What is Congenital Myotonic Dystrophy?
Congenital Myotonic Dystrophy (CMD) is a genetic disorder that you inherit from your parents. It’s a result of a specific genetic mutation – an abnormal repetition of the ‘CTG’ sequence in a gene found on chromosome 19. This gene, known as the DMPK gene, is key in this disease. CMD is not just about muscle weakness but affects other parts of the body as well, leading to issues like cataracts, heart rhythm problems, insulin resistance, and learning disabilities.
Medical literature generally talks about two main versions of this condition. Myotonic dystrophy type 1, or DM1, is also called Steinert disease. Then there’s Myotonic dystrophy type 2 (DM2), which is like DM1 but typically less severe. One interesting thing about these diseases is that the more repetitions of the ‘CTG’ sequence a person has in their genes, the worse the disease tends to be.
Looking at its occurrence and progression, CMD occurs in about 1 in 47,619 live births. Unfortunately, up to 40% of babies with CMD do not survive the newborn stage. CMD has a unique “two-phase” progression: symptoms can improve or stabilize in babies who do survive, but adults may experience symptoms later in life.
What Causes Congenital Myotonic Dystrophy?
Congenital myotonic dystrophy is a genetic condition that happens because of specific, repeating patterns in our DNA. These repeating patterns, called “CTG” (cytosine-thymine-guanine), occur in a gene that is involved in muscular movement, found in chromosome 19q 13.3. Another version of the disease, myotonic dystrophy type 2, happens due to a similar repeating pattern “CCTG” in another gene involved in our bodily functions. What’s similar between the two conditions is that these repeating patterns in our DNA create health problems.
How severe the disease affects someone, depends on how many of these repeating patterns (“alleles”) they have. A healthy person typically has less than 30 repeats. In someone with the disease, there could be more than 11,000 repeats. But even people with many repeats can have mild cases.
When talking about genetic diseases, two key terms are “penetrance” and “anticipation”. Penetrance is basically a way of saying how many people who have the disease gene actually show symptoms. If everyone with the disease gene shows symptoms, we say the disease is ‘fully penetrant’. Anticipation refers to the fact that sometimes a genetic disease can become more severe and start at an earlier age in each new generation.
In myotonic dystrophy, all versions of the disease except one display full penetrance and anticipation.
If someone has more than 50 of these repeats, they would typically show symptoms of the disease. In one type of the disease, the repeats could be over 1,000, compared to less than 37 in healthy people, and 38-49 in people who carry the disease gene but have no symptoms. These “silent” carriers can pass on an increased number of repeats to their children, which can enhance the disease risk and cause earlier start of symptoms in the new generation (anticipation). Interestingly, this mainly happens when the disease gene is inherited from the mother (in about 90% of cases). Exactly why this happens isn’t fully understood, but experts think that factors related to the mother’s body and pregnancy play a role.
Risk Factors and Frequency for Congenital Myotonic Dystrophy
Myotonic dystrophy is the most common adult muscular dystrophy, particularly among Europeans, with a minimum rate of around 12 incidents for every 100,000 people. In specific areas such as Quebec, Canada, it is even more prevalent, affecting one in every 47,619 live births.
The rates differ around the world, like in:
- Spain – an incidence of 0.08 per 10,000 live births
- Canada – an incidence of 2.1 per 100,000 live births
- South Africa – an incidence of 3 per 100,000 live births
- Taiwan – an incidence of 0.46 per 100,000 adults
In a review of all muscular dystrophies, the rate of cases was found to be between 19.8 and 25.1 per 100,000 person-years. Among these, the muscular dystrophies that were most frequently seen were myotonic dystrophy, Duchenne muscular dystrophy, and facioscapulohumeral muscular dystrophy.
Signs and Symptoms of Congenital Myotonic Dystrophy
A complete patient history is critical for identifying congenital myotonic dystrophy (CMD). This includes a thorough birth history, past medical and surgical history, as well as a three-generation family history.
Clinical symptoms linked with CMD often appear at different life stages, including prenatally, neonatally, and during infancy and childhood. These symptoms vary but might include things like:
- Pregnancy-related complications (e.g., too much amniotic fluid, decreased fetal movement, premature birth, small birth weight)
- Newborn symptoms (e.g., low muscle tone, sluggish reflexes, muscle weakness, issues with facial muscles and posture, vision problems, breathing difficulties, recurring infections, feeding problems, problems with bowel movements, heart issues, and in severe cases, early death)
- Symptoms during infancy and childhood (e.g., while they might be able to walk, a resurgence of muscle weakness tends to occur in adolescence leading to cognitive issues, vision problems, excessive sleepiness, breathing difficulties, psychiatric disorders, heart and hormonal complications)
Muscle weakness can lead to a range of complications including spine issues, speech and language problems, and toe walking. Cognitive impairment tied with CMD can cause issues related with learning and memory. Children with CMD often face psychiatric challenges, such as phobias, depression, anxiety, avoidance, apathy and may show signs of autism. There is also an increased risk of various types of cancer. Sleep complications like excessive sleeping and sleep apnea may affect their learning abilities, memory, cognitive processes, and physical functioning. It’s worth noting that classical signs of myotonic dystrophy in adults like eye cataracts, significant heart disorders, and diabetes are not usually present in children.
During a physical examination, the doctor will measure vital signs, weight, height and take note of the circumference of the child’s head. A detailed examination will be conducted from head to toe to observe any abnormal signs including dysmorphic features, curvature of the spine, abnormal chest rise or hear murmurs, organ enlargement and issues with the musculoskeletal and neurological systems. The doctor may also check the mother for evidence of CMD, like issues with releasing their grip promptly or the presence of “percussion myotonia”, which is an involuntary muscle contraction that takes time to relax.
