LMNA-related congenital muscular dystrophy (L-CMD)

LMNA-related congenital muscular dystrophy (L-CMD) is a type of congenital muscular dystrophy, a group of genetic conditions that usually appear at birth or within the first few months of life.

L-CMD causes severe progressive muscle weakness, joint stiffness, and problems with the heart and breathing. Babies with L-CMD are often born with low muscle tone, which makes them seem ‘floppy’. Some people with L-CMD may need support with feeding and nutrition.

L-CMD is also part of a group of conditions called laminopathies, which happen due to changes in the LMNA gene. These conditions can affect the muscles, heart, or nerves.

Symptoms of L-CMD could be present before birth. During pregnancy scans, doctors may notice reduced movements or stiff joints in the baby. However, usually symptoms appear at birth or within the first few months of life.

Muscle weakness

The first signs of L-CMD are floppiness (hypotonia), muscle wasting, and weakness. The severity, and which muscles are affected, can vary from person to person. Typically, muscles in the torso and neck are most severely affected. Children may find it difficult to hold their head up, which is a condition known as head drop. Muscles in the arms, legs, shoulders, and hips are also affected.

A loss of strength and function may occur in the first two years of life. Children may take longer to achieve motor milestones like sitting unaided, crawling, or walking. As the condition progresses, they may lose the ability to do these things. Many children with L-CMD may not be able to walk independently, particularly after the age of 14.

Joints and spine

Contractures happen when joints become tight and lose their range of movement. Sometimes this tightness starts in the womb and affects joints at birth (a condition called arthrogryposis). The ankles, elbows, fingers, and wrists are usually the first joints to be affected. Over time, the knees and hips may also become affected.

Weak muscles often cause the spine to become stiff or misaligned, especially in the middle and lower parts. This can limit movement, including making it harder to breathe or bend the body. In contrast, the neck region of the spine is usually floppy. Children with L-CMD can develop a curved spine (scoliosis).

Respiratory

Weakness of the muscles that help with breathing is common in people with L-CMD. It can cause respiratory insufficiency though the severity varies. This can result in frequent chest infections and nocturnal hypoventilation (shallow breathing at night). Most children will eventually need breathing support by their teenage years. But those never able to walk may need it earlier. Signs of respiratory weakness include breathlessness, headaches, disturbed sleep, and poor appetite. It’s important to share these symptoms with specialist doctors.

Cardiac

Children with L-CMD have a higher risk of heart problems, including arrhythmias (irregular heart rhythms) and cardiomyopathy (enlargement and impairment of the heart’s ability to pump blood properly) leading to heart failure. These problems become more common as a child with L-CMD gets older, but not everyone will experience severe heart symptoms.

Feeding

Feeding can be difficult because of weakness in the muscles involved in chewing and swallowing. This may make it hard to get enough nutrition, which can result in longer mealtimes and difficulty in gaining weight. There is also a higher risk of choking and aspiration, which is when food or drink enters the airway and lungs. Frequent aspiration can lead to aspiration pneumonia, which is a type of lung infection that requires antibiotics.

Genetic changes

L-CMD is caused by changes in one of the two copies of the LMNA gene. The LMNA gene provides instructions to make proteins called Lamin A and Lamin C. These proteins help form a structure called the nuclear lamina, which is important for maintaining the shape of a cell’s nucleus and organising DNA within it. If Lamin A and Lamin C are not made, or are not working properly, muscles can become damaged. Over time, muscles are replaced by scar tissue and fat, leading to muscle weakness. Some specific types of changes to the LMNA gene can make L-CMD progress more quickly or severely.

Changes in the LMNA gene can lead to various medical conditions, collectively known as laminopathies. These include conditions that affect the heart (cardiomyopathies), muscles (muscular dystrophies), nerves (peripheral neuropathies), fat tissue (lipodystrophies), or multiple organs at the same time. One related muscle wasting condition is Emery-Dreifuss muscular dystrophy (EDMD), which can also be caused by changes in the LMNA gene.

