Malignant Hyperthermia and Central Core Disease in a Child With Congenital Dislocating Hips

Central core disease

“…An association between CCD and MHS had been suspected early, as individuals with MHS may have central cores on muscle biopsy [38], and patients with CCD may be prone to malignant hyperthermia episodes [13,39,40]. The RYR1 gene had been considered as a candidate for malignant hyperthermia based on the finding of a founder mutation in the porcine isoform resulting in the porcine stress syndrome (PSS), a naturally occurring animal model with almost identical clinical features [41].…”

Novel mutations at a CpG dinucleotide in the ryanodine receptor in malignant hyperthermia

“…The other six mutations in the RYR1 gene associated with MHS are Gly248Arg (Gillard et al, 1992), Arg163Cys (Quane et al, 1993), Gly341Arg (Quane et al, 1994a), Arg2434His (Zhang et al, 1993), Tyr522Ser (Quane et al, 1994b), and Gly2433Arg (Keating et al, 1994;Phillips et al, 1994). Of these, the Arg163Cys, Tyr522Ser, and Arg2434His have been identified in MHS families who also have central core disease (CCD), a rare myopathy closely associated with MHS (Eng et al, 1978). An additional mutation Ile403Met (Quane et al, 1993) is also associated with CCD.…”

Muscle Weakness in a 16 Year-Old Girl

“…Core-like lesions can be induced experimentally in muscle by tenotomy [19][20][21] or reinnervation following denerva 98 Macaulay/Sladky/Jay Muscle Weakness in a 16-Ycar-Old Girl tion, but there are differences between these lesions and cores seen in CCD [22], In cores induced by tenotomy, marked degenerative changes of myofibrils and mito chondria have been noted, with degenerating mitochon dria in autophagic vacuoles [21]. Tenotomy-induced core formation can be prevented by simultaneous denerva tion, and experimentally induced cores disappear after several weeks, whereas cores of CCD appear to be a per manent change in the myofiber [22], The association between CCD and malignant hyper thermia (MH) was first reported by Denborough et al [23], and subsequent reports indicate a high risk of MH among patients with CCD [24][25][26][27], In a recent report, 11 of 11 patients with CCD who underwent in vitro contrac ture testing showed MH susceptibility [9], Patients with CCD should be considered at risk for MH until proven otherwise [28]. Conversely, most muscle biopsies from MH-susceptible patients show nonspecific or absent changes, and the incidence of CCD among MH patients is low [29], Recently, the gene for CCD has been localized to the same region of chromosome 19 [30,31] which harbors the gene for ryanodine receptor, the likely site of the genetic defect in MH [32], Although these diseases may involve separate genes, the strength of the linkage suggests that they may be allelic [30,31 ].…”