ANO5-related limb-girdle muscular dystrophy mimicking inflammatory myopathy:first Tunisian case report

Abstract

Objective:

Limb-girdle muscular dystrophy type R12 (LGMDR12), caused by biallelic ANO5 mutations, is an autosomal recessive myopathy characterized by adult-onset asymmetric weakness and marked hyperCKemia. Its phenotypic spectrum remains incompletely defined, particularly in North African populations. This study aimed to report the first genetically confirmed Tunisian case of LGMDR12 with inflammatory myopathy-like features and early subclinical cardiac involvement.

Methods:

We describe the clinical, laboratory, muscle imaging, histological, genetic, and cardiac findings of a 36-year-old Tunisian man with progressive asymmetric proximal lower-limb weakness.

Results:

The patient, born to first-degree consanguineous parents, had severe hyperCKemia (60 times the upper limit of normal), negative myositis-specific antibodies, and a myopathic electromyographic pattern. Muscle MRI showed hamstring fatty infiltration and focal fascicular STIR hyperintensities of the right vastus lateralis. Muscle biopsy revealed dystrophic changes with focal pseudo-granulomatous inflammatory infiltrates, leading to an initial inflammatory myopathy suspicion. Corticosteroid therapy resulted in transient CK reduction but no sustained response. Next-generation sequencing identified a homozygous pathogenic ANO5 variant (c.172C>T, p.Arg58Trp), confirming LGMDR12. Cardiac MRI performed for palpitations despite normal ECG and echocardiography demonstrated septal hypertrophy and diffuse myocardial oedema without late gadolinium enhancement or fibrosis, suggesting early subclinical cardiac involvement.

Conclusions:

This case highlights the diagnostic challenge of ANO5-related myopathy, which may mimic inflammatory myopathy histologically and clinically. Genetic testing is essential in atypical myopathies with persistent hyperCKemia and may reveal previously unrecognized cardiac involvement.