Inheritance

L-CMD usually happens without a family history of the condition, and neither parent is affected. This is known as a ‘de novo’ variant, meaning the change in the gene happens for the first time in the affected person.

If someone with L-CMD has children, the condition can be passed on in an autosomal dominant inheritance pattern. This means that only one copy of the changed gene is needed for the condition to be inherited.

For more information, see our inheritance and genetics page.

L-CMD is often first noticed when a baby seems ‘floppy’ or weak. Because symptoms can look like other conditions, doctors need to carry out a series of tests to confirm if it’s L-CMD.

This may include:

• Blood test to measure creatine kinase (CK) levels
• Electromyography (EMG) to measure electrical activity
• Heart tests like an echocardiogram (ECHO) and electrocardiogram (ECG)
• Muscle biopsy, where a small muscle sample is taken and examined under a microscope to assess muscle fibre size and structure
• Genetic testing

To confirm the diagnosis of L-CMD, doctors will carry out genetic testing using a blood sample to look for specific changes in the LMNA gene known to cause L-CMD. If the condition is caused by a new or rare genetic change, it may take longer to get results.

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. While there is currently no cure for L-CMD, management can make a big difference to quality of life.

Access to a healthcare team

It’s important to have access to a multi-disciplinary healthcare team, led by a neurologist, to review symptoms on a regular basis. A neurologist is a doctor who specialises in conditions that affect the muscles and nervous system.

Reviews should include monitoring heart and lung function, weight, muscle strength, bone health (e.g. vitamin D levels and supplementation), spine health (e.g. scoliosis), and joint range of movement. In some limited and specific cases, a specialist might consider a trial of medications currently in use for other muscle wasting conditions, like corticosteroids, to help manage symptoms.

Respiratory

Breathing muscles weaken over time, so early and frequent monitoring of respiratory function is important. This is typically done in clinic with spirometry, a lung function test, for children older than five years. Other tests, such as overnight sleep studies, may be needed to check breathing quality during sleep.

Flu vaccinations are strongly recommended to reduce the risk of chest infections. A weak cough is likely, and some may require regular antibiotics to prevent recurring chest infections, and a cough assist machine to help clear mucus and other secretions from the lungs.

Many children will need non-invasive ventilation (NIV), which is a small machine that delivers air pressure into the lungs through a mask over the face or nose. Some may need this for short periods at night, while others may need it more often. If breathing problems are severe, invasive ventilation may be considered, where a tube is placed in the windpipe. The most appropriate type of support should be discussed with a respiratory specialist.

Cardiac

Early and regular cardiac monitoring is essential, as heart problems are common in L-CMD and laminopathies. This is typically done by a specialist cardiologist, a doctor that diagnoses and treats heart problems. Several tests may be arranged at the time of diagnosis, including an electrocardiogram (ECG) and an echocardiogram (ECHO). Additional tests may be needed, such as advanced heart scans (e.g. cardiac MRI) and prolonged monitoring of heart rhythm using a Holter monitor. Cardiac follow up is usually scheduled at least annually. Some people may need a small device to track the heart’s activity, called a loop recorder. Depending on the severity, the cardiologist may recommend different medications, devices, or procedures to manage heart problems.

Feeding

Children may find it hard to eat enough orally to meet their nutritional needs, because of swallowing difficulties or lack of energy. A specialist dietitian can recommend nutritional supplements to provide optimal nutrition. For those with swallowing issues, a nasal or abdominal feeding tube may be necessary. These tubes can be placed through the nose or into the stomach through the wall of the abdomen.

Exercise and physiotherapy

Physiotherapy can help maintain breathing capacity, delay spine problems, and slow the progression of contractures. This includes exercises to strengthen muscles and stretches to maintain flexibility. Those on ventilators will also need daily respiratory physiotherapy to help clear their airways.

A physiotherapist is a healthcare professional who helps manage symptoms through movement, exercise, and manual therapy. They can put together a suitable exercise routine and identify a need for orthotics, which are devices like ankle splints that help support joint movement. Children will need support from caregivers to guide them through exercises and provide encouragement.