Myotonic Dystrophy

Myotonic dystrophy is a complex inherited condition that affects muscles and many other parts of the body. People with this condition experience progressive muscle weakness, difficulty relaxing muscles after contraction, and a range of other symptoms that can affect the heart, eyes, and other organs.

Table of contents

• What is Myotonic Dystrophy?
• Types of Myotonic Dystrophy
• What Causes Myotonic Dystrophy?
• How Common is Myotonic Dystrophy?
• Symptoms and Signs
• Diagnosis
• Treatment and Management
• Outlook and Life Expectancy
• Living with Myotonic Dystrophy

What is Myotonic Dystrophy?

Myotonic dystrophy is a complex, inherited condition that mainly causes progressive muscle loss and weakness. It is a form of muscular dystrophy, which refers to a group of more than 30 genetic conditions that cause muscles to become weaker and lose mass over time^[1].

The defining feature of myotonic dystrophy is myotonia, which is the inability to relax muscles at will after using them. For example, a person with this condition may have difficulty letting go of a door handle after grasping it, or they may experience temporary locking of their jaw^[1][4]. Myotonia improves with repeated exercise and worsens with exposure to cold^[3].

Myotonic dystrophy is the most common form of muscular dystrophy that begins in adulthood, although certain types can affect infants and children^[1][3].

DM, dystrophia myotonica, Steinert disease, myotonia atrophica, myotonia dystrophica, Curschmann-Batten-Steinert syndrome

Types of Myotonic Dystrophy

There are two main types of myotonic dystrophy. Their symptoms overlap, but they are caused by mutations in different genes and can differ in severity^[1].

Myotonic dystrophy type 1 (DM1), also known as Steinert disease, is the more common and often more severe form. DM1 has four subtypes based on the age when symptoms begin^[1]:

• Classic DM1: This form usually begins in the 20s, 30s, or 40s and is the most common presentation^[1].
• Mild DM1: This form affects people between 20 to 70 years old, typically after age 40, with milder symptoms^[1].
• Congenital DM1: This severe form affects infants from birth and can cause serious breathing and feeding difficulties^[1].
• Childhood-onset DM1: This form usually begins around age 10^[1].

Myotonic dystrophy type 2 (DM2), also known as proximal myotonic myopathy, tends to be milder than DM1. It typically begins in adulthood, with an average age of onset around 48 years^[1][2]. The muscle weakness in DM2 primarily affects muscles closer to the center of the body, such as those of the neck, shoulders, elbows, and hips^[4].

What Causes Myotonic Dystrophy?

Myotonic dystrophy is a genetic disorder caused by mutations in specific genes. Both types are inherited in an autosomal dominant pattern, which means that only one copy of the altered gene is needed to cause the condition^[4].

DM1 is caused by an abnormal expansion of a DNA section called a CTG repeat in the DMPK gene on chromosome 19. Normally, this section contains fewer than 35 repeats, but people with DM1 typically have more than 50 repeats. The more repeats present, the more severe the disease tends to be^[3][4].

DM2 results from an abnormal expansion of a CCTG repeat in the CNBP (also called ZNF9) gene on chromosome 3^[2][3].

These expanded DNA sections produce abnormally long messenger RNA that forms clumps inside cells. These clumps interfere with the production of many other proteins, preventing muscle cells and cells in other tissues from functioning normally. This leads to the wide range of symptoms seen in myotonic dystrophy^[4].

An important feature of myotonic dystrophy is that it generally worsens with each generation. This phenomenon, called anticipation, occurs because the number of DNA repeats tends to increase when passed from parent to child, particularly from mother to child^[1][3].

How Common is Myotonic Dystrophy?

Myotonic dystrophy affects at least 1 in 8,000 people worldwide, though this varies among different geographic and ethnic populations^[1]. Recent genetic studies suggest the condition may be more common than previously thought, with one study estimating prevalence at approximately 1 in 2,100 people^[11].

