Investigations showed normal CK with a myopathic pattern on EMG. His ECG showed atrial fibrillation with left bundle branch block and echocardiography demonstrated biatrial enlargement. Given his presentation and family history a muscle biopsy was performed. This revealed numerous atrophic fibers and an increase in internal nucleation, with scattered cytoplasmic vacuoles. There was also a mild increase in type 1 fibre and abnormal Desmin staining. Sequencing of the VCP (valosin containing protein) gene did not identify any abnormality. Then sequencing of the DES (Desmin) gene was performed and identified a mis–sense mutation c.1346A>C (p.Lys449Thr), diagnosing a desminopathy.

Desminopathy is part of the myofibrillar myopathies (MFMs). They are a group of muscular dystrophies, associated with myofibrillar disorganisation and accumulation of myofibrillar degradation products. Diagnosis is via muscle pathology and electron microscopy. Inheritance can be autosomal dominant, autosomal recessive, X–linked and rarely sporadic. Age of onset can vary between third and seventh decades. Patients present with progressive muscle weakness which can be distal, limb–girdle or scapuloperoneal in distribution. Cardiomyopathy may precede muscle weakness and cardiac arrhythmias may occur. Respiratory insufficiency, including diaphragm paralysis, peripheral neuropathy and spinal rigidity can be associated with some subsets. Desmin is a 53kDa intermediate filament which is involved in the formation of cellular cytoskeleton. Over 40 mutations have been described, the majority clustering in the alpha–helical head domain but there is also newer evidence that mutations in the “tail” region can lead to similar phenotypes.^1–4

Recognising MFMs is important because of their myriad of implications. Although there is no active treatment for the muscular dystrophy, cardiac and respiratory interventions can be used. Furthermore, it is crucial to identify family members at risk and counsel them appropriately.