essentially confirms the clinical diagnosis.
Ocular Motor Apraxia
Ocular motor apraxia is a difficulty initiating voluntary horizontal saccades, and children with this finding compensate by using a head thrust: turning the head past the target and then rolling the eyes back to fixate, rather than making a normal, direct saccadic eye movement.
This compensatory head-thrust pattern is a recognizable clinical sign and, in the right systemic context, particularly with hypotonia and developmental delay, should prompt consideration of Joubert syndrome and referral for MRI.
Ocular motor apraxia is not unique to Joubert syndrome and occurs in other conditions, but its combination with the systemic features of Joubert syndrome is a useful diagnostic pattern.
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From Choroida — the team behind this siteOther Ocular Findings
- Retinal dystrophy, ranging from a mild pigmentary retinopathy to a severe Leber congenital amaurosis-like presentation, reflecting the shared ciliopathy biology with other ciliary gene disorders
- Coloboma of the iris, retina, or optic nerve
- Nystagmus
- Ptosis and strabismus in some patients
Not every child with Joubert syndrome has significant retinal involvement, and the presence and severity of retinal disease vary depending on the specific causative gene, since Joubert syndrome is genetically heterogeneous.
Systemic Features
- Hypotonia in infancy, often the presenting feature
- An irregular breathing pattern in infancy, alternating episodes of hyperpnea and apnea, a distinctive early clue
- Developmental delay and intellectual disability of variable severity
- Renal disease, similar in mechanism to Senior-Loken syndrome, in a subset of patients (see Senior-Loken syndrome)
- Hepatic fibrosis in some genetic subtypes
- Polydactyly and other skeletal features in some patients
Joubert syndrome is now understood as part of a broader spectrum of related ciliopathies, with overlapping features and, in some cases, overlapping causative genes with Meckel syndrome, Bardet-Biedl syndrome, and other conditions.
Diagnosis
- MRI showing the molar tooth sign is the key diagnostic imaging finding
- Genetic testing, since Joubert syndrome is caused by mutations in any of a large number of ciliopathy genes, useful for confirming the diagnosis and for family counseling
- Ophthalmic examination, including assessment of eye movements, retinal examination, and electroretinography when retinal dystrophy is suspected
- Renal and hepatic screening, given the multisystem nature of the disease
Management
Management is multidisciplinary and supportive, since there is no treatment for the underlying ciliopathy.
- Developmental and physical therapy for hypotonia and developmental delay
- Ophthalmic correction of refractive error and management of strabismus
- Low-vision support for children with significant retinal disease
- Monitoring of renal and hepatic function over time
- Genetic counseling for the family, given the range of causative genes and inheritance patterns
Prognosis
Outcome depends heavily on the severity of the central nervous system malformation and on which additional organ systems are involved.
Many children survive into adulthood with variable degrees of developmental and motor impairment, and the ocular prognosis depends on the extent of retinal involvement, which ranges from mild to severely vision-limiting.
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From Choroida — the team behind this siteReferences
- Joubert M, Eisenring JJ, Robb JP, Andermann F. Familial agenesis of the cerebellar vermis: a syndrome of episodic hyperpnea, abnormal eye movements, ataxia, and retardation. Neurology. 1969;19:813-825.
- Parisi MA, Doherty D, Chance PF, Glass IA. Joubert syndrome (and related disorders) (OMIM 213300). Eur J Hum Genet. 2007;15:511-521.
- Brancati F, Dallapiccola B, Valente EM. Joubert syndrome and related disorders. Orphanet J Rare Dis. 2010;5:20.
- Maria BL, Hoang KB, Tusa RJ, et al. “Joubert syndrome” revisited: key ocular motor signs with magnetic resonance imaging correlation. J Child Neurol. 1997;12:423-430.
