8/12/2008 Case 3: Myofibrillary myopathy

Presented by: Dr. Mary Fowkes - Mt. Sinai Hospital

Clinical History:

The patient is a 25 year old man who presented with an elevated serum CK but was otherwise normal (no weakness, no pain, no abnormalities on physical exam).  His father walks with a cane, and his grandfather also has weakness issues.  The patient had a muscle biopsy and images were sent via the Web.

Paraffin sections showed a marked increase in internally placed nuclei in some but not all fibers.  There was fiber splitting.  Modified Gomori Trichrome showed dark cytoplasmic inclusions which were blue to green and occasionally red.  There were rare red rimmed vacuoles.  The inclusions were negative on NADH and ATPase staining.  Type 1 fibers had more inclusions than Type 2 fibers.  Ultrastructural study showed z-band streaming, and there was z-band material at the edge of dense inclusions.  The myofibrillar network was disorganized.

Diagnostic Notes:

The diagnosis was myofibrillar myopathy, and the findings could represent either a primary or secondary desminopathy, i.e. desminopathy or myopathy with desmin accumulation.  Other proteins (desmin, alpha B-crystallin, myotilin, filanein C, selenoprotein N, ZASP and others) are abnormally expressed and could interact with the desmin connections.  Desmin binds to ankyrin, spectrin, synemin, desmusclin, nebulin, plectin and syncoilin.  Differential diagnosis includes reducing body myopathy (a rare disease with abnormal inclusions which are positive for menadione-NBT staining). 

This pathology produces a slowly progressive painless limb girdle muscular dystrophy, which is typically distal but can be proximal.  Facial weakness is mild, if present at all, and extra-ocular movements are usually intact. CK is normal to slightly elevated.  Onset is at 20-40 years of age.  Most are autosomal dominant, but rare cases are autosomal recessive.  50% of patients have a cardiomyopathy, but respiratory failure may occur and even be a presenting symptom.