[P3-71] Familial Cases of Progressive Myoclonic Epilepsy with KCNC1 mutation Inherited from Asymptomatic Mosaic Mother
Progressive myoclonic epilepsies(PMEs) are genetically inherited disorders characterized by myoclonus, generalized tonic-clonic(GTC) seizures, and progressive neurological deterioration, resulting in demetia, ataxia, and tremor. To date, many genetic causes of PME have been revealed.
A 12-year-old boy visited our clinic with chief complaints of worsening tremor, myoclonus, and three events of GTC seizure. He was born uneventfully, and had no familial history of neurologic or genetic disease. On neurologic exam, he revealed abnormal cerebellar function and his brain MRI showed atrophy of pons and both cerebellum. Electroencephalography showed frequent bursts of generalized spike and wave complexes with background slowing. He was prescribed valproic acid for seizure control. Genetic tests for dentatorubral-pallidoluysian atrophy, spinocerebellar ataxia, and EPM2A gene were negative. Through whole exom sequencing, we figured out pathogenic variant of c.959G>A (p.Arg320His) in KCNC1, which was confirmed by sanger sequencing. In trio whole exom sequencing, we found that mother had mosaicism of same variant. During the work-up, his younger brother noted two events of generalized tonic-clonic seizures, who also has same variant of proband. Patient’s seizures and tremor were well controlled with clonazepam and valproic acid. Recently, Muona et al. reported de novo mutation c.959G>A (p.Arg320His) in KCNC1 in 11 of 84 patients (13%) with PME. Our cases are the second report of PME with recurrent KCNC1 mutation and first familial cases with the mother having somatic mosaicism.
A 12-year-old boy visited our clinic with chief complaints of worsening tremor, myoclonus, and three events of GTC seizure. He was born uneventfully, and had no familial history of neurologic or genetic disease. On neurologic exam, he revealed abnormal cerebellar function and his brain MRI showed atrophy of pons and both cerebellum. Electroencephalography showed frequent bursts of generalized spike and wave complexes with background slowing. He was prescribed valproic acid for seizure control. Genetic tests for dentatorubral-pallidoluysian atrophy, spinocerebellar ataxia, and EPM2A gene were negative. Through whole exom sequencing, we figured out pathogenic variant of c.959G>A (p.Arg320His) in KCNC1, which was confirmed by sanger sequencing. In trio whole exom sequencing, we found that mother had mosaicism of same variant. During the work-up, his younger brother noted two events of generalized tonic-clonic seizures, who also has same variant of proband. Patient’s seizures and tremor were well controlled with clonazepam and valproic acid. Recently, Muona et al. reported de novo mutation c.959G>A (p.Arg320His) in KCNC1 in 11 of 84 patients (13%) with PME. Our cases are the second report of PME with recurrent KCNC1 mutation and first familial cases with the mother having somatic mosaicism.