<i><scp>BRAT</scp>1</i> encephalopathy: a recessive cause of epilepsy of infancy with migrating focal seizures

Abstract

Epilepsy of infancy with migrating focal seizures ( EIMFS ), one of the most severe developmental and epileptic encephalopathy syndromes, is characterized by seizures that migrate from one hemisphere to the other. EIMFS is genetically heterogeneous with 33 genes. We report five patients with EIMFS caused by recessive BRAT 1 variants, identified via next generation sequencing. Recessive pathogenic variants in BRAT 1 cause the rigidity and multifocal seizure syndrome, lethal neonatal with hypertonia, microcephaly, and intractable multifocal seizures. The epileptology of BRAT 1 encephalopathy has not been well described. All five patients were profoundly impaired with seizure onset in the first week of life and focal seizure migration between hemispheres. We show that BRAT 1 is an important recessive cause of EIMFS with onset in the first week of life, profound impairment, and early death. Early recognition of this genetic aetiology will inform management and reproductive counselling.