Joubert et al. (1969) described 4 French Canadian sibs, born of distantly related parents, with a severe neurologic disorder characterized by episodic hyperpnea, abnormal eye movements, ataxia, and global psychomotor retardation. Partial or complete agenesis of the cerebellar ... Joubert et al. (1969) described 4 French Canadian sibs, born of distantly related parents, with a severe neurologic disorder characterized by episodic hyperpnea, abnormal eye movements, ataxia, and global psychomotor retardation. Partial or complete agenesis of the cerebellar vermis was demonstrated by autopsy or pneumoencephalogram. One patient also had an occipital meningomyelocele. The oldest living sib was 8 years old. Srour et al. (2012) reported 10 patients from 7 French Canadian families with Joubert syndrome. Two sibs were part of the original family described by Joubert et al. (1969). All patients showed global developmental delay, with the onset of independent walking between 30 months and 8 years of age. Cognitive impairment was present in all individuals but was variable, ranging from borderline intelligence to mild intellectual disability. Most also showed oculomotor apraxia and breathing abnormalities, mainly episodic hyperventilation. Two individuals had limb abnormalities; 1 had preaxial and postaxial polydactyly, and another had syndactyly of the third and fourth fingers on 1 hand. Brain MRI showed the molar tooth sign in all patients examined. None had evidence of retinal or kidney involvement.
In affected individuals from 7 French Canadian families with Joubert syndrome-17, Srour et al. (2012) identified 6 different potentially pathogenic mutations in the C5ORF42 gene (614571.0001-614571.0006). The mutations were found by exome sequencing and confirmed by Sanger sequencing. ... In affected individuals from 7 French Canadian families with Joubert syndrome-17, Srour et al. (2012) identified 6 different potentially pathogenic mutations in the C5ORF42 gene (614571.0001-614571.0006). The mutations were found by exome sequencing and confirmed by Sanger sequencing. Three of the mutations were found in multiple families, and haplotype analysis showed that each was linked to a distinct haplotype. The higher frequency of these mutations in the Lower St. Lawrence region might be explained by a founder effect with the coincidental occurrence of the 3 mutations in the same group of settlers, or by multiple regional founder effects corresponding to sequential pioneer fronts.