Fig. 35.1
Muscle biopsy. Muscle biopsy of myofibrillar myopathy – myotilinopathy. Haematoxylin-Eosin stained sections (a, d) show variation in fibre size, frequent rimmed vacuoles and eosinophilic inclusions in many of the fibres. NADH histochemical preparation reveals disrupted myofibre pattern in a proportion of the fibres (b). Gomori trichrome accentuates inclusions which are dark green or red in colour. Rimmed vacuoles are also apparent (c). The inclusions show positive labelling for ubiquitin (e), p62 (f), alpha-B-crystallin (g), desmin (h) and myotillin (i). Scale bar: 100 μm (a–c); 50 μm (d–i) (Image courtesy of Zane Jaunmuktane and Sebastian Brandner)
Diagnosis and Management
A diagnosis of inclusion body myositis was made. The patient received no specific treatment, and continued to be followed. His weakness progressed gradually, particularly of ankle dorsiflexion and he required ankle foot orthoses. He also developed wasting around the shoulder girdle with weakness of infraspinatus and supraspinatus. Weakness of knee extension did not worsen and he did not develop swallowing difficulties or weakness of long finger flexors and therefore his clinical phenotype was not typical of sporadic inclusion body myositis. The muscle biopsy was reviewed, and additional immunostaining was performed which showed very strong cytoplasmic immunoreactivity in several fibres for p62 and myotlin. There was no MHC Class I upregulation on the sarcolemma, the number of COX negative fibres was probably within normallimits for his age and electron microscopy did not show the microfilaments seen in inclusion body myositis. The pathological diagnosis was modified to myofibrillar myopathy. MRI of the lower limb muscles was performed and is shown in Fig. 35.2. Echocardiogram demonstrated regional wall motion abnormalities with a preserved ejection fraction. A subsequent coronary angiogram did not demonstrate an ischaemic cause for these cardiac changes. The genetic analysis for FSHD1, desmin, alpha-Beta-crystallin were negative. A myotilin heterozygous c.179C > G (p.Ser60Cys) mutation was found which has previously been reported as pathogenic.
