What is Myotonic Dystrophy

Myotonic dystrophy (DM) is a genetic disorder characterized by progressive muscle wasting causing two main problems: muscles that don’t relax quickly (myotonia) and that gradually get weaker over time. It is a multi-system disorder, and symptoms can affect various organs and tissues, not just muscles. Performing daily activities can become challenging as this condition may also impact different parts of the body, including the heart, lungs, digestive system, eyes, hormone-producing glands, and the brain, as well as the skeletal muscles. 

This is a progressive condition that may cause a wide range of health issues as it gradually worsens over time. The progression of myotonic dystrophy can vary widely among individuals, and it is difficult to predict the exact course of the disease for a specific person. Navigating myotonic dystrophy can be complex, necessitating a personalized approach for each individual.  

Types of Myotonic Dystrophy

There are two main types of myotonic dystrophy: Type 1 myotonic dystrophy (DM1) and Type 2 myotonic dystrophy (DM2).  

Type 1 myotonic dystrophy (DM1)

• DM1, also known as Steinert’s disease, is the most common type. It can manifest at almost any age, but typically it manifests in adulthood. Symptoms may include muscle weakness (particularly in the face, neck, hands, and feet), myotonia (difficulty relaxing muscles after contraction), cataracts, heart issues, hormone imbalances, and intellectual disabilities in some cases. 

• • Congenital myotonic dystrophy is a variation of DM1 presenting in newborns, characterized by muscle weakness, respiratory problems, and developmental issues. 

Type 2 myotonic dystrophy (DM2)

• DM2: This type is usually less severe than DM1 and has a later onset. Its symptoms are similar but tend to be milder and progress more slowly. It tends to affect muscles in the shoulder, elbows and hips. 

Both types of myotonic dystrophy result from genetic mutations that disrupt how certain proteins work in cells. And both can affect multiple body systems, resulting in a wide range of symptoms that extend beyond muscle-related issues. 

Due to this complexity, this blog will focus on the more common type of myotonic dystrophy, DM1. 

Symptoms of DM1

DM1 varies widely from person to person, affecting many body parts and causing many symptoms. Some people with myotonic dystrophy might have more serious muscle problems, while others might experience additional symptoms like learning difficulties or mood changes. There may also be other psychological challenges, for example feeling a lack of motivation after developing blurry vision due to cataracts, or patients can experience difficulties with mood and memory. The cardiac muscles, vital for heart function, might develop irregularities, which can cause symptoms like dizziness due to abnormal heart rhythms.  If involuntary muscles are affected, it can lead to a range of issues: digestive problems such as constipation or indigestion, circulation challenges due to dysfunctional blood vessels, and breathing difficulties resulting from compromised control of the airways. This complexity underscores the need for a personalized approach to care. 

Diagnosis and Genetic Testing

To diagnose myotonic dystrophy in general, doctors typically begin by doing a physical examination. They look for characteristic symptoms such as muscle weakness, myotonia, and cataracts. The next step is genetic testing to determine the type of myotonic dystrophy. This involves checking for specific gene mutations, in the DMPK gene (Dystrophia Myotonica Protein Kinase) for DM1, and in the CNBP gene (Cellular Nucleic Acid Binding Protein, also known as ZNF9, which stands for Zinc Finger Protein 9) for DM2.  

Imagine the genetic code as a long, complex instruction manual for building and maintaining the human body. In myotonic dystrophy, there’s a section in this manual (the DNA) where a phrase is mistakenly repeated many times, leading to faulty instructions. The repeated phrase is an abnormal repetition of DNA building blocks in a particular gene. 

Normally, this sequence of building DNA building blocks is repeated a few times in everyone’s DNA, but in people with DM1, this sequence is repeated far more. The number of these repeats can vary greatly among individuals with DM1. Research is beginning to suggest that the higher the number of these repeats a person has, the more severe their symptoms may be and the earlier the disease may appear. 

For someone with DM1, genetic testing may not only confirm their diagnosis but may also suggest how future generations may be impacted by the disease. When a person with DM1 has children, the number of repeats is expected to increase in the next generation. As a result, the child may develop symptoms of the disease earlier and more severely than the parent did. This trend of increasing severity and earlier onset in each successive generation is referred to as “anticipation.” People receiving a diagnosis may be referred to genetic counselling for more information and support. 

Daily Challenges with Myotonic Dystrophy

A study exploring the lived experience of people with various types of DM found the most common complaints overall were muscle weakness, fatigue, and daytime sleepiness. For people with DM1, the most challenging daily life activities were going up and down stairs, standing, and maintaining balance.  Living with myotonic dystrophy involves adapting daily routines to manage progressive symptoms like muscle weakness and stiffness, which impact activities and independence. For example, scheduling regular breaks or time to rest may be one way to adapt. Another challenge people with DM1 may face is cognitive changes such as memory and concentration difficulties, leading to stress and frustration. These daily life changes may feel like a loss of independence and increased reliance on others. Depending on the needs, support is in most cases available. 

Caregivers can support with daily tasks, like medication management and/or transportation. Counselling, patient advocacy groups, and support groups may be helpful resources in learning to navigate these life changes. Support may also come from family and friends. Finding a space to share experiences and learning coping strategies help both patients and caregivers as they adjust. 

Treatment

There is currently no cure for myotonic dystrophy. The approach to treatment places a focus on alleviating its symptoms. DM1 has a greater impact on various body systems and requires specialized care and monitoring. Therefore, clinical recommendations emphasize a comprehensive approach. Usually, a team of experts from different medical fields is necessary to manage the wide-ranging symptoms of DM1. They focus on understanding the disease’s progression and adapting care accordingly.
DM1 can be categorized into two main groups:

Clinical Recommendations for Severe Symptoms and Conditions: 

• Skeletal Muscle Weakness and Rehabilitation: Regular evaluations and referrals to specialists like physical therapists and occupational therapists. 
• Skeletal Muscle Myotonia: Treatment options for muscle stiffness and pain. 
• Ocular Symptoms: Managing eye conditions like cataracts and recommending annual eye exams. 
• Gastrointestinal Symptoms: Addressing digestive issues and recommending dietary adjustments and medications. 
• Neuropsychiatric Symptoms: Cognitive and behavioral assessments and referrals to mental health professionals. 
• Psychosocial Symptoms: Assessing social circumstances and referring to support services. 
• Excessive Daytime Sleepiness (EDS): Evaluating and treating sleep-related issues. 
• Endocrine and Metabolic Symptoms: Monitoring and managing conditions like diabetes and thyroid disorders. 
• Tumors: Detection and management of skin tumors and following cancer screening guidelines. 

Clinical Recommendations for Life-Threatening Symptoms: 

• Surgery, Anesthesia, and Pain: Managing anesthesia risks and adverse reactions to medications specific to patients with DM1. 
• Respiratory Symptoms: Monitoring and managing respiratory complications. 

• Cardiovascular Symptoms: Addressing cardiac complications like arrhythmias and conducting routine cardiac evaluations. 
• Pregnancy and Obstetric Management: Special care for women with DM1 during pregnancy and delivery, including genetic counselling.
  

Research Exploring New Treatment Options 

Research on myotonic dystrophy is exploring new ways to tackle the disease’s genetic roots. These treatments are experimental and need more research to ensure they are safe and effective. They share a common goal: addressing the underlying genetic cause of myotonic dystrophy. 

• Gene Therapy: This method focuses on either fixing or replacing the specific genes that are faulty in myotonic dystrophy, like repairing or substituting a broken part in a machine. 
• Antisense Oligonucleotides (ASOs): Designed to act like a sticky note placed over a mistake to cover it up and prevent the machine from reading the faulty instructions. 
• RNA-mediated Therapies: These act like specialized inspectors who go through the instruction manual to find the misprints and either fix them or remove them to ensure the machine runs smoothly. 
• Small Molecule Drugs: Suppose a misprint in the instruction manual is causing the gears (muscles) to function improperly. An example analogy of this type of treatment is like a special oil. It doesn’t rewrite the instruction manual, but it may help the gears work more smoothly. 
• CRISPR/Cas9 Technology: This technique edits the gene directly to correct the mistake, like editing a typo in the instruction manual. 

While their end goal is similar, each approach works at a different stage or aspect of the genetic problem in myotonic dystrophy. This diversity in approaches is important to help increase the chances of finding effective treatments for the condition. 

Conclusion  

Myotonic dystrophy, a complex genetic disorder, has varied manifestations and requires a multi-faceted approach for diagnosis, treatment, and daily management. The process of diagnosing myotonic dystrophy involves a physical examination followed by genetic testing. Understanding the implications of a positive diagnosis, including the likelihood of passing myotonic dystrophy through inheritance, is important.  

Living with myotonic dystrophy involves a continuous process of adaptation to manage an evolving set of symptoms, impacting both physical and emotional aspects of life for patients and their caregivers. Staying informed and proactive is key for patients and their families in navigating this condition.  

myTomorrows is dedicated to helping patients with myotonic dystrophy. We can support with finding and if patients wish so, help with accessing clinical trials. Click here to get started and speak with one of our patient navigators. 

The information in this blog is not intended as a substitute for a medical consultation. Always consult a doctor before receiving a diagnosis or treatment. 

The myTomorrows team
Anthony Fokkerweg 61-2
1059CP Amsterdam
The Netherlands