What is LAMA-2 CMD?
Laminin α2 congenital muscular dystrophy, known better as LAMA2-CMD, is a rare muscle disease present from birth.
- Caused by a mutation in the laminin α2 gene, sometimes referred to as merosin deficient congenital dystrophy type 1 (MDC1A), due to the lack of the protein merosin in the cells.
- This protein ensures the stability of muscle cells, and its deficiency leads to muscle weakness and lack of muscle tone.
- Estimated to affect 1 in 30,000 to 100,000 individuals worldwide.
- One of the most common congenital muscular dystrophies, accounting for 38% to 48% of cases.
- The gene mutation is recessive, meaning a person can carry the gene mutation without showing symptoms.
- Inherited in an autosomal recessive pattern, where both parents must have a mutated version of the gene for a child to be affected.
- Carriers often do not know they are carriers as they do not exhibit symptoms.
What are Symptoms of Lama2 CMD
The spectrum ranges from severe phenotypes presenting with Hypotonia, muscle weakness, and contractures at birth or early infancy (complete deficiency) to milder, late-onset limb girdle muscular dystrophy (LGMD)-like phenotypes (partial deficiency).
About 90% of cases are congenital-onset severe phenotypes.
Motor Milestones: Affected children often reach motor milestones later, with more than 90% not achieving independent walking.
Muscle Contractures: Development of contractures restricting limb and joint movement.
Chest Deformities and Scoliosis: Many children develop these deformities.
Respiratory Issues: Weakness of respiratory muscles can lead to frequent chest infections and poor breathing at night.
Cardiac Involvement: Severe cardiac issues are rare, but rhythm abnormalities can occur.
Seizures: Around 30% experience seizures, typically manageable with antiepileptic medications.
Severity: Partial loss of laminin-211 leads to milder symptoms, with independent walking typically achieved, but the clinical course and progression are not fully known.
How is Lama2 Diagnosed
LAMA2-CMD is usually suspected based on the person's symptoms. A specific diagnosis can be made by muscle biopsy (taking a piece of muscle to examine it) and by looking at the person's blood. Blood testing measures the level of an enzyme called Creatine Kinase (CK). This is an enzyme that is often very elevated in individuals with LAMA2-CMD.
Symptoms of LAMA2-CMD can start to appear as a newborn. Depending on the type of LAMA2 -CMD, the age that symptoms start to appear at can change. When there is a partial deficiency of the merosin protein, symptoms usually range between early childhood to adulthood. In the case of a complete absence of the merosin protein, symptoms usually start after birth into early childhood.
Congenital muscular dystrophy type 1A (MDC1A) These symptoms are usually seen when children are born or within the first six months of life. Babies born with LAMA2 CMD often have weaker muscles. They become more floppy and may not move as much as other children. They may find it hard to sit without help or lift up their heads. Babies may also have a harder time feeding and breathing. This might mean that LAMA2 CMD children take longer to physically develop (longer to reach motor milestones). As they get older, children can also start to develop a curve in their back, called scoliosis.
Late-onset LAMA2-MD (clinically heterogeneous group) These symptoms are usually seen during childhood or even adulthood. Similarly to MDC1A, people with late onset LAMA2 CMD often also struggle with muscle weakness. They also take longer to physically develop. Only a very small proportion of children with LAMA2 are able to walk independently. Muscle weakness does not tend to rapidly progress and motor function remains relatively stable throughout childhood. When children reach puberty however, and grow taller and heavier, children might experience additional difficulties.
What are the current Treatments for Lama2 CMD
There is currently no cure for LAMA2-related muscular dystrophy (CMD), but there are variety of treatments and therapies being researched in an effort to lessen the severity of Lama2 CMD that can help manage symptoms. The focus of treatment for LAMA2 CMD is on managing symptoms and improving the quality of life.
Feeding supplementation: Often the swallowing muscles are weak and feeding supplements are needed. In some cases, swallowing problems can occur since the muscles responsible for swallowing may be weak. To address this, a small surgical procedure, called a gastrostomy can be performed. It is also important to make sure that children with LAMA2-CMD are well nourished.
Monitoring of respiratory and cardiac function: It is particularly important to monitor respiratory function during the night and children may need to use a ventilator at night with a special facial or nasal mask to assist them breathing. For some patients this is insufficient, and a tracheostomy procedure is needed. Respiratory issues usually stabilise or improve in the first few years, but if respiratory function starts to decline during adolescence, further ventilator support may be required.
Physiotherapy: For joint contractures, spinal defects, and other issues. Specific exercise programme should be led by a physiotherapist as early as possible.
Medications for seizures: these can usually be well controlled with anti-epileptic medication.
Occupational therapy: For LAMA2-related MD
Speech therapy: For LAMA2-related MD
Braces or splints: For LAMA2-related MD
What new therapies are currently being researched?
Yes, there are numerous promising research advances on the horizon. These trials include studies to understand symptom progression, studies to understand how LAMA2 CMD develops, and studies to develop new therapies.
A lot has been learned about LAMA2-CMD by scientists in recent years and there is growing evidence on several new therapeutic approaches for LAMA2-CMD.
One approach is autologous stem cell therapy. Here, muscle stem cells are withdrawn from patients themselves and the mutated gene is replaced with a healthy version in the lab. The corrected muscle stem cells are then returned to the patients so that they can generate new healthy muscle and counteract the muscle weakness for an extended period of time. Such an approach is currently being investigated in a Phase I/II clinical trial by a new European research collaboration.
A second approach is gene therapy. Here, a replacement version of the LAMA2 gene, or other replacement proteins can be introduced directly into the patient’s muscle cells, allowing them to grow and function more normally.
Another approach is using drug treatments that buffer the muscle loss caused by genetic mutations. Protein replacement therapy is also being developed and will undergo testing clinical trials in the future. These treatments are also an option that are currently being explored and could be combined with other therapies.
While these options are promising, more research and communication between experts, clinicians and biotechnology companies is needed to improve their efficacy and accelerate their implementation into the standard of care for LAMA2-CMD.
What is Life Expectancy of a Child in Lama2 CMD
Children with MDC1A reach motor milestones later than other children and only a very small proportion of children with MDC1A are able to walk independently.
The changes in the brain of the children with LAMA2 CMD usually don’t cause any problems and intellect is normal. Only a small proportion of children with MDC1A (less than seven percent) have a mild intellectual disability or communication difficulties. Just like every child is different, the life of someone with LAMA2 CMD will be different as well. Children and adults with LAMA2-CMD should meet regularly in a specialist neuromuscular clinic, with access to physiotherapy, The changes in the brain of orthotic, respiratory, orthopedic, spinal and genetic specialists as needed.
There are children who still can pursue higher education or even an university degree. You can find many personal stories on this website:
How do I cope with the diagnosis of LAMA2 CMD?
A Lama2-MD diagnosis can leave you feeling helpless and isolated. The emotions you are experiencing—guilt, fear, sadness, uncertainty—are valid and completely normal. There is no need to feel guilty for these feelings. Taking care of your mental wellbeing allows you to be a source of strength for your child and navigate the challenges ahead. Prioritize your relationships, especially with your partner or other close family members, as you navigate the adjustments following a diagnosis. Spending time together is crucial for adapting as a united team. Various professional counselors and therapy options are available to support families in coping. Seeking help or advice is a positive and constructive action, not a sign of weakness or failure. It can benefit the entire family in dealing with the challenges at hand.
How can I talk to my child about their diagnosis?
It's crucial to engage in open communication with your child about their diagnosis, as avoiding the topic can cause unnecessary stress. Children are often more resilient than we realize and benefit from understanding their condition to develop independence and advocacy skills. Starting discussions early, tailored to their age and understanding, creates a safe environment for on-going conversations, helping them grasp the information gradually and correct any misunderstandings along the way. Offer simple explanations, encourage questions, and avoid negative language to foster understanding and comfort.
How can I support my other children?
A LAMA2-MD diagnosis can impact the family dynamic as attention will be centered on the affected child. It's crucial not to overlook the needs of other siblings and ensure they experience as normal and happy a childhood as possible. Some siblings may hesitate to share their struggles, fearing it adds to parental stress, so actively check in with them and encourage open communication. Siblings can contribute to caregiving but be mindful not to turn it into a burdensome responsibility. Express gratitude without making it feel like a job. Prioritize individual time with each sibling to support their interests and personal development. There are various support systems available for siblings. For example, sibshop provide young brothers and sisters with peer support and information (https://siblingsupport.org/sibshops/)Beads of Courage is another organization that provides support for children coping with serious illness (https://beadsofcourage.org/)
What Future Steps should be taken
Build a LAMA2_CMD_INDIA Community and work on the following points so that we can collectively face the challenges in the future.
Support Network: Building a community provides emotional support, shared experiences, and practical advice for families and patients affected by LAMA2-CMD.
Leveraging best healthcare infrastructure - leveraging our existing healthcare infrastructure for doing the research and trial here in India, as it will help speed up treatment and reduce financial burden.
Advocacy and Awareness: Strengthens advocacy efforts to raise awareness among healthcare professionals, policymakers, and the public about the challenges faced by LAMA2-CMD patients. Organizing educational seminars, webinars and public awareness programs.
Social Media and Online Groups: Utilize platforms like Facebook groups and patient forums to connect with other families, share stories, and access up-to-date information.
Global Initiative: Accelerate access to cutting-edge treatments and clinical trials for Indian patients, collaborating with medical institutions, NGOs, information and support network groups for wider access. Increase knowledge sharing and participation in international research initiatives on LAMA2-CMD. Linking up with other global organizations like Cure CMD and Muscular Dystrophy Association (MDA). Promoting partnerships with leading research institutions and biopharmaceutical companies.
Crowd-funding for research and support: With a view to help Lama2-CMD affected we can approach various corporate sponsors and philanthropists to fund studies, research projects, and community efforts for specialized care. Mobilize financial resources by contacting donors.
Local Support: Establish local support groups or networks to facilitate in-person meetings, events, and mutual assistance.
How Doctors Can Help us
Increase Awareness: Educate medical peers about LAMA2-CMD to facilitate timely diagnosis and appropriate management.
Clinical Expertise: Collaborate with multidisciplinary teams to enhance care standards and treatment options.
Research Advocacy: Participate in clinical trials, share insights, and contribute to global research efforts.
Priority diseases: Health Ministry recently prioritized 13 rare diseases with low prevalence. Approach Health Ministry to get LAMA2 prioritized?
Shortening of clinical research and Drug discovery period: requesting your support to shortening the 21 year journey to 2 years.
Advance therapies: more exposure and awareness about physiotherapy, aqua therapy, TMR (Total motion release pediatric therapy) TOTs and other therapies.
Get In Touch
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