Juvenile Myelomonocytic Leukemia in a Child with Underlying Mutations in Neurofibromatosis Type 1 and FLT3 Genes: A Case Report

Background: Juvenile myelomonocytic leukemia (JMML) is known to be associated with certain genetic variants involved in the RAS pathway. We describe a child with JMML associated with Neurofibromatosis Type 1 ( NF1 ) variant. Clinical Description: A 3-year-old boy presented with chronic, progressive abdominal distension for 1.5 years associated with acute-onset fever. On examination, he was pale, malnourished, with massive hepatosplenomegaly and multiple café-au-lait spots over the trunk and abdomen. Management and Outcome: Investigations revealed marked leukocytosis with a left shift including myeloblasts and monoblasts, along with monocytosis, with increased lactate dehydrogenase (1260 IU/l). Abdominal ultrasound showed hepatosplenomegaly without lymphadenopathy. Bone marrow was hypercellular, with increased myeloid: erythroid ratio and approximately 18%–22% blasts. High-performance liquid chromatography revealed elevated fetal hemoglobin (22%). Whole-exome sequencing identified a biallelic likely pathogenic duplication variant in NF1 gene, along with a variant of uncertain significance in FLT3 gene. Along with supportive care, hydroxyurea and 6-mercaptopurine were started, later supplemented with azacytidine and sorafenib. Over the next 12 weeks, condition improved, peripheral counts stabilized, organomegaly regressed, and the child was referred for stem cell transplantation. Conclusion: Chronic progressive hepatosplenomegaly, with pallor with absolute monocytosis could be due to JMML. A thorough clinical examination is required to check for the presence of café-au-lait spots which may indicate underlying NF1 gene variant as a driver of JMML.