Myotonic dystrophy is the most common muscular dystrophy in people of European ancestry. Among nonwhite populations, DM1 is uncommon or rare^[2][3]. In most populations, type 1 is more common than type 2, though reports from Europe suggest the prevalence of DM2 may be similar to that of DM1^[2].

Globally, myotonic dystrophy has an incidence of about 1 per 3,000 people, though some regions, such as Quebec in Canada, have demonstrated a higher incidence of 1 per 500^[3].

Symptoms and Signs

Myotonic dystrophy causes a wide range of symptoms that can affect many parts of the body. The main symptoms include muscle wasting, muscle weakness, and myotonia, all of which get progressively worse over time^[1].

Classic Myotonic Dystrophy Type 1

In classic myotonic dystrophy type 1, which begins in adulthood, myotonia is often the main initial symptom. It is typically more noticeable after rest and improves with muscle activity^[1].

Other symptoms include^[1]:

• Distal muscle weakness: Weakness affects muscles farthest from the center of the body, such as those in the hands and lower legs. This results in difficulty with fine motor tasks involving the hands and problems with walking due to foot drop.
• Myopathic face: A thin, sharp facial appearance due to wasting of facial muscles.
• Heart conduction abnormalities and irregular heartbeat.
• Early development of cataracts, which are clouding of the lens of the eye.
• Excessive daytime sleepiness and fatigue.
• Difficulty swallowing.
• Problems with cognitive function and executive tasks.

Congenital Myotonic Dystrophy Type 1

Congenital myotonic dystrophy type 1 is a severe form that affects infants from birth. It should be suspected in newborns who present with^[11]:

• Weak muscle tone (hypotonia)
• Clubfoot
• Feeding difficulties
• Breathing problems and respiratory distress
• Delayed development
• Intellectual disability

Some of these health problems can be life-threatening^[4].

Childhood-Onset Myotonic Dystrophy Type 1

Childhood-onset myotonic dystrophy type 1 typically begins between ages 1 and 10 years and is characterized by learning difficulties, attention problems, and delayed motor development^[11].

Myotonic Dystrophy Type 2

DM2 causes muscle weakness that primarily involves muscles closer to the center of the body, such as those of the neck, shoulders, elbows, and hips. Overall, DM2 tends to be milder than DM1^[1][4].

Other Body Systems Affected

Beyond muscles, myotonic dystrophy can affect several body systems^[1][12]:

• Heart and cardiovascular system: Cardiac conduction defects and abnormalities of the electrical signals that control the heartbeat
• Eyes: Early-onset cataracts (before age 50)
• Endocrine system: Development of diabetes mellitus, in which blood sugar levels can become dangerously high; fertility issues and early balding in men
• Respiratory system: Breathing muscle weakness
• Gastrointestinal system: Digestive disturbances
• Central nervous system: Reduced cognitive function and personality changes

• Skeletal muscles
• Heart muscle
• Eyes
• Central nervous system
• Endocrine system
• Respiratory system
• Gastrointestinal system

Diagnosis

Many people with myotonic dystrophy experience a significant delay from symptom onset to diagnosis. In one analysis of 679 patients in a US registry, individuals had an average 7-year delay from symptom onset to diagnosis. This delay was attributed to the wide variety of clinical findings and the variable age at which symptoms begin^[11].

Diagnosis of myotonic dystrophy is confirmed by genetic testing. Blood tests can identify the abnormal DNA expansions in the DMPK gene for DM1 or the CNBP gene for DM2^[1][4].

Before genetic testing, healthcare providers may notice several signs during physical examination, including myotonia, muscle weakness, facial muscle wasting, and cataracts. Additional tests that may be performed include^[3]:

• Electromyography (EMG): A test that measures the electrical activity of muscles
• Electrocardiogram (ECG): A test to evaluate heart rhythm and conduction
• Eye examination to detect cataracts
• Blood sugar testing to check for diabetes

Prenatal testing and predictive testing for at-risk family members are available through genetic counseling services^[4].

Treatment and Management

There is currently no cure for myotonic dystrophy and no treatments that slow the progression of the disease itself. However, symptomatic treatments are available that can reduce suffering and improve quality of life for patients^[3][8].

Medications

Various medications may be used to manage specific symptoms^[8][2]:

• Anti-myotonic drugs: Medications such as mexiletine or carbamazepine can help relax muscles when myotonia impairs normal activities.
• Pain management: Nonsteroidal anti-inflammatory drugs (NSAIDs) can help manage muscle pain. Tricyclic antidepressants may also be used for pain relief.
• Anti-diabetic drugs: To normalize blood sugar levels and address diabetic symptoms.

Rehabilitative Therapies

Several types of therapy can help maintain function and address specific problems^[8]:

• Physical therapy: For muscle weakness, myotonia, and joint contractures
• Speech therapy: For swallowing and pronunciation difficulties
• Psychiatric therapy: For behavioral and psychological issues such as attention deficit, depression, and anxiety disorders
• Individualized support: For learning disabilities and cognitive delays

Devices and Equipment

Various assistive devices and medical equipment may be needed^[8][2]:

• Assistive devices such as neck braces, arm and foot braces, canes, walkers, scooters, and wheelchairs to ensure safe mobility
• Eye crutches for droopy eyelids
• Pacemaker or implantable cardioverter defibrillator (ICD) to address irregular heartbeat issues
• Devices to assist with breathing, such as incentive spirometry and cough-assist machines

Monitoring and Surveillance

Regular monitoring by healthcare professionals is essential to manage complications. Multidisciplinary surveillance and management of symptoms is optimal^[10].

Important Anesthesia Warning

An unusually high rate of complications and even deaths associated with general anesthesia during surgery have been reported in people with DM1. This can occur even if the disease is mild. It is critical to inform the entire medical team, especially those responsible for anesthesia, that you or your family member has myotonic dystrophy. The medication succinylcholine should be avoided. Adverse reactions to anesthesia do not seem as serious in DM2, but caution is still advised^[10].

Outlook and Life Expectancy

The severity and rate at which symptoms develop vary widely among people with myotonic dystrophy, even among members of the same family^[1][12]. Many people with myotonic dystrophy do not exhibit all, or even most, of the possible symptoms. Often the disorder is mild, and only minor muscle weakness or cataracts are seen late in life^[12].

Patients with congenital, childhood-onset, and classic adult-onset myotonic dystrophy type 1 are at higher risk for early mortality. A study of 367 patients in Canada observed over a 10-year period reported a 20% mortality rate, with a mean age at death of 53.2 years. Among the 75 deaths, 43% were respiratory-related, 20% cardiovascular-related, 11% cancer-related, and 11% from sudden death^[11].

Early detection of myotonic dystrophy and effective management are important for reducing time to diagnosis, initiating supportive care, and decreasing mortality^[11].

Living with Myotonic Dystrophy

Although myotonic dystrophy is a form of muscular dystrophy, it is misleading to think of it merely as a muscle disease. The condition can be highly variable in both symptoms and severity, which makes it important for people with the condition to understand and prepare for potential challenges^[12].

Because myotonic dystrophy can vary significantly among those affected, it is impossible for clinicians to predict exactly how it will affect any individual. Today, researchers are working to understand why the range of systems affected and the severity of symptoms can vary so greatly^[12].

Learning as much as possible about the condition is important so that people with myotonic dystrophy can talk effectively with their doctors and educate those around them. Myotonic dystrophy is not well understood by the general medical community, making patient knowledge especially valuable^[15].

Taking part in care and actively managing symptoms can improve quality of life. Working with a multidisciplinary healthcare team and ongoing monitoring can help avert or reduce complications^[8].