Overlapping Aicardi–Goutières and Singleton–Merten syndromes with a heterozygous gain-of-function mutation in IFIH1 mimicking juvenile idiopathic arthritis

Abstract

Aicardi–Goutières syndrome (AGS) and Singleton–Merten syndrome (SMS) are associated with heterozygous gain-of-function mutations in the interferon induced with helicase C domain 1 (IFIH1) gene. Recent reports describe patients exhibiting overlapping clinical features of AGS and SMS, along with marked type I interferon (IFN) overproduction. However, the clinical characteristics and optimal treatment strategies remain unclear. Herein, we present a patient with overlapping clinical features of AGS and SMS who was initially misdiagnosed with juvenile idiopathic arthritis. Surgical soft tissue release of the hip and knee joints improved joint deformities and spastic paraparesis. Baricitinib effectively treated refractory chilblains and skin ulcers while reducing IFN-stimulated gene overexpression in peripheral blood. These findings indicate that baricitinib may be a safe and effective treatment for AGS–SMS overlap, and surgical intervention may be a viable option for refractory joint deformities with spastic paraparesis.