title: Familial neuromyelitis optica.
abstract: BACKGROUND
  Detection of aquaporin-4-specific immunoglobulin G (IgG) has expanded the spectrum of neuromyelitis optica (NMO). Rare reports of familial aggregation have suggested a component of genetic susceptibility but these reports mostly antedated the discovery of the NMO-IgG biomarker and recently updated diagnostic criteria.
  
  
  METHODS
  We report a case series describing the demographic, clinical, neuroimaging, and NMO-IgG serologic status of 12 multiplex NMO pedigrees with a total of 25 affected individuals.
  
  
  RESULTS
  Twenty-one patients (84%) were women. Families were Asian (n = 5), Latino (n = 4), white (n = 1), or African (n = 2). Apparent transmission was either maternal (n = 5) or paternal (n = 2). In 1 family, 3 individuals had NMO; in the others, 2 individuals were affected. Sibling pairs (n = 6), parent-child (n = 4), and aunt-niece (n = 3) pairs were observed. Nineteen patients (76%) were NMO-IgG positive. Twelve (48%) had clinical or serologic evidence of another autoimmune disease. Familial occurrence of NMO occurs in approximately 3% of patients with well-established diagnosis of NMO.
  
  
  CONCLUSIONS
  A small proportion of patients with NMO have relatives with this condition, but familial occurrence is more common than would be expected from its frequency in the general population. Familial NMO is indistinguishable from sporadic NMO based on clinical symptoms, age at onset, sex distribution, and frequency of NMO-IgG detection. One or 2 generations were affected and affected individuals represented a small fraction of family members. Taken together, these data suggest complex genetic susceptibility in NMO.
authors.affiliation: Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: M
authors.initials: M
authors.lastname: Matiello
authors.forename: H J
authors.initials: HJ
authors.lastname: Kim
authors.forename: W
authors.initials: W
authors.lastname: Kim
authors.forename: D G
authors.initials: DG
authors.lastname: Brum
authors.forename: A A
authors.initials: AA
authors.lastname: Barreira
authors.forename: D J
authors.initials: DJ
authors.lastname: Kingsbury
authors.forename: G T
authors.initials: GT
authors.lastname: Plant
authors.forename: T
authors.initials: T
authors.lastname: Adoni
authors.forename: B G
authors.initials: BG
authors.lastname: Weinshenker
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D051401:Aquaporin 4 / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005190:Family; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D008297:Male; D008875:Middle Aged; D009471:Neuromyelitis Optica / Q000208:ethnology* / Q000235:genetics*; D010375:Pedigree; D015995:Prevalence; D044469:Racial Groups / Q000706:statistics & numerical data*; D016036:Seroepidemiologic Studies
chemical_list: C496030:AQP4 protein, human; D051401:Aquaporin 4; D015415:Biomarkers; D007074:Immunoglobulin G