Limb Girdle Muscular Dystrophy
Fact Sheet # 13
Is Limb Girdle Muscular Dystrophy also known by other names?
No, this type of muscular dystrophy (MD) is only known by its original name, but its abbreviation "LGMD" or "LGD" is often used.
What is Limb Girdle Muscular Dystrophy?
The muscular dystrophies are inherited progressive disorders that cause breakdown of muscle fibres. In the early days of muscular dystrophy research only four main types of muscular dystrophy were known: Duchenne, Facioscapulohumeral, Myotonic and a final group which was given the name of Limb Girdle Muscular Dystrophy (LGMD). It is now known that a number of conditions with different causes and different genetic implications may present with symptoms similar to LGMD. Therefore:
- Some individuals earlier diagnosed as having LGMD did not have muscular dystrophy at all, but one of several clinically similar disorders such as spinal muscular atrophy (an inherited disorder of spinal nerve cells) or polymyositis (an inflammation of muscles which is not inherited).
- There are several types of muscular dystrophy that can have rather similar features, but different inheritance patterns. Only a minority of people with muscular dystrophy that present with weakness in the limb and girdle muscles actually have Limb Girdle muscular dystrophy.
It is therefore evident that the term Limb Girdle Muscular Dystrophy is still used to refer to many disorders that may be quite different. This is important to note because these disorders differ in their rate of progression, outcome and especially in their mode of inheritance - so that misleading genetic advice may be given if a more precise diagnosis is not obtained. Some doctors now consider that the name "Limb Girdle Muscular Dystrophy" should no longer be used at all. It is advised that individuals who have been given this diagnosis should receive up to date advice about the particular type of MD that is affecting them or members of their family. In paragraph 12 there is a list of disorders that may have been labelled as LGMD in the past.
What causes Limb Girdle Muscular Dystrophy?
Many different types of LGMD have been identified, and have been associated with genes (or regions) on the following chromosome (chr): Type 1A - chr 5q, type 1B - non-5q type, type 1C - chr 3p, type 2A - chr 15q, type 2B - chr 2p, type 2C - chr 13q, type 2D - chr 17q and type 2E - chr 4q. Not all the genes or mutations (in these regions on the different chromosomes) have been identified. However, the adhalin gene (chr 17q), the caveolin-3 gene (chr 3p), the calpain-3 gene (chr 15q), gamma sarcoglycan gene (chr 13q) and the beta sarcoglycan gene (chr 4q) are some of the genes that have been identified to date.
What are the symptoms?
The LGMDs differ widely in clinical severity and age of onset. Muscle weakness and wasting of the proximal and pelvic girdle muscles are the typical features of LGMD.
Which muscles are affected?
The main features of the Limb Girdle type are that the muscles of the upper or "proximal", parts of the limbs are mainly involved, the muscles of the face are spared and the symptoms of weakness are usually first noted in late childhood, adolescence or adult life (thus differing from the Duchenne type). Both males and females might be affected and their brothers or sisters are generally much more often affected than their parents or children.
How is Limb Girdle Muscular Dystrophy inherited?
LGMD is inherited in an autosomal recessive or autosomal dominant pattern. Types 1A - 1C are all inherited in an autosomal dominant manner. Here each child of an affected individual has a 50% chance of inheriting the disorder. All the forms of Type 2 are inherited in an autosomal recessive manner. Each child of a couple that are both carriers, has a 25% chance of being affected. As this is a genetic condition, genetic counselling is strongly recommended. Genetic counselling provides information on the inheritance pattern, risks to other family members, prognosis, psycho-social support, as well as information about diagnostic testing, carrier testing, preclinical and prenatal testing (where available).
How is Limb Girdle Muscular Dystrophy diagnosed?
In the past the diagnosis of LGMD use to be made solely on a clinical evaluation. However, the genes responsible for some forms of LGMD have recently been identified. There is therefore a DNA test that can confirm the diagnosis of some of the forms of LGMD, particularly in individuals who have a strong family history of LGMD. It is still important that the diagnosis of LGMD only be made after all the alternatives have been considered and excluded by modern diagnostic procedures.
Is there a cure?
No, unfortunately there is no cure for this type of muscular dystrophy yet.
Is there any treatment?
There is no specific treatment for LGMD.
Is there a risk during anaesthesia?
It is always recommended that the presence of a muscular disorder be mentioned to your doctor.
Has research been conducted on Limb Girdle MD in South Africa?
No research has been conducted on LGMD in South Africa, although a number of South African patients and families have been included in overseas research efforts. There are multiple international research efforts underway to unravel the causes of LGMD.
