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Limb-girdle muscular dystrophy

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Limb-girdle muscular dystrophy
Classification and external resources
ICD-10 G710
ICD-9 359.1
OMIM 159000 159001 607801 603511 602067 608423 609115 253600 253601 253700 608099 604286 601287 601954 254110 607155 608807 609308 611307 611588 607439 606822
DiseasesDB 32189
MedlinePlus 000711
eMedicine neuro/189
MeSH D049288
GeneReviews Template:Citation/make link

Limb-girdle muscular dystrophy or Erb's muscular dystrophy is an autosomal class of muscular dystrophy that is similar but distinct from Duchenne muscular dystrophy and Becker's muscular dystrophy. Limb-girdle muscular dystrophy encompasses a large number of rare disorders. Currently, there is no cure and the disease inevitably worsens over time.


The term "limb-girdle" is used to describe these disorders because the muscles most severely affected are generally those of the hips and shoulders—the limb girdle muscles.

Common symptoms of limb-girdle muscular dystrophy are muscle weakness, myoglobinuria, pain, myotonia, cardiomyopathy, elevated serum CK, and rippling muscles.

The disease inevitably gets worse over time; although some individuals feel the affects more rapidly than others. Eventually the disease involves other muscles such as the ones located in the face. The disease causes loss of movement or dependence on a wheelchair within twenty to thirty years. [1]

The muscle weakness is generally symmetric, proximal, and slowly progressive.

In most cases, pain is not present with LGMD, and mental function is not affected.

LGMD can begin in childhood, adolescence, young adulthood or even later. The age of onset is usually between 10 and 30. Both genders are affected equally. When limb-girdle muscular dystrophy begins in childhood the progression appears to be faster and the disease more disabling. When the disorder begins in adolescence or adulthood the disease is generally not as severe and progresses more slowly.

There is no sensory neuropathy or autonomic or visceral dysfunction at presentation. The specific dermatomes affected can be demonstrated clinically, and although lower limb deep tendon reflexes and plantar reflex are lost, abdominal reflexes are preserved.


A person with LGMD generally has difficulty walking, going both up and down stairs and raising from a chair or a squatting position. Difficulty bending over and falling on a regular basis are also common. Difficulty lifting certain objects is also a common presentation of LGMD as well as difficulty holding your arms out or above your head.[2] Eventually the ability to walk/run becomes non-existent. It is advised that someone with the disorder not put themselves in situations of potential peril. For example, walking on floors that have even the slightest incline can cause the individual to lose balance and fall. It is not recommended for someone with the disease to walk on terrain which is not stable such as ice or other slippery surfaces to avoid a severe injury. This is mainly due to the fact that LGMD weakens the leg muscles so an individual with LGMD would be more inclined to fall than someone who does not suffer from the disorder. At times a palpitation in the heart can occur.[3]


The distal muscles are affected late in LGMD, if at all. The disease causes loss of movement or a dependence of a scooter/wheelchair within a 20 to 30 year timeframe.[3] The various forms of LGMD are highly variable, and can be variable even among persons with the same form of LGMD. In its most severe form, LGMD2C, the symptoms are usually similar to Duchenne Muscular Dystrophy, with individuals losing the ability to walk between ages 10 and 12.

While LGMD isn't typically a fatal disease, it may eventually weaken the heart and respiratory muscles, leading to illness or death due to secondary disorders. In its most severe form, LGMD2C, lifespans are typically limited to the 20s or early 30s.


A muscle biopsy will show the presence of muscular dystrophy, and genetic testing is used to determine which type of muscular dystrophy a patient has.

Currently a "CHIP" is being developed by an organization called "NMD CHIP"

The project is designing chips for the diagnosis of mutations already known to cause Duchenne / Becker muscular dystrophies (DMD/BMD), limb girdle muscular dystrophies (LGMD), congenital muscular dystrophies (CMD), and hereditary motor-sensory neuropathies or Charcot-Marie-Tooth neuropathies (CMT). These diagnostic chips are described as "known-gene chips".

A project website has been set up at which enables dissemination of information about the project to stakeholders.


LGMD is typically an inherited disorder, though it may be inherited as a dominant, recessive, or X-linked genetic defect. The result of the defect is that the muscles cannot properly form the proteins needed for normal muscle function. Several different proteins can be affected, and the specific protein that is absent or defective identifies the specific type of muscular dystrophy. Among the proteins affected are α, β, γ and δ sarcoglycans. The sarcoglycanopathies could be possibly amenable to gene therapy.


