OVERVIEW
Joubert syndrome, first reported by Joubert et al. in 1969, is a relatively rare developmental malformation, mostly inherited as an autosomal recessive disorder. Typical neuropathologic changes include hypoplasia or hypoplasia of the cerebellar vermis, hypoplasia of the dentate nucleus, basal part of the pontine plexus, and nuclei of the medulla oblongata, and almost complete absence of the pyramidal crossings. Symptoms appear at a very young age and include hypotonia, ataxia, motor and mental retardation, intermittent deep and rapid breathing, and abnormal eye movements. The prevalence is reported to be about 1 per 100,000, with a male to female ratio of about 3:2 in the literature.
Etiology
The disease is a rare developmental abnormality. 34 causative genes have been identified, of which 33 are autosomal recessive and 1 is X-linked.
Symptoms
The common symptom is episodes of shortness of breath, with shortness of breath or apnea in the neonatal period. Other major clinical manifestations include hypotonia, ataxia, motor and mental retardation, and eye movement abnormalities. Some patients have retinal defects or retinal dysplasia, tongue extension, cleft palate, cleft lip, polycystic kidneys and polydactyly. Episodic asthenia, hypotonia and ataxia are the most prominent manifestations.
Examination
1. Magnetic resonance imaging (MRI)
MRI is the neuroimaging method of choice for this syndrome, which can clearly show the posterior cranial fossa malformation and related supratentorial malformations. The characteristic features are partial or complete absence of the cerebellar vermis and abnormal brainstem development. In the case of complete absence of the cerebellar peduncle, the two cerebellar hemispheres are juxtaposed at the midline, but not fused; CT scan and MRI scan peripherally show low-density shadows between the two cerebellar hemispheres and a long T1, T2 signal shadow called the midline fissure. Due to the widening and deformation of the midbrain-brain pontine junction, the cephalic to caudal fourth ventricle is widened with a triangular shape in the middle and a batwing shape in the upper part, which is known as the batwing sign. Thinning and lengthening of the isthmus (midbrain-brain pontine junction) results in a deepening of the pedunculopontine fossa, and the superior cerebellar peduncle is lengthened and thickened to be nearly perpendicular to the brainstem. The deepened fossa, thickened and prolonged superior cerebellar peduncle, and hypoplastic cerebellar peduncle resemble molars in the axial view through the isthmus, which is called the molar sign.
2. Nuclear medicine examination
16F-FDG PET brain imaging showed that: in sagittal position, glucose metabolism of the cerebellar thalamus was significantly decreased in the earthy part of the cerebellum, and the fourth ventricle was enlarged; in coronal position, glucose metabolism of the right side of the cerebellum was significantly decreased; in transverse view, radioactivity of the cerebral cortex was lower than the radioactivity of the basal ganglia, and that radioactivity of the right visual cortex was decreased compared with that of the left side.
Diagnosis
The clinical diagnosis is based on the symptoms of hypotonia, developmental delay, episodes of shortness of breath and/or apnea, combined with the typical imaging changes, i.e., cerebellar brainstem malformation (molar sign). Genetic testing is required.
Differential Diagnosis
Joubert syndrome often needs to be differentiated from Dindy-Walker syndrome, rhombencephalic association, Down syndrome, etc. The following are the differential diagnosis of Joubert syndrome
1. Patients with Dandy-Walker syndrome have a normal width of the brainstem isthmus and no molar sign, which can be used as a point of differentiation between the two.
2. The rhombencephalic coalition is the fusion of the cerebellar hemispheres on both sides and the absence of the cerebellar peduncle, with no midline fissure present between the cerebellar hemispheres on both sides, and the clinical manifestations characteristic of Joubert’s syndrome can help in the differentiation.
3. Down syndrome can be clearly diagnosed according to the typical clinical manifestations or the chromosome grouping of chromosome 21-3.
Treatment of Joubert syndrome
Joubert’s syndrome is mostly treated with a combination of rehabilitation training, nerve blocks, and medications, with rehabilitation training before the age of 1 year.
Prevention
According to the genotype of the pre-diagnosed person, parents carry out genetic counseling, prenatal diagnosis and so on.