Background: Malformations of cortical development (MCDs) can lead to peculiar neuroradiological patterns and clinical presentations (i.e., seizures, cerebral palsy, and intellectual disability) according to the specific genetic pathway of the brain development involved; and yet a certain degree of phenotypic heterogeneity exists even when the same gene is affected. Here we report a man with an malformations of cortical development extending beyond occipital lobes associated with a novel stop-gain variant in LAMC3. Case presentation: The patient is a 28-year-old man suffering from drug-resistant epilepsy and moderate intellectual disability. He underwent a brain magnetic resonance imaging showing polymicrogyria involving occipital and temporal lobes bilaterally. After performing exome sequencing, a novel stop-gain variant in LAMC3 (c.3871C>T; p. Arg1291*) was identified. According to the cortical alteration of the temporal regions, temporal seizures were detected; instead, the patient did not report occipital seizures. Different pharmacological and non-pharmacological interventions (i.e., vagus nerve stimulation) were unsuccessful, even though a partial seizure reduction was obtained after cenobamate administration. Conclusion: Our case report confirms that variants of a gene known to be related to specific clinical and neuroradiological pictures can unexpectedly lead to new phenotypes involving different areas of the brain.
LAMC3 case report; cortical malformations; epilepsy; exome sequencing; genetic mutations.
Copyright © 2023 Falcicchio, Riva, La Neve, Iacomino, Lastella, Suppressa, Sciruicchio, Trojano and Striano.
Conflict of interest statement
GF received consultancy fee from Angelini Pharma. AR has received honoraria from Kolfarma s. r.l, Proveca Pharma Ltd., and PTC Therapeutics. PS has served on a scientific advisory board for the Italian Agency of the Drug (AIFA); has received honoraria from GW pharma, Kolfarma s. r.l., Proveca Pharma Ltd., and Eisai Inc.; and has received research support from the Italian Ministry of Health and Fondazione San Paolo. MT has served on scientific Advisory Boards for Biogen, Novartis, Roche, Merck, and Genzyme; has received speaker honoraria from Biogen Idec, Merck, Roche, Teva, Sanofi-Genzyme, and Novartis; and has received research grants for her Institution from Biogen Idec, Merck, Roche, and Novartis. AN has received speaker’s or consultancy fees or travel support from Eisai, Mylan, Sanofi, Bial, GW, UCB Pharma, Arvelle Therapeutics, Angelini Pharma and Neuraxpharma. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.