Congenital muscular dystrophies
Introduction to Congenital Muscular Dystrophies
Congenital muscular dystrophies (CMDs) are a group of inherited rare neuromuscular diseases.
They belong to the group of diseases known as ‘muscular dystrophies’. Muscular dystrophies occur when mutations (faults) in different genes disrupt the production of proteins needed to produce and maintain healthy muscle.
The congenital muscular dystrophies as a group encompass great clinical and genetic heterogeneity (diversity) so that achieving an accurate genetic diagnosis has become increasingly challenging, even in the age of next generation sequencing1.
CMDs are ‘congenital’ because symptoms are usually apparent at birth, or from a very early age. Babies are born with hypotonia (low muscle tone), and often referred to as ‘floppy babies’.CMD may be diagnosed at an older age either because a definitive CMD diagnosis has not yet been established despite congenital onset or because symptom onset or symptom recognition had been delayed1.
All CMDs are characterised by muscle weakness, joint contractures (stiffness) and delays in reaching motor milestones. There may be feeding problems, and weak breathing muscles can cause respiratory problems. Some CMDs can also affect the brain, resulting in learning difficulties.
People with the same subtype of CMD and within the same family may have a very different experience of the disease. The early onset of symptoms does not necessarily mean that the CMDs are more severe than other muscular dystrophies.
Individual CMD forms are rare so that only highly specialised centres have the combined diagnostic experience and technology to cover all subtypes1. The subtypes of CMD can have symptoms similar to other conditions, such as the Limb Girdle Muscular Dystrophies (LGMDs) and the Congenial Myopathies.
The incidence and prevalence of CMD in various populations is not sufficiently known1. The relative frequency of individual types also varies in different populations1.
The extracellular matrix (ECM) surrounds and supports muscle cells and other tissues. It is important for the survival and regeneration of muscle, and plays an important role in transmitting force from the muscle fibres onto the tendons and bones.
Glycoproteins are one of the many kinds of proteins in the ECM. The majority of CMD subtypes occur when a genetic mutation disrupts or halts the production of glycoproteins. This leads to an increased risk of cell damage from normal muscle contraction. There may also be a reduction in the ability of the muscle to repair this damage.
A small number of CMD subtypes occur due to a problem with the proteins that determine the behaviour of muscle fibres.
Some CMD subtypes occur from genetic mutations in the proteins that ‘sugar-coat’ (glycosylate) an ECM protein and allow it to connect to other proteins.