LAMA2-related muscular dystrophies (LAMA2-RDs)

LAMA2-related muscular dystrophies (LAMA2-RDs) are inherited conditions that cause muscle weakness and wasting. There are two main forms – a severe form that starts from birth (congenital) and a milder form with later onset which is similar in appearance to limb girdle muscular dystrophy (LGMD). How severely a person is affected depends on the specific genetic change.

• Severe early-onset LAMA2-RD: Typically starts at birth, infancy, or early childhood with delayed motor development, muscle weakness, difficulty walking, and breathing problems. Children with this form are often unable to walk. Severe early-onset LAMA2-RD is a type of congenital muscular dystrophy and was previously known as merosin-deficient congenital muscular dystrophy (MDC1A).
• Mild late-onset LAMA2-RD: Typically starts later in childhood, adolescence, or adulthood. This is a milder form that progresses more slowly. Symptoms are less severe and include muscle weakness and fatigue during physical activity. This form is also referred to as limb girdle muscular dystrophy R23 (LGMDR23).

Muscle weakness

Severe early-onset LAMA2-RD: Babies and young children with LAMA2-RD often have low muscle tone (hypotonia) and muscle weakness. This may be noticed when they have difficulties holding their head up (head control) or when there is a delay in reaching motor milestones, such as sitting unaided and crawling. Most children with early onset LAMA2-RD are unable to walk on their own. Facial weakness and an enlarged tongue are common and can affect feeding and quality of speech.

Mild late-onset LAMA2-RD: In this type of LAMA2-RD, muscle weakness is milder, and people affected are likely to achieve independent walking. However, they may lose the ability to walk as they grow, because the muscles may not be able to cope with greater strain and keep up with the increasing size of the body.

Respiratory

Weakness of the muscles that help with breathing is a common symptom. This can result in frequent chest infections and nocturnal hypoventilation (shallow breathing at night). Nocturnal hypoventilation is common, particularly in people with early-onset LAMA2-RD, and can happen from a young age. It can lead to symptoms of daytime sleepiness, morning headaches, and poor appetite. People with severe early-onset LAMA2-RD may need machines like a cough assist device or non-invasive ventilation (NIV) to support breathing. It’s important that those affected are monitored and that carers are aware of the potential symptoms.

Weakness of the breathing muscles may make people with LAMA2-RD more vulnerable to chest infections.

Nutrition

Severe early-onset LAMA2-RD: Feeding is difficult in severe early-onset LAMA2-RD because of weakness in the muscles needed for latching and swallowing. This can result in longer mealtimes and trouble gaining weight. Weakness in the chewing muscles and those controlling the safety and coordination of swallowing and airway protection can increase the risk of choking and aspiration (where food or drink enters the airway and lungs). It’s important to be cautious, and that carers are aware of these potential risks. The input of a speech and language therapist, who specialises in swallowing and communication, and a dietitian, who advises on nutrition and feeding, can be very helpful in managing these challenges.

Mild late-onset LAMA2-RD: People may sometimes experience mild difficulties with swallowing or chewing tougher foods, and experience fatigue while eating. They may take longer to finish meals. Input from a speech and language therapist and dietitian could be necessary.

Joints and spine

As the muscles are weak and mobility is limited, children may be born with, or develop, joint stiffness. This is known as contractures. The muscle tendons tighten up and limit the range of movement of the limbs. It’s likely to impact the hips, knees, and elbows. Physiotherapy can help slow the progression of contractures by using specific exercises and movement techniques to maintain flexibility as much as possible.

Severe early-onset LAMA2-RD: Severe contractures can be present from as early as birth. This is caused by muscle weakness leading to reduced movement in the womb. This can significantly limit movement. Children are likely to develop scoliosis (sideways curvature of the spine) and lordosis (inwards curvature of the spine). It’s important to monitor the spine in a specialist clinic – a child may require a spinal brace to improve posture and slow the progression of the curvature. In some cases, scoliosis surgery will be needed. The impact on the hips means a child’s hips may become dislocated, which reflects the weakness and does not necessarily require intervention – unless it’s causing other problems.

Mild late-onset LAMA2-RD: Contractures may occur but vary in severity.

Nervous system

Brain MRI scans of people affected may show white matter changes, indicating some change in how the brain functions or is structured. Seizures are reported in approximately 3 in 10 cases of LAMA2-RD and are more commonly seen in more severe cases, though this is not always the case. They can be managed with antiepileptic medications. A minority of those affected may have mild cognitive difficulties, more likely in severe early-onset cases.

Some people may have a form of peripheral neuropathy, which refers to damage or dysfunction of the peripheral nerves. This can result in symptoms such as weakness, numbness, or tingling sensations, particularly in the hands and feet. Peripheral neuropathy in LAMA2-RD may vary in severity and presentation, but it’s generally less common compared to other features of the condition.

Genetic changes

LAMA2-RD is caused by changes in the LAMA2 gene. This gene helps make laminin alpha-2 (also called merosin), a protein important for muscle structure and function. People with LAMA2-RD have changes in both copies of the LAMA2 gene, leading to a reduced amount of laminin in their muscles, or none. This disrupts muscle development, resulting in muscle weakness and related symptoms.

The severity of the condition depends on how much laminin is still being produced. In severe early-onset LAMA2-RD, little to no protein is produced, causing serious symptoms from birth. In the milder late-onset form, some protein is produced, leading to less severe, slower-progressing symptoms. The type of genetic change can sometimes help predict the severity of symptoms.

Inheritance

LAMA2-RD is usually inherited in an autosomal recessive pattern, where both copies of the gene (one from each parent) must be changed for the condition to occur.

For more information, see our inheritance and genetics page.

A GP can make a referral to a neurologist for investigations and testing. A neurologist is a doctor who specialises in conditions that affect the muscles and nervous system. They will generally use a combination of physical examination, family history, blood tests, magnetic resonance imaging (MRI) scans of the brain and muscles, genetic testing, or a muscle biopsy to diagnose LAMA2-RD.

Genetic testing, using a blood sample, is the key test to confirm a genetic diagnosis of LAMA2-RD by identifying the specific changes in the LAMA2 gene.

For more information, see our diagnosis page.

There is currently no specific treatment or cure for this condition, but management is anticipatory and supportive. Multidisciplinary care is essential to address symptoms and improve quality of life and wellbeing.

Access to a healthcare team

It’s important to have access to a multi-disciplinary healthcare team – a team of health care specialists working together. Usually, the lead professional will be a neurologist in a specialist neuromuscular clinic who works closely with the specialist therapists and liaises with local teams. This might also include a local general paediatrician (dependent on age) and community-based therapists. If you do not have contact with a neurologist or specialist doctor, speak to your GP to get access.

Respiratory

Respiratory function and lung capacity should be monitored from an early age at a specialist neuromuscular clinic. Overnight sleep studies can be used to assess breathing while sleeping and diagnose nocturnal hypoventilation. This is when low oxygen levels and high carbon dioxide levels, while sleeping, can cause symptoms such as frequent chest infections, morning headaches, and daytime fatigue. Non-invasive ventilation (NIV) can help treat nocturnal hypoventilation by helping with breathing while sleeping. People with serious breathing problems may also need chest physiotherapy and machines to help with coughing. This is important as it can reduce the need for hospitalisation and help avoid life-threatening episodes.

Nutrition

It may be hard to eat enough and maintain enough calories, especially with difficulties in chewing and swallowing. In such cases, an early referral to a specialist speech and language team and a dietetics service is essential. A dietitian can suggest ways to make eating easier and may recommend special diets or nutritional supplements. If a person is having trouble getting enough nutrition from food orally, a feeding tube (gastrostomy) may be considered. Caregivers must be trained in the use and care of a feeding tube.

Bone health

Monitoring and maintaining bone health may be important in people with LAMA2-RD, as limited movement can affect bone strength and make bones more vulnerable to fractures. Low-impact fractures should be considered when there is pain, tenderness, and limited or reduced mobility. It’s useful to ensure adequate nutrition, including sufficient vitamin D and calcium, to support bone strength.

Orthopaedics

Orthopaedics is the care of bones, joints, and muscles. For people with LAMA2-RD, this means managing joint stiffness (contractures) in the upper and lower limbs and spine problems, like scoliosis (curvature of the spine). This may involve the use of splints, braces, and other orthotic devices depending on specific needs. In some cases, surgery may be needed to correct severe contractures to improve posture and motor function. For scoliosis, spinal surgery may be necessary to realign the spine. It’s important to discuss and coordinate surgical options with a specialist and multidisciplinary team, with careful consideration of respiratory function.

Cardiac

Heart problems are uncommon in LAMA2-RD, but cardiac monitoring is recommended to look for cardiomyopathies or conduction issues, particularly as a person gets older.