Summary

STING-associated vasculopathy with onset in infancy (SAVI) is a rare monogenic type I interferonopathy that may present with heterogeneous clinical manifestations and mimic common inflammatory disorders of childhood. We report the first familial case of SAVI in Israel, affecting a father and daughter carrying an identical pathogenic gain-of-function TMEM173 variant. The daughter initially presented with features fulfilling criteria for rheumatoid factor-positive juvenile idiopathic arthritis (JIA), later developing growth failure and progressive interstitial lung disease. In contrast, the father developed adolescent-onset inflammatory arthritis, subsequently lung disease, and a severe infectious neurological complication during treatment. This case highlights marked intrafamilial phenotypic variability, the diagnostic challenges posed by atypical inflammatory arthritis and the importance of genetic testing in treatment-refractory or systemic disease. Our findings underscore both the benefits and limitations of JAK inhibition in SAVI, particularly with respect to pulmonary disease and growth outcomes.