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Acetylcholine receptor (AChR) antibodies are identified in approximately 85% of patients with generalized myasthenia gravis (MG) and approximately 50% of patients with ocular MG¹.  The specificity of AChR antibodies for MG is extremely high, approaching 99%².  AChR antibodies have rarely been reported in individuals with hereditary myopathies, such as progressive external ophthalmoplegia (PEO)³, oculopharyngeal muscular dystrophy (OPMD)⁴, and facioscapulohumeral muscular dystrophy (FSHD)⁵. 

We report two patients with hereditary myopathies associated with extraocular muscle (EOM) weakness and concurrent AChR antibody-positive MG.  Patient 1 is a 79-year-old woman who presented with severe, non-fluctuating, bilateral ptosis, mild dysphagia, and proximal weakness that did not improve with pyridostigmine.  Workup revealed positive AChR binding Ab, elevated CK level, and a homozygous repeat expansion in the PABPN1 gene, confirming a diagnosis of OPMD.  Facial nerve RNS demonstrated abnormal CMAP decrement, suggesting coexistent MG despite her lack of fluctuating symptoms or response to pyridostigmine.  Patient 2 is a 61-year-old man who presented with bilateral ptosis and diplopia since his teens followed later by dysarthria and dysphagia that only mildly improved with pyridostigmine and prednisone.  His exam showed ophthalmoparesis with markedly restricted horizontal and upward eye movements.  Workup revealed positive AChR binding and modulating antibodies, elevated CK level and lactate, and a pathogenic heterozygous mutation in the RRM2B gene, confirming a diagnosis of PEO.  Facial nerve RNS demonstrated abnormal CMAP decrement consistent with MG, and his ptosis and bulbar weakness subsequently improved with IVIG without change in his ophthalmoparesis. 

Patients with hereditary myopathies associated with EOM weakness may be at increased risk for MG due to muscle fiber degeneration, loss of immune tolerance, and consequent generation of AChR antibodies⁵.  Clinicians should consider appropriate genetic testing in patients with seropositive MG and EOM weakness that fails to improve with standard MG therapies.