Novel LAMC3 pathogenic variant enriched in Finnish population causes malformations of cortical development and severe epilepsy.
agyria (HPO 0031882)
atonic seizure (HPO 0010819)
atypical absence seizure (HPO 0007270)
atypical absence status epilepticus (HPO 0011151)
bilateral tonic–clonic seizure (HPO 0002069)
epileptic spasm (HPO 0011097)
focal‐onset seizure (HPO 0007359)
pachygyria (HPO 0001302)
polymicrogyria (HPO 0002126)
tonic seizure (HPO 0032792)
Journal
Epileptic disorders : international epilepsy journal with videotape
ISSN: 1950-6945
Titre abrégé: Epileptic Disord
Pays: United States
ID NLM: 100891853
Informations de publication
Date de publication:
17 May 2024
17 May 2024
Historique:
revised:
30
04
2024
received:
01
12
2023
accepted:
05
05
2024
medline:
17
5
2024
pubmed:
17
5
2024
entrez:
17
5
2024
Statut:
aheadofprint
Résumé
Recessive LAMC3 mutations are recognized to cause epilepsy with cortical malformations characterized by polymicrogyria and pachygyria. The objective of this study was to describe the clinical picture and epilepsy phenotype of four patients with a previously undescribed LAMC3 variant. All epilepsy patients treated in Kuopio Epilepsy Center (located in Kuopio, Finland) are offered the possibility to participate in a scientific study investigating biomarkers in epilepsy (Epibiomarker study). We have collected a comprehensive database of the study population, and are currently re-evaluating our database regarding the patients with developmental and/or epileptic encephalopathy (DEE). If the etiology of epilepsy remains unknown in the clinical setting, we are performing whole exome sequencing to recognize the genetic causes. Among our study population of 323 DEE patients we recognized three patients with similar homozygous LAMC3 c.1866del (p.(Phe623Serfs*10)) frameshift variant and one patient with a compound heterozygous mutation where the same frameshift variant was combined with an intronic LAMC3 c.4231-12C>G variant on another allele. All these patients have severe epilepsy and either bilateral agyria-pachygyria or bilateral polymicrogyria in their clinical MRI scanning. Cortical malformations involve the occipital lobes in all our patients. Epilepsy phenotype is variable as two of our patients have DEE with epileptic spasms progressing to Lennox-Gastaut syndrome and intellectual disability. The other two patients have focal epilepsy without marked cognitive deficit. The four patients are unrelated. LAMC3 c.1866del p.(Phe623Serfs*10) frameshift variant is enriched in the Finnish population. Only a few patients with epilepsy caused by LAMC3 homozygous or compound heterozygous mutations have been described in the literature. To our knowledge, the variants discovered in our patients have not previously been published. Clinical phenotype appears to be more varied than previously assumed and patients with a milder phenotype and normal cognition have probably remained unrecognized.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Saastamoinen Foundation
Organisme : Vaajasalo Foundation
Organisme : Finnish Government Research Funding
Informations de copyright
© 2024 The Author(s). Epileptic Disorders published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.
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