Case Study 85 Leonidas Arvanitis

Question 1: A 25 year old female complains of hypotonia and muscle weakness CK levels are mildly elevated Describe the histologic findings on the H&E and Gomori trichrome stains Click here to view H&E and Gomori stains

Answer 1: H&E stained frozen sections Abnormal variation in myofiber sizes (15-80 microns) Mild excess of internalized nuclei Gomori trichrome reacted sections Dark staining inclusions which are cytoplasmic and clustered at the periphery of the fibers

Question 2: Based on the most likely diagnosis what would electron microscopy show?

Answer 2: Electron dense rods or ovoid structures derived from Z-line material

Question 3: What is the major constituent of theses rods?

Answer 3: A-actinin

Question 4: What is your diagnosis?

Answer 4: Nemaline myopathy

Question 5: Nemaline myopathy is caused by mutations in which genes?

Answer 5: The most common mutations involve the ACTA1 and NEB genes ACTA1 gene encodes skeletal muscle α-actin NEB gene encodes nebulin

Question 6: Are rods specific to nemaline myopathy?

Answer 6: No, they can also be seen in Myotendinous junctions External ocular muscles Aging muscles