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The new era in the various medical fields is going to be dealing mainly with genes and hereditary disorders, as they are becoming the commonest medical problems. One of the serious hereditary disorders that have been like a nightmare for some parents in USA, when affecting their child, is the muscular dystrophy disorder. Muscular dystrophies are of many types with each of them having its own characteristics which can be shared with other types of the disease. In this essay, muscular dystrophy will be described briefly and the focus will be mainly on the Duchenne and Becker muscular dystrophies.
They are a group of hereditary disorders that are characterized by progressive muscle wasting and weakness(1).
There have been several attempts to classifying the different types of muscular dystrophy. Walton and Nattrass proposed an original classification scheme which depends on two considerations: the mode of inheritance and the distribution of predominant muscle weakness(1) . Classification according to the mode of inheritance of muscular dystropy groups classifies certain types into a specific category as follow: 1,2,3 X-linked recessive
Autosomal recessive
Autosomal dominant
As was previously mentioned, MD is a group of hereditary disorders. Therefore, genes' abnormalities are considered the basic issue in such disorders. Like their variation in the mode of inheritance, each type of MD has its own unique genetic defect. If we consider Duchenne MD (DMD) and Becker MD (BMD) together, they are both X-linked recessive disorders in thier inheritance and the defect is caused by a mutation in the large (2.5 Mb) dystrophin gene which is located on the short arm of chromosome 21 (Xp21) (2,4). However, BMD is a mild form of the disease while DMD is a lethal one and affects one in 3500 males. That's because deletion or duplication (2/3 familial & 1/3 due to new mutations) in the dystrophin gene causes absence of the dystrphin protein in DMD while in BMD there is a mutation in the gene but only causing a defect in the dystrophin protein (5). In other words, the defect is quantitative in DMD while is qualitative in BMD.
As can be noticed from the previous paragraphs, muscular dystrphies are caused by genetic abnormalities. Genetic linkage techniques have been used in order to identify the area of the X-chromosome containing the defective gene (6). In the case of DMD, there is an absence of the dystrophin protein. Dystrophin is a long rod shaped protein that binds to actin at its N terminal and to a cell membrane associated glycoprotein. Therefore, it acts as a link between the contractile cytoskeleton and the cell membrane(5).
The main feature in muscular dystrophies is muscle weakness and wasting. Different dystrophies show variable symptoms, signs and rate of progression. In some types, skeletal deformities and contractures are common (3). Duchenne Mascular Dystrophy (DMD): DMD is the commonest and most serious form of the dystrphies (1). Affected boys with DMD may have normal muscles up to the age of 1-3 years. However, their milestones are delayed, i. e. they learn to stand and walk later than they are supposed to do and speech may be slow in development. The weakness progresses since it initially involves the proximal muscles of the pelvic girdle, later the shoulder girdle and terminally, the face 3,7. Gowers sign is a sign that can be seen in boys with DMD when the child can't rise from the floor easily. Hypertrophy of the calf muscles is another sign of DMD. Contractures at the knees and elbows are common. In addition, there is deformity and exaggeration of the normal lumbar lordosis As this disorder is progressive, it will lead most boys to use wheelchairs by the age of 10, and end them dead before or at the age of 20. The commonest cause of death is cardiac muscles involvement that will lead to cardiac faliure and consequently to respiratory failure (3,7). Becker dystrophy: This dystrophy can be described as a mild form of DMD. Usually, symptoms
onset is in the second decade of life, with inability to walk occurring about 20
years after the onset of symptoms. There is no cardiac involvement in this type
of dystrophy (3,6). Limb-girdle Muscular Dystrophy (LGMD): This muscular dystrophy is clinically and genetically a heterogeneous group of conditions. It consists of 11 subtypes characterized by predominately proximal muscle weakness and autosomal recessive inheritance. Autosomal dominant inheritance can be seen in few types of LGMD. Onset of symptoms occurs usually in the 2nd or 3rd decades associated with difficulty in climbing stairs and rising from the floor. Some subtypes are found to be caused by a muscle specific protease ( calpain 3) deficiency while others caused by sarcoglycans (dystrophin associated glycoproteins) deficiency. Like DMD, Gower sign is present but progression of muscle weakness is slow. Therefore, many patients loose walking ability by the age of 30 (1,6). Facioscapulohumeral Dystrophy: This is an autosomal dominant dystrophy and it varies in severity amongst affected individuals. Generally, onset of symptoms is towards the end of the first decade or the beginning of the second decade. Typically, weakness is first manifested in the facial muscles followed by the shoulder girdle with scapular winging and inability to elevate the arms (6).
Taking a proper history and performing a good and thorough physical examination constitute the first step in the establishment of a diagnosis. When suspecting any type of the muscular dystrophies , assay of muscle enzymes is performed as these leak from the diseased muscle cells. Creatinine kinase is the most useful and is elevated in DMD and less as elevated as in DMD as in BMD and other muscular dystrophies 6. EMGs and nerve conduction tests are used to distinguish neurogenic and myopathic electrical changes, and it is useful in identifying the underlying cause of muscle wasting and weakness (3). To confirm the diagnosis of myopathy, muscle biopsy is done. However, it doesn't in general distinguish different types of muscular dystrophy. Moreover, molecular assay (DNA testing) for dystrophin gene abnormality is diagnostic in many patients with DMD (6).
For detecting female carriers of Duchenne and Becker dystrophies and for prenatal diagnostic testing, molecular genetic studies are essential. When a family has an affected male, it is often necessary to know the specific gene mutation occurring in the family. However, some problems may arise in genetic counseling in DMD, an example is that when a mother has been identified as a transmitter of a mutation to more than one offspring and the tests yeild her not having the disease causing mutation. In general, if a mother gives birth to an affected son, prenatal testing must be considered in subsequent pregnancies because it can't be guaranteed that his dystrophy is a result of a new mutation and is therefore unlikely to recur (1).
In conclusion, muscular dystrophies are a heterogenous group of hereditary disorders. The commonest and most severe type is the Duchenne muscular dystrophy. Genetic counseling is becoming an essential measure to take in order to avoid or at least be able to manage such serious disorders. Therefore, preventive measures and good knowledge are the cornerstones in dealing with hereditary disorders in general.
1. Alan E H Emery. The muscular dystrophies. BMJ 1998 Oct 10; 317
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Introduction.