Central core disease

Central core disease falls under the category of congenital myopathies, which is a group of conditions characterised by muscle weakness and wasting.

Central core disease is a rare condition and symptoms usually become apparent at birth or early infancy, although cases have been reported where symptoms are present in the developing foetus. The condition is generally non-progressive – or slowly-progressive – and people affected usually have a normal life span.

In most cases, symptoms become apparent at birth or shortly after. They include hypotonia (floppiness) and weakness of the muscles closest to the trunk of the body. There is often a delay in achieving motor milestones, but most people affected should eventually be able to walk.

Muscle cramps are common and mild facial weakness has been seen in some cases, specifically involving the eyes. Weakness around the hips can lead to hip dislocations or tightening of the joints (contractures), particularly the knees and hips. Curvature of the spine (scoliosis) may also occur. Generally the heart and respiratory function are not affected.

Malignant hyperthermia (MH) is an acute reaction triggered by certain general anaesthetics or muscle relaxants (which are used for general anaesthesia). Symptoms of MH include high fever, muscle rigidity, dark brown colouration of urine and acute kidney failure. MH is potentially fatal if not treated immediately with a drug called dantrolene. MH can be prevented by avoiding the triggering anaesthetic agents with alternative drugs. Local anaesthetics are quite safe. Both MH and central core disease are associated with abnormalities in the RYR1 gene, so it is important to inform the consultant surgeon or anaesthetist if surgery is being considered.

In some families, central core disease is caused by a mutation in the ryanodine receptor (RYR1) gene, located on chromosome 19. This gene carries the instructions for a protein that is involved in calcium release in muscle. It is not known exactly how mutations in this gene cause the condition. In many other families, the genetic cause has not been determined.

Central core disease is inherited in an autosomal dominant pattern, although many cases occur sporadically, sometimes caused by autosomal recessive inheritance with no previous family history. Autosomal dominant inheritance means if a parent has the condition, there is a 50 percent chance that each child will also have the condition. Either of the parents can pass on the mutation, and both male and female children can be affected.

Generally, the diagnosis is made through a muscle biopsy, in which a sample of muscle is taken and examined under a microscope. This is done in one of two ways: either a small piece of muscle is taken under general anaesthetic (avoiding the drugs which may cause malignant hyperthermia) or a small sample is removed through a needle biopsy.

Muscle from people affected by Central core disease has a distinctive pattern, with core structures centrally located within the muscle cells. It is important to note however that these structures are also seen in other unrelated conditions. It is important, therefore, for the muscle sample to be considered in conjunction with the physical signs and symptoms and/or molecular tests, in order for a diagnosis of central core disease to be made.

In families where the mutation is known to occur in the RYR1 gene, molecular testing is available. This involves taking a blood sample and analysing the DNA for the presence of a mutation. This process can take up to several months to complete.

Currently there is no treatment or cure for central core disease, but there are some important ways to manage the condition.

Physiotherapy. The primary aim of managing a muscle wasting condition is to increase or at least maintain function and mobility. Physiotherapy can assist in doing this, and it can also maintain breathing capacity, delay the onset of curvature of the spine (scoliosis) and help prevent the development of contractures. It is important that the physiotherapist involved is familiar with the treatment of people with muscle wasting conditions.

Exercise. There is some debate over whether people with muscle wasting conditions should undertake strenuous physical exercise. Some say that putting additional strain on already weakened muscles will cause additional harm, while others believe that the exercise may increase muscle strength. Insufficient evidence exists to support either, but it is believed that moderate non-weight-bearing exercise such as swimming, walking or pedalling may be the best solution. This sort of aerobic exercise helps to maintain a healthy cardiovascular system and a steady weight. It is however important that this is discussed fully with a clinician.

Corrective surgery. Scoliosis, or curvature of the spine, is common in central core disease. Spinal surgery aims to correct the posture by re-aligning the spinal column, and involves the insertion of rods, screws or wires. There are benefits and risks associated with this surgery, and more information is available if you call our Muscular Dystrophy UK helpline. As with other treatments, it is very important that options are discussed fully with a consultant or specialist before a decision is made. Young children might use a spinal brace and children who do not walk might use moulded seating.