Joubert Syndrome and related disorders

The term Joubert Syndrome and Related Disorders (JSRD) has been recently adopted to describe all disorders presenting the "molar tooth sign" (MTS) on brain imaging. Thus, JSRD include Joubert syndrome (JS, also known as Joubert-Boltshauser syndrome [OMIM#213300]), as well as any related condition showing the MTS, such as the cerebello-oculo-renal syndrome, Dekaban-Arima syndrome [OMIM%243910], COACH syndrome [OMIM216360], Varadi-Papp syndrome (or Orofaciodigital type VI, [OMIM%277170]), Malta syndrome and a minority of cases with Senior-Loken syndrome [OMIM#266900].Joubert syndrome (JS) was originally described in 1968 in four siblings with agenesis of the cerebellar vermis presenting episodic hyperpnoea, abnormal eye movements, ataxia and intellectual disability [1]. Several years later, a pathognomonic midbrain-hindbrain malformation, the "molar tooth sign" (MTS), was detected first in JS [2], and then in several other conditions previously considered as distinct entities [3] (see section "Disease name and synonyms"). The term "Joubert Syndrome and Related Disorders" (JSRD) was then coined to group all conditions sharing the MTS [4], and this neuroradiological sign now represents the mandatory criterion to diagnose JSRD.The MTS results from hypo-dysplasia of the cerebellar vermis, abnormally deep interpeduncular fossa at the level of the isthmus and upper pons, and horizontalized, thickened and elongated superior cerebellar peduncles [5] (Figure 1). At the pathological level, these abnormalities correspond to a picture of severe hypo-dysplasia of the cerebellar vermis with midline clefting, fragmentation of cerebellar nuclei and heterotopia of Purkinje-like neurons, along with dysplasia of pontine and medullary structures such as the basis pontis, reticular formation, inferior olivary, dorsal column and solitary tract nuclei. Moreover, typical findings are represented by the lack of decussation both of the superior cerebellar peduncles and of the corticospinal tra