Testing for Congenital Myotonic Dystrophy
In the case of suspected genetic disorders, testing is the first step. Specifically, doctors can perform a targeted analysis of the DMPK gene. This testing almost always shows a unique change (pathogenic variant) in individuals who have the condition. If the initial test results are not clear, the doctor can do more comprehensive testing. This additional testing, known as a multigene panel, can provide information about other genes that may be involved.
Doctors may also perform a blood test to measure an enzyme called creatine kinase (CK). In people with the condition, the level of CK in the blood is usually normal or slightly higher than normal.
In cases where the genetic testing does not confirm the condition, a muscle biopsy can be done. This test can reveal certain characteristic changes in the muscle cells, such as an increase in internalized nuclei, ring fibers, sarcoplasmic masses, as well as shrinking of a type of muscle fiber identified as type 1 fiber.
An electromyography (EMG), a test measuring the electrical activity in muscles, can also show disturbances in the muscle’s electrical activity. It can indicate the presence of unhealthy muscle fibers and unusual bursts of electrical activity.
Finally, a brain MRI may be used. This imaging technique can reveal various brain abnormalities, such as enlargement of the fluid-filled spaces in the brain (ventricles), thinning of the brain tissue (atrophy), underdevelopment of the corpus callosum (the part of the brain that connects the two hemispheres), and abnormalities in the white matter, which contains nerve fibers that transmit signals between different parts of the brain.
Treatment Options for Congenital Myotonic Dystrophy
Severe congenital myotonic dystrophy, a hereditary muscle disorder, often requires intensive care mainly for feeding and respiratory support. Techniques such as tube feeding and mechanical ventilation can be used, with some patients also needing braces for foot deformity. Genetic counseling and discussions about end-of-life care are also crucial aspects of treatment.
A team of various medical professionals is essential for managing symptoms, monitoring the patient’s condition, and providing family support. Patients should receive regular check-ups, with the frequency depending on their age. The care team often includes nurses, physical therapists, speech therapists, social workers, and genetic counselors. It’s important to address the financial and emotional strains this condition can cause, and referrals to eye specialists and other health services are recommended.
Monitoring respiratory function is vital as issues with breathing could occur. Regular tests are conducted to measure lung capacity and blood gases, and to establish overall respiratory function. Vaccinations against respiratory infections like pneumonia and influenza are also recommended.
Since this disease can affect the heart, patients should be checked twice a year, with more frequent check-ups if they’re experiencing symptoms like lethargy and breathlessness.
In terms of digestive health, regular surveillance of nutrition and growth is recommended, along with managing conditions like acid reflux and constipation. Some patients may require feeding tubes and medications like antacids and probiotics.
Oral issues are common in these patients, so they might need an orthodontist to address problems like misaligned teeth and gum disease.
Orthopedic treatments and rehabilitation are necessary for managing joint contractures and deformities of the foot and spine. These interventions could include bracing, splinting, and mobility aids. Physical activity is crucial as it can help improve muscle strength around the hips and shoulders.
Pain management is pivotal in maintaining a good quality of life as the disease can cause painful muscle spasms and joint pain. Also, special care is needed when children with this condition require surgery, due to their higher risk for complications.
This disorder can also have psychological implications; Therefore, referrals to a psychiatrist or psychologist should be part of the care plan. Depression and anxiety are common among these patients due to their disability.
Additionally, regular surveillance involving dental assessments, electrocardiograms (ECGs), lung function tests, and eye exams are recommended, among other tests.
What else can Congenital Myotonic Dystrophy be?
When a doctor suspects a patient may have congenital myotonic dystrophy, other conditions with similar symptoms also need to be considered. These include:
- Prader-Willi syndrome – a complex genetic condition affecting many parts of the body.
- Temple syndrome – a rare condition characterized by specific features and health problems.
- Congenital myopathies – a group of muscle disorders that appear at birth or in infancy, this includes multiminicore, nemaline, and centronuclear conditions.
- Hereditary inclusion body myopathy – a condition that primarily causes muscle weakness and wasting.
- Welander distal myopathy – a condition that causes weakness and wasting in the hand muscles.
- Limb-girdle muscular dystrophy types 2B and 2L – a group of disorders that cause weakness and wasting of muscles around shoulders and hips.
By ruling out these conditions, the doctor can accurately diagnose whether the patient has congenital myotonic dystrophy.
What to expect with Congenital Myotonic Dystrophy
The mortality rate can reach 40% in newborns, mainly due to respiratory illnesses. On average, the lifespan is expected to be around 45 years.
Possible Complications When Diagnosed with Congenital Myotonic Dystrophy
Severe CDM typically needs intensive care, particularly for feeding and assistance with breathing. Occasionally, this might involve inserting a tube into the stomach or small intestine for feeding and a tracheostomy (an opening in the neck for a breathing tube) for mechanical ventilation.
Preventing Congenital Myotonic Dystrophy
Congenital myotonic dystrophy (CMD) is a complex condition that affects many parts of the body. This disease is caused by a malfunction in a specific gene, known as the DMPK gene.
Infants with CMD often show signs of weakness, and may need assistance with basic activities like breathing and eating.
The method typically used to diagnose this condition is a genetic test that looks specifically for changes in the targeted gene.
While CMD unfortunately has no cure, medical teams work closely with patients to manage their symptoms, monitor their health, and provide support to them and their families.
Regrettably, up to 40% of infants with CMD pass away during the newborn period due mainly to difficulties with breathing.
