A 1.5-year-old boy presented to us with a history of normal growth and developmental parameters until 6 months of age. However, at 7 months of age, he developed multiple types of seizures consisting initially of complex febrile seizures, followed by afebrile seizures. Multifocal clonic, generalized tonic–clonic, and myoclonic (multifocal and generalized) were the evolving seizure types. He had truncal hypotonia, but his appendicular hypotonia progressed to hypertonia over the next few months and further to decorticate posturing. Brain magnetic resonance imaging (MRI) showed generalized atrophy, predominantly frontotemporal, without any focal signal abnormalities or contrast enhancement. Computed tomography (CT) showed speckled calcification in subcortical white matter. Electroencephalogram showed bilateral frontotemporal epileptiform discharges with secondary generalization. His cerebrospinal fluid had normal cytology and biochemical results but was positive for anti–gamma aminobutyric acid B antibodies. Whole exome sequencing showed likely pathogenic, novel autosomal recessive homozygous variation of NRROS gene on chromosome 3 [c.1487G > A (p.Trp496Ter)], which impairs the functioning of anti-inflammatory cytokine transforming growth factor beta, resulting in a proinflammatory state within the central nervous system and thereby promoting autoimmune encephalitis. Parental Sanger sequencing validated the variation in both his parents. He was treated with both pulse methylprednisolone (30 mg/kg/day for 5 days) and intravenous immunoglobulin (2 g/kg), followed by slowly tapering of oral prednisolone and monthly intravenous immunoglobulin infusion (1 g/kg). There was significant reduction in seizure frequency and disappearance of epileptiform discharges from the electroencephalogram. However, the motor and cognitive improvement did not occur, and he had microcephaly and growth failure at the last follow-up. This is the 11th case report of neurodegeneration associated with NRROS gene variations, but the first report of autoimmune encephalitis being triggered by the variation in a child.