RT Journal Article
SR Electronic
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
FD BMJ Publishing Group Ltd
SP 697
OP 705
DO 10.1136/jmedgenet-2020-107470
VO 59
IS 7
A1 Velmans, Clara
A1 O'Donnell-Luria, Anne H
A1 Argilli, Emanuela
A1 Tran Mau-them, Frederic
A1 Vitobello, Antonio
A1 Chan, Marcus CY
A1 Fung, Jasmine Lee-Fong
A1 Rech, Megan
A1 Abicht, Angela
A1 Aubert Mucca, Marion
A1 Carmichael, Jason
A1 Chassaing, Nicolas
A1 Clark, Robin
A1 Coubes, Christine
A1 Denommé-Pichon, Anne-Sophie
A1 de Dios, John Karl
A1 England, Eleina
A1 Funalot, Benoit
A1 Gerard, Marion
A1 Joseph, Maries
A1 Kennedy, Colleen
A1 Kumps, Camille
A1 Willems, Marjolaine
A1 van de Laar, Ingrid M B.H
A1 Aarts-Tesselaar, Coranne
A1 van Slegtenhorst, Marjon
A1 Lehalle, Daphné
A1 Leppig, Kathleen
A1 Lessmeier, Lennart
A1 Pais, Lynn S
A1 Paterson, Heather
A1 Ramanathan, Subhadra
A1 Rodan, Lance H
A1 Superti-Furga, Andrea
A1 Chung, Brian H.Y.
A1 Sherr, Elliott
A1 Netzer, Christian
A1 Schaaf, Christian P
A1 Erger, Florian
YR 2022
UL http://jmg.bmj.com/content/59/7/697.abstract
AB 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.