PMC4456612_01
Family history. II-2 had pacemaker placement at 38 years of age and sudden cardiac death at age 62. III-3 had dizziness and syncope onset at age 30, cardiac conduction block requiring pacemaker placement at age 30, extremity weakness and calf muscle wasting onset in the mid-50 s; choking episodes beginning in the 50 s, and hand numbness and tingling onset in the late 20 s that largely resolved following carpal tunnel surgery. In addition, she developed obesity, photophobia, a progressively enlarging palatal cyst protruding to her right nostril resulting in limited sense of smell at age 30, difficulty hearing with background noise in her mid-50 s; and irritable bowel syndrome with alternating constipation and diarrhea in her early 50 s. III-2 has intellectual disability and autism. I-1 died at age 39 from presumed sudden cardiac death, had a history of "dropsy" with recurrent syncope, edema, and dizzy spells. I-2 died at age 92 years from cancer and required pacemaker placement in her 70 s. IV-3 had tachycardia requiring ablation at 10 years of age.
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F1
Proband's skeletal muscle cryostat sections. Muscle sections stained with (A) H&E or (B) modified Gomori trichrome stain demonstrate marked variability in fiber size, with fiber atrophy and fatty infiltration. Ragged red fibers are marked by arrows in both panels. (C) SDH/COX staining demonstrated several fibers (arrow) with SDH activity (blue) that lack COX activity (brown). Original magnifications: (A), 200X; (B,C), 400X.
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F2
Ragged red fibers and SDH positive/COX negative fibers consistent with a mitochondrial myopathy were identified (Figure 2).