Central Core Myopathy
This is an autosomal-dominant disorder with gene locus at 19q13.1, the same gene locus as the malignant hyperthermia gene (ryanodine receptor gene, RYR1). Indeed, these patients have a high incidence of malignant hyperthermia with inhalational anesthetic agents.
Histologically, the muscle fibers have amor- phus-looking central areas within the muscle that may be devoid of enzyme activity. There are densely packed disorganized myofibrils (“cores”) in the center of the majority of type 1 fibers. Electron microscopy shows the virtual absence of mitochondria and sarcoplasmic reticulum in the core region, reduced muscle enzymes (cytochrome oxidase, NADH), a marked reduction in the interfibrillary space, and an irregular zig-zag pattern (streaming) of the Z-lines. This gives rise to the characteristic central pallor. There is a predominance of high oxidative, low glycolytic type I fibers and a relative paucity of type II fibers, resulting in a relative deficiency of glycolytic enzymes.Clinically, patients generally demonstrate mild and relatively nonprogressive muscle weakness, either proximal or generalized, and arreflexia, which presents in either early infancy or later. There may be mild facial weakness but normal extraocular movements. Patients often achieve gross motor milestones, such as walking, rather late, and they continue to have difficulty going upstairs. Proximal limb weakness is typical, and patients may show a Gower's sign. The disorder remains fairly static over the years. There may be a frequent occurrence of congenital dislocation of the hip, kyphoscoliosis, and pes cavus. The condition is largely nonprogressive, with affected children remaining ambulatory into adult life. One-third show anesthesia-related malignant hyperthermia. Central core myopathy and familial malignant hyperthermia appear to be allelic, as the ryanodine receptor chain implicated in malignant hyperthermia has the same locus. Individuals within the same family can exhibit one or both phenotypes.