Centronuclear Myopathies (CNM): Treatment, Types, Diagnosis
Centronuclear Myopathies (CNM) are a group of neuromuscular disorders; primarily of the muscles responsible for movement; called the skeletal muscles. These are the conditions in which the cell nuclei in the skeletal muscle cells are abnormal leading to difficulty in movement and effective muscle use. Normally the skeletal muscle cell nuclei are located at the periphery of the cell, but in this condition, many nuclei are abnormally located at the centre.
This is a very rare condition and only few cases have been reported so far. As the skeletal muscles are affected, the ability to move is compromised. Patients may have complaints ranging from some dependence on walking aids to total physical dependence and use of wheelchairs.
Types of Centronuclear Myopathies (CNM)
The two types of centronuclear myopathies to be considered are:
- Myotubular Myopathy – Genetic abnormality is associated with X-chromosome in X-linked myolutubular myopathy, like genetic mutations or deletions.
- Autosomal Centronuclear Myopathies – Genetic abnormality is not on X-chromosome and can be autosomal dominant or autosomal recessive.
About Myotubular Myopathy
This is the commonest and the more severe form of centronuclear myopathies. This is an inherited form and affects skeletal muscles, thus having problems with the tone and proper contraction of these muscles.
Causes Myotubular Myopathy
This condition is inherited through X-linked patterns and affects boys who inherit the defective gene from their mothers. Girls may be carriers or if affected, it is less in severity. The condition is caused by mutation in genes responsible for providing instructions to make a particular protein. This protein, called myotubularin is responsible for cellular transport and promotes normal muscle development. Mutations or deletions in the gene controlling this protein can lead to defective function of cell transportation, causing the nuclei to be abnormally located.
Symptoms of Myotubular Myopathy
Severe low muscle tone or hypotonia and muscle weakness is noticeable since birth. The appearance of the infants may include long face, bell shaped chest and high arched palate.
Motor developmental milestones like sitting, crawling, standing, walking may be delayed. Lack of muscle tone can affect the movement and the posture of the infant. Weakness of respiratory and other muscles can lead to corresponding issues with respiration and feeding. Such complications can be life threatening and can sometimes lead to infection or failure of lungs and lead to death during infancy. Some infants may require ventilator support and feeding tube and can survive into childhood.
About Autosomal Centronuclear Myopathies
These forms of centronuclear myopathies are also inherited and affect the skeletal muscles but are comparatively milder in nature.
Autosomal centronuclear myopathies are caused due to genetic mutations, which are not on the X-chromosome or any sex chromosome. The defect is noted on a chromosome, which are numbered or the autosomes. When only one cope of the defective gene from the chromosome pair is sufficient to cause the condition, it is called autosomal dominant. When the condition occurs because both the copies of the genes are defective, it is called autosomal recessive.
Causes of Autosomal Centronuclear Myopathies
Genetic mutations in many genes can cause this condition. Most of these genes control proteins that are responsible for effective functioning of the muscle development, regeneration, maintenance of muscle fibers and transportation of substances within the cells. Some of these genes that may be defective are for amphiphysin 2 protein, dynamin 2 protein and myogenic factor 6.
Symptoms of Autosomal Centronuclear Myopathies
The autosomal type of centronuclear myopathies is also present with low muscle tone and weakness but it is not as severe as the earlier form. The feeding and respiratory compromise is usually not serious and may not be fatal.
Muscle weakness can be slowly progressive and may appear by early adulthood. It can be diffuse in nature or it can have specific affinity for the central or the peripheral muscles of the body. Other commonly observed features include drooping of eyelids and muscles contractures. Some may have neuromuscular difficulties as their development progresses.
Diagnosis of Centronuclear Myopathies (CNM)
Diagnosis of centronuclear myopathies is based on certain parameters and clinically observed myopathy by the physician should raise suspicion. A muscle biopsy may be ordered to determine the location of the nuclei and other relevant details. Genetic testing may be essential for further understanding.
Other investigations that may be required include nerve conduction studies, electromyography, which can help to differentiate myopathies from neuropathies for better medical management.
Treatment of Centronuclear Myopathies
While there is no proper cure for centronuclear myopathies, symptomatic treatment is given and mechanical aids are provided. Medical management is aimed at minimizing complications, functional limitations and providing care and support wherever possible.
Considering the possible complications, effective management to treat lung infections and prevent pulmonary complications is important. In cases of muscle weakness leading to spinal deformities like scoliosis, surgical correction for spinal alignment may be considered.
Physical rehabilitation plays an important role in these cases and includes specialty areas like physical therapy, occupational therapy and other rehabilitative services that provide mechanical aids for physical support. Support groups can help affected families and provide information on rehabilitative services and mechanical aids.