Muscle
Congenital myopathies
Central core disease

Author: Wesley Hiser, M.D. (see Authors page)
Editor: Jesse L. Kresak, M.D.

Revised: 17 September 2017, last major update September 2017

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: (Central core disease [title]) muscle "loattrfree full text"[sb]

Cite this page: Hiser, W. Central core disease. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/musclecentralcoredisease.html. Accessed February 25th, 2018.
Definition / general
  • First described in 1956 by Magee and Shy (Brain 1956;79:610)
  • One of the more common forms of congenital myopathy
  • Characterized by the presence of central cores in skeletal muscle histologically in addition to the clinical features of congenital myopathy
Essential features
  • Skeletal muscle with areas of reduced to absent staining of enzymes such as NADH, SDH and COX
  • Most commonly associated with mutation in RYR1 gene
  • Presence of cores in a muscle biopsy without associated clinical symptoms and weakness is insufficient for diagnosis of central core disease
Terminology
  • "Central core" refers to areas of reduced oxidative and glycolytic enzymatic activity along the longitudinal axis of skeletal muscle fibers, as seen on enzymatic stains such as NADH
ICD-10 coding
  • G71.2
Epidemiology
  • One of the more common congenital myopathies but true incidence is unknown
Sites
  • Predominantly involves proximal musculature
  • Most frequently hip girdle and axial muscles
Pathophysiology
Etiology
  • Typically caused by mutations in the skeletal muscle ryanodine receptor (RYR1)
  • Less commonly caused by selenoprotein N (SEPN1) mutations (Semin Pediatr Neurol 2011;18:239)
Clinical features
  • Variable presentation
  • Static to slowly progressive disease course
    • May worsen or progress during or after pregnancy
  • Usually presents in infancy or early childhood
  • Most common symptoms: myalgias, muscle stiffness, exertional weakness
  • Common orthopedic symptoms include congenital hip dislocation, scoliosis and foot deformities (Neurology 2013;80:1584), but most patients can walk independently
  • Extraocular, respiratory, cardiac muscle involvement is uncommon
  • Precautions with general anesthesia due to risk of malignant hyperthermia (associated with RYR1 mutation)
Diagnosis
  • Histologic finding of central cores in skeletal muscle combined with clinical features of congenital myopathy
  • Presence of cores in a muscle biopsy without associated clinical symptoms and weakness is insufficient for diagnosis of central core disease
Laboratory
  • CK levels are typically within normal range but may be elevated
Radiology description
  • Ultrasound shows localized increased echogenicity within quadriceps
  • MRI shows pattern of selective muscle involvement with predilection for vasti muscles, sartorius and adductor magnus of thigh, as well as soleus and peroneal group of lower leg
  • Relative sparing of gracilis, adductor longus and rectus femoris (Neurology 2013;80:1584)
Prognostic factors
  • Autosomal dominant mutations are typically associated with a favorable prognosis
  • Autosomal recessive mutations may be associated with more severe complications
Case reports
Treatment
  • No current treatment
  • Supportive care
Microscopic (histologic) description
  • Large areas of reduced oxidative and glycolytic enzymatic activity along longitudinal axis of muscle fiber
  • Fibers may have multiple cores; cores may be central or eccentrically placed
  • Usually involves type 1 fibers, with some degree of hypertrophy or predominance
  • Internal nuclei may be seen
  • Myofiber necrosis and regeneration are not seen (Yachnis: Neuropathology - A Volume in the High Yield Pathology, 1st Edition, 2014)
Microscopic (histologic) images

Images hosted on PathOut server:

Images contributed by Jesse L. Kresak, M.D.

H&E

NADH and NADH1

SDH

Positive stains
Negative stains
  • NADH stain shows absence of enzyme activity within the cores
  • SDH and COX stains may also show absence of enzyme activity within cores
Electron microscopy description
Molecular / cytogenetics description
  • Most commonly caused by autosomal dominant mutations in RYR1 gene on chromosome 19q13.1
  • Less commonly caused by selenoprotein N (SEPN1) gene mutations (Semin Pediatr Neurol 2011;18:239)
  • RYR1 encodes ryanodine receptor, which is ligand gated release channel for calcium stored in terminal cisterna
  • RYR1 gene is also implicated in malignant hyperthermia sensitivity (MHS) phenotype
  • Dominant mutations affecting N terminal or central domains of RYR protein give rise to MHS phenotype, while those affecting C terminal give rise to central core disease phenotype
  • Recessive mutations are uncommon and typically present as multiminicore disease on histology (Yachnis: Neuropathology - A Volume in the High Yield Pathology, 1st Edition, 2014)
Differential diagnosis
Board review question #1
The term "central core" refers to which of the following:

  1. Areas of increased oxidative and glycolytic enzymatic activity along the longitudinal axis of skeletal muscle fibers, as seen on enzymatic stains such as NADH
  2. Areas of reduced oxidative and glycolytic enzymatic activity along the longitudinal axis of skeletal muscle fibers, as seen on enzymatic stains such as NADH
  3. Centrally located accumulation of red to purple, rod-like inclusions within skeletal muscle fibers, visible with Gömöri trichrome stain
  4. Centrally placed, rimmed vacuole within skeletal muscle fibers, visible with Gömöri trichrome stain
Board review answer #1
B. Areas of reduced oxidative and glycolytic enzymatic activity along the longitudinal axis of skeletal muscle fibers, as seen on enzymatic stains such as NADH