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central core disease

Saturday 28 July 2007

Ent. 1956

Central core disease (CCD) is an inherited neuromuscular disorder characterised by central cores on muscle biopsy and clinical features of a congenital myopathy. Prevalence is unknown but the condition is probably more common than other congenital myopathies.

CCD typically presents in infancy with hypotonia and motor developmental delay and is characterized by predominantly proximal weakness pronounced in the hip girdle; orthopaedic complications are common and malignant hyperthermia susceptibility (MHS) is a frequent complication.

CCD and MHS are allelic conditions both due to (predominantly dominant) mutations in the skeletal muscle ryanodine receptor (RYR1) gene, encoding the principal skeletal muscle sarcoplasmic reticulum calcium release channel (RyR1).

Altered excitability and/or changes in calcium homeostasis within muscle cells due to mutation-induced conformational changes of the RyR protein are considered the main pathogenetic mechanism(s).

Central core disease is a nonprogressive, congenital myopathy presenting in infancy with hypotonia, gross motor delay, moderate muscle weakness (maximal in the proximal lower limbs), and secondary musculoskeletal abnormalities including congenital hip dislocation, foot deformities, scoliosis, and joint contracture. These patients have a particular susceptibility to malignant hyperthermia.

Diagnosis

The diagnosis is usually made by muscle biopsy (amorphous central cores).

ETiology

Central core disease is usually inherited in an autosomal-dominant manner. In a few families, inheritance was shown to be autosomal-recessive.

Many sporadic cases have also been described. Several mutations of the ryanodine receptor (RYR1) described above were shown to cause this congenital myopathy.

References

- Jungbluth H. Central core disease. Orphanet J Rare Dis. 2007 May 15;2:25. PMID: 17504518