Although exercise and physical therapy are advised to maintain as much muscle strength and joint flexibility as much as possible, there are few studies that are able to detail the effectiveness of exercise. Physical therapy and exercise may prevent the development of the disease. However, this is mainly used to prevent the rapid development of the disease rather than halt it, or get better.[4] Calipers may be used to maintain mobility and quality of life. Careful attention to lung and heart health is also required. IVIg may increase strength in some forms and prevent progression in others, possibly through the prevention of fibrosis and inflammation without the secondary weakening caused by corticosteroids.


Because it is a hereditary disorder, there is nothing an individual can do to prevent contraction of the disease. Because the weakness can affect heart muscles, it is recommended that a doctor is aware of any heart related symptoms so a cardiac pacemaker or defibrillator can be administered to reduce the risk of sudden death due to an abnormal heart rhythm caused from the disease.[3]


There is a variety of research underway targeted at various forms of LGMD. Methods thought to hold significant promise for an effective treatment include "exon skipping" and gene therapy. Several clinical trials are underway and seeking to apply these methodologies to various limb girdly dystrophies.

GENETHON - LGMD 2C(Gamma-sarcoglycanpathy)


JERRY MENDELL - LGMD 2D(alpha-sarcoglycanpathy)

Researchers in the US led by Prof. Jerry Mendell have published the results of a gene therapy trial for limb girdle muscular dystrophy type 2D (LGMD2D). Individuals affected by this condition have a fault in their 'alpha-sarcoglycan' gene which contains the instructions for a protein which is essential for muscle function. In this clinical trial three teenagers with LGMD2D had a virus containing a healthy copy of the alpha-sarcoglycan gene injected into a muscle in their foot. Not only was the gene therapy deemed to be safe, a significant amount of alpha-sarcoglycocan protein was produced which persisted for at least three months.

The researchers inserted a healthy copy of the human alpha-sarcoglycan gene into the AAV1 virus along with a molecular 'switch' that would only allow the alpha-sarcoglycan protein to be produced in muscle. This virus was injected into one small muscle in the foot. The same muscle in the other foot was injected with saline (salty water) as a control. Either six weeks (two patients) or 3 months (one patient) after the injection the production of alpha-sarcoglycan protein was assessed.

The muscles injected with the virus strongly produced the alpha-sarcoglycan protein in up to 69% of muscle fibres and was correctly located in the muscle membrane. This in turn restored the structure of a cluster of proteins that is normally found in muscle cells but is missing in muscles that lack alpha-sarcoglycan. This protein cluster is vital for the structure of the muscle fibres.

The results of this phase I clinical trial of gene therapy for LGMD2D are very promising. However, delivery of the gene therapy to the whole body, for example via the blood stream, is required for an improvement in symptoms to be seen in patients. This will be the next step in the development of gene therapy for LGMD2D. Clinical trials will be needed to determine the optimal route of administration, dose and the long term safety of the treatment.

The success of the AAV1 virus to deliver the gene to the muscles in this trial also bodes well for the development of gene therapy for other neuromuscular conditions.

List of limb-girdle muscular dystrophiesEdit

The "LGMD1" family is autosomal dominant, and the "LGMD2" family is autosomal recessive.

Name OMIM Location
LGMD1A 159000 TTID
LGMD1B 159001 LMNA
LGMD1C 607801 CAV3
LGMD1D 603511 7q
LGMD1E 602067 6q23
LGMD1F 608423 7q32.1-q32.2
LGMD1G 609115 4q21
LGMD2A 253600 CAPN3
LGMD2B 253601 DYSF
LGMD2C 253700 SGCG
LGMD2D 608099 SGCA
LGMD2E 604286 SGCB
LGMD2F 601287 SGCD
LGMD2G 601954 TCAP
LGMD2H 254110 TRIM32
LGMD2I 607155 FKRP
LGMD2J 608807 TTN
LGMD2K 609308 POMT1
LGMD2L 611307 ANO5
LGMD2M 611588 FKTN
LGMD2N 607439 POMT2

References Edit

External linksEdit

|} Template:Inherited disorders of trafficking Template:Cytoskeletal defects Template:Other cell membrane protein disorders


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