The limb-girdle muscular dystrophies

Written by Prof. K.M.D.Bushby MD FRCP, Professor of Neuromuscular Genetics, University of Newcastle upon Tyne

This fact sheet is for people for whom a diagnosis of limb-girdle muscular dystrophy (LGMD) has been suggested. This is a complicated subject since there are many different types of limb-girdle muscular dystrophy. Not all of the things that we talk about in this fact sheet will be relevant to everybody with the diagnosis.

What is limb-girdle muscular dystrophy?

Muscular dystrophy is the name given to a group of inherited conditions where there is a progressive wasting and weakening of muscle. There are many different types of muscular dystrophy. One of the ways in which the different types of muscular dystrophy are distinguished is by noting the groups of muscles that are involved first. The limb-girdle group of muscular dystrophies are so called because generally they cause weakness in the shoulder and pelvic girdle i.e. the big muscles around the top ( proximal) part of the arms and legs. Usually weakness of the legs is noticed before that of the arms and usually the muscles of the face are unaffected. Specialised tests for LGMD are now available through the scheme for specialised diagnosis funded by the Department of Health. Contact details can be found at the end of this fact-sheet

How has our understanding of the limb-girdle muscular dystrophies improved?

Our understanding of the LGMDs has improved dramatically over the last few years. When the term ‘limb-girdle’ muscular dystrophy was first coined by Dr Walton and Dr Nattrass in 1954 there was no clear understanding of what the condition really involved. It was something of a ‘catch all’ term used fairly widely to distinguish people with predominant limb-girdle weakness from other types of muscular dystrophy, such as Duchenne, facioscapulohumeral and congenital. Because this was not a very specific use of the term, a lot of people who were thought initially to have had LGMD in fact turned out to have other conditions. On the other hand, the diagnosis of LGMD has been delayed in other people. This was partly because there are MANY other conditions that can cause weakness of the big muscles of the arms and legs. Research over the last few years has changed things very dramatically. We can now understand the real cause for a number of different types of limb-girdle muscular dystrophy and can even distinguish different types.

What are the different types of limb-girdle muscular dystrophy?

The different types of LGMD have all gone through various name changes and reclassifications over the last few years. They are listed at the end of this fact sheet. All forms of LGMD have a genetic (inherited) basis. The LGMDs are divided into two main groups depending on the way they are passed on in families. On this basis, they are grouped into autosomal recessive or type 2 LGMD and the much rarer group of autosomal dominant or type 1 LGMD. They can be further subdivided on the basis of more complicated gene or muscle protein tests which may tell us exactly where the problem lies.

Please note that sophisticated diagnostic tests will not be possible in all hospitals and may not be possible at all if appropriate samples are not available. Please speak to your consultant if you wish to find out more.

How is limb-girdle muscular dystrophy diagnosed?

The first clue towards the diagnosis of LGMD is usually obtained when your doctor takes your medical history and examines you. Occasionally the pattern of the muscle involvement may suggest a particular form of muscular dystrophy but usually a number of different tests will be needed to make the diagnosis. These will include a selection of blood tests, electrical tests and very importantly a muscle biopsy. Each of the tests on their own can indicate that LGMD might be a likely diagnosis. It is, however, usually by studying a muscle biopsy that we can be most clear about what type of LGMD someone might have. This is because we are now able to look directly at the proteins which may be reduced or absent in different types of LGMD. These proteins are essential to the health of the muscle but when they are abnormal, present in low levels or even absent muscle breaks down more easily. In most situations the muscle biopsy gives the best chance of reaching a precise diagnosis. However, even today we cannot be sure of the precise type of LGMD in some people. At present it is not usually possible to make the diagnosis simply on a blood test though sometimes this may be useful to confirm a diagnosis which is already suspected.

What are the genetic implications?

Approximately 90% of LGMD is inherited as an autosomal recessive disorder. For someone to have one of these conditions they have to have two faulty copies of the gene responsible. All of our genes come in pairs, one from our mother and one from our father. If someone has an autosomal recessive type of LGMD both of their parents must be carriers (see diagram).

These parents will, together, have a 1 in 4 chance of having another baby with LGMD.

People with autosomal recessive types of LGMD rarely have affected children (for the risk of meeting and having a child by a carrier of the same faulty gene will be rare); all of their children will have inherited one copy of the faulty gene but are unaffected.

The different types of recessive LGMD

For autosomal dominant types of LGMD, only one copy of the gene needs to be faulty. Every time an affected individual has a child, whatever their sex, that child has a 50% risk of inheriting the same condition. These types of LGMD are relatively rare.

Alternative namesInheritanceProtein involvedWhat type of Muscular Dystrophy?Test available?
LGMD2A calpain deficency, calpainopathyARcalpain 3Often presents aged 8-15, though may be earlier or later. Not usually very rapidly progressiveY
LGMD2B, dysferlinopathy (dysfe-rlin defiency), Miyoshi myopathyARdysferlinOften presents in late teens. People may notice difficulty standing on toes as an early feature. Usually slow worsening of problemsY
LGMD2C,2D,2E,2F Sarcoglycan defiency, sarcoglycano-pathy. Previously called autosomal recessive muscular dystrophy of childhood.AROne of the sarcoglycan proteins (a ,b,g,d)Very variable. Sometimes causes other childhood problems: otherwise may be later in lifeY
LGMD2GARtelethoninSo far only reported in BrazilN
LGMD2HARnot knownSo far only reported in Canada 
LGMD2IARnot knownSo far only reported in Tunisia   

The different types of dominant LGMD

Alternative namesInheritanceProtein involvedWhat type of Muscular Dystrophy?Test available?
LGMD1AADmyotilinSo far only reported in one large family in AmericaN
LGMD1BADlamin A/CMay have a heart problem as well as muscle weaknessY
LGMD1CADcaveolin3So far rarely seenY
LGMD1D,1EADnot knownVery rarely reported so farN

AD =Autosomal Dominant
AR = Autosomal Recessive