Conditions that may have been labelled as LGMD in the past
Some of the conditions that may have been labelled as LGMD are listed below, together with an indication of how they are inherited, or alternatively their non-genetic nature. Most of the non-dystrophic disorders (that is conditions which are not strictly speaking muscular dystrophies at all), which may be clinically similar to LGMD, are relatively easily distinguished from it and from each other on muscle biopsy, though this may sometimes require specialised techniques - which are not always available in South Africa. It can be more difficult to tell one sort of muscular dystrophy from another on muscle biopsy alone. The following muscular dystrophies were most likely to have been misdiagnosed as LGMD in the past:
- Becker muscular dystrophy: A milder variant of Duchenne MD; affects males; now identifiable by measurement of a protein called dystrophin that is partially deficient in the muscle tissue in this disorder. In some cases it is possible to make a diagnosis without muscle biopsy if a special blood test is able to detect that a tiny part of the gene is missing (this is called a DNA deletion). Becker MD should be excluded in all males who were thought to have LGMD. All the daughters of an affected male are carriers of the gene and the boy’s mother, sisters and maternal aunts may be carriers. The sons of carriers each have a 50% chance of being affected.
- Manifesting female carriers of the gene for Duchenne Muscular Dystrophy: Women who can transmit the gene for Duchenne or Becker muscular dystrophy are known as carriers. Usually they have no muscle weakness, but occasionally they have a relatively mild form of muscular dystrophy and are then known as manifesting carriers. If they have no near male relative who is affected, the true nature of their weakness may be far from obvious and very difficult to identify and they may have been diagnosed as having "Limb Girdle Muscular Dystrophy". However for these women there is a 50% chance that each time they have a son he could have Duchenne or Becker MD, so the diagnosis is important. Women diagnosed as having LGMD, especially if they have no family history of MD, should seek specialist advice about this possibility. Research in molecular biology and on dystrophin in the next few years may help to make diagnosis easier - at present it requires rather specialised and laborious laboratory techniques. A very rare and special category of manifesting carriers has identifiable chromosome anomalies (translocations) that are helpful in diagnosis.
- Scapulohumeral muscular dystrophy: An uncommon disorder characterised by predominant involvement of the shoulder muscles beginning in adolescence or early adult life. The facial muscles are not affected.
- Scapuloperoneal muscular dystrophy: A group of disorders in which weakness of the muscles of the shoulders and below the knees is characteristic. There are various modes of inheritance.
- Emery-Dreifuss muscular dystrophy: Muscle weakness, rather similar in distribution to the scapuloperoneal type, shortening of muscles (giving contractures especially at the ankles, elbows and back of the neck) and cardiac conduction problems are the main features of this X-linked disorder. It is not related to Duchenne or Becker MD, although its pattern of inheritance is the same.
- Autosomal recessive muscular dystrophy of childhood: This condition may be confused with Duchenne Muscular Dystrophy (DMD) in boys, and in girls may be difficult to distinguish from the manifesting carrier state, though the mode of inheritance is completely different. Either sex may be affected, and creatine kinase levels are very high. The progression of the muscle weakness may be fast but is usually somewhat milder than DMD. Muscle biopsy shows an active muscular dystrophy, but the protein dystrophin that is defective in DMD is normal in the autosomal recessive form. This form of muscular dystrophy is common in some North African areas, but relatively rare elsewhere. Research involving a group of families from North Africa has localised the gene responsible for one form of muscular dystrophy to chromosome 13. A protein associated with dystrophin has been shown to be abnormal in some of the affected individuals. It is not known whether the form of autosomal recessive muscular dystrophy of childhood seen elsewhere, is caused by the same genetic defect as the North African form or not.
- Autosomal recessive proximal muscular dystrophy of later onset: This category is much rarer than originally thought, before techniques existed to distinguish LGMD from the other conditions discussed earlier. There is variability again within this category, with some individuals presenting in late childhood and others much later. The progression of the disorder is also variable. A gene on chromosome 15 is responsible for some, but not all, cases of this condition.
- Autosomal dominant proximal muscular dystrophy: This condition may be very difficult to distinguish clinically from the recessive form. It is rare, may occur in either sex and may be transmitted from parent to child through several generations. It is usually relatively mild. In theory, this disorder may be seen in isolated cases as the result of a spontaneous "mutation" in the gene. In one large American family the gene for their condition has been localised to chromosome 5, but it is not yet known whether the condition in other families is caused by problems in the same gene or not. It is still important that the diagnosis of LGMD only be made after all the alternatives have been considered and excluded by modern diagnostic procedures.
- Non-dystrophic disorders, and muscular dystrophies, that may resemble LGMD are listed below:
- Spinal muscular atrophy (Kugelberg-Welander syndrome)
- Glycogen storage myopathies
- Lipid storage myopathies
- Mitochondrial myopathies
- Central core disease
- Centronuclear myopathy
- Multicore myopathy
- Inclusion body myositis
- Muscular dystrophies which may be diagnosed as LGMD
- Becker MD
- Facioscapulo humeral MD
- Manifesting Duchenne carriers
- Scapulohumeral MD
- Scapuloperoneal MD
- Emery-Dreifuss MD
Please contact your local MDF office for further information.
Please note: The treatments and drugs mentioned in this fact sheet are for information purposes ONLY. Please consult your physician or other health care specialist for information regarding the use of any of the above. The MDF encourages duplication of this fact sheet, under the following condition: that it is duplicated in its entirety - including the MDF logo and full text. Only individuals authorised by the MDF may make changes to this fact sheet (the information "updated by" and "last update" should be completed). Alterations to this fact sheet by any other party are strictly prohibited.