Myotonic muscular dystrophy type 2 (DM2) is a genetic disorder that primarily affects muscles, leading to progressive weakness and stiffness. It is an inherited condition that impacts various body systems, making it a multisystemic disorder. Understanding DM2 involves recognizing its genetic underpinnings and the wide array of ways it can manifest. The condition is progressive, meaning its effects tend to worsen over time, influencing daily life and physical capabilities.
Understanding Myotonic Muscular Dystrophy Type 2
Myotonic muscular dystrophy type 2 is also known as Proximal Myotonic Myopathy (PROMM), a term reflecting its typical pattern of muscle involvement. This condition stems from a specific genetic defect: an expansion of a CCTG repeat sequence within the CNBP gene on chromosome 3. The number of CCTG repeats in a pathogenic expansion can range from approximately 75 to over 11,000 repeats.
This genetic expansion leads to the production of abnormal RNA molecules. These toxic RNA molecules accumulate within cells and interfere with normal cellular functions, particularly by sequestering RNA-binding proteins like MBNL1. This sequestration disrupts the proper processing of other gene transcripts, ultimately leading to the diverse symptoms seen in DM2, affecting muscle cells and other tissues throughout the body.
Recognizing the Symptoms of DM2
The symptoms of myotonic muscular dystrophy type 2 can vary significantly, but certain patterns are commonly observed. One characteristic feature is myotonia, difficulty relaxing muscles after contraction. In DM2, myotonia is often less severe than in other forms and can be localized, frequently noticeable in the hands or jaw. This muscle stiffness may improve with repeated muscle activation, known as the ‘warm-up effect’.
Muscle weakness in DM2 typically presents in a proximal pattern, affecting muscles closer to the body’s center, such as the shoulders, hips, and neck. This can make activities like climbing stairs or rising from a chair challenging. Weakness may also be observed in the elbow extensors and finger flexors. Facial weakness and ankle dorsiflexor weakness are less common in DM2 compared to other types.
Chronic muscle pain and debilitating fatigue are common and significant features of DM2, often impacting quality of life. The muscle pain can feel like aching or cramping and may fluctuate or occur episodically. Beyond muscle-related issues, DM2 can involve other body systems, leading to posterior subcapsular cataracts (which can occur before age 50), heart conduction abnormalities, insulin resistance leading to type 2 diabetes mellitus, and various gastrointestinal problems such as bloating, abdominal pain, and issues with digestion.
DM2 Versus DM1
Myotonic muscular dystrophy type 2 (DM2) and Myotonic Muscular Dystrophy type 1 (DM1) share similar names but arise from distinct genetic causes and present with differing symptom patterns. DM2 is caused by an expansion of a CCTG repeat in the CNBP gene on chromosome 3, while DM1 results from a CTG repeat expansion in the DMPK gene on chromosome 19. This genetic difference underlies their varied clinical presentations.
The pattern of muscle weakness differs significantly between the two types. In DM2, weakness is typically proximal, affecting muscles around the hips, shoulders, and neck. DM1, in contrast, often presents with distal weakness, impacting muscles farther from the body’s center, such as those in the lower legs, hands, and face. Myotonia is generally milder in DM2 compared to DM1, where it can be a more prominent initial symptom.
Chronic muscle pain and debilitating fatigue are more pronounced in DM2. DM1, while also causing fatigue, tends to have more severe progressive muscle wasting and weakness. The age of onset also varies; DM2 typically begins in adulthood, often in the third to fourth decade, whereas DM1 can have a broader range of onset, including severe congenital and childhood forms. Importantly, DM2 does not have a congenital form.
Diagnosis and Management of DM2
Diagnosing myotonic muscular dystrophy type 2 typically begins with a thorough clinical examination and a review of family history, as it is an inherited condition. The definitive diagnosis of DM2 is established through genetic testing, which identifies the specific CCTG repeat expansion in the CNBP gene. This genetic test can detect the pathogenic expansion in over 99% of cases. Other supportive tests, like electromyography (EMG), may assess muscle electrical activity, and electrocardiograms (ECGs) or eye exams can evaluate for heart or eye involvement.
There is currently no cure for DM2, so management focuses on alleviating symptoms and enhancing the individual’s quality of life. Medications like mexiletine or lamotrigine can be beneficial in managing myotonia, though treatment is not always required as myotonia rarely causes severe symptoms in DM2. Pain management strategies are often employed, including medications such as gabapentin or pregabalin, nonsteroidal anti-inflammatory drugs, and tricyclic antidepressants, alongside physical therapy.
Physical and occupational therapy are important to help maintain muscle strength, flexibility, and overall mobility, and routine physical activity can support muscle health. Regular monitoring for systemic complications is also a component of care, involving periodic check-ups for cardiac issues, ophthalmic problems like cataracts, and endocrine abnormalities such as insulin resistance. Lifestyle adjustments and supportive care, including managing excessive daytime sleepiness with medication if needed, contribute to comprehensive management.