Familial neuromyelitis optica spectrum disorders: Case series and systematic review

• Main Author: Wannaphut C.
• Other Authors: Mahidol University
• Format: Article
• Published: 2023
• Subjects: Neuroscience
• Online Access: https://repository.li.mahidol.ac.th/handle/123456789/81569

Background: Neuromyelitis optica spectrum disorders (NMOSD) is considered a complex multifactorial disorder. Most cases are sporadic, and familial NMOSD is assumed as a rare occurrence. However, few studies reported familial aggregation of the disorder. Objectives: To report familial NMOSD cases in Thailand and conduct a systematic review of familial NMOSD. Methods: A retrospective chart review of familial NMOSD patients at the university hospital was performed. Articles related to “genetic” and “NMOSD” were systematically searched and reviewed. We included NMOSD patients whose one or more relatives were diagnosed with the same disease or multiple sclerosis (MS). Data regarding demographics, clinical features, disease outcomes, and genetic testing were collected and analyzed using descriptive statistics. Results: We identified 6 familial cases from 165 NMOSD cases (3.6%) at our hospital and gathered 77 cases from a systematic review, totaling 83 cases from 40 families. The mean (SD) age at onset was 37.2 (18.0) years. Familial NMOSD involved 1–2 generations with mainly 2 affected individuals. The most common kinship pattern was siblingship in 21 families (52.5%). Initial syndromes were mostly optic neuritis and transverse myelitis. Serum aquaporin-4 IgG was positive in 79.7% of cases. Median number of relapses was 3 (range 1–26). Median expanded disability status scale in the last visit was 2 (range 0–8). Reported human leukocyte antigens (HLA) alleles shared between familial cases were HLA-A*01 and HLA-DRB1*03. Conclusion: Familial clustering of NMOSD is more common than would be expected in the general population. The demographic, clinical, and outcome profiles of familial cases were not different from sporadic cases. Certain specific HLA haplotypes were shared among familial cases. Our systematic review highlighted complex genetic predisposition to NMOSD.