PT - JOURNAL ARTICLE AU - Aia Elise Jønch AU - Elise Douard AU - Clara Moreau AU - Anke Van Dijck AU - Marzia Passeggeri AU - Frank Kooy AU - Jacques Puechberty AU - Carolyn Campbell AU - Damien Sanlaville AU - Henrietta Lefroy AU - Sonia Richetin AU - Aurelie Pain AU - David Geneviève AU - Usha Kini AU - Cédric Le Caignec AU - James Lespinasse AU - Anne-Bine Skytte AU - Bertrand Isidor AU - Christiane Zweier AU - Jean-Hubert Caberg AU - Marie-Ange Delrue AU - Rikke Steensbjerre Møller AU - Anders Bojesen AU - Helle Hjalgrim AU - Charlotte Brasch-Andersen AU - Emmanuelle Lemyre AU - Lilian Bomme Ousager AU - Sébastien Jacquemont ED - , TI - Estimating the effect size of the 15Q11.2 BP1–BP2 deletion and its contribution to neurodevelopmental symptoms: recommendations for practice AID - 10.1136/jmedgenet-2018-105879 DP - 2019 Oct 01 TA - Journal of Medical Genetics PG - 701--710 VI - 56 IP - 10 4099 - http://jmg.bmj.com/content/56/10/701.short 4100 - http://jmg.bmj.com/content/56/10/701.full SO - J Med Genet2019 Oct 01; 56 AB - Background The 15q11.2 deletion is frequently identified in the neurodevelopmental clinic. Case–control studies have associated the 15q11.2 deletion with neurodevelopmental disorders, and clinical case series have attempted to delineate a microdeletion syndrome with considerable phenotypic variability. The literature on this deletion is extensive and confusing, which is a challenge for genetic counselling. The aim of this study was to estimate the effect size of the 15q11.2 deletion and quantify its contribution to neurodevelopmental disorders.Methods We performed meta-analyses on new and previously published case–control studies and used statistical models trained in unselected populations with cognitive assessments. We used new (n=241) and previously published (n=150) data from a clinically referred group of deletion carriers. 15q11.2 duplications (new n=179 and previously published n=35) were used as a neutral control variant.Results The deletion decreases IQ by 4.3 points. The estimated ORs and respective frequencies in deletion carriers for intellectual disabilities, schizophrenia and epilepsy are 1.7 (3.4%), 1.5 (2%) and 3.1 (2.1%), respectively. There is no increased risk for heart malformations and autism. In the clinically referred group, the frequency and nature of symptoms in deletions are not different from those observed in carriers of the 15q11.2 duplication suggesting that most of the reported symptoms are due to ascertainment bias.Conclusions We recommend that the deletion should be classified as ‘pathogenic of mild effect size’. Since it explains only a small proportion of the phenotypic variance in carriers, it is not worth discussing in the developmental clinic or in a prenatal setting.