Denis Graber1, Eri Imagawa2, Noriko Miyake3, Naomichi Matsumoto4, Satoko Miyatake5, Marianne Graber6, Bertrand Isidor7. 1. Département de Médecine Infantile, Groupe Hospitalier Littoral Atlantique, Centre Hospitalier Saint-Louis, Rue du Dr Schweitzer, 17000 La Rochelle, France. Electronic address: denis.graber@ch-larochelle.fr. 2. Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: eri.imagawa@mssm.edu. 3. Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan. Electronic address: nmiyake@yokohama-cu.ac.jp. 4. Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan. Electronic address: naomat@yokohama-cu.ac.jp. 5. Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; Clinical Genetics Department, Yokohama City University Hospital, Yokohama, Kanagawa 236-0004, Japan. Electronic address: miyatake@yokohama-cu.ac.jp. 6. UMR 7266 LIENSs, CNRS La Rochelle Université Bâtiment Marie Curie, Avenue Michel Crépeau, 17042 La Rochelle Cedex 1, France. Electronic address: mgraber@univ-lr.fr. 7. Service de génétique médicale, Unité de Génétique clinique, CHU de Nantes, Hôtel Dieu, 1 place Alexis Ricordeau, 44093 Nantes, CEDEX 1, France. Electronic address: bertrand.isidor@chu-nantes.fr.
Abstract
BACK GROUND: Polymicrogyria is a malformation of cortical development with overfolding of the cerebral cortex and abnormal cortical layering. Polymicrogyria constitutes a heterogenous collection of neuroimaging features, neuropathological findings, and clinical associations, and is due to multiple underlying etiologies. In the last few years, some glutamate and sodium channelopathies have been associated with cortical brain malformations such as polymicrogyria. The potassium calcium-activated channel subfamily M alpha 1 (KCNMA1) gene encodes each of the four alpha-subunits that make up the large conductance calcium and voltage-activated potassium channel "Big K+". KCNMA1-related channelopathies are associated with various neurological abnormalities, including epilepsy, ataxia, paroxysmal dyskinesias, developmental delay and cognitive disorders. CASE REPORT: We report the observation of a patient who presented since the age of two months with drug-resistant epilepsy with severe developmental delay initially related to bilateral asymmetric frontal polymicrogyria. Later, exome sequencing revealed a de novo heterozygous variation in the KCNMA1 gene (c.112delG) considered pathogenic. CONCLUSION: This first case of polymicrogyria associated with KCNMA1-related channelopathy may expand the phenotypic spectrum of KCNMA1-related channelopathies and enrich the recently identified group of developmental channelopathies with polymicrogyria.
BACK GROUND: Polymicrogyria is a malformation of cortical development with overfolding of the cerebral cortex and abnormal cortical layering. Polymicrogyria constitutes a heterogenous collection of neuroimaging features, neuropathological findings, and clinical associations, and is due to multiple underlying etiologies. In the last few years, some glutamate and sodium channelopathies have been associated with cortical brain malformations such as polymicrogyria. The potassium calcium-activated channel subfamily M alpha 1 (KCNMA1) gene encodes each of the four alpha-subunits that make up the large conductance calcium and voltage-activated potassium channel "Big K+". KCNMA1-related channelopathies are associated with various neurological abnormalities, including epilepsy, ataxia, paroxysmal dyskinesias, developmental delay and cognitive disorders. CASE REPORT: We report the observation of a patient who presented since the age of two months with drug-resistant epilepsy with severe developmental delay initially related to bilateral asymmetric frontal polymicrogyria. Later, exome sequencing revealed a de novo heterozygous variation in the KCNMA1 gene (c.112delG) considered pathogenic. CONCLUSION: This first case of polymicrogyria associated with KCNMA1-related channelopathy may expand the phenotypic spectrum of KCNMA1-related channelopathies and enrich the recently identified group of developmental channelopathies with polymicrogyria.