Congenital myopathy with a specific histologic pattern
and high susceptibility to malignant hyperthermia.
Muscle Core Disease; Muscular Central Core Disease;
Central Fibrillary Myopathy; Shy-Magee Syndrome.
Accounts for approximately 15% of all congenital
myopathies. No sexual predilection.
Autosomal dominant trait with the gene locus
mapped to 19q13.1, which is in close proximity to one of the genes for malignant
hyperthermia (ryanodine receptor gene). Expression is variable.
Can be caused by at least 22 different mutations in the
ryanodine receptor-1 gene (RyR1). According to one common hypothesis, these
mutations could result in the formation of excessively leaky sarcoplasmic
reticulum Ca2+ release channels. The ryanodine receptor is a protein
involved in calcium release into the sarcoplasm from the sarcoplasmic
reticulum. It has been postulated that after the exposition to trigger
agents, the ryanodine receptor releases excessive amounts of calcium
resulting in sustained muscle contraction and hypermetabolism.
Requires muscle biopsy. The “central core” is a
histopathologic description related to an area of low staining that extends
the length of the muscle fibers and is devoid of mitochondria and other cell
organelles. Type 1 muscle fibers are predominately affected. Nerve
conduction studies are normal and electromyography is nonspecific. Normal
plasma levels of creatinine phosphokinase do not rule out central core
disease. Susceptibility to malignant hyperthermia is determined by in vitro
contraction testing with halothane and caffeine.
There is a wide variation in the clinical
spectrum of this disease. The myopathy is asymptomatic in some patients, but
in others (although rarely) it can be severe. Most commonly, it already
presents in infancy with hypotonia and delayed motor milestones. A history
of decreased fetal movement and/or breech presentation is often given.
However, the first signs of this disease can be a slowly progressive
limb-girdle syndrome with onset in adolescence or an attack of malignant
hyperthermia. Central core
disease may not be symptomatic until late in life. Proximal muscle weakness is common and manifests as
difficulties in walking or climbing the stairs. Deep tendon reflexes may be
significantly reduced or even absent. Muscle wasting occurs. Skeletal
abnormalities may be part of the clinical picture and include
kyphoscoliosis, congenital hip dislocation, patella dislocation, feet
deformities (pes planus, pes cavus), and joint contractures. Mandibular hypoplasia has
been reported in a few cases. These patients are mentally normal.
As in all myopathies, evaluate
cardiac (increased incidence of mitral valve prolapse) and respiratory
function (e.g., clinically, chest radiographs, echocardiography,
radionuclide scintigraphy, pulmonary function tests, arterial blood gases
analysis), particularly in the presence of kyphoscoliosis. Blood work should
include serum levels of electrolytes (including calcium) and creatinine
Patients are susceptible to malignant
hyperthermia, and at least one death related to malignant hyperthermia has
been reported. Until proven otherwise, these patients should be considered
at high risk for malignant hyperthermia. Even asymptomatic family members
should be considered at risk for malignant hyperthermia until susceptibility