Original article Epileptic encephalopathy and amelogenesis imperfecta: KohlschüttereTönz syndrome Anna Schossig a , Nicole I. Wolf c , Ines Kapferer b , Alfried Kohlschütter d , Johannes Zschocke a, * a Division of Human Genetics, Medical University Innsbruck, Schöpfstr. 41, 6020 Innsbruck, Austria b Department of Restorative and Operative Dentistry, Medical University Innsbruck, Innsbruck, Austria c Dept. of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands d University Hospital for Child and Adolescent Medicine, Hamburg, Germany article info Article history: Received 30 December 2011 Accepted 17 February 2012 Available online 28 March 2012 Keywords: KohlschüttereTönz syndrome Genetic heterogeneity Enamel defect Epilepsy abstract KohlschüttereTönz syndrome is a rare genetic disorder with epilepsy, psychomotor regression, and a severe enamel defect with yellow or brownish discoloration of the teeth. The first affected family was described in 1974, and 25 patients in 11 families have been reported until now. Inheritance is autosomal recessive. Epilepsy usually starts within the first or second year of life. All affected individuals show a psychomotor regression after onset of epilepsy or a developmental delay from birth on. Clinical course and disease severity are variable even within families. There are no known biochemical or other diag- nostic markers of the condition. Very recently it has been shown that the condition is caused by mutations in the gene ROGDI but molecular data have only been reported for three families. It remains to be seen whether KohlschüttereTönz syndrome has the same molecular basis in all affected individuals. Ó 2012 Elsevier Masson SAS. All rights reserved. 1. Introduction The combination of epilepsy and yellow teeth as a genetic syndrome was first described in 1974 by Kohlschütter, Tönz, and colleagues in a Swiss non-consanguineous family [1]. The index patient had epilepsy, spastic tetraparesis, and intellectual disability. A peculiar additional finding was a discoloration of his teeth which had a yellowish color due to enamel hypoplasia. Dental radiographs showed reduced enamel layer in both primary and secondary teeth. Four of his ten siblings had similar symptoms and the same dental phenotype. Psychomotor development in the affected children was initially normal; the index patient was able to sit at age eight months and stand at age eleven months. Epilepsy in the affected family members started between age eleven months and four years; it was refractory to treatment and was associated with regression of psychomotor abilities. All children died during childhood due to complications of epilepsy. All healthy siblings had normal white teeth. Since the first report, 20 other patients with the clinical diagnosis of KohlschüttereTönz syndrome from 10 families have been published (Table 1). Clinical summaries of three patients previously published in German [2] are enclosed in Supplement 1 . 2. Clinical features KohlschüttereTönz syndrome is characterized by dental enamel hypoplasia in combination with epilepsy starting in infancy or early childhood and intellectual disability or psychomotor regression (Textbox 1). Onset of epilepsy has been described between age five weeks and four years; in most patients seizures start within the first year of life. All affected children reported so far had patho- logical EEG findings with loss of normal background activity. EEG does not show specific changes, and KohlschüttereTönz syndrome is not known to be associated with any recognizable epilepsy syndromes. Seizures are often resistant to treatment even with newer antiepileptic drugs but no systematic studies on the best medication have been reported. There is marked intrafamilial variability: one published patient had only two seizure episodes while his sister had severe epilepsy that was difficult to treat [3]. Most patients show severe global developmental delay which often becomes apparent after onset of seizures but may be present from birth onwards. Many affected children do not acquire active language or independent ambulation, some develop spastic tetra- paresis. Severe progressive psychomotor decline and fatal outcome has only been reported in seven out of the 25 patients. * Corresponding author. Tel.: þ43 512 9003 70500; fax: þ43 512 9003 73510. E-mail address: johannes.zschocke@i-med.ac.at (J. Zschocke). Contents lists available at SciVerse ScienceDirect European Journal of Medical Genetics journal homepage: http://www.elsevier.com/locate/ejmg 1769-7212/$ e see front matter Ó 2012 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.ejmg.2012.02.008 European Journal of Medical Genetics 55 (2012) 319e322