What Is Myotonic Dystrophy?
Myotonic dystrophy is a disorder that affects the muscles and other parts of the body. It is the most prevalent type of muscular dystrophy that manifests in adults, typically between 20 to 30 years of age. Muscle loss and weakness are common symptoms of this condition. Myotonic dystrophy is divided into two forms, each affecting a distinct muscle group. Myotonic dystrophy is characterized by chronic muscle tenseness or myotonia and the inability to relax some muscles after use. The severity of the condition keeps varying from person to person, even within the same family.
What Are the Causes of Myotonic Dystrophy?
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A mutation or change in the myotonic dystrophy protein kinase (DMPK) gene causes myotonic dystrophy type 1. A modification or alteration in the nucleic acid-binding protein (CNBP) gene, also known as the ZNF9 gene, causes myotonic dystrophy type 2.
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Genes give instructions for creating proteins, which are needed for bodily functions. When a gene has a mutation, the protein output may be defective, inefficient, or missing. This can affect numerous organ systems of the body, including the brain, depending on the functions of the specific protein. A repeat expansion is a change or alteration that impacts these genes. This indicates that a section of the gene's DNA is repeated several times.
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The repeating segment in myotonic dystrophy type 1 contains three DNA-building components or nucleotides. The severity of the symptoms will increase as the number of repeats increases. People with the moderate type of myotonic dystrophy type 1, for example, had fewer repetitions than those with the classic or congenital versions. The congenital form has the greatest number.
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The repeating region in myotonic dystrophy type 2 contains four DNA-building components or nucleotides. There is no link between the severity of symptoms and the extent of the repeat expansion in myotonic dystrophy type 2. The DNA repeat expansions seen in myotonic dystrophy type 1 and myotonic dystrophy type 2 have no effect on the genes to which they are linked. Instead, they work through a genetic mechanism known as RNA gain of function, in which they interfere with the coding of a muscle chloride channel, an insulin receptor, and a heart muscle protein gene, among others. This explains the disease's systemic impact on skeletal muscle, diabetes risk, and heart difficulties.
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Myotonic dystrophy type 1 and myotonic dystrophy type 2 are autosomal dominantly inherited diseases. The condition of the two copies of a gene, one obtained from the mother and one from the father, determines the majority of genetic illnesses. When only one copy of a defective gene is required to induce disease, it is known as a dominant genetic illness. The defective gene can be inherited from either parent or caused by a new mutation or gene alteration in the affected person.
What Are the Signs and Symptoms of Myotonic Dystrophy?
Myotonic dystrophy is divided into two types:
Myotonic Dystrophy Type 1: In this type of myotonic dystrophy, mutations occur in the myotonic dystrophy protein kinase gene (DMPK). It could affect the way the heart, brain, and skeletal muscles work, as all of them are involved in the movement.
Myotonic dystrophy type 1 is divided into two types:
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Moderate Type: This usually appears in mid to late adulthood and is a congenital form that generally starts at birth. Symptoms of mild myotonic dystrophy type 1 are usually milder.
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Congenital Type: People with the congenital type may have weak muscular tone, respiratory problems, clubfoot, a condition where the foot turns inward and upward, intellectual handicap, or developmental delays.
Myotonic Dystrophy Type 2: It is caused by mutations in the CNBP gene. The CNBP gene produces a protein that is found in the heart and skeletal muscles. It aids in the regulation of other genes in the human body.
Myotonic dystrophy is caused by an alteration in the structure of any of these genes. A portion of the DNA in the genes repeats itself far too often. This causes problems with a variety of other proteins. This could eventually cause both muscle and tissue cells to stop functioning normally.
While the symptoms of myotonic dystrophy type 1 and type 2 are identical, type 2 symptoms are usually milder. The following are included in both forms:
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Myotonia.
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Speech slurring.
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Temporary lockjaw.
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Defects in cardiac conduction are the electrical signals that control the heartbeat.
Muscle weakening in myotonic dystrophy type 1 usually affects muscles that are farthest from the body's center. These muscles are referred to as distal muscles. These are the lower legs, hands, face, and neck. Myotonic dystrophy type 1 can also lead to swallowing problems, constipation, and gallstones. Myotonic dystrophy can cause the uterus muscles to perform abnormally. This could cause problems during pregnancy and labor. Muscle weakness in myotonic dystrophy type 2 usually affects muscles closer to the center of the body, known as proximal muscles. Elbows, hips, neck, and shoulder show signs of weakness.
How Is Myotonic Dystrophy Diagnosed?
The clinical history, which includes family history, physical examination, and supportive laboratory results, is used to diagnose myotonic dystrophy. Blood tests, electrodiagnostic testing (EMG), and muscle biopsies are examples of supporting laboratory studies. Muscle biopsy is frequently performed to assess if weakness is due to muscular dystrophy, a hereditary disease, or other acquired reasons for muscle degeneration, such as inflammation or chemical exposure. A blood test can generally pinpoint the precise genetic abnormality that causes myotonic dystrophy type 1 or type 2 and provide a definitive diagnosis.
How Is Myotonic Dystrophy Managed, and What New Therapies Are Included in Management?
Myotonic dystrophy currently has neither a cure nor a treatment. The focus of treatment is on the disease's life-threatening consequences, particularly those involving the lungs and heart. The majority of myotonic dystrophy type 1-related deaths are due to complications involving the cardiopulmonary system. Compromises in lung function during anesthesia and pregnancy can lead to life-threatening consequences. Lung problems are the major cause of death in people with myotonic dystrophy type 1; hence lung function should be checked every six