Sporadic Late-Onset Nemaline Myopathy

Clinical History:

The patient is a 69-year-old male who presented with complaints of proximal lower extremity muscle weakness and BMI of 37. His home medication list includes atorvastatin. Bilateral thigh biopsies were performed to evaluate for myopathy.

The significant finding can be seen in all of the following, except:

A. SLONM

B. ACTA1 mutations

C. HIV

D. Duchenne muscular dystrophy

Answer:

Duchenne muscular dystrophy

The images demonstrate abnormal accumulations of myofibrillar material near z bands so called “nemaline rods”. Nemaline rods are not entirely specific but are seen in sporadic late onset nemaline myopathy (SLONM), congenital myopathies such as inherited nemaline myopathy, can be seen in HIV, and can be an incidental finding when present near vessels or at myotendinous insertion sites. Inherited nemaline myopathies have variable clinical expression, ranging from severe disease in newborns to mild adult onset forms. Inherited nemaline myopathies are associated with heterogeneous genetic defects in various genes (including, ACTA1, NEB, TPM2, TPM3, TNNT1, CFL2, and KBTBD13). Nemaline rods are not associated with Duchenne muscular dystrophy.

Reference(s) / Additional Reading:

SLONM

• Chahin N, et al. Sporadic late onset nemaline myopathy. Neurology 2005;65:1158-1164
• Schnitzler LJ, et al. Sporadic late-onset nemaline myopathy: clinic-pathological characteristics and review of 76 cases. Orphanet J Rare Dis 2017 May 11;12(1):86. doi: 10.1186/s13023-017-0640-2.

Inherited Nemaline Myopathy

• Sewry CA, et al. Nemaline myopathies: a current view. J Muscle Res Cell Motil. 2019;40(2):111-126.
• Laitila J, et al. Recent advances in nemaline myopathy. Neuromuscul Disord. 2021;31(10):955-967.
• Bodamer, O. (2022). Congenital myopathies. In Patterson, MC and Dashe, JF (Eds.), UpToDate website.