central core disease of muscle (CCD)

Pathology

• predominance of type 1 muscle fibers containing amorphous areas (cores)
• cores do not stain with oxidative & phosphorylase histochemical methods

Genetics

• autosomal dominant
• associated with defects in RyR1 gene
• coexpression of normal & mutant Thr-4898 RYR1 in a 1:1 ratio, produces RYR1 channels with normal halothane & caffeine sensitivities, but maximal levels of Ca+2 release are reduced by 67%; binding of [3H]ryanodine indicates that the heterozygous channel is activated by Ca+2 concentrations 4-fold lower than normal; single-cell analysis of cotransfected cells shows a significantly increased resting cytoplasmic Ca+2 level & a significantly reduced luminal Ca+2 level; data suggests a leaky channel, possibly caused by a reduction in the Ca+2 concentration required for channel activation; the Thr-4898 mutation gives rise to the severe & penetrant phenotype
• allelic with malignant hyperthermia

Clinical manifestations

• congenital myopathy
• hypotonia & proximal muscle weakness in infancy
• delay of motor milestones
• slow or nonprogressive in adulthood
• severity of the symptoms may vary from normal to significant muscle weakness

More general terms

• genetic disease of muscle (inherited myopathy)

Additional terms

• ryanodine receptor 1; RYR-1; RyR1; skeletal muscle-type ryanodine receptor; skeletal muscle Ca+2 release channel (RYR1, RYDR)

Database

• OMIM: https://mirror.omim.org/entry/117000