Limb-Girdle Muscular Dystrophies-LGMD
They include dystrophies that show symptoms in childhood or adulthood and are not associated with X chromosome mutations, such as in Duchenne or Becker Muscular Dystrophy. They are distinguished in many categories according to the location of the mutation and the protein damaged and can be inherited autosomally either in a recessive or dominant way. They are generally present at 1: 14,500 to 123,000 births worldwide, but sarcoglycanopathies in 1: 178,000 births.
Clinical features mainly involve muscle weakness, either in the muscles near torso or in distant muscles secondarily, as well as in the muscles of the abdomen or neck rarely. Moreover, in the most rare cases, orthopedic complications such as scoliosis, respiratory and cardiac problems such as cardiomyopathy are present. Muscles may be either hypertrophic or atrophic, depending on the type of mutation. Finally, incidents with rigid spine and speech problems have been recorded.
Limb-Girdle autosomal recessive muscular dystrophies
Here are the four subgroups of sarcoglycanopathies (α or LGMD2D or LGMD R3 Alpha-sarcoglycan-related, β or LGMD2E or R4 Beta-sarcoglycan-related, γ or LGMD2C or LGMD R5 Gamma-sarcoglycan-related and δ or LGMD2F or LGMD R6 Delta-sarcoglycan-related), calpainopathy (LGMD2A or LGMD R1 Calpain3-related), dysferlinopathy (LGMD2B or LGMD R2 Dysferlin-related) and other very rare dystroglycanopathies. In particular dysferlinopathy is distinguished in three additional subcategories: Miyoshi myopathy, DMAT and rigid spine dysferlinopathy.
In the first category, the mutations are related to sarcoglycans, which normally support the cytoskeleton of muscle cells and the binding of dystrophies to the sarcoglycans, while calpain and dysferline are proteins that normally help in the repair and reconstruction of muscle cells when necessary.
Furthermore, there are the LGMD 7-21 subcategories related to the protein mutated.
In this category, after renaming all LGMDs, recessive Bethlem myopathy is considered LGMD R22 collagen 6-related.
Autosomal dominant Limb-Girdle muscular dystrophies
They are very rare and are characterized by LGMD1D (renamed as LGMD D1 DNAJB6-related), LGMD 1F (LGMD D2 TNP03-related), LGMD 1G (LGMD D3 HNRPNL-related) and LGMD 1I (LGMD D4 calpain3-related). They mainly concern adults, without excluding the case of childhood onset. Generally symptoms are related to gradually generalized muscle weakness, respiratory and cardiac problems, speech problems, but again they depend on the type of mutation.
Additionally, dominant Bethlem myopathy (LGMD D5 Collagen 6-related) and Muscular Dystrophy related to laminin a2 (LGMD R23 Laminin a2-related) and Muscular Dystrophy related to POMGNT2 (LGMD R24 POMNGT2-related) are included in this category.
There is no cure and symptom management should be proportional to each type of LGMD. General guidelines that can increase life expectancy and improve quality of life are:
- Monitor weight and avoid obesity.
- Physiotherapy and stretching exercises to promote movement and avoid muscle contractions.
- Assistive devices e.g. wheelchairs, orthotics for ease of movement.
- Surgical interventions for the correction of orthopedic complications e.g. scoliosis.
- Use of respirators in case of respiratory problems and regular monitoring by a pneumologist.
- Cardiac monitoring especially in cases of cardiomyopathy.
- Social and emotional support for social inclusion management.
Guideline summary by the American Association of Neuromuscular & Electrodiagnostic Medicine:
Information about clinical trials conducted globally: https://www.centerwatch.com/clinical-trials/listings/condition/350/muscular-dystrophy/ and https://clinicaltrials.gov/ct2/home.
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