Differences in behavioural phenotype between parental deletion and maternal uniparental disomy in Prader–Willi syndrome: an ERP study Johannes E.A. Stauder a, * , Harm Boer b , Rolf H.A. Gerits a , Anke Tummers a , Joyce Whittington c , Leopold M.G. Curfs a,d a Section Biological Developmental Psychology, Department of Psychology, University of Maastricht, P.O. Box 616, 6200 MD Maastricht, The Netherlands b Janet Shaw Clinic, North Warwickshire NHS Trust, North Warwickshire, UK c Section of Developmental Psychiatry, Department of Psychiatry, University of Cambridge, Cambridge, UK d Department of Clinical Genetics, Research Institute Growth and Development (GROW), Academic Hospital Maastricht, Maastricht, The Netherlands Accepted 21 February 2005 Available online 26 April 2005 Abstract Objective: Paternal deletion and maternal uniparental disomy are the principal genetic subtypes associated with Prader–Willi syndrome (PWS). Recent clinical findings suggest differences in phenotype between these subtypes. The present experimental study addresses this issue using a cognitive psycho-physiological setup. Methods: Behaviour and event-related brain activity (ERP) was recorded by a continuous performance response inhibition task (CPT-AX) in adults with paternal deletion PWS (nZ11), maternal uniparental disomy PWS (nZ11) and normal controls (nZ11). The dependent behavioural variables of the CPT-AX task were reaction time and correct scores. For the ERPs the N200 and P300 components were included which are related to early modality-specific inhibition and late general inhibition, respectively. Results: The disomy group had fewer correct scores and increased reaction times as compared to the CPT-AX task than the control and deletion group. Both PWS subgroups differed significantly from the control group for the N200 amplitude. Only the control group showed the typical task modulation for the N200 amplitude. The amplitude of the P300 component was considerably smaller in the uniparental disomy group than in the deletion and control groups. Conclusions: The ERP results suggest that early modality specific inhibition is impaired in both PWS genetic subtypes. Late general inhibition is impaired in the uniparental disomy group only. Thus, although the ERP data suggests a common impairment in early visual inhibition processing, uniparental disomy and parental deletion genetic PWS subtypes clearly differ in their behavioural and brain activation phenotypes. Significance: The present study is the first experimental demonstration which explains the two principal genetic mechanisms that hinder the expression of the genes at 15q11-q13g in PWS result in different behavioural phenotype. q 2005 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. Keywords: Prader–Willi syndrome; Parental deletion; Maternal uniparental disomy; Response inhibition; Event related potentials 1. Introduction Till date the Prader–Willi syndrome has been considered as a unitary syndrome despite the existence of three genetic subtypes. However, recently some anecdotal clinical differences have been reported between the two main genetic subtypes in Prader–Willi Syndrome. The present study seeks experimental confirmation to differentiate the two major experimental subtypes in Prader–Willi Syndrome. Prader–Willi Syndrome (PWS) is a genetically determined neurodevelopmental disorder associated with abnormal or absent expression of imprinted, paternally Clinical Neurophysiology 116 (2005) 1464–1470 www.elsevier.com/locate/clinph 1388-2457/$30.00 q 2005 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.clinph.2005.02.019 * Corresponding author. Tel.: C31 43 3881933; fax: C31 43 3884125. E-mail address: h.stauder@psychology.unimaas.nl (J.E.A. Stauder).