Background: Thrombocytopenia-absent radius (TAR) syndrome is a rare congenital disorder characterized by bilateral radial aplasia with preserved thumbs and early-onset thrombocytopenia. While hematologic and skeletal abnormalities are hallmarks of the condition, its association with hematologic malignancies is exceedingly rare, with only a few reported cases of leukemia. Juvenile myelomonocytic leukemia (JMML) is an uncommon pediatric myelodysplastic/myeloproliferative neoplasm frequently linked to RAS pathway mutations. The co-occurrence of JMML in a patient with TAR syndrome has not been previously documented. Case Presentation: We report the case of a male infant diagnosed with TAR syndrome based on clinical features and molecular confirmation of a homozygous RBM8A c.-21G>A mutation. The patient presented initially with persistent thrombocytopenia, skeletal deformities, and neonatal sepsis-like symptoms. At two years of age, he developed pancytopenia and progressive splenomegaly. Bone marrow examination and molecular studies confirmed JMML with a pathogenic NF1 mutation. He underwent successful haploidentical hematopoietic stem cell transplantation (HSCT) from a sibling donor, following a conditioning regimen of melphalan, treosulfan, cyclophosphamide, and anti-thymocyte globulin. The patient achieved full donor chimerism and hematologic remission with stable engraftment. Conclusion: This case represents, to our knowledge, one of the very few—if not the first—reported instances of successful HSCT for JMML in a patient with TAR syndrome. It underscores the importance of vigilant surveillance in TAR patients for potential malignant transformation and demonstrates the curative potential of HSCT in complex congenital and hematologic overlap syndromes.
