Efficacy of azacitidine and trametinib against leptomeningeal melanosis associated with congenital melanocytic nevus syndrome

Congenital melanocytic nevus syndrome is a disorder characterized by postzygotic, mosaic NRAS Proto-Oncogene, GTPase mutations. Clinical manifestations include melanotic skin lesions and, optionally, central nervous system melanosis typically noted during early infancy. Affected individuals have an increased risk of developing malignant melanomas at an early age. We report a child with neurocutaneous melanosis due to this syndrome, who had innumerable nevi at birth and diffuse leptomeningeal thickening. He developed increased intracranial pressure at 4 weeks of age. The nucleoside analogue azacitidine and the Mitogen-Activated Protein Kinase, Kinase inhibitor trametinib were started at 6 weeks of age resulting in rapid reduction of leptomeningeal thickening. At 53 months of age, the patient still takes trametinib and has met all developmental milestones. There has been no evidence of melanoma, and he exhibits minimal residual leptomeningeal changes. To our best knowledge, this is the first child with this syndrome who has undergone successful therapy to reduce leptomeningeal thickening.