What is Myotonic Dystrophy?
Myotonic dystrophy is a genetic disorder that causes weakness, deterioration, and prolonged contractions in skeletal muscles. Its symptoms usually begin in young adulthood, and it is the most common form of adult-onset muscular dystrophy.
Muscular dystrophy (MD) is a collective term that refers to a group of more than 30 diseases. The common characteristic of all the diseases is that they cause muscle weakness and a progressive loss of muscle tissue. Unfortunately, there is no known cure for any of the conditions.
Myotonic dystrophy is commonly abbreviated DM, which stands for dystrophia myotonia.
Types of Myotonic Dystrophy
DM can be divided into two main types and several subtypes. Symptoms can vary depending on the type.
Myotonic Dystrophy Type 1
DM Type 1 is further divided into mild, classical, and congenital types. Symptoms of DM Type 1 may include:
- Muscle weakness and deterioration
- Muscle contractions
- Clouding of the lenses of the eyes (cataracts)
- Heart problems
Congenital DM Type 1 typically causes breathing problems, intellectual disabilities, and shortened life expectancy.
Myotonic Dystrophy Type 1
Symptoms of DM Type 2 are similar to those of Type 1 but are generally milder. Type 2 also does not cause the symptoms produced by congenital DM Type 1.
Myotonic Dystrophy and the Brain
Although DM’s effect on the brain is not yet well understood, research has identified a link between the disease and abnormal connections between specific types of brain cells. DM has also been associated with numerous neurological and psychiatric symptoms, including:
- Memory impairment
- Executive function impairment
- Intellectual disabilities
- Egocentric, avoidant, paranoid, and aggressive behavioral traits
What Causes Myotonic Dystrophy?
Muscular dystrophy occurs when the body cannot produce the proteins needed to build and protect muscle cells. Genes control the production of these proteins, and each type of MD is characterized by a gene abnormality that affects protein production.
In myotonic dystrophy, gene mutations cause clumps of genetic material called RNA to form inside cells. These RNA clumps interfere with the normal production of proteins and cause the symptoms of DM.
DM Type 1 is caused by mutations of the DMPK gene. Type 2 is caused by mutations in the CNBP gene.
Is Myotonic Dystrophy Hereditary?
Most types of muscular dystrophy run in families, and the genetic trigger for the disease is passed from parent to child. Myotonic dystrophy is inherited in an autosomal dominant pattern, meaning that a child may develop the disorder if they inherit even one copy of the mutated gene from either of their parents. If a parent carries the disorder-causing mutation, they will have a 50 percent chance of having an affected child with each pregnancy. The parent will also likely have DM themselves.
DM Type 1 is associated with a genetic phenomenon called “anticipation,” in which children who inherit the disease tend to experience an earlier onset and more severe symptoms than their parents experienced. Congenital DM Type 1 is also usually inherited from the mother.
How Is Migraine Disorder Detected?
The onset of DM varies significantly from case to case, and different types of the disease can first appear at various stages of life.
Congenital DM Type 1 is present at birth. Symptoms may include:
- Weak, floppy muscles
- Inward-turned feet (clubfoot)
- Feeding difficulties
- Poor growth
- Breathing difficulties
A juvenile form of this type first appears in childhood, often before age 12. The adult-onset form of DM Type 1 is the most common. Its symptoms typically first appear when a person with the disease is in their 30s.
DM Type 2 typically emerges in a person’s 20s, but symptoms may first appear as late as the 50s. Weakness in the fingers and neck is often the first sign of the disease.
How Is Myotonic Dystrophy Diagnosed?
If a doctor is presented with symptoms that look like muscular dystrophy, they will begin the diagnostic process by conducting a physical exam and gathering a medical history. If it appears that a muscle disease is likely, several different tests can help determine if there is a muscle problem and which disease is the cause.
Possible diagnostic tests include:
- Creatine kinase (CK) test. Creatine kinase (CK) is a type of protein called an enzyme. CK in the blood is normal, but higher enzyme levels are created when muscles are damaged. Therefore, an elevated CK level when there is no apparent muscle injury can show the presence of a muscle disease like DM.
- Electromyography. This test uses an electricity-sensing needle probe to measure muscle function. The test can detect muscle abnormalities that could be a sign of DM.
- Muscle biopsy. This test involves removing and examining a small amount of muscle tissue. A biopsy may be able to detect muscle abnormalities caused by MD.
- Magnetic resonance imaging (MRI). This imaging scan may show degeneration in the part of the brain called the cerebellum, a condition sometimes associated with DM.
- Genetic testing. These blood tests look for the specific genetic abnormalities that are responsible for DM.
PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.
How Is Myotonic Dystrophy Treated?
There is no cure for DM, and no treatment will reverse the progression of its symptoms. With treatment, symptoms can sometimes be managed to help prevent severe, life-threatening complications. Possible treatment options include:
- Medications to manage pain
- Physical therapy
- Occupational therapy
- Mobility aids
- Cataract surgery
- Respiratory support
- Feeding assistance
- Hormone therapies
- Regular monitoring of the patient’s heart health
How Does Myotonic Dystrophy Progress?
DM symptoms worsen over time, but people with milder forms of the disease may have only moderate disabilities and an average lifespan. Mobility problems are common, although people with DM Type 2 may be able to walk until late in life.
People with congenital DM or severe DM Type 1 symptoms may have a significantly shortened life expectancy. The most common causes of death are respiratory and heart complications.
How Is Myotonic Dystrophy Prevented?
There is no known way to prevent the onset of myotonic dystrophy in someone born with a genetic mutation responsible for the disease. Therefore, people who have a family history of the disease should seek the advice of a genetic counselor to assess their risk if they plan to have children.
Myotonic Dystrophy Caregiver Tips
Studies have shown that caring for someone with muscular dystrophy can significantly negatively impact the caregiver’s life. Caregivers are at risk for depression, sleep problems, stress, anxiety, relationship problems, and low self-esteem. Caregivers are also likely to have difficulty performing well at work, and many caregivers quit working entirely to care for their loved one.
Because of these risks, caregivers must take advantage of support systems to keep themselves healthy. The Muscular Dystrophy Association maintains a collection of resources for caregivers that includes educational resources, guides, and links to caregiver networks and support groups.
Myotonic Dystrophy Brain Science
The reason DM affects the brain is unclear, but most scientists agree that there is a connection between the disease and abnormalities in brain cells. Most forms of muscular dystrophy are caused by deficient production of proteins vital to muscle-cell health. However, DM seems to be different in that its genetic mutations cause tangles of fibers inside cells rather than impair the production of a specific protein.
These tangles bear a resemblance to protein tangles found in the brain cells of people with degenerative brain diseases such as Alzheimer’s disease. Alzheimer’s and other related disorders are called “tauopathies” because they involve abnormalities of molecules called tau proteins. Therefore, classifying DM as a tauopathy and examining its relationship to other tauopathies may lead to a better understanding of DM’s effect on the brain.
Myotonic Dystrophy Research
Title: Assessing Clinical Endpoints and Biomarkers in Myotonic Dystrophy Type-1 and Type 2 (ASCEND-DM)
Principal investigator: Ami K Mankodi, MD
National Institute of Neurological Disorders and Stroke (NINDS)
Objective: In adults, myotonic dystrophy type 1 (DM1) and type 2 (DM2) are the most common inherited skeletal myopathies. RNA toxicity is the core disease mechanism, good molecular targets have been identified, and there has been rapid progress in developing targeted therapies. However, incomplete characterization and limited biologic understanding of phenotypic heterogeneity, and lack of reliable clinical endpoints and biomarkers remain a significant obstacle in the road to therapeutic success in these diseases. The present study seeks to overcome these roadblocks building on previous work of the Myotonic Dystrophy Clinical Research Network (DMCRN) (14-N-0132 study) with the following added features: 1) larger DM1 cohort including 11 – 70-year-old individuals; 2) including DM2 individuals, 3) longer study duration; 4) allowing validation of NIH custom-built devices for longitudinal measurements; and 5) including non-muscle endpoints and biomarkers specifically respiratory and central nervous system (CNS) function, which are important for survival and quality of life. The goal of the current study is to prospectively assess the disease progression over two years in individuals with DM1 and DM2. Selected tests, imaging, and patient-reported outcomes will be assessed for the ability to quantify disease burden, detect disease progression and predict changes. Additionally, we will examine muscle and cerebrospinal fluid (CSF) RNA alternative splice events as biomarkers of DM1 and DM2 severity and explore genetic modifiers of DM1 and DM2 severity by genome-wide association (GWA) study.
Study population: This study plans to enroll up to 180 participants: 120 individuals with DM1 and 60 individuals with DM2 (open to both juvenile and adult individuals (11 to 70 years old, inclusive)) at the NIH Clinical Center.
Title: Myotonic Dystrophy and Facioscapulohumeral Muscular Dystrophy Registry
Principal investigator: Richard T. Moxley, III, MD
University of Rochester Medical Center
Myotonic dystrophy (DM) and facioscapulohumeral muscular dystrophy (FSHD) are inherited disorders characterized by progressive muscle weakness and loss of muscle tissue. The purpose of this registry is to connect people with DM or FSHD with researchers studying these diseases. In addition, the registry will offer individuals with DM and FSHD an opportunity to participate in research that focuses on their conditions. The registry will also help scientists accomplish research on DM and FSHD and distribute their findings to patients and care providers.
Title: Extracellular RNA Biomarkers of Myotonic Dystrophy
Principal investigator: Thurman M. Wheeler, MD
Massachusetts General Hospital
Current methods of measuring the response to new treatments for muscular dystrophies involve examining small pieces of muscle tissue called biopsies. The investigators are interested in finding less invasive methods that reduce the need for muscle biopsies. The purpose of this research is to learn about the possibility of detecting and measuring the activity and severity of muscular dystrophies by examining a urine sample and a blood sample.