title: The molar tooth sign: a new Joubert syndrome and related cerebellar disorders classification system tested in Egyptian families.
abstract: Joubert syndrome and related cerebellar disorders (JSRD) are a group of recessive congenital ataxia conditions usually showing neonatal hypotonia, dysregulated breathing rhythms, oculomotor apraxia, and mental retardation. The pathognomonic finding in JSRD is the unique molar tooth sign (MTS) on brain imaging. There is a tremendously broad spectrum of signs and symptoms mainly including kidney, retina, and liver disease, along with polydactyly and facial dysmorphisms. Here we propose a new diagnostic classification within JSRD that includes four major subtypes. To test this classification, we performed a systematic recruitment and genetic evaluation from a single referral center in Egypt. Thirteen families were identified, four showed evidence of linkage to one of the four known genetic loci, three showed novel AHI1 mutations, and nine were excluded from known loci. Each family could be classified into one of the four subtypes. This classification may thus be useful in the evaluation of patients with JSRD.
authors.affiliation: Clinical Genetics Department, National Research Centre, Neuromotor Institute, Cairo, Egypt.
authors.forename: M S
authors.initials: MS
authors.lastname: Zaki
authors.forename: A
authors.initials: A
authors.lastname: Abdel-Aleem
authors.forename: G
authors.initials: G
authors.lastname: Abdel-Salam
authors.forename: S E
authors.initials: SE
authors.lastname: Marsh
authors.forename: J L
authors.initials: JL
authors.lastname: Silhavy
authors.forename: A J
authors.initials: AJ
authors.lastname: Barkovich
authors.forename: M E
authors.initials: ME
authors.lastname: Ross
authors.forename: S N
authors.initials: SN
authors.lastname: Saleem
authors.forename: W B
authors.initials: WB
authors.lastname: Dobyns
authors.forename: J G
authors.initials: JG
authors.lastname: Gleeson
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D001284:Atrophy / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D002526:Cerebellar Diseases / Q000145:classification / Q000175:diagnosis* / Q000235:genetics*; D002531:Cerebellum / Q000473:pathology* / Q000503:physiopathology*; D025063:Chromosome Disorders / Q000145:classification / Q000175:diagnosis / Q000235:genetics; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D004534:Egypt; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007674:Kidney Diseases / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology; D008107:Liver Diseases / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics*; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology; D010641:Phenotype; D011237:Predictive Value of Tests; D012162:Retinal Degeneration / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D013577:Syndrome; D014463:Ultrasonography