Myotonic Dystrophy Type 1 vs. Type 2: Key Differences

Myotonic dystrophy is a multisystem genetic disorder recognized as the most common form of muscular dystrophy that begins in adulthood. It is defined by progressive muscle wasting and weakness, along with prolonged muscle contractions. The condition presents in two primary forms, type 1 (DM1) and type 2 (DM2), which share overlapping features but are distinct disorders. While both types affect muscles and other body systems, they differ in their genetic underpinnings, clinical presentation, and progression.

Genetic Origins and Inheritance Patterns

Myotonic dystrophy is an autosomal dominant inherited condition, meaning an individual only needs one copy of the altered gene from a parent to be affected. Both DM1 and DM2 arise from an unstable expansion of a short DNA sequence repeated within a specific gene. The resulting messenger RNA becomes unusually long and forms clumps inside the cell, which interferes with the function of many other proteins and leads to the disorder’s symptoms.

Myotonic dystrophy type 1 is caused by a mutation in the DMPK gene on chromosome 19, involving an expansion of a cytosine-thymine-guanine (CTG) nucleotide repeat. In contrast, myotonic dystrophy type 2 results from a mutation in the CNBP gene on chromosome 3. The repeat sequence involved in DM2 is a cytosine-cytosine-thymine-guanine (CCTG) expansion.

A genetic distinction is the phenomenon of anticipation, a hallmark of DM1 that is not associated with DM2. Anticipation describes the tendency for the disease to increase in severity and appear at an earlier age as it is passed down through successive generations. This occurs because the unstable CTG repeat in the DMPK gene often expands when passed from parent to child, and the number of repeats correlates with the severity and age of onset in DM1.

Distinguishing Clinical Symptoms

In DM1, weakness and wasting begin in the distal muscles—those farthest from the center of the body. This includes the muscles of the hands, feet, lower legs, face, and neck, which can lead to difficulty with fine motor skills, foot drop, and a characteristic facial appearance. Conversely, DM2 involves the proximal muscles, which are closer to the center of the body. The muscles of the neck, shoulders, hips, and upper legs are the first to show weakness, resulting in difficulty climbing stairs or rising from a seated position.

While both types feature myotonia, or the inability to relax muscles after contraction, it is often more pronounced in DM1. Muscle pain, known as myalgia, is a more common complaint for individuals with DM2.

Both types are multisystemic, but the extent of involvement differs. DM1 is associated with more frequent and severe complications, including cardiac conduction abnormalities, respiratory weakness, and cognitive impairment. While people with DM2 can also experience issues like cataracts and heart problems, they are milder and less frequent than in DM1.

Age of Onset and Disease Progression

Myotonic dystrophy type 1 is characterized by a wide spectrum of onset, ranging from birth to late adulthood. The most severe form, congenital myotonic dystrophy, is apparent at birth. Other forms include a childhood-onset, a classic adult-onset that appears in a person’s twenties or thirties, and a mild, late-onset form.

The progression of DM1 is linked to the size of the expanded CTG repeat, with larger repeats correlating with earlier onset and more severe symptoms. The disease worsens slowly, though the rate of progression varies among individuals. The involvement of the heart and respiratory muscles can lead to a shortened life expectancy in more severe cases.

In contrast, myotonic dystrophy type 2 presents in adulthood, with symptoms emerging between the ages of 20 and 60. A congenital form of DM2 is not seen. The progression of DM2 is slower and the overall course of the disease is milder than that of classic adult-onset DM1, and many individuals with DM2 have a normal life expectancy.

Diagnostic and Management Approaches

A definitive diagnosis for either type of myotonic dystrophy requires genetic testing. A blood test can identify the specific repeat expansion, looking for a CTG repeat expansion in the DMPK gene for DM1 or a CCTG repeat expansion in the CNBP gene for DM2. The pattern of muscle weakness, such as distal versus proximal, is a primary indicator that guides which test to perform first.

As there is currently no cure for myotonic dystrophy, management focuses on supportive care tailored to the specific symptoms of each type. For individuals with DM1, this means proactive monitoring for systemic complications. Regular cardiac evaluations to check for electrical conduction problems, pulmonary function tests, and eye exams for cataracts are standard components of care.

For those with DM2, management priorities may differ due to the different symptom profile. While cardiac and eye monitoring is still necessary, a greater emphasis is often placed on managing the muscle pain that can accompany DM2. Physical therapy and mobility aids are also used to address the proximal muscle weakness.