Genetics and Autoimmunity: Two Sides of the Same Coin or an Epiphenomenon?

Abstract

Distinguishing hereditary forms of myopathy from certain forms of inflammatory myopathy can be challenging. We present 3 cases where a certain degree of overlap was observed between genetics and autoimmunity. A child with juvenile dermatomyositis where heterozygosity for a pathogenic mutation implicated in LGMD1C resulted in a delayed diagnosis. A young lady with anti-SRP positive insidious proximal polymyositis worsening post-partum, diagnosed eventually as LGMD2. An adolescent child referred for proximal myopathy in view of paternal history of LGMD2 but found to have signs of systemic sclerosis with overlap myositis with excellent recovery on therapy. While improvements in whole genome sequencing and detection of myositis specific antibodies have revolutionised the diagnosis and treatment of these diseases, they are still not robust enough and may cloud good clinical judgement in accurate diagnosis and management. Higher sensitivity of these assays is bringing to the fore the possibility that these diagnoses may not be mutually exclusive and might plausibly be concurrent, pending further investigation. These are three interesting cases depicting the difficulties frequently encountered by rheumatologists and neurologists in distinguishing inflammatory from genetic myopathies.

Keywords: hereditary myopathy; immunosuppressants; inflammatory myopathy; juvenile dermatomyositis; myositis-specific autoantibodies; paediatric rheumatology; whole genome sequencing.

Figure 1.

(a) Gottron’s papules present on the knuckles of both hands in case 1. (b) Erythematous oedema of the eyelids in case 1.