Teaching Case

A 47-year-old male with mild cognitive impairment was referred to our hospital due to episodic cephalic tremors lasting one minute. He did not report ataxia. The physical exam revealed nystagmus and ocular apraxia, with impairment in following a moving object.

A malformation characterised by elongated and thickened superior cerebellar peduncles (with a parallel and horizontal disposition) and a deep interpeduncular fossa is seen, giving the radiological appearance of a molar tooth, corresponding with the “molar tooth sign” (Figure 1). A mega cisterna magna and a midline cerebellar cleft of cerebrospinal fluid (CSF) due to vermian hypoplasia is present (Figures 2a and 2b), associated with changes in the arrangement of cerebellar folia as an indirect sign of cerebellar architectural distortion (Figure 3). The superior cerebellar peduncles are thickened and show horizontalisation (Figures 4a and 4b). Sometimes, a fourth ventricle with a bat-wing shape can be observed (Figure 5).

Background

Joubert syndrome and related disorders (JSRD) are a large group of hereditary disorders, most of which are autosomal recessive, clinically and genetically related, and currently considered ciliopathies. The genetics of JSRD are complex, with mutations affecting 10 identified genes, showing phenotypic variability among patients, and exhibiting both allelic and locus heterogeneity [1,2].

Clinical Perspective

Joubert Syndrome was first described by Joubert in 1969 and is most frequently diagnosed in young children. Clinically, it is characterised by hypotonia, ataxia, and oculomotor abnormalities. Most patients have a variable degree of cognitive impairment. Other findings may include polycystic kidney disease (nephronophthisis), hepatic fibrosis, retinal abnormalities, polydactyly, and colobomas [1–3].

Imaging Perspective

The neuroimaging hallmarks of JSRD patients include vermian hypoplasia and the molar tooth sign.

The molar tooth refers to the characteristic image of an abnormal development of the cerebellar vermis and the brainstem that resemble a molar tooth on imaging (CT or MR).

The vermian hypoplasia is based on partial or complete absence of cerebellar vermis, which leads to the separation of the cerebellar hemispheres at the midline, showing a fine line of cerebrospinal fluid between them (the characteristic midline cleft) with thickened, prominent superior cerebellar peduncles arranged horizontally [1–4].

Additional imaging features may include [1–4]:

• On diffusion tensor imaging: Absence of fibre decussation in the superior cerebellar peduncles and pyramidal tracts.
• Dysplasia and heterotopia of the cerebellar nuclei.
• Fourth ventricle with a bat-wing shape.
• Ventriculomegaly, mega-cisterna magna (6%–20% of cases), and corpus callosum dysgenesis (6%–10%) [4].
• The association with abnormal migration defects and cortical organisation defects has also been reported, including periventricular nodular heterotopias and polymicrogyria [1].

Outcome

The prognosis depends on the type of genetic mutations and phenotype, being favourable for moderate forms of the disease. It is variably associated with liver, kidney, and ocular dysfunction. In patients with nephronophthisis, end-stage renal disease tends to appear in the second decade of life. If present, liver disease does not recur in the transplanted liver [1–2].

Take Home Message / Teaching Points

Joubert syndrome and related disorders (JSRD) are an increasingly large group of hereditary disorders with phenotypic variability among patients. Radiological findings are extremely valuable for diagnosis and raising clinical suspicion, with the molar tooth sign being the most distinct sign on imaging.

All patient data have been completely anonymised throughout the entire manuscript and related files.