Familial aggregation of myasthenia gravis in affected families: a population-based study

Abstract

Introduction: Myasthenia gravis (MG) is clinically heterogeneous and can be life-threatening if bulbar or respiratory muscles are involved. However, relative contributions of genetic, shared, and nonshared environmental factors to MG susceptibility remain unclear. The aim of this study was to examine the familial aggregation and heritability of MG and the relative risks (RRs) of other autoimmune diseases in the relatives of patients with MG.

Methods: A population-based family study using the Taiwan National Health Insurance (NHI) Database was conducted. Participants included all individuals (N=23,422,955) who were actively registered in the NHI Database in 2013, 15,066 of whom had at least one first-degree relative with MG. We identified 8,638 parent-child relationships, 3,279 with an affected offspring, 3,134 with affected siblings, and 26 with affected twins. Prevalence and RRs of MG and other autoimmune diseases in the relatives of patients as well as the relative contributions of heritability, shared, and nonshared environmental factors to MG susceptibility were measured.

Results: RRs (95% confidence intervals [CIs]) for MG were 17.85 (8.71-36.56) for patients' siblings, 5.33 (2.79-10.18) for parents, 5.82 (3.03-11.16) for offspring, and 1.42 (0.20-10.10) for spouses without genetic similarities. RRs (95% CIs) in individuals with a first-degree relative with MG were 2.18 (1.53-3.12) for systemic lupus erythematosus, 1.73 (1.09-2.74) for primary Sjögren's syndrome, 1.90 (1.66-2.18) for autoimmune thyroid disease, and 1.68 (1.22-2.30) for rheumatoid arthritis. Accountability for the phenotypic variance of MG was 82.1% for familial transmission and 17.9% for nonshared environmental factors.

Conclusion: Individual risks of MG and other autoimmune diseases are increased in the relatives of patients with MG. Familial transmission of MG was estimated to be 82.1%.

Keywords: familial risk; myasthenia gravis; population based family study.

Figure 1

Age-specific prevalence of myasthenia gravis in individuals with a first-degree (circle) relative affected with MG and in the general population (hollow circle) in Taiwan in 2013. Note: This figure demonstrates a significantly higher prevalence of MG in most age bands among those with a family history than the general population. Abbreviation: MG, myasthenia gravis.

Figure 2

Comparison of the onset age of MG in affected patients with (circle) and without (hollow circle) a family history in 2013. Abbreviation: MG, myasthenia gravis.