Congenital Myopathies Central core myopathy

Written by Dr Paola Nicolaides, Consultant Paediatric Neurologist for the Muscular Dystrophy Campaign. What is a myopathy? The term myopathy is derived from the Greek and it means muscle disorder. The congenital myopathies are a group of conditions causing weakness and wasting of the muscles. In general symptoms are present at birth but may not be recognised until later on in childhood or even in adult life. What is a congenital myopathy? The name ‘central core’ was initially given in 1958 and refers to the abnormal central part of th affected muscle fibre which is occupied by one or several “cores” or abnormal areas, running along its length. How does the disease present? Central core myopathy usually present with delay in walking or with mild muscle weakness. Central core disease is often associated with muscle contractures and bony defects such as congenital dislocation of the hips, spinal curvature and high arched feet. In rare cases newborn babies may present with hypotonia (floppiness), swallowing and breathing difficulties, facial weakness or with dislocation of the hip and foot deformities. Later on, the child may show delayed motor development (crawling, standing and walking) and continue to show either non-progressive or slowly progressive muscle weakness, affecting the facial muscles and the “proximal” musculature (muscles near the trunk, such as shoulders and thigh muscles). Children may experience a variety of symptoms ranging from drooping of the eyelids, drooling, swallowing difficulties and muscle weakness. Are the patients at risk of developing any complications? Children with central core myopathy may develop a curvature of the spine. In addition they may be at increased risk of respiratory infections. Constipation may be a feature of the disease and this may be as a direct result of the muscles of the gut being affected, or caused by lack of exercise and insufficient mobility. Hearing, vision and intelligence are usually unaffected.
In some cases the muscle weakness is so mild that an affected parent may have a “life long” history of weakness which may be accepted as normal and the diagnosis in the parent is only made after diagnosis is made in the child. The severity of muscle involvement may vary from one affected person to another within the same family.

Is central core myopathy an inherited disorder? Yes, usually. The exact genetic cause is known to be linked to mutations in the CCD (skeletal muscle ryanodine receptor) gene on chromosome 19 and the usual mode of inheritance is autosomal dominant. This means that one (either) of the two parents is affected, may be only very mildly so, but carries the abnormal gene, and each child (of any sex) of that affected parent has a 50% (1 in 2) chance of being affected. In the remaining cases there does not appear to be a clear pattern of inheritance and these are described as ‘sporadic’ cases, which means they occur randomly, in other words as a one-off situation with very little risk of other children in the family being affected. However, people who are themselves sporadic cases will be at risk of passing the disorder on to their children. Recent advances in Central Core Myopathy In some families this condition is due to a genetic defect found on chromosome 19. A number of genetic defects have been identified in different families and in some of these there appears to be a relationship with a gene known as the ryanodine receptor gene. This gene is related to a calcium “channel” which is involved in the way the muscle contracts and relaxes. Both central core myopathy and malignant hyperthermia (see below) may be related through abnormalities on this gene. How is central core myopathy diagnosed? The diagnosis of a ‘myopathy’ is usually suspected from the history and examination. However, the specific diagnosis of central core myopathy is nearly always made by looking at a piece of muscle (muscle biopsy). Before doing a muscle biopsy (which involves taking out a small piece of muscle usually from the thigh) a few other tests may be done, one of which is a blood test which measures the level of a muscle enzyme (creatine kinase or CK level), which is usually normal but may be slightly raised. The other is an electrical test of the muscles and the nerves supplying the muscle. This test involves the placing of a fine needle into the muscle which then measures the electrical activity arising from that muscle. Although this test may be able to show “a myopathic” pattern of abnormal muscle activity (seen in any myopathy) it is unable to define the exact type. The muscle biopsy is therefore the most important test which will precisely identify the diagnosis. The muscle in this condition shows evidence of abnormal “cores” or fibrils which are usually found in the centre of the muscle fibre. Is the condition progressive? The rate of progression of the condition is variable. In general the earlier the onset the more severe the disorder is. In most cases the disease is only slowly progressive. A few patients may eventually lose the ability to walk. Occasionally muscle weakness may progress quite rapidly and these patients experience serious breathing problems. Is there an anaesthetic risk? Some people with central core myopathy are sensitive to certain types of anaesthetic and muscle relaxants. This is related to a condition known as malignant hyperthermia which can occur during general anaesthesia. If a patient is exposed to these anaesthetic agents or muscle relaxants, the body temperature may rise very quickly causing a very fast heart rate and muscle stiffness and rigidity. It is therefore essential that both the surgeon and the anaesthetist know if someone has central core myopathy before surgery so that appropriate measures are taken, and certain anaesthetic drugs can be avoided. It is also wise to wear a medic alert tag or bracelet stating the condition and risks. Is there a treatment or a cure? At the moment, there is no cure, nor any drug treatment for central core myopathy. However, other very helpful measures can be taken such as physiotherapy, the use of antibiotics to treat chest infections, or naso-gastric tube feeding when necessary. What help is available? Physiotherapy is one of the main forms of help. An initial physiotherapy assessment at the time of the diagnosis should be followed by an exercise programme and regular check-ups. The main aim of physiotherapy is to keep the muscles as active as possible to prevent the formation of ‘contractures’ (muscle tendon tightness causing restriction in the range of joint movement). It is also important to provide good seating and to ensure a proper sitting and standing posture to prevent scoliosis (curvature of the spine). The other role of physiotherapy is to help with provision of appliances, such as splints, calipers, standing frames (mechanical aids helping to keep children on their feet) and wheel chairs where necessary. Children and adults are encouraged to remain as active as possible and ensure that they do not become overweight, so that the strain imposed on already weakened muscles is kept to a minimum. Swimming is a particularly good form of exercise.