Central Core Disease

Central core disease (CCD) is an inherited neuromuscular disorder characterised by central cores on muscle biopsy and clinical features of a congenital myopathy.

Epidemiology

Prevalence is unknown.

Clinical description

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.

Etiology

CCD and MHS are allelic conditions, both caused by (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 in the RyR protein are considered to be the main pathogenetic mechanism(s).

Diagnostic methods

The diagnosis of CCD is based on the presence of suggestive clinical features and central cores on muscle biopsy. Muscle MRI may show a characteristic pattern of selective muscle involvement and aid the diagnosis in cases with equivocal histopathological findings. Mutational analysis of the RYR1 gene may provide genetic confirmation of the diagnosis.

Management and treatment

Management is mainly supportive and has to anticipate susceptibility to potentially life-threatening reactions to general anaesthesia. Further evaluation of the underlying molecular mechanisms may provide the basis for future rational pharmacological treatment.

Prognosis

In the majority of patients, weakness is static or only slowly progressive, with a favourable long-term outcome.