Long-term survival in MIRAGE syndrome: Insights into systemic manifestations and management with review of literature

MIRAGE syndrome is a multisystemic disorder with a poor prognosis, caused by gain-of-function mutations in the SAMD9 gene. To date, no comprehensive reports on the systemic manifestations and management of MIRAGE syndrome in adult survivors. Here, we present the case of a 22-year-old man long-term survivor of MIRAGE syndrome with a wide range of clinical presentations and complications. From the neonatal period, he exhibited the core features of MIRAGE syndrome: myelodysplasia, recurrent infection, growth retardation, adrenal hypoplasia, atypical external genitalia, and enteropathy. Additionally, brain imaging at 5 years of age revealed new findings, including basal ganglia and white matter lesions, calcification, infarction, and ventricular enlargement. Subsequently, proteinuria was detected at 6 years of age, which gradually progressed to end-stage renal disease. At 21 years of age, he received a living-donor kidney transplant from his father, the first transplant reported for this syndrome. Genetic analysis identified a congenital SAMD9 mutation (p.Gln1286Lys) and three acquired reversion mutations. These revision mutations mitigated his hematologic complications but did not fully restore immune function. In addition to persistent immunological and endocrine dysfunction, the patient has developed progressive neurological and metabolic abnormalities over time. Multidisciplinary management, including prophylactic intravenous immunoglobulin therapy, renal replacement therapy and transplantation, and endocrine support, was provided and may have contributed to his long-term survival. This case highlights the evolving clinical spectrum of MIRAGE syndrome and underscores the importance of careful longitudinal monitoring for patients who survive beyond early childhood.