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myofibrillar myopathies

Sunday 7 March 2004

The term myofibrillar myopathy was proposed in 1996 to encompass the spectrum of disorders characterized by an accumulation of myofiber degradation products with abnormal expression of various proteins.

Myofibrillar myopathy (MFM) is a non-committal term for a pathological pattern of myofibrillar dissolution associated with accumulation of myofibrillar degradation products and ectopic expression of multiple proteins that include desmin, alphaB-crystallin (alphaBC), dystrophin and congophilic amyloid material.

The presence of intra-myocyte inclusions composed of myofibrillar material, places this in the broad category of a myofibrillar myopathy. The most commonly expressed proteins are myotilin, desmin, alphaB-crystallin, dystrophin, and beta-amyloid precursor protein.

Myofibrillar myopathy is a rare condition with subtle histologic findings and varied clinical presentations and inheritance patterns. Slowly progressive muscle weakness, which may be either proximal or distal, is the most common symptom.

Reports of associated cardiomyopathy vary greatly, from 16% - 63%. Arrhythmias and congestive heart failure are frequent associations, but sudden death from conduction defects may be the initial clinical manifestation.

Although the majority of cases are sporadic, the most common pattern of inheritance is autosomal dominant. Autosomal recessive inheritance of desmin mutations has been described in a few patients with aggressive myopathy and cardiomyopathy. It is rare for patients with myofibrillar myopathy to present clinically before 20 years of age, although the age at first manifestations varies from infancy to 64 years.

Etiology

- mutation in DES gene coding for desmin
- mutation in CRYAB gene coding for alpha-B crystallin
- mutation in FLNC gene coding for filamin C

Localization

- myofibrillar cardiomyopathy