Congenital Muscular Dystrophy (CMD)

Overview of Congenital Muscular Dystrophy (CMD)

Congenital muscular dystrophies (CMD) are a group of genetic disorders in which weakness and dystrophic pattern on muscle biopsy are present at birth or emerge during the first months of life. In contrast to progressive muscular dystrophies with later onset, muscle weakness tends to be more stable overall, depending on the individual disease, but complications of the dystrophy can become more prominent over time. In 1903, Batten published the first case reports of a congenital form of muscular dystrophy. The mode of inheritance for most CMD is autosomal recessive, except for Ullrich's CMD, which can be inherited in either autosomal dominant or autosomal recessive fashion.

Regulating Factors of CMD

Several of the proteins affected (primary and secondary) in CMDs are associated with the sarcolemma and are involved in the interaction between the muscle cell and the extracellular matrix. These include cell surface receptors, such as integrins, basal lamina proteins, such as laminin-α2, and extracellular matrix proteins, such as collagen VI. Disruption of the mechanical and probably also the signaling links provided by these proteins is thought to be at the center of the pathological mechanism in each condition. The other major group of proteins includes those with known or putative enzyme activity that resides, and probably act, intracellularly, such as POMT1 (protein O-mannosyl transferase 1) and POMGnT1 (protein Omannose b1,2-N-acetylglucosaminyltransferase 1). In addition, the function of some of the proteins involved has yet to be proven. These include fukutin, fukutinrelated protein (FKRP), LARGE, and selenoptotein-1 (SEPN1). There is a degree of association between all these proteins either by means of direct interaction (such as laminin-α2 and integrin α7), a common binding partner (such as dystroglycan, collagen VI, and biglycan), or by acting upon each other (the glycosyltransferases that act on dystroglycan).

Table.1 CMD forms where the causative gene is known.

Treatment of CMD

The clinical care of patients with CMD is difficult because the clinical course and progression is very diverse between, and even within, the different subtypes and there is only very limited published evidence about the best treatment strategy. Currently, there is no curative treatment for any of these diseases, but symptomatic care is very important and can significantly improve quality of life. Many treatment decisions are derived from other neuromuscular disorders or based on consensus statements and personal experience. The main areas of care in patients with CMD include, but are not limited to, respiratory care, nutritional care, orthopedic care/rehabilitation, and cardiology. From this list, it is obvious that patients with CMD require an experienced interdisciplinary team to cover all their needs.

Perspective

Although advances in the field of molecular genetics, cell biology, and biochemistry have substantially improved the understanding of pathogenic mechanisms in the different types of CMD, the development of curative treatment strategies is still at a preclinical stage. For future clinical trials, exact classification, and characterization of patients with CMD are a prerequisite and patient registries for CMD have recently been established as a helpful tool.

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