Different clinical phenotypes of AQP4-IgG positive NMOSD in two first degree relatives.

Background: Aquaporin-4 antibody (AQP4-IgG)–positive neuromyelitis optica spectrum disorder (NMOSD) has not been reported in members of the same family in Sub Saharan Africa. We report the uncommon scenario in which a Ugandan middle aged HIV positive woman was diagnosed with AQP4-IgG positive NMOSD presenting with severe longitudinally extensive transverse myelitis one year after her HIV negative daughter had been diagnosed with AQP4-IgG positive NMOSD presenting with asymmetric bilateral moderately severe optic neuritis. We discuss pathogenic mechanisms that may underlie familial presentation of AQP4-IgG positive NMOSD. Case Presentation: Case 1 a 54-year-old female teacher with a 20-year history of HIV infection, who was virally suppressed on Tenofovir, Lamivudine and Dolutegravir-HAART regimen and presented with 8 months of progressive quadriparesis and urinary incontinence with a T6 sensory level. She had gadolinium enhancing longitudinally extensive transverse myelitis on MRI and was AQP4-IgG positive on serum studies. She received IV Methylprednisone 1g daily for 3 days as a pulse and was continued on tapering doses of oral Prednisone with maintenance doses of Azathioprine. She showed slow improvements in limb motor function. Her daughter, case 2, is a 35-year-old HIV negative nutritionist, independently ambulant, with no known comorbidities or precedent autoimmune disease. She presented 1 year before her mother's AQP4-IgG positive NMOSD diagnosis with 7 months history of bilateral visual loss of rapid onset, with gadolinium-enhancing optic nerves on Brain and orbit MRI, in keeping with bilateral optic neuritis. She was AQP4-IgG positive on serum studies. She stabilized on tapered doses of oral Prednisone and continues daily oral Azathioprine with moderate improvement in her vision and no further relapses. Conclusions: : We add to existing literature and hypothesize that NMOSD appears to show a complex genetic background. To our knowledge, this is the first report in Sub-Saharan Africa, of familial AQP4-IgG positive NMOSD presenting with clinical heterogeneity between first degree relatives. A better understanding of the pathogenic mechanisms involved, including genome wide studies for particular risk loci for familial NMOSD, will be pivotal for future preventative and therapeutic strategies.