Neuromyelitis optica spectrum disorder associated with Kabuki syndrome: First reported case and immunopathogenic considerations.

Abstract

Kabuki syndrome, caused by KMT2D or KDM6A mutations, is a multisystem disorder with immune dysregulation. Its association with aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder has not been reported. A 17-year-old male with autoimmune hypothyroidism presented with acute visual loss and was diagnosed with AQP4-IgG-positive optic neuritis. He received corticosteroids, plasma exchange, and rituximab, achieving full recovery and remaining relapse-free during follow-up. Genetic testing showed a likely pathogenic KMT2D variant. This case documents the first association between these conditions, where immune dysregulation, including FOXP3-dependent regulatory T-cell dysfunction and Th17-skewed inflammation, suggests a mechanistic link with implications for diagnosis and management.