Muscular dystrophy

Muscular dystrophies (MD) form a clinically and genetically heterogenous group of inherited, progressive disorders of muscle. Common symptom of all MD is a progressive muscle weakness and atrophy, which vary in distribution and severity between the different forms of MD. In general, the morphological analysis of a muscle biopsy already leads to the diagnosis MD, but it often does not allow classification within the group of these diagnoses. 

MD can become symptomatic in any age group. Children suffering from congenital muscular dystrophies (MDC) show a generalized hypotonia ("floppy infant") already shortly after birth, whereas patients with oculopharyngeal MD (OPMD) notice the first symptoms only in their 5th or 6th decade. 

It is estimated that one out of 2000 or 3000 persons of the German population suffer from an inherited neuromuscular disease.  

The most frequent form of muscular dystrophy is the X-linked recessive Duchenne Muscular Dystrophy, which was described first by G. Duchenne in 1861. In 1986, the disease causing gene was identified, and shortly afterwards also the gene product, allowing the molecular diagnosis of DMD and its milder variant Becker-Kiener Muscular Dystrophy (BMD).

About 50 years later, Batten published the first cases of congenital Muscular Dystrophy (MDC). In contrast to the Duchenne/Becker phenotype, muscle weakness and dystrophic changes in muscle are already present at birth.

For centuries the molecular causes for MD remained elusive. MD were therefore classified into a few subgroups based on mere clinical aspects. Major breakthroughs in molecular genetics in the late 1980s led to the identification of the dystrophin gene and its protein product dystophin. Mutations in the dystrophin gene result in dystrophin deficiency, the pathogenic basis of dystrophinopathies. Numerous MD are caused by mutations in other genes resulting in deficient proteins on the sarcolemmal, cytoplasmatic or nuclear level. An increasing number of genes has been associated to different forms of MD in the course of the last century. These findings have led to radical changes in the classification of MD, accentuating the molecular basis as compared to clinical symptoms like age of onset, severity, inheritance and primarily affected muscle groups.

Many forms of MD are caused by deficient proteins of the sarcolemma. But also proteins associated with the nucleus, enzymes or sarcomer can induce MD. However, the underlying pathogenic mechanism eventually leading to a degeneration of muscle cells is still unclear for most forms of MD. In spite of a genetical and clinical heterogeneity, all forms histologically show a myopathic morphology with muscle fibre degeneration and fibrosis.