Neurodegeneration, Intracranial Calcifications, Microcephaly and Drug-Resistant Epilepsy Caused by a Novel Homozygous Missense Variant in the NRROS Gene: A Case Report.

Abstract

Negative regulator of reactive oxygen species (NRROS)-related microgliopathy (MIM# 618875) is a rare autosomal recessive neurodegenerative disorder. This case report describes a Saudi Arabian child with a novel homozygous NRROS variant, NM_198565.2: c.257T>C (p.Leu86Pro) presenting with drug-resistant epilepsy, rapid developmental regression, microcephaly, dystonia, and intracranial calcifications. Neuroimaging revealed bilateral intracranial calcifications, generalized brain volume loss, and connatal cysts; EEG showed a slow, suppressed background with multifocal epileptiform discharges. The variant is predicted to be deleterious by multiple in silico tools, suggesting a pathogenic effect on microglial function. This case underscores the importance of considering NRROS-related microgliopathy in children with early-onset neurodegeneration, drug-resistant epilepsy, and intracranial calcifications, enabling targeted genetic testing, diagnosis, and counseling.