Limb girdle muscular dystrophy R1 (LGMDR1)

Limb girdle muscular dystrophies (LGMD) are a group of rare genetic conditions that cause gradual weakening of the muscles, mainly in the ‘limb girdle’. This includes muscles around the hips, thighs, shoulders, and upper arms.

There are many different types of LGMD as they are caused by changes in many different genes.

LGMDR1 is a form of LGMD caused by changes in the CAPN3 gene. In the past, LGMDR1 was called LGMD2A or a calpainopathy. Old names may still be used sometimes.

Being diagnosed with LGMDR1 can lead to changes in your daily life. It can affect your independence, access to education and work, and relationships. Your healthcare team can help you learn about and manage your condition and tell you about local support groups. You can also find out about the support services we offer.

The symptoms of LGMDR1 can vary from person to person, even within the same family. They usually start between the ages of 8 and 15 but can start at any age between 2 and 40 years.

Symptoms develop over several years. In more severe forms, people lose the ability to walk from around 10 to 30 years after first getting symptoms. In milder forms, this may happen after the age of 60 – they may need to use walking aids or a wheelchair.

Cardiac and respiratory muscle are generally not affected. However, some people may experience mild breathing difficulties. Swallowing problems are unlikely.

Life expectancy is generally not affected, and is expected to be the same as for the general population.

Muscle weakness

At first, people usually have weakness and wasting (loss of muscle bulk) in the muscles around the hips, thighs, and shoulders. Most people notice becoming tired more quickly than before. The weakness is usually symmetrical, affecting both sides of the body in the same way.

It often starts in the legs before affecting the shoulders and arms. This can make it harder to run, walk uphill, climb up stairs, or get up from the floor. People may fall more often, may have muscle pain or cramps, and get tired easily after exercising.

Shoulder and arm weakness can make it more difficult to do overhead activities like wash your hair, reach high cupboards, or lift heavy items onto shelves. People may develop scapular winging, where the shoulder blades stick out more than usual. This is a sign of muscle weakness around the shoulders and the back, which can limit movement in later stages

Joint stiffness

Stiffness in some joints may develop. This is called a contracture. Tightness in the ankles can lead to toe walking, where the heel does not touch the ground.

Contractures can also cause a curve in the spine, which can lead to back pain. This is called scoliosis.

Genetic changes

Genes contain instructions for our cells to make proteins. In LGMDR1, changes in the CAPN3 gene affect the calpain-3 protein. This protein is important for repairing muscle damaged during normal daily living.

As a result, the protein cannot repair damaged muscles properly. The muscles are gradually replaced by scar tissue and fat, causing muscle weakness.

Inheritance

LGMDR1 is a genetic condition, which means people are born with the gene change that causes the condition. They usually inherit the changed gene from their parents.

The changed gene passes from parent to child in an autosomal recessive pattern. This means a child needs two changed genes, one from each parent, to have the condition.

People with LGMDR1 would not usually pass the condition on to their children. This is because children usually inherit an unaffected gene from the parent who does not have LGMDR1. But the child will be a carrier of the changed gene.

Very rarely, a single change in the CAPN3 gene can cause muscle weakness. This happens with a specific change called the c.643_663del21 deletion. In this case, the condition is passed on in an autosomal dominant inheritance pattern, and is called LGMDD4 instead of LGMDR1.

For more information, see our inheritance and genetics page.

A GP can make a referral to a specialist doctor. This is likely to be a neurologist – a doctor who specialises in conditions that affect the muscles and nervous system. The neurologist will ask about symptoms and any family history of the condition. They may carry out a physical examination to see how the muscles are working.

If a muscle wasting condition is suspected, the doctor will arrange some tests. These may include:

• Blood test to measure levels of creatine kinase (CK) – CK levels may be high in LGMDR1
• CT or MRI scan to show which muscles are affected
• Needle exam (Electromyography – EMG) to see how your muscles work
• Genetic testing to look for changes in the CAPN3 gene
• Biopsy of the affected muscle, to test for the calpain-3 protein

For more information, see our diagnosis page.

People with LGMDR1 should have access to a multi-disciplinary healthcare team to help manage the condition and symptoms – a team of health professionals working together. Usually, the lead professional will be a neurologist.

There is a Highly Specialised Service for LGMD based at the John Walton Muscular Dystrophy Research Centre, part of Newcastle upon Tyne Hospitals NHS Foundation Trust. It’s a national centre and you can ask your doctor to refer you to this service for a second opinion or for specialist advice on managing your condition. Your day-to-day care will remain with your local healthcare team. The service offers advice to both clinicians and patients to achieve a diagnosis or to help manage LGMD. Referrals can be addressed to Prof Chiara Marini-Bettolo and Dr Lizzie Harris.

Exercise and physiotherapy

Keeping mobile helps keep your joints flexible and muscles as strong as possible. It’s important to do the right amount and type of exercise. In general, it’s recommended to exercise regularly, but aim to feel fully recovered by the day after. Some mild muscle soreness is okay, but exercise should not cause pain or weakness that limits your everyday activities.

A physiotherapist is a healthcare professional who helps manage symptoms through movement, exercise, and manual therapy. They can assess symptoms and suggest exercises that are suitable. Finding activities that are enjoyable can make it easier to do them regularly.

Exercise can help in three main ways:

• Keeping your joints and muscles flexible

  This is done through stretching exercises, which target specific joint contractures (tightness) or improve overall mobility. Often, tightness can develop if the joints have more limited movement due to the weakness. It’s important to stretch regularly – ideally four to six times a week – to feel the benefits.

• Keeping your muscles as strong as possible

  Strengthening exercises involve working against resistance. This could include using your own body weight, resistance bands, or small weights. These exercises should allow you to do only a few repetitions (around 12 to 15). Aim to do strength training two to three times a week.

• Maintain your heart and lung response to exercise

  Aerobic exercise involves activities done for a longer period of time (around 45 minutes), at an effort level where it becomes too difficult to talk during it. Depending on your ability, this could involve walking, Nordic walking (a type of walking that uses poles to work your upper body as well as your legs), swimming, dancing, arm cycling, or driving a powered wheelchair. Aerobic activity is recommended three to four times a week.

For advice for adults, see exercising with a muscle wasting condition.

If fatigue is a concern, see our fatigue management guide for practical tips and support.

Orthotics

Physiotherapists may suggest using orthotics. These are devices worn to help make it easier to stand and move. They can support the muscles in the feet, knees, shoulders or back. A specialist can put in a referral to the local orthotics team for an assessment.

Breathing problems

Breathing problems are not common in LGMDR1. But some people have mild breathing problems as the condition develops.

Symptoms can include:

• Poor sleep
• Headaches when waking up the morning
• Sleepiness during the day
• A higher chance of getting chest infections

Those with breathing problems should see a specialist for regular checks. They are likely to recommend yearly flu and pneumonia vaccines. Some people may need to use a machine to help them breathe at night.

Anaesthesia stops a person feeling pain during a procedure or surgery. In general, people with LGMDR1 do not have problems with anaesthetics, but this can vary from person to person.

Some medicines, such as neuromuscular junction blockers, should not be used routinely. This is because they can take much longer to wear off in people with muscular dystrophy and may cause serious complications.

It’s crucial to tell the surgeon and anaesthetist about a diagnosis of LGMDR1. They will carry out an assessment and arrange extra care before, during, and after the anaesthetic.

For more information, see our anaesthetics page.