Muscle & peripheral nerve nontumor
Congenital myopathies
Nemaline myopathy


Topic Completed: 1 June 2017

Minor changes: 6 October 2020

Copyright: 2002-2020, PathologyOutlines.com, Inc.

PubMed Search: Muscle Nemaline Myopathy [title]


Wesley Hiser, M.D.
Jesse L. Kresak, M.D.
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Cite this page: Hiser W. Nemaline myopathy. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/musclenemalinemyo.html. Accessed October 29th, 2020.
Definition / general
  • One of the most common non dystrophic congenital myopathies, with a heterogeneous clinical presentation and characteristic rod-like inclusions (nemaline bodies) within myofibers
Essential features
  • Skeletal muscle with red to purple rod-like inclusions on Gomori trichrome stain and electron dense deposits on electron microscopy
  • Congenital myopathy primarily involving proximal musculature and with variable age of onset and severity
  • Most common mutations are NEB (recessive) and ACTA1 (dominant)
Terminology
  • Nemaline myopathy (NM), nemaline rod myopathy
  • "Nemaline" means thread-like, describes the appearance of rods (Semin Pediatr Neurol 2011;18:230)
    • Greek nema = thread
ICD coding
  • G71.2
Epidemiology
Sites
Pathophysiology
  • Congenital forms caused by mutations involving the thin filament of the sarcomere and cause contractile dysfunction, leading to muscle weakness (J Neuromuscul Dis 2017;4:99)
Etiology
Clinical features
  • Progressive myopathy which most commonly has a congenital onset
  • Large variation in clinical presentation, ranging from normal lifespan with mild symptoms to neonatal death (Mol Med Rep 2014;10:175)
  • Subdivided into six clinical categories (Semin Pediatr Neurol 2011;18:230)
    • Typical congenital form
    • Intermediate congenital form
    • Severe congenital form
    • Mild nemaline myopathy with childhood onset
    • Adult onset nemaline myopathy
    • Other forms with unusual associated features (Amish NM)
  • Usually symmetric, generalized weakness with preference for neck flexors, facial muscles, axial muscles and proximal extremities (Neuropathol Appl Neurobiol 2017;43:5)
  • Can have late involvement of distal musculature
  • Bulbar and respiratory muscles are frequently affected and may be a presenting feature (Semin Pediatr Neurol 2011;18:230)
    • Patients are at risk for nocturnal hypoxia and recurrent lower respiratory tract infections
    • Feeding and nutritional difficulties are common
  • Cardiac and extraocular muscles typically spared, but involvement can be seen with specific mutations (Curr Opin Neurol 2016;29:642, Semin Cell Dev Biol 2017;64:191, Circulation 1989;79:1282)
  • Frequently show weak deep tendon reflexes and joint hypermobility
  • May develop joint and spine abnormalities (J Med Genet 1997;34:705)
  • Congenital forms often show facial elongation, tent shaped mouth and high arched palate (J Med Genet 1997;34:705)
Diagnosis
  • Clinicopathologic diagnosis
  • Muscle biopsy
  • Laboratory findings are typically nonspecific
Radiology description
Prognostic factors
Case reports
Treatment
  • No proven effective therapy other than symptomatic treatment
  • Symptomatic treatment has shown to be helpful in many patients (Semin Pediatr Neurol 2011;18:230)
    • Mechanical nighttime ventilation
    • Orthoses
    • Nasogastric feeding and nutritional support
    • Aggressive treatment of respiratory infections
    • Physical and speech therapy
  • While lacking in objective evidence, low impact exercise and L-tyrosine may provide some benefit
  • Medications targeting thin filaments or muscle atrophy have been developed and show promise
Microscopic (histologic) description
  • Variation in myofiber size with areas of atrophy, hypertrophy and grouping
  • Fatty replacement or fibrosis may be seen but necrosis, fiber regeneration, or inflammation is uncommon (J Med Genet 1997;34:705)
  • Gomori trichome stain shows red to purple colored inclusions, frequently rod shaped, in sarcoplasm and subsarcolemmal region of myofibers (Semin Pediatr Neurol 2011;18:230, J Med Genet 1997;34:705)
    • Often more prominent in type I myofibers
    • No correlation between number of rods and clinical severity
    • Not specific for nemaline myopathies
  • Nemaline rods can also be visualized on plastic sections with toluidine blue (Semin Pediatr Neurol 2011;18:230)
  • Fiber typing will typically show predominantly type I fibers with atrophy and grouping
Microscopic (histologic) images

Contributed by Wesley M. Hiser, M.D.

H & E 60x

Gomori trichrome 40x

Gomori trichrome 60x

Positive stains
  • Gomori trichrome stain highlights red to purple colored rods within sarcoplasm of myofibers
  • Nemaline bodies positive for alpha-actinin
  • Myofiber typing shows type I predominance
Electron microscopy description
Electron microscopy images

Images hosted on other servers:

Nemaline rods

Molecular / cytogenetics description
Videos


Differential diagnosis
Additional references
Board review style question #1
In which gene are de novo mutations most commonly associated with nemaline myopathy?

A. NEB
B. KLHL40
C. TPM3
D. ACTA1
E. TNNT1

Board review answer #1
D. ACTA1

De novo mutations in ACTA1 are the most common cause of nemaline myopathy. Mutations in NEB are the most common cause of autosomal recessive nemaline myopathy.
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