ß 2006 Wiley-Liss, Inc. American Journal of Medical Genetics Part A 140A:2091–2109 (2006) Normal Values for Morphological Abnormalities in School Children Johannes H.M. Merks, 1 * Heval M. O ¨ zgen, 2 Theresia L.M. Cluitmans, 3 Jaqueline M. van der Burg-van Rijn, 4 Jan Maarten Cobben, 2 Flora E. van Leeuwen, 5 and Raoul C.M. Hennekam 2,6 1 Department of Pediatric Oncology, Emma Children’s Hospital, Academic Medical Center, Amsterdam, The Netherlands 2 Department of Pediatric Genetics, Emma Children’s Hospital, Academic Medical Center, Amsterdam, The Netherlands 3 Department of Epidemiology, Community Health Care Department Kennemerland, Haarlem, The Netherlands 4 Department of Youth Health Care, Community Health Care Department Kennemerland, Haarlem, The Netherlands 5 Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands 6 Institute of Child Health, Great Ormond Street Hospital for Children, University College London, London, UK Received 6 October 2005; Accepted 11 May 2006 Clinical morphology has proven to be a strong tool in the delineation of many syndromes and a helpful instrument in molecular studies. Numerous studies have been performed investigating the prevalence of minor anomalies in various disorders; all concluding that minor anomalies can well be utilized as indicators of altered embryonic differentiation. However, for adequate evaluation, normal values for phenotypic abnormalities are essential. So far, only few studies on the frequency of phenotypic abnormalities in the normal population have been done having one thing in common: all were performed in newborn infants. We studied morphological characteristics in a group of 1,007 school children, representative for the Dutch population, through a body surface examination using detailed definitions for all morphological findings. The region of study and distribution of children over various school types was chosen in such a way that it represented the general Dutch population. The median age of the studied children was 11 years (range 8– 14 years), sex ratio (M:F) was 0.93. Nine hundred twenty- three children were of Caucasian descent, 84 others of mixed ethnic backgrounds. The reliability of the examinations was tested by independent scoring of 111 children by two observers, showing a kappa score of 0.85. Normal values for the morphological findings are presented together with their age-adjusted classification. These normal values provide a valuable source for validation of classifications of phenotypic abnormalities, especially those that are depending on frequency, that is, minor anomalies and common variants. Furthermore, they will allow a proper evaluation of patterns of phenotypic abnormalities found in patient groups with specific disorders. ß 2006 Wiley-Liss, Inc. Key words: clinical morphology; phenotypic abnormality; congenital abnormality; minor anomaly; normal values; Caucasian; school children How to cite this article: Merks JHM, O ¨ zgen HM, Cluitmans TLM, van der Burg-van Rijn JM, Cobben JM, van Leeuwen FE, Hennekam RCM. 2006. Normal values for morphological abnormalities in school children. Am J Med Genet Part A 140A:2091 – 2109. INTRODUCTION Physical examination for evaluation of morpholo- gical characteristics of patients is a major tool in clinical genetics. Normal values are indispensable for validation of the morphological findings, especially for those that depend on frequency such as minor anomalies and common variants [Merks et al., 2003]. The incidence of minor physical anomalies has also been studied in search of relationships between various non-syndromic disorders and abnormal embryogenesis or phenogenesis. Well-known examples are the studies in childhood cancer [Kobayashi et al., 1968; Stojimirovic, 1981; Me ´hes et al., 1985, 1994, 1998; Fe ´ke ´te ´ et al., 1987; Roganovic et al., 2002; Merks et al., 2003], diabetes mellitus [Me ´hes et al., 1986], metabolic disorders [Me ´hes, Johannes H.M. Merks and Heval M. O ¨ zgen equally contributed to the manuscript. Grant sponsor: Emma Children’s Hospital Foundation (Stichting Steun Emma Kinderziekenhuis). *Correspondence to: Johannes H.M. Merks, M.D., Ph.D., Department of Pediatric Oncology, Floor F8-Room 245, Emma Children’s Hospital- Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. E-mail: j.h.merks@amc.uva.nl. DOI 10.1002/ajmg.a.31355