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Article Dans Une Revue Journal of Medical Genetics Année : 2022

O’Donnell-Luria-Rodan syndrome: description of a second multinational cohort and refinement of the phenotypic spectrum

1 Institute of Human Genetics [Cologne]
2 Manton Center for Orphan Disease Research
3 Program in Medical and Population Genetics, Broad Institute of Harvard and MIT
4 UCLA - University of California [Los Angeles]
5 Department of Neurology [San Francisco, CA, USA]
6 UF6254 - Unité fonctionnelle d' Innovation en Diagnostic Génomique des Maladies Rares (CHU Dijon)
7 PADYS - Physiopathologie des Dyslipidémies (CTM UMR 1231)
8 FHU TRANSLAD (CHU de Dijon)
9 Department of Paediatrics and Adolescent Medicine [HKU]
10 BCM - Baylor College of Medicine
11 LMU - Ludwig-Maximilians University [Munich]
12 Service Génétique Médicale [CHU Toulouse]
13 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
14 Department of Medical Genetics and Metabolism
15 Pediatrics Specialty Clinics
16 CHU Montpellier
17 Department of Medical Genetics
18 Center for Mendelian Genomics and Medical and Population Genetics Program
19 Department of Clinical Genetics
20 Service de Génétique [CHU Caen]
21 BIOTARGEN - Biologie, génétique et thérapies ostéoarticulaires et respiratoires
22 Division of Genetic Medicine
23 Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier]
24 DCG - Department of Clinical Genetics
25 Department of Pediatrics
26 Genetic Services
27 Metabolism Initiative and Program in Medical and Population Genetics
28 Division of Genetics and Program in Genomics, The Manton Center for Orphan Disease Research,
29 Department of Neurology, Children's Hospital [Boston]
30 Department of Molecular and Human Genetics
31 Institute of Human Genetics
32 Jan and Dan Duncan Neurological Research Institute
Clara Velmans
Christine Coubes
  • Fonction : Auteur
Daphné Lehalle
Kathleen Leppig
  • Fonction : Auteur
Andrea Superti-Furga
Florian Erger

Résumé

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.

Dates et versions

hal-04453172 , version 1 (12-02-2024)

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Citer

Clara Velmans, Anne O'Donnell-Luria, Emanuela Argilli, Frederic Tran Mau-Them, Antonio Vitobello, et al.. O’Donnell-Luria-Rodan syndrome: description of a second multinational cohort and refinement of the phenotypic spectrum. Journal of Medical Genetics, 2022, 59 (7), pp.697-705. ⟨10.1136/jmedgenet-2020-107470⟩. ⟨hal-04453172⟩
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