Muscle diseases and muscular dystrophy

1. Age of onset of signs of the disease - in some diseases, the muscle disorder appears immediately after birth or in infancy. In others it only starts at an older age or even in adulthood.
   
   
2. Inheritance pattern - in some of these diseases inheritance is X-linked, and in others it is autosomal recessive or autosomal dominant.
   
   
3. Muscles in different parts of the body are affected in the different types of muscular dystrophies in some, only the limb girdles are involved, manifesting mainly in difficulties in getting up from a lying position without the help of the hands. In another, the facial muscles and/or the limb muscles become weak, and in another all the muscles are affected.
   
   
4. Severity of the muscle impairment and the pattern of progression - in some types, the disease progresses rapidly and causes death by the age of 20, whereas in others it progresses more slowly and does not cause death.
   
   
5. Laboratory test findings - the different diseases can be differentiated by the type of changes in the muscle that can be seen under the microscope in a muscle biopsy, the type of metabolic changes (enzymes and proteins that are altered in the muscle and that can be measured in muscle biopsy), the type of changes visible on electromyography (EMG), and according to the genes responsible for each type of disease.
   
   

The different groups of muscle diseases are listed below

1. Muscular dystrophy - this is a group of varied and common congenital muscle diseases. The common denominator of all of them is a characteristic picture of progressive muscle destruction visible under the microscope. It eventually results in gradual loss of function of the muscles involved in the disease.
   A number of common types of muscular dystrophy are listed below - See separate information sheet on each one:
   
   
   1. Duchenne or Becker muscular dystrophy (DMD or BMD).
   2. Limb girdle dystrophy (LGMD).
   3. Facioscapulohumeral muscular dystrophy (FSHD).
   4. Congenital muscular dystrophy (CMD).
   
   
   Dozens of different genes that are associated with these types of muscular dystrophy have been identified. Most, but not all, of the proteins produced by these genes actually constitute a complex surrounding a central protein (known as dystrophin) and other proteins connected to it. The function of this complex is to attach the muscle fibers to one another. Each muscle is composed of many fibers that contract and relax at the same time. When the dystrophin complex is normal, all the muscle fibers move together without friction. When this complex is impaired, the resulting friction between the fibers causes progressive destruction of the fibers. The severity and the distribution of the muscles affected are determined by which of the proteins in this complex is involved.
   
   
2. Other muscle diseases there are many other muscle diseases that are not included in the group of muscular dystrophies. These diseases are each characterized by properties differing from those mentioned above, and the defect in them is not associated with the dystrophin complex, but with other complexes in the muscle.
   
   Muscle diseases not defined as muscular dystrophy are listed below:
   
   
   1. Myotonic dystrophy apart from muscle weakness, the characteristic difficulty in this disease is the relaxation of contracted muscles.
   2. Muscular metabolic disorders arising from defects in the complexes that provide energy to the muscle. The metabolic defects can be demonstrated by measuring the activity of the enzymes of the muscle respiratory chain. This is the enzyme chain that converts oxygen extracted from the air that is breathed into a chemical substance known as ATP. This provides the energy to the muscle.
   
   
   
3. Other problems manifesting as defects in muscle function that are not diseases of the muscle itself some of these diseases appear to be disorders of the muscles, but are in fact diseases of the nerves that conduct the stimuli from the brain to the muscles, or a disorder in the brain itself. There may also be metabolic disorders of the blood that are associated with muscular weakness, and other problems. The precise diagnosis of the disorder must therefore be made by a neurologist. The final tests and the verification of the diagnosis are carried out by a geneticist whenever possible.
   
   

Disorders manifesting as muscle weakness that are not diseases of the muscle itself are listed below
(see separate information sheet on each):

1. Spinal muscular atrophy: in this condition the muscle weakness is caused by a defect in the nerves in the spinal column. The disease is therefore not a muscle disease but a nerve disease. It manifests as generalized muscle weakness and tremor that is present in the tongue in particular. There are different types of varying severity.
   
   
2. Cerebral palsy.
   
   
3. Charcot Marie Tooth (CMT): This is a disease of the peripheral nerves that mainly affects the legs. The onset is in adulthood between the ages of 20 and 40. The legs are thin and have a characteristic shape caused by atrophy of the gastrocnemius muscles in the leg. This disease is transmitted by autosomal dominant inheritance and is slowly progressive. 70% of the patients have a genetic mutation that is demonstrable relatively easily this is a duplication of part of the gene known as 1CMT on chromosome 17. For other patients the diagnosis is difficult, time-consuming, and it involves considerable laboratory effort.
   
   

Clinical signs

Inheritance pattern

Penetrance

Associated features that can be demonstrated in tests performed during pregnancy

What is the risk of recurrence in a subsequent pregnancy?

Molecular genetic information

Genetic testing

What should be done before genetic counseling?

• Is an exact diagnosis known? If so, it will be relatively easy to give you an explanation and an evaluation of your risk level. It will also be possible to consider appropriate tests.
  
  
• Are the affected family members male only, and does the disease start in early childhood? If so, there are a number of possibilities of which the main ones are Duchenne muscular dystrophy or Becker muscular dystrophy. As noted, there are also other types of childhood muscular dystrophy. With the data you have, you can assist in the diagnostic process at the genetic institute during your counseling.
  
  
• Are the patients of both sexes and do they have muscular dystrophy dating from birth, or did the signs only appear at a few weeks of age? If so, there are a number of possibilities, such as myotonic dystrophy or SMA type 1.
  
  
• Did the disease begin in the second decade of life or later? If so, there are a number of other possibilities, such as CMT, myotonic dystrophy, etc.
  
  
• Is there evidence of hereditary transmission between parents and children? If so, this suggests autosomal dominant inheritance.
  
  
• Do you know whether the muscle or the nerves are affected? This is important for establishing the group of diseases.
  
  
• Did the weakness start in the upper or lower body? This is important for establishing the group of diseases.