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Objectives Monogenic lupus is a rare but severe form of lupus, commonly affecting children with very early disease onset, high disease activity, and atypical clinical manifestations. With availability of next-generation sequencing, single-gene defects involving innate and adaptive immune pathways have been identified in patients presenting with lupus or lupus-like phenotypes.To describe the clinical characteristics, immunological findings, genetic spectrum, treatment approaches, and outcomes of pediatric patients diagnosed with monogenic lupus.Methods This retrospective observational cohort study included pediatric patients with genetically confirmed monogenic lupus followed at a tertiary pediatric rheumatology center. All data were extracted from medical records. Organ involvement was classified c using standard definitions. Patients were assessed according to the SLICC 2021 and ILE classification criteria. Treatment modalities, including hydroxychloroquine, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biologic therapies, JAK inhibitors, and intensive care interventions, were recorded. Disease activity status and mortality were evaluated at the last follow-up visit. Descriptive statistics were used for analysis.Results Seventeen pediatric patients with monogenic lupus caused by nine disease-causing genes were identified; 70.6% were female. The median age at symptom onset was 24 months, whereas the median age at diagnosis was 109 months, indicating a marked diagnostic delay. Consanguinity and a positive family history were each present in 64.7% of patients. Cutaneous involvement was the most frequent manifestation (88.2%), followed by musculoskeletal (47.1%), hematological (35.3%), neurological (29.4%), and renal involvement (29.4%). Four patients presented with MAS at diagnosis, all requiring pediatric intensive care admission. ANA positivity was observed in 88.2% and anti-dsDNA positivity in 52.9%. Eight patients fulfilled SLICC 2021 criteria, while nine met ILE criteria. During follow-up, hydroxychloroquine was used in 14 patients, csDMARDs in 9, JAK inhibitors in 10, and rituximab in 4. At last visit, 10 patients had chronic active disease, 5 were inactive, and 2 had died, corresponding to a mortality rate of 11.8%.Conclusions Pediatric monogenic lupus is characterized by very early onset, significant diagnostic delay, severe multisystem involvement, frequent MAS, and substantial treatment burden, highlighting the need for early genetic evaluation and individualized, precision-based management strategies.