To discuss a child with a history of Noonan syndrome (PTPN11 mutation) and spontaneously regressing juvenile myelomonocytic leukemia (JMML) in infancy now with aquaporin-4 (AQP4) antibody positive neuromyelitis optica spectrum disorder (NMOSD) at age seven.

Noonan syndrome is a genetic condition affecting the RAS pathway caused by multiple genetic mutations and associated with many manifestations, including the rare leukemia subtype JMML. Systemic autoimmunity and RAS-associated leukoproliferative disorders have been associated with JMML, and this is suggestive of an autoimmune phenotype in RAS pathway dysfunction. MOG-antibody disease (MOGAD) has been reported in at least 2 patients with prior JMML. NMOSD is an autoimmune astrocytopathy caused by AQP4-antibodies (detectable in up to 80% of patients). However, NMOSD has not been associated with JMML in the literature.

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Our patient is a seven-year-old girl with Noonan syndrome (PTPN11 mutation) and spontaneously regressing JMML in infancy (which is associated with Noonan syndrome) who was admitted for pneumonia and then developed acute left-sided arm and leg weakness. She was found to have an enhancing internal capsule/brainstem lesion and positive AQP4 serum antibodies, consistent with a diagnosis of NMOSD. The patient received intravenous corticosteroids as well as rituximab induction. She received inpatient rehabilitation services and had good recovery. She was discharged without any long-term mobility aids or devices and is maintained on long-term rituximab. At seven-month follow-up, she had only mild left-sided hand grip weakness (4 out of 5 strength).

To our knowledge, no other cases have been reported of NMOSD patients who also had either juvenile myelomonocytic leukemia (JMML) or Noonan-associated myeloproliferative neoplasm. Since Noonan syndrome is a RASopathy and NMOSD is rare in the general population, more research is indicated to study the role of the RAS/MAPK pathway in the pathophysiology of NMOSD.