TY - JOUR T1 - O’Donnell-Luria-Rodan syndrome: description of a second multinational cohort and refinement of the phenotypic spectrum JF - Journal of Medical Genetics JO - J Med Genet SP - 697 LP - 705 DO - 10.1136/jmedgenet-2020-107470 VL - 59 IS - 7 AU - Clara Velmans AU - Anne H O'Donnell-Luria AU - Emanuela Argilli AU - Frederic Tran Mau-them AU - Antonio Vitobello AU - Marcus CY Chan AU - Jasmine Lee-Fong Fung AU - Megan Rech AU - Angela Abicht AU - Marion Aubert Mucca AU - Jason Carmichael AU - Nicolas Chassaing AU - Robin Clark AU - Christine Coubes AU - Anne-Sophie Denommé-Pichon AU - John Karl de Dios AU - Eleina England AU - Benoit Funalot AU - Marion Gerard AU - Maries Joseph AU - Colleen Kennedy AU - Camille Kumps AU - Marjolaine Willems AU - Ingrid M B.H van de Laar AU - Coranne Aarts-Tesselaar AU - Marjon van Slegtenhorst AU - Daphné Lehalle AU - Kathleen Leppig AU - Lennart Lessmeier AU - Lynn S Pais AU - Heather Paterson AU - Subhadra Ramanathan AU - Lance H Rodan AU - Andrea Superti-Furga AU - Brian H.Y. Chung AU - Elliott Sherr AU - Christian Netzer AU - Christian P Schaaf AU - Florian Erger Y1 - 2022/07/01 UR - http://jmg.bmj.com/content/59/7/697.abstract N2 - Background O’Donnell-Luria-Rodan syndrome (ODLURO) is an autosomal-dominant neurodevelopmental disorder caused by pathogenic, mostly truncating variants in KMT2E. It was first described by O’Donnell-Luria et al in 2019 in a cohort of 38 patients. Clinical features encompass macrocephaly, mild intellectual disability (ID), autism spectrum disorder (ASD) susceptibility and seizure susceptibility.Methods Affected individuals were ascertained at paediatric and genetic centres in various countries by diagnostic chromosome microarray or exome/genome sequencing. Patients were collected into a case cohort and were systematically phenotyped where possible.Results We report 18 additional patients from 17 families with genetically confirmed ODLURO. We identified 15 different heterozygous likely pathogenic or pathogenic sequence variants (14 novel) and two partial microdeletions of KMT2E. We confirm and refine the phenotypic spectrum of the KMT2E-related neurodevelopmental disorder, especially concerning cognitive development, with rather mild ID and macrocephaly with subtle facial features in most patients. We observe a high prevalence of ASD in our cohort (41%), while seizures are present in only two patients. We extend the phenotypic spectrum by sleep disturbances.Conclusion Our study, bringing the total of known patients with ODLURO to more than 60 within 2 years of the first publication, suggests an unexpectedly high relative frequency of this syndrome worldwide. It seems likely that ODLURO, although just recently described, is among the more common single-gene aetiologies of neurodevelopmental delay and ASD. We present the second systematic case series of patients with ODLURO, further refining the mutational and phenotypic spectrum of this not-so-rare syndrome.All data relevant to the study are included in the article or uploaded as supplementary information. ER -