CT and MR Imaging Findings in the Joubert Syndrome,a“Ciliopathy”

A 7-year-old boy presented with cerebellar ataxia with reduced tonicity, deficits of the fine and gross motor coordination skills and vestibular stimulus processing, as well as significantly delayed language development. MR imaging showed the so-called “molar tooth sign”, which was highly pathognomonic for the Joubert-Syndrome—an inherited cerebellar ataxia with a variety of clinical symptoms—and related entities. It is caused by a complex malformation of the cerebellar vermis and the midbrain. The cerebellar vermis is hypoplastic or completely absent;at the same time, the superior cerebellar peduncles are thickened. There is a lack of normal decussation of the fiber tracts in mesencephalon, which follow an abnormal horizontal course, as well as a lack of the decussation of the corticospinal fiber tracts in the caudal medulla oblongata and deformity of the 4th ventricle. Clinically, the triad of cerebellar ataxia, developmental retardation, and abnormal eye movements is indicating a related syndrome of this spectrum. The appearance of the involved children is characterized by dysmorphic facial features with epicanthus, broad nose bridge, low set ears and typically triangularly shaped and opened mouth. The diagnosis is usually made by imaging and clinical findings. Recently, advantages were made in genetic research on the Joubert syndrome and interesting findings published about diffusion tensor imaging and tractography. However, standard MR imaging, applying an adequate imaging protocol including sequences with excellent T1 contrast and 3D imaging with isotropic spatial resolution allowing reconstructions in all orientations, remains an essential tool for making this diagnosis.

The Joubert Syndrome Gene arl13b is Critical for Early Cerebellar Development in Zebrafish

Joubert syndrome is characterized by unique malformation of the cerebellar vermis.More than thirty Joubert syndrome genes have been identified,including ARL13 B.However,its role in cerebellar development remains unexplored.We found that knockdown or knockout of arl13b impaired balance and locomotion in zebrafish larvae.Granule cells were selectively reduced in the corpus cerebelli,a structure homologous to the mammalian vermis.Purkinje cell progenitors were also selectively disturbed dorsomedially.The expression of atoh1 and ptf1,proneural genes of granule and Purkinje cells,respectively,were selectively down-regulated along the dorsal midline of the cerebellum.Moreover,wnt1,which is transiently expressed early in cerebellar development,was selectively reduced.Intriguingly,activating Wnt signaling partially rescued the granule cell defects in arl13b mutants.These findings suggested that Arl13 b is necessary for the early development of cerebellar granule and Purkinje cells.The arl13b-deficient zebrafish can serve as a model organism for studying Joubert syndrome.