Investigators at Neurogenetics Unit, Mendel Laboratory, Rome, and University of Salerno, Italy, review the clinical features and genetic basis of Joubert syndrome, overlap with other ciliopathies, and the multifaceted roles of primary cilia in CNS development. Joubert M. and colleagues first described a familial agenesis of the cerebellum, manifested by episodic hyperpnea, abnormal eye movements, ataxia and retardation . The characteristic malformation involving the cerebellum and brainstem, the MRI hallmark of the syndrome, is called the “molar tooth sign.” Associated CNS defects include ventriculomegaly, meningo-encephalocele, polymicrogyria, periventricular nodular heterotopia, hypothalamic hamartoma, and corpus callosum defects. Specific Joubert syndrome subgroups are correlated with different causative genes, one known by the acronym COACH (cerebellar vermis hypoplasia, oligophrenia, ataxia, coloboma, and hepatic fibrosis). A total of 21 causative genes have been identified, all encoding for proteins of the primary cilium that has a key role in development. An increasing number of heterogeneous disorders are being causally related to mutations in ciliary genes. 
COMMENT. Prenatal abnormal features of the fourth ventricle in fetuses with Joubert syndrome and related disorders are reported in 7 subjects, all showing the molar tooth sign using ultrasound and/or MRI . The term “Joubert syndrome” now encompasses all molar tooth sign-related disorders, and the term “Joubert syndrome and related disorders” is no longer in favor. Variable clinical manifestations associated with the molar tooth sign are not distinct syndromes, but part of a wide phenotypic range characteristic of Joubert syndrome.