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O'Donnell-Luria-Rodan syndrome
- Source :
- Journal of Medical Genetics, 59(7), 697-705. BMJ Publishing Group, Journal of medical genetics, vol 59, iss 7, J Med Genet
- Publication Year :
- 2022
- Publisher :
- BMJ Publishing Group, 2022.
-
Abstract
- BackgroundO’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.MethodsAffected 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.ResultsWe 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.ConclusionOur 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.
- Subjects :
- 0301 basic medicine
Pediatrics
Autism Spectrum Disorder
behavioural
Autism
Medical and Health Sciences
0302 clinical medicine
Neurodevelopmental disorder
Intellectual disability
2.1 Biological and endogenous factors
Aetiology
Child
Exome
Genetics (clinical)
Pediatric
Genetics & Heredity
Syndrome
Biological Sciences
Mental Health
Autism spectrum disorder
Cohort
medicine.symptom
medicine.medical_specialty
Genetic counseling
Intellectual and Developmental Disabilities (IDD)
human genetics
Article
03 medical and health sciences
Seizures
Clinical Research
Intellectual Disability
Exome Sequencing
medicine
Genetics
Humans
business.industry
Human Genome
Macrocephaly
Neurosciences
medicine.disease
Human genetics
Megalencephaly
Brain Disorders
030104 developmental biology
Neurodevelopmental Disorders
Congenital Structural Anomalies
mutation
business
030217 neurology & neurosurgery
genetic counselling
Subjects
Details
- Language :
- English
- ISSN :
- 14686244 and 00222593
- Volume :
- 59
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Journal of Medical Genetics
- Accession number :
- edsair.doi.dedup.....77c510a325c2e94649d338b1b96fa5aa