LGMDR1 with Prominent Limb–Joint Contractures and Inflammatory Changes Misdiagnosed as Scleromyositis with a Novel <i>CAPN3</i> Mutation: A Case Report

Abstract

Muscle diseases with prominent limb–joint contractures (LJCs) are a subgroup of rare neuromuscular disorders. Prominent LJCs are not specific to genetic myopathies. Myositis can also induce severe contractures, especially in the late stages. We report the case of a 12-year-old girl with a 3-year history of painful muscular weakness with generalized LJCs. The inflammatory pattern associated with positive anti-PM/ Scl antibodies on muscle biopsy allowed us to initially retain the diagnosis of scleromyositis. After 12 months of corticosteroids and immunosuppressive treatment, there was no clinical improvement, and creatine kinase levels remained high (over 10 times the normal value). A second muscle biopsy showed persistent inflammatory infiltrate with the appearance of dystrophic features. Immunohistochemical analysis showed the absence of class 1 major histocompatibility complex expression on muscle fibres, raising the possibility of the diagnosis of muscular dystrophy. Whole-exome sequencing revealed a missense homozygous novel mutation c.386G&gt;T (p.Arg129Ile) on the calpain 3 gene, finally confirming the diagnosis of autosomal recessive limb–girdle muscular dystrophy recessive type 1 (or calpainopathy). This case report highlights the diagnostic challenges and the importance of a comprehensive evaluation in cases of muscle diseases with prominent LJCs.