A Novel Splice Variant Expands Thelamc3-Associated Cortical Phenotype To Frontal Only Polymicrogyria And Adult-Onset Epilepsy

Bi-allelic loss-of-function variants inLAMC3, encoding extracellular matrix protein laminin gamma 3, represent a rare cause of occipital polymicrogyria with epilepsy, developmental delay and cognitive impairment. So far, only five families have been reported. We now identified a novel, homozygous splice variant inLAMC3in an individual with an unusual manifestation of cortical malformation. She presented with polymicrogyria in the frontal but not the occipital lobes, with adult-onset seizures and normal psychomotor development and cognition. Additionally, ictal asystole, requiring implantation of a pacemaker, and nonepileptic seizures occurred. This case expands the spectrum ofLAMC3-associated cortical malformation phenotypes to frontal only polymicrogyria and adult-onset of epilepsy.