A Definite Maybe

73 yo M French-Candian background with longstanding history of diplopia, severe unvarying limitation of extraocular movements, severe ptosis, dysarthria, and left facial weakness presents to neuro-ophthalmology for another opinion after undergoing additional extensive genetic testing. He had been diagnosed 15 years ago based on his phenotypic presentation with Oculopharyngeal Dystrophy and had negative acetylcholine receptor and MUSK antibody testing for Myasthenia Gravis. Deltoid muscle biopsy from 15 years ago showed evidence of neurogenic atrophy with small angular myofibers of both fiber types some of which are esterase rich on histochemical preparations and without ragged red fibers.Temporalis muscle biopsy from 15 years ago showed severe atrophy with no evidence of ragged red fibers. The muscle was severely abnormal with rounding and collagen proliferation. MRI showed severe atrophy of the extra ocular muscles. PABP2, ANT1, TWINKLE, and POLG gene testing negative. Gene Panel 21 gene (ACO2, AUH, C10ORF2, C12ORF65, CISD2, MFN2, MTPAP, NDUFS1, OPA1, OPA3, POLG, POLG2, RRM2B, SLC19A3, SLC25A4, TIMM8A, TK2, TMEM126A, and TYMP) indicated no disease-causing variant identified. Mitochondrial Respiratory Chain Enzyme Analysis indicated severe reduction in all respiratory chain complexes with major deficiencies in complex II, II+III, and IV. Mitochondrial qPCR analysis of skeletal muscle content indicated 130% compared to matched control. Comprehensive mtDNA Analysis by Massively Parallel Sequencing (MitoNGS) indicated low level multiple mtDNA deletions with no known pathogenic variants detected. Two homoplasmic LHON secondary pathogenic variants were detected. Anti-LRP4 testing was positive, indicating that patient has double-seronegative Myasthenia Gravis. In follow up, he has not responded significantly to pyridostigmine and prednisone treatment.