The epileptology of Wiedemann-Steiner syndrome: Electroclinical findings in five patients with KMT2A pathogenic variants

Ahmed N Sahly; Myriam Srour; Daniela Buhas; Ingrid E Scheffer; Kenneth A Myers

doi:10.1016/j.ejpn.2023.04.001

The epileptology of Wiedemann-Steiner syndrome: Electroclinical findings in five patients with KMT2A pathogenic variants

Eur J Paediatr Neurol. 2023 May:44:46-50. doi: 10.1016/j.ejpn.2023.04.001. Epub 2023 Apr 14.

Authors

Ahmed N Sahly¹, Myriam Srour², Daniela Buhas³, Ingrid E Scheffer⁴, Kenneth A Myers⁵

Affiliations

¹ Division of Neurology, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada; Department of Neurosciences, King Faisal Specialist Hospital & Research Centre, Jeddah, Saudi Arabia.
² Division of Neurology, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada; Research Institute of the McGill University Medical Centre, Montreal, Quebec, Canada; Department of Neurology and Neurosurgery, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
³ Division of Medical Genetics, Department of Specialized Medicine, McGill University Health Centre, Montreal, Quebec, Canada; Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
⁴ Epilepsy Research Centre, Department of Medicine, Austin Health, The University of Melbourne, Victoria, Australia; Murdoch Children's Research Institute and Department of Paediatrics, The University of Melbourne, Royal Children's Hospital, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia.
⁵ Division of Neurology, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada; Research Institute of the McGill University Medical Centre, Montreal, Quebec, Canada; Department of Neurology and Neurosurgery, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada. Electronic address: kenneth.myers@mcgill.ca.

PMID: 37075569
DOI: 10.1016/j.ejpn.2023.04.001

Abstract

Background: Wiedemann-Steiner Syndrome (WSTS) is a rare chromatinopathy caused by pathogenic variants in KMT2A. WSTS is characterized by neurodevelopmental disorders and distinct dysmorphic features. Epilepsy has been reported in only 33 individuals with WSTS, with only limited clinical details described.

Methods: We identified patients with pathogenic KMT2A variants and epilepsy, and performed thorough phenotyping.

Results: Five patients were identified, all of whom presented with developmental and epileptic encephalopathy (DEE). Epilepsy syndromes observed included Lennox-Gastaut syndrome [2], infantile epileptic spasms syndrome, and DEE with spike-wave activation in sleep. Seizure types observed included absence, generalized tonic-clonic, myoclonic, tonic, atonic, epileptic spasms, and focal seizures.

Conclusions: The spectrum of epilepsy phenotypes in patients with WSTS can be broad, but presentation is typically severe, usually involving a form of DEE.

Keywords: Continuous spike-wave in sleep; Developmental and epileptic encephalopathy; Infantile epileptic spasms syndrome; KMT2A; Lennox-gastaut syndrome; Wiedemann-Steiner syndrome.

MeSH terms

Electroencephalography
Epilepsies, Myoclonic* / genetics
Humans
Intellectual Disability*
Seizures
Spasm
Spasms, Infantile* / genetics

Supplementary concepts

Wiedemann Grosse Dibbern syndrome