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Muscle pathology of the patients with SRPK3/TTN myopathy. a–h, Examples of muscle histopathology (n = 23). a, Myopathic changes with increased internalized nuclei and fiber size variability (22/23) shown by hematoxylin and eosin (H&E) staining, as seen in patient XIII:1. b,c, Minicores and core-like structures (15/23) shown by NADH histochemistry, as seen in patients BII:1 and WIII:3. d,e, Type I fiber predominance and type I uniformity (19/23) shown by ATPase pH 4.6 and pH 9.2 staining, as seen in patients CII:2 and BII:1, respectively. f, More severe end of the disease spectrum, with vacuoles, necrosis, regeneration and fibrosis shown by H&E in patient YII:3. g,h, EM images confirmed the presence of core structures and revealed Z-line misalignment, accumulation of Z-band material and branching of myofibrils, as seen in patients XIII:1 and WIII:3. Representative images have been obtained as part of the diagnostic workup in accredited pathology laboratories. i, Lower limb MRI T1-weighted images from four patients with SRPK3/TTN myopathy (VII:1, YII:3, MIII:3 and ZIV:1). A pattern of fatty replacement involving the subscapularis muscle in the shoulder girdle was observed. In the pelvic girdle, the gluteus maximus was affected (arrows), but the gluteus minimus and medius muscles were spared even in the advanced stages of the disease. In the thigh, there was a predominant involvement of the hamstring muscles, while the sartorius and gracilis muscles were not involved in the advanced stages of the disease, with the adductor magnus muscle (arrowheads) almost completely spared. In the lower legs, there was predominant involvement of the medial gastrocnemius muscle (arrows) associated with the involvement of the soleus muscle. The peroneus and tibialis anterior muscles were also involved, but only in advanced stages.
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