title: Kohlschutter-Tonz syndrome: clinical and genetic insights gained from 16 cases deriving from a close-knit village in Northern Israel.
abstract: BACKGROUND
  Kohlschutter-Tonz syndrome (KTS; MIM 22675) is a rare autosomal recessive disorder characterized by intellectual impairment, spasticity, epilepsy, and amelogenesis imperfecta. We have recently identified the causative gene and mutation underlying KTS, namely, p.R157X, corresponding to ROGDI c.571C>T, which creates a premature stop codon in ROGDI homolog (Drosophila), a gene of unknown function, in KTS patients of Druze origin.
  
  
  METHODS
  To better delineate the phenotype of KTS, 16 cases (eight female, eight male), from seven families (five kindreds) originating from a Druze village in Northern Israel, all homozygous for the same deleterious mutation, were investigated. Medical records were reviewed, and a detailed medical history was obtained by interview of parents.
  
  
  RESULTS
  Age at onset between six and 12 months of age and the intensity of convulsions were variably manifested by affected sibs and mirror the progression of mental and motor deterioration. Amelogenesis imperfecta and deficient speech occur in all cases. By late adolescence and early twenties, individuals with KTS are bedridden, fed by a gastrostomy tube, spastic, and practically have no cognitive and language perception.
  
  
  CONCLUSIONS
  KTS, a genetic disease heralded by convulsions, "yellow teeth," and severe mental impairment, allows for a clinical variability as regarding age of onset and severity of seizures that per se predict the speed of mental deterioration. In all cases, however, the morbid course of the disease is ultimately equally devastating by the twenties.
authors.affiliation: Institute of Human Genetics, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Adi
authors.initials: A
authors.lastname: Mory
authors.affiliation: Institute of Human Genetics, Rambam Health Care Campus, Haifa, Israel; Department of Nursing, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel.
authors.forename: Efrat
authors.initials: E
authors.lastname: Dagan
authors.affiliation: Department of Pediatrics, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Ishai
authors.initials: I
authors.lastname: Shahor
authors.affiliation: Department of Pediatrics, Rambam Health Care Campus, Haifa, Israel; The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Hanna
authors.initials: H
authors.lastname: Mandel
authors.affiliation: CSS-Mendel Institute, Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Illi
authors.affiliation: Institute of Human Genetics, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Jenny
authors.initials: J
authors.lastname: Zolotushko
authors.affiliation: Institute of Human Genetics, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Alina
authors.initials: A
authors.lastname: Kurolap
authors.affiliation: 'Clalit' Health Services Haifa and North, Western Galilee District, Israel.
authors.forename: Emilia
authors.initials: E
authors.lastname: Chechik
authors.affiliation: CSS-Mendel Institute, Rome, Italy.
authors.forename: Enza M
authors.initials: EM
authors.lastname: Valente
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U.933, Université Pierre et Marie Curie, Hôpital Armand-Trousseau, Paris, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Amselem
authors.affiliation: Institute of Human Genetics, Rambam Health Care Campus, Haifa, Israel; The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. Electronic address: rgershoni@rambam.health.gov.il.
authors.forename: Ruth
authors.initials: R
authors.lastname: Gershoni-Baruch
mesh_terms: D000293:Adolescent; D000567:Amelogenesis Imperfecta / Q000235:genetics* / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D003704:Dementia / Q000235:genetics* / Q000503:physiopathology*; D004827:Epilepsy / Q000235:genetics* / Q000503:physiopathology*; D005190:Family; D005260:Female; D006720:Homozygote; D006801:Humans; D007223:Infant; D007557:Israel; D008297:Male; D009154:Mutation; D010375:Pedigree; D055815:Young Adult
keywords: Kohlschutter–Tonz syndrome; ROGDI homolog (Drosophila) (FLJ22386); amelogenesis imperfecta; epilepsy; intellectual impairment