Joubert Syndrome

Joubert syndrome (JS)—first reported in 1969—has advanced from a case report to the best studied midbrain-hindbrain malformation. JS is very heterogeneous in clinical expression, genetics, and neuroimaging. In this presentation the focus is mainly on imaging aspects and their potential pitfalls. The demonstration of the “Molar Tooth Sign” (MTS) is the key to the diagnosis of JS. It is made up by the mesencephalon with a deepened interpeduncular fossa and the elongated and thickened superior cerebellar peduncles (SCP) on an axial MRI cut. Sagittal views demonstrate vermis hypoplasia/dysplasia and a rostral displacement of the fastigium of the fourth ventricle. Parasagittal cuts are very helpful as they show the thickened and abnormally horizontal orientation of the SCP. In addition to the MTS infratentorial (such as cerebellar vermis dysplasia, macrocerebellum, encephaloceles) and supratentorial anomalies (such as ventriculomegaly, hippocampal malrotation) are prevalent. JS is also characterized by abnormal axonal guidance (navigation) as demonstrable in vivo by tractography: the pyramidal tracts as well as tracts in the SCP do not cross the midline. Actually (January 2017) more than 35 genes are associated with JS, with one exception (OFD1, X-linked) these are autosomal recessively inherited. All genes are expressed in the primary nonmotile cilia, allowing to classify JS as a ciliopathy. The variability of the clinical presentations is explained by the variability of mutations in different organs (brain: cognitive impairment, ataxia; retina: retinal dystrophy, coloboma; kidney: nephronophthisis; liver: hepatic fibrosis with portal hypertension). Intrafamilial variability is often observed among affected siblings.