Limb girdle muscular dystrophy (LGMD) is in fact not one single condition but a number of different inherited muscular dystrophies that are grouped under the label “limb girdle” because they generally affect the pelvic and shoulder girdles, causing weakness in the muscles in the top part of the arms and shoulders and the hips and thighs. These muscles are often called the “proximal” muscles because they are nearest to the body. The weakness usually affects the legs first, followed by the arms. It rarely affects the face. Some types of LGMD may also cause weakness in the “distal” muscles – those in the feet, ankles and calves, and the hands and wrists. A few specific types may cause heart problems or weakness of the breathing muscles.
To date, over 20 different types of LGMD have been identified and an overview is provided in the table at the end of the page. The different types of LGMD are caused by different genetic faults. The genes that may be affected in LGMD are responsible for various aspects of muscle function, and when there is a fault in one of these genes, the muscles cannot work properly and weakness occurs.
The common features all people with any type of LGMD experience include weakness of the large muscles of the legs and/or arms. This may result in frequent falls, difficulty in running, climbing stairs and rising from the floor or from a chair. As the condition progresses, they may start to have problems with walking and may need to use a wheelchair over time. However, each different type has some specific features and characteristics, such as age of onset of symptoms, rate of progression, particular muscles involved, and heart and respiratory involvement.
The types of LGMD are split into two groups: those that are inherited in an autosomal recessive fashion (type 2) and those that are inherited in an autosomal dominant fashion (type 1), which are much rarer. About 90% of the LGMDs are inherited in an autosomal recessive fashion. This means that two copies of the faulty gene need to be inherited, one from each parent, who are both carriers.
LGMDs all progress at different rates, even within the same family. While there is no specific treatment to correct the mutations that cause the LGMDs, there is a lot that can be done to manage the condition. Maintaining good levels of mobility is important and receiving the right physiotherapy to achieve this is paramount. Monitoring heart and respiratory function is also vitally important as the heart and respiratory muscles are known to be affected in particular types of LGMD. Early and prompt treatment and early surveillance is much better than waiting for problems to occur and then trying to deal with them.
The LGMDs are diagnosed using a combination of both the medical history and clinical signs when the patient is seen, and by further testing. These tests include genetic tests which may confirm the diagnosis that was suspected by the clinician. A muscle enzyme blood test (CK), DNA analysis, a muscle biopsy (taking a small sample of an affected muscle) and electrical tests (EMG) may also be performed. Imaging of the muscles as in MRI (Magnetic Resonance Imaging) scans may also be done to look at potential muscles for biopsy as well, to show the clinican the pattern of muscle involvement.
A muscle biopsy looks at the muscle fibres and whether they appear normal or not. Someone with LGMD will demonstrate a loss and change of some of these muscle fibres as well as a substitution of muscle with fat in some cases. In other tests such as (A) immunochemistry and (B) immunoblotting we can look directly at the muscle proteins which are reduced or absent in different types of LGMDs.
Whilst there is not yet a specific treatment other than optimal management, there is ongoing research in the limb girdle muscular dystrophy field, including registries for patients and research studies aiming at developing possible outcome measures for clinical trials.