Distal myopathies

Distal myopathies are a group of inherited muscle conditions that progress slowly and are caused by several different genes. The term ‘distal’ refers to the parts of the body that are furthest away from the centre. Unlike most muscle conditions that start in larger muscles – such as those in the hips, shoulders, or torso – distal myopathies begin with weakness in the feet, ankles, calves, and sometimes the hands. Symptoms, age of onset, and how the condition is inherited can vary based on the genes involved. Some people with distal myopathy may also have problems with the heart or breathing muscles.

The classification of distal myopathies is complicated. There have been several different names and classification systems over the years, which have included using symptoms and signs, muscle biopsy features, and/or genetic testing. In addition, some distal myopathies are included in the limb girdle muscular dystrophy (LGMD) classification, while some are also known as distal muscular dystrophies.

Genetic testing is now the main method for classifying distal myopathies based on the gene causing the condition. This approach is clearer, helps predict how the condition will progress, identifies the risk of other organ involvement, and supports genetic counselling and family planning.

A table of different distal myopathies is included below.

Muscle weakness

In most cases, distal myopathy begins with muscle weakness in the feet, ankles, and/or lower legs but it can also affect the hands. The weakness is usually symmetrical, roughly affecting both sides of the body equally. When weakness starts in the back of the lower legs, people may have difficulty standing on tiptoes. If weakness begins in the front of the lower leg, it can cause foot drop (dragging of one or both feet), leading to a high stepping way of walking to avoid tripping. Walking on uneven ground can become particularly challenging.

If the hands are affected, tasks using fine motor skills (e.g. buttoning clothes or opening packets) can be difficult. As the condition progresses, other muscles closer to the centre of the body may also become affected.

People with distal myopathy usually have normal sensation and feeling in their hands and feet. This helps to distinguish distal myopathies from peripheral neuropathies (such as Charcot-Marie-Tooth disease) which also cause distal muscle weakness and wasting.

Genetic changes

Distal myopathies are caused by genetic changes that affect proteins important for muscle structure and function, leading to progressive muscle weakness and wasting. So far, changes in over 20 different genes have been linked to various forms of distal myopathy.

Historically, these conditions have been categorised into three groups: classic distal myopathies, myofibrillar myopathies, and genes where most patients show other patterns of weakness but sometimes also have some distal weakness. However, these distinctions are becoming less important, as modern genetic testing typically examines all relevant genes together.

Today, patients are usually classified based on their symptoms and the specific gene responsible for their condition, such as ‘distal myopathy ANO5-related’. In some cases, despite testing all known genes, the genetic change isn’t found. Even in these instances, a diagnosis of distal myopathy can still be made based on typical symptoms and tests that confirm the main problem is in the muscle.

A table of different distal myopathies and their genetic cause is below.

If a person has symptoms of a muscle wasting condition, a GP can refer them to a neurologist. A neurologist is a doctor who specialises in conditions that affect the muscles and nervous system. They will diagnose distal myopathy using a combination of clinical symptoms, family history, a physical exam, a creatine kinase (CK) blood test, and electromyography. An MRI of the leg muscles can help confirm the diagnosis and sometimes helps predict which gene is responsible. A muscle biopsy may be done, but advances in genetic testing mean this is less common.

If a family member already has a genetic diagnosis, testing can focus on that gene. Otherwise, genetic testing in the UK uses a panel that checks multiple genes known to cause distal myopathy – in a single test.

Depending on the symptoms and type of distal myopathy, tests for heart and breathing muscle involvement may also be conducted. These tests may include electrocardiogram (ECG), echocardiogram (ECHO), lung function tests, overnight oximetry, and carbon dioxide measurement.

For more information, see our diagnosis page.

A multi-disciplinary approach is important in not only managing the condition and symptoms of distal myopathies but in improving wellbeing too. Condition management will vary based on the type of distal myopathy. Although there is currently no gene therapy for these conditions, clinical trials are underway for genes linked to distal myopathy.

Access to a healthcare team

People with distal myopathies should have access to a multi-disciplinary healthcare team. Usually, the lead professional will be a neurologist. If you don’t have contact with a neurologist or specialist doctor, ask your GP to refer you to one.

If heart or breathing muscles are affected, you may also need support from a cardiologist and/or respiratory specialist to monitor this and arrange specialist treatment if necessary. This can include medications and support with breathing (non-invasive ventilation).

Exercise and physiotherapy

People with distal myopathies are encouraged to stay as physically active as possible. A physiotherapist is a healthcare professional who helps manage symptoms through movement, exercise, and manual therapy. They can assess individual needs and put together a suitable exercise plan to help maintain muscle strength and flexibility. Moderate exercise such as swimming, walking, and pedalling is recommended. This type of aerobic exercise helps maintain a healthy cardiovascular system and a steady weight. Rest is required after exercise and time to fully recover the next day is important.

Orthotics and specialist equipment

For those experiencing lower leg weakness and foot drop, orthotic devices may be recommended to improve walking and reduce the risk of falls. Options may include insoles in shoes, ankle braces, or leg braces. These can be prescribed by an orthotics service, following a referral by a GP or specialist. Orthotics services need to be contacted again if supports or braces are uncomfortable, or ill-fitting, as adjustments can be made.

Some people may need to use a wheelchair. A range of other equipment, usually provided by an occupational therapist, may also help address practical challenges and improve quality of life.

The following table shows the different types of distal myopathies. It includes their genetic causes, how they are inherited, when symptoms usually start, and what symptoms are expected. This information is helpful to understand the different types of distal myopathies and how they affect muscle function. Some rarer distal myopathies are not included in this table.

We also have information on GNE myopathy, myofibrillar myopathies, and limb girdle muscular dystrophies.

For information on inheritance patterns, see our inheritance and genetics page.

Abbreviation key:

Autosomal dominant (AD): only one copy of the gene from an affected parent can cause the condition

Autosomal recessive (AR): two copies of the changed or defective gene have been inherited, one from each parent

LGMD: limb girdle muscular dystrophy