One mutation, divergent journeys: expanding the clinical spectrum of homozygous <i>SAMHD1</i> deficiency in childhood

Homozygous SAMHD1 deficiency demonstrates striking phenotypic heterogeneity in childhood, extending beyond classical AGS. SAMHD1 mutations should be considered in children with unexplained systemic inflammation, even in the absence of typical neuroimaging findings. Clinical responses to JAK inhibition across diverse phenotypes support a shared interferon-driven pathogenesis and highlight the value of early genetic diagnosis to guide targeted therapy.