Elif Kucuk, Fatih Haslak
Trends in Pediatrics - 2025;6(3):123-134
Type 1 interferonopathies are rare genetic disorders characterized by abnormal type 1 interferon (IFN) signaling. They cause chronic inflammation and multisystemic symptoms typically present in early childhood. Neurological, dermatological, and musculoskeletal features are common and often resistant to conventional therapies. Mutations in genes involved in nucleic acid sensing, degradation, proteasome function, and IFN signaling lead to the accumulation of self-deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) in the cytoplasm and a sustained type 1 IFN response, causing tissue damage and autoimmunity. This group includes various syndromes, such as Aicardi-Goutières syndrome (AGS), STING-associated vasculopathy (SAVI), and COPA syndrome. Diagnosis involves clinical evaluation, IFN signature analysis, and genetic testing. Treatment aims to modulate the IFN response by using JAK inhibitors, anti-IFN antibodies, and reverse transcriptase inhibitors. However, these therapies are not curative and have limited efficacy. Further research is needed to develop targeted treatments and improve outcomes, and a multidisciplinary management approach is essential because of the complexity and rarity of these disorders.
