NRROS-associated Microgliopathy With Cerebral Calcification and Resistant Epilepsy: A Case Report

Background: The negative regulator of reactive oxygen species (NRROS) gene encodes a protein that functions as a general NRROS production in phagocytes. Reactive oxygen species (ROS) produced by phagocytes are essential for host defense, but excessive ROS can cause collateral tissue damage during inflammatory processes and therefore need to be tightly regulated. Microglia are tissue-resident macrophages that play essential roles in the development and homeostasis of the central nervous system. NRROS is associated with transforming growth factor beta-۱ (TGF-β۱) and anchors it to the cell surface. TGF-β۱ is essential for neural cell survival and for inhibiting induced microglial activation and associated inflammatory cytokine production. A deficiency in functional NRROS protein can lead to uncontrollable microglial activation by disrupting TGF-β۱’s inhibitory function. Microglial dysregulation causes neurological disease and cerebral calcification. Case Presentation: To the best of our knowledge, there are ۵ published case reports of biallelic NRROS variants that involve ۱۲ patients in total. The manifestations described in these reports include refractory seizures, developmental regression, and hypotonia. In this case, we report an ۸-year-old boy with global developmental delay, refractory seizures, encephalopathy from early in life, and intracranial calcification due to a novel homozygous likely pathogenic mutation: c.۱۴۸۷delG (p.val۴۹۸phefs*۲) in the NRROS gene. Conclusions: A severe infantile-onset neurodegenerative disorder results from biallelic loss-of-function variants in the NRROS gene, and is characterized by intracranial calcification, neurodevelopmental regression, and refractory epilepsy that consists of febrile seizures first, followed by afebrile seizures.

کلیدواژه ها:

NRROS ، Microgliopathy ، Intracranial calcification ، Refractory seizures ، Case report