Sarcoglycanopathies (LGMDR3, LGMDR4, LGMDR5, and LGMDR6)

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.

Sarcoglycanopathies are types of LGMD caused by changes in the sarcoglycan genes. You may sometimes see the old names of these types being used. We have shown the old names in brackets below. There are four sarcoglycanopathies:

• LGMDR3 (LGMD2D) – caused by a change in the SGCA gene
• LGMDR4 (LGMD2E) – caused by a change in the SGCB gene
• LGMDR5 (LGMD2C) – caused by a change in the SGCG gene
• LGMDR6 (LGMD2F) – caused by a change in the SGCD gene

Symptoms can vary from person to person, even within the same family. They usually start during childhood and can develop quickly. Milder forms can start later and develop more slowly.

Hip and thigh muscle weakness

Weakness in the hip and thigh muscles usually affects both sides of the body at the same time. The first signs of muscle weakness may include:

• Problems running or climbing up stairs
• Problems getting up from the floor
• Walking problems
• Getting tired easily after exercise
• Large calf muscles

As walking problems develop, it may be helpful to use a wheelchair. People often start using a wheelchair about ten years after symptoms first start.

Shoulder and arm muscle weakness

Sarcoglycanopathies can cause shoulder muscle weakness on both sides of the body. This can mean that people may find it hard to lift their arms above their head. For example, when washing their hair. Some people have trouble carrying heavy objects or holding their arms out in front of them. In many people, the shoulder blades can stick out. This is called scapular winging.

Breathing and heart problems

Breathing (respiratory insufficiency) and heart problems (cardiomyopathy) can vary from person to person. They are less common in people with LGMDR3 and usually start later.

Breathing problems can develop over time. They can cause:

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

People who have 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 called a ventilator to help them breathe at night. In case of chest infection, prompt use of antibiotics is recommended.

Heart problems are common in all types of the condition except LGMDR3. They can cause breathlessness and tiredness in some people. A heart doctor (cardiologist) should monitor symptoms and may offer treatment to protect the heart.

Breathing and heart problems can cause life-threatening complications, which could affect life expectancy. People with severe symptoms may live until the teenage years or early adulthood. Milder forms of the condition do not usually affect life expectancy. See the Condition management section below for information on monitoring and treatment.

Other symptoms

People with sarcoglycanopathies may also have stiff joints (contractures) and a large tongue. In more severe cases, the spine can be affected. These changes may include:

• Lordosis – an exaggerated inward curve of the lower back, which may cause the stomach to stick out and affect posture.
• Scoliosis – a sideways curve of the spine, which can cause uneven shoulders or hips.

Both lordosis and scoliosis can develop because of muscle weakness and may affect comfort and mobility.

Genetic changes

Genes contain instructions for our cells to make proteins. Changes in the SGCA, SGCB, SGCG, or SGCD genes affect the sarcoglycan proteins.

These proteins work together to protect the muscle from damage. When one of the proteins is missing, the muscle becomes easily damaged and is gradually replaced by scar tissue and fat, causing muscle weakness.

Inheritance

Sarcoglycanopathies are genetic conditions, which means people are born with the gene changes that cause the conditions. They usually inherit the changed genes from their parents.

The changed genes pass from parent to child in an autosomal recessive pattern. This means a child needs two of the same changed genes, one from each parent, to have one of the conditions.

People with a sarcoglycanopathy 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 the condition. But the child will be a carrier of the changed gene.

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. They 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 are usually high in sarcoglycanopathies
• 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 SGCA, SGCB, SGCG, or SGCD genes
• Biopsy of the affected muscle, to test for the sarcoglycan proteins

For more information, see our diagnosis page.

People with sarcoglycanopathies 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 get a diagnosis or to help manage LGMD. Referrals can be addressed to Prof Chiara Marini-Bettolo and Dr Lizzie Harris.

Breathing problems

Breathing problems are more common as the condition develops but can happen at any time. Regular monitoring of respiratory function is recommended.

These checks usually include:

• Forced vital capacity (FVC) – a test that measures how much air you can breathe out. It should be done both sitting up and lying down.
• Peak cough flow (PCF) – a test to check how strong your cough is.
• Sometimes, an overnight pulse oximetry test is needed to check your breathing while you sleep.

FVC and PCF are usually done at your muscle clinic appointments. If results show any problems, you may benefit from using a breathing machine at night (assisted ventilation).

Symptoms of breathing problems can include:

• Poor sleep
• Headaches when waking up in 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.

For more information, see our breathing page.

Heart problems

Heart problems are common in most sarcoglycanopathies. They’re less common in LGMDR3.

Regular checks with a heart specialist (cardiologist) will help monitor heart health, and medication may be offered to protect the heart. This usually involves an ECG (electrocardiogram) and echocardiogram. At times a cardiac MRI is also needed.

For more information, see our heart page.

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 regularly do them.

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, swimming, dancing, arm cycling, or driving a powered wheelchair. Aerobic activity is recommended three to four times a week.

We have exercise advice for children and for adults.

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.

Anaesthesia stops a person feeling pain during a procedure or surgery. In general, people with sarcoglycanopathies 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.