Maria Salvado1, Merce Canela1, Jose Maria Ponseti1, Laura Lorenzo1, Cecilia Garcia1, Sonia Cazorla1, Gisela Gili1, Nuria Raguer1, Josep Gamez2. 1. Myasthenia Gravis Unit, Clinic of Neuromuscular Disorders and Rare Diseases, Neurology Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute, Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain. 2. Myasthenia Gravis Unit, Clinic of Neuromuscular Disorders and Rare Diseases, Neurology Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute, Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain. Electronic address: josepgamez.bcn@gmail.com.
Abstract
BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease caused by a failure of neuromuscular transmission. Familial clustering has been reported despiteMG usually manifesting as a sporadic condition presumed not to be inherited. Our study investigated the prevalence of FAMG in a Spanish cohort, characterizing their phenotype,antibody titres and thymus findings. MATERIAL/ METHODS: We investigated the presence of familial cases in 462 MG patients, characterizing by age and MGFA class at debut, quantitative MG score, antibody titres, MGFA post-intervention status and thymus pathology. RESULTS: Sixteen cases from8 unrelated pedigrees were identified. The prevalence of FAMG caseswas 3.46%.Mean age at onset was 57.8 ± 17.4 years (range=23–82). Distribution at debut was: 6 ocular, 4 IIa, 4IIb, 1 IIIa and 1 IIIb. Thymoma was identified in two of the 7 thymectomized individuals. CONCLUSIONS: The prevalence of FAMG in Spain is similar to other populations. Post-intervention status did not differ from sporadic autoimmune MG. As in other neuromuscular disorders, phenotype and inheritance heterogeneity are present in FAMG. In addition to the interfamilial heterogeneity observed, members of the same family affected with FAMG may even present different ages of onset, severity and thymus involvement. Further studies are necessary to clarify the role of genetic risk factors in this form of autoimmune MG.
BACKGROUND:Myasthenia gravis (MG) is an autoimmune disease caused by a failure of neuromuscular transmission. Familial clustering has been reported despiteMG usually manifesting as a sporadic condition presumed not to be inherited. Our study investigated the prevalence of FAMG in a Spanish cohort, characterizing their phenotype,antibody titres and thymus findings. MATERIAL/ METHODS: We investigated the presence of familial cases in 462 MGpatients, characterizing by age and MGFA class at debut, quantitative MG score, antibody titres, MGFA post-intervention status and thymus pathology. RESULTS: Sixteen cases from8 unrelated pedigrees were identified. The prevalence of FAMG caseswas 3.46%.Mean age at onset was 57.8 ± 17.4 years (range=23–82). Distribution at debut was: 6 ocular, 4 IIa, 4IIb, 1 IIIa and 1 IIIb. Thymoma was identified in two of the 7 thymectomized individuals. CONCLUSIONS: The prevalence of FAMG in Spain is similar to other populations. Post-intervention status did not differ from sporadic autoimmune MG. As in other neuromuscular disorders, phenotype and inheritance heterogeneity are present in FAMG. In addition to the interfamilial heterogeneity observed, members of the same family affected with FAMG may even present different ages of onset, severity and thymus involvement. Further studies are necessary to clarify the role of genetic risk factors in this form of autoimmune MG.
Authors: Daniel B Drachman; Bryan J Traynor; Joshua D Green; Richard J Barohn; Emanuela Bartoccion; Michael Benatar; Derrick Blackmore; Vinay Chaudhry; Manisha Chopra; Andrea Corse; Mazen M Dimachkie; Amelia Evoli; Julaine Florence; Miriam Freimer; James F Howard; Theresa Jiwa; Henry J Kaminski; John T Kissel; Wilma J Koopman; Bernadette Lipscomb; Michelanglo Maestri; Mariapaola Marino; Janice M Massey; April McVey; Michelle M Mezei; Srikanth Muppidi; Michael W Nicolle; Joel Oger; Robert M Pascuzzi; Mamatha Pasnoor; Alan Pestronk; Carlo Provenzano; Roberta Ricciardi; David P Richman; Julie Rowin; Donald B Sanders; Zaeem Siddiqi; Aimee Soloway; Gil I Wolfe; Charlie Wulf Journal: BMJ Open Date: 2020-09-18 Impact factor: 2.692