Adi Mory1, Efrat Dagan2, Ishai Shahor3, Hanna Mandel4, Barbara Illi5, Jenny Zolotushko1, Alina Kurolap1, Emilia Chechik6, Enza M Valente5, Serge Amselem7, Ruth Gershoni-Baruch8. 1. Institute of Human Genetics, Rambam Health Care Campus, Haifa, Israel. 2. 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. 3. Department of Pediatrics, Rambam Health Care Campus, Haifa, Israel. 4. Department of Pediatrics, Rambam Health Care Campus, Haifa, Israel; The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. 5. CSS-Mendel Institute, Rome, Italy. 6. 'Clalit' Health Services Haifa and North, Western Galilee District, Israel. 7. Institut National de la Santé et de la Recherche Médicale (INSERM) U.933, Université Pierre et Marie Curie, Hôpital Armand-Trousseau, Paris, France. 8. 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.
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. PATIENTS: 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.
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. PATIENTS: 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.