Four families with linkage to two loci for Jouberts syndrome (JS), JBTS1 or JBTS2, and clinical and radiographic correlations for 4 known genetic causes of JS-related disorders (JSRD) are described in a report from University of California-San Diego, La Jolla, CA, and centers in Europe and the Middle East. The clinical manifestations of JS are hypotonia, ataxia, mental retardation, oculomotor apraxia, and dysregulation of neonatal breathing. The molar tooth sign (MTS) is the diagnostic neuroradiological feature of JS, a complex midbrain-hindbrain malformation consisting of cerebellar vermis hypoplasia, deep interpeduncular fossa, and thickened, elongated, maloriented superior cerebellar peduncles. JSRD are characterized by the association of the MTS with abnormalities of other organs, including retinal dystrophy and polycystic and fibrotic kidneys, optic coloboma, Polydactyly, liver fibrosis, and other CNS malformations (eg polymicrogyria). JBTS1 and -3 features are restricted to the CNS, whereas JBTS2 involves multiple organs, including kidney, retina, and liver as well as CNS. [1]

COMMENT. In addition to Jouberts, syndromes of cerebellar vermis agenesis or hypoplasia include Dandy-Walker malformation, Walker-Warburg (lissencephaly, retinal abnormalities and hydrocephalus), Meckel-Gruber (occipital encephalocele, polycystic kidneys, poydactyly and hydrocephalus), and atypical Dandy-Walker with facial angioma. Some cases of vermian agenesis are associated with urinary excretion of succinyl-purines and pipecolic acid (See Progress in Pedeiatric Neurology I, 1991;312-313). [2]