• RYR1
• central core disease
• malignant hyperthermia
• ryanodine receptor

• CCD, central core disease
• CK, creatine kinase
• MH(S), malignant hyperthermia (susceptibility)
• MmD, multi mini-core disease
• IVCT, in vitro contracture test
• EC, excitation contraction

The congenital myopathies are a group of disorders that are difficult to distinguish. Diagnosis is frequently dependent on the result of histological examination of muscle biopsy specimens in conjunction with clinical diagnosis. There is a significant degree of overlap in the clinical features of different congenital myopathies: identification of genetic determinants may therefore aid in establishing a firm diagnosis.

Central core disease (CCD) is a rare congenital myopathy. Histologically, using oxidative enzyme stains, it is identified by the abundance of central cores, characterised by localised areas of mitochondrial depletion and sarcomere disorganization exclusively in type 1 skeletal muscle fibres, and extending throughout their length. Cores are often central and unique, but may be eccentric or multiple within one fibre. Affected patients may present with congenital muscle hypotonia, pronounced proximal weakness, delayed motor development, and slightly elevated creatine kinase (CK) levels. In addition, skeletal anomalies such as congenital hip displacement and scoliosis are frequent. Later in life muscle strength may improve, but in rare cases progressive muscle weakness is observed. Respiratory insufficiency is rare.^1,2 Overall, the disorder demonstrates significant phenotypic variability; in a study of 13 cases, as many as 40% of patients with histological signs of disease were clinically asymptomatic.³

CCD is predominantly reported as an autosomal dominant trait. However, there is evidence that inheritance may be autosomal recessive in some families,^4,5 and sporadic cases have been documented.^6,7 It is recognised as the primary disorder associated and allelic with the pharmacogenetic disorder malignant hyperthermia (MH).⁸ However, characteristic muscle cores have been reported in association with several other myopathies, namely multi-mini core disease (MmD), nemaline myopathy, and hypertrophic cardiomyopathy. All have additional definitive characteristics in their own right, although in some cases the phenotypic boundaries are difficult to assert.

MH also shows autosomal …