Epilepsy of Infancy With Migrating Focal Seizures (EIMFS): Expansion of Clinical Phenotypic And Genotypic Spectra

EIMFS is a rare early infantile epileptic encephalopathy with unknown etiology and poor prognosis. This study included 36 patients who were diagnosed with EIMFS. 17/36 cases had causative variants across 11 genes, including 6 novel EIMFS genes: PCDH19 , ALDH7A1 , DOCK6 , PRRT2 , ALG1 and ATP7A . 13/36 patients had ineffective seizure control, 14/36 patients had severe retardation and 6/36 patients died. Of them, the genes for ineffective seizure control, severe retardation or death include KCNT1 , SCN2A , SCN1A , ALG1 , ATP7A and WWOX . 17 patients had abnormal MRI, of which 8 had ineffective seizure control, 7 had severe retardation and 4 died. 13 patients had hypsarrhythmia, of which 6 had ineffective seizure control, 6 had severe retardation and 2 died. Also, 7 patients had burst suppression, of which 1 had ineffective seizure control, 3 had severe retardation and 3 died. This study is the first to report that ALDH7A1 , ATP7A , DOCK6 , PRRT2 , ALG1 , and PCDH19 mutations cause the phenotypic spectrum of EIMFS to expand the genotypic spectrum. The genes KCNT1 , SCN2A , SCN1A , ALG1 , ATP7A and WWOX may be associated with poor prognosis. The patients presenting with MRI abnormalities, hypsarrhythmia and burst suppression in EEG may be associated with poor prognosis.