Bethlem myopathy

Bethlem myopathy is a type of congenital muscular dystrophy (CMD), and part of the spectrum of conditions called collagen VI-related dystrophy (COL6-RD). Bethlem myopathy causes progressive muscle weakness and joint stiffness – typically from childhood.

Bethlem myopathy is the mildest form of the COL6-RD group, while Ullrich congenital muscular dystrophy (UCMD) is the most severe. There is an intermediate form between them. These conditions are caused by changes in the COL6A1, COL6A2 and COL6A3 genes, which help make a protein called collagen type VI.

Symptoms usually show in childhood but could show at any time from birth through to adulthood. In childhood, symptoms include low muscle tone or floppiness (hypotonia), bendy joints (hypermobility), muscle weakness, and delays in reaching motor milestones such as sitting unaided or walking. The severity and progression of symptoms can vary for each person.

Muscle weakness

People affected have low muscle tone (hypotonia) and mild muscle weakness and wasting, particularly in the muscles near the centre of the body such as the hips and shoulders. This can make it difficult to lift the arms above the head, stand up from a seated position, and climb stairs. Many people also experience poor stamina and fatigue easily.

Weakness is expected to be slowly progressive. Some people may need to use mobility aids or a wheelchair in their mid to late adulthood, depending on how their condition changes over time.

Joints and spine

People with Bethlem myopathy may be born with, or later develop, significant stiffness in their joints. This is known as contractures, where the tendons in the muscle tighten up and limit the range of movement. This typically affects the wrists, fingers, elbows, and Achilles tendons, and can make fine motor skills (coordination of small muscles in the fingers and hands for activities like brushing your teeth) challenging. Stiffness of the spine and scoliosis (curvature of the spine) can also develop over the years.

Skin abnormalities

Cuts and injuries to the skin may heal slowly and leave thick, raised scars called keloid scars. These scars can happen after surgical procedures, injuries, or pressure sores caused by prolonged immobility. The skin on the arms and legs may also feel rough or bumpy (hyperkeratosis pilaris). This happens because the skin contains collagen VI. Taking steps to prevent injuries and skin damage where possible is important.

Respiratory

Breathing problems can occur because of weakness in the respiratory muscles (including the diaphragm) in combination with a stiff chest wall. Problems can begin from an early age, despite reasonably good mobility. Regular monitoring of chest problems, like frequent chest infections, and of breathing problems during sleep (shallow or altered breathing at night) is important. Overnight breathing problems may result in symptoms of daytime sleepiness, morning headaches, poor appetite, and weight loss. The presence of these symptoms should be reviewed promptly by a doctor.

Genetic changes

Bethlem myopathy is caused by changes in one of three genes that produce the collagen VI protein – COL6A1, COL6A2, and COL6A3. Changes may be to one or sometimes both copies of the COL6 gene. Collagen VI proteins form supportive networks around muscle cells and act like scaffolds to hold and support them. When collagen VI is faulty, or there isn’t enough of it, the muscle cells are not supported properly. Over time, this leads to muscle weakness and damage.

Inheritance

Bethlem myopathy is usually inherited in an autosomal dominant pattern, where a person only needs to inherit one changed gene from either parent to have the condition. In rare cases, the condition can be inherited in an autosomal recessive pattern, meaning a person needs to inherit two copies of the changed gene, one from each parent, to develop the condition. Sometimes there is no family history of the condition.

For more information, see our inheritance and genetics page.

Bethlem myopathy is usually suspected from a person’s medical history and diagnosed with a clinical assessment and genetic testing. A GP or paediatrician can refer to a neurologist for specialist investigations and testing. A neurologist is a doctor who specialises in conditions that affect the muscles and nervous system.

A neurologist will generally use a combination of:

• Physical examination and family history
• Muscle imaging, such as ultrasound or MRI, to look for specific changes linked to collagen VI-related conditions
• Genetic testing, using a blood sample, to check for changes in the COL6A1, COL6A2, or COL6A3 genes
• Muscle biopsy, where a small muscle sample is taken and examined under a microscope for changes in the appearance and quantity of collagen VI proteins

Genetic testing, using a blood sample, is the key test to confirm the diagnosis of Bethlem myopathy, as it can identify the exact gene causing the condition.

For more information, see our diagnosis page.

A multi-disciplinary approach is important in not only managing the condition and symptoms but in improving wellbeing too. It involves different healthcare professionals working together.

Access to a healthcare team

It’s important to have access to a multi-disciplinary healthcare team. Usually, the lead professional will be a neurologist in a specialist neuromuscular clinic. If you do not have a neurologist or specialist doctor, speak to your GP about getting access to one.

Exercise and physiotherapy

Physiotherapy and mild exercise are encouraged to maintain muscle strength and mobility. It can also maintain breathing capacity and slow the progression of joint stiffness (contractures). A physiotherapist is a healthcare professional who helps manage symptoms through movement, exercise, and manual therapy. They can help put together a suitable exercise plan. Moderate exercise, such as swimming and walking are highly recommended. This type of aerobic exercise helps maintain a healthy cardiovascular system and a steady weight. Physiotherapists and/or occupational therapists can also provide advice on walking aids and wheelchairs if necessary. To find out more about advice for adults, see exercising with a muscle wasting condition.

Orthopaedics

Orthopaedic management refers to the treatment and care of bones, joints, and muscles and can help with contractures and scoliosis. This might include using splints, braces, and other tailored orthotic devices. In some cases, surgery may be needed to correct more severe joint contractures – for example releasing the Achilles tendon to improve foot and ankle posture. This can help with standing and walking, although it does not strengthen weak muscles.

Spinal surgery may be recommended to realign the spine. Surgical treatment should be carefully considered and coordinated by a specialist multi-disciplinary team with experience in treating people with neuromuscular conditions. This is important because there are key considerations for anaesthesia, post-operative care, and rehabilitation. It’s important to discuss all the options and goals of treatment before making a decision.

Respiratory

Respiratory function and lung capacity should be monitored regularly by a specialist team. Lung function testing is usually done in sitting and lying positions. Overnight sleep studies may be recommended to assess breathing while sleeping and to diagnose night-time breathing problems. While this is not common, it can be treated with non-invasive ventilation (NIV) if diagnosed.

It’s also recommended to get a flu vaccination every year. People who need NIV at night, should ask their GP about getting the pneumococcal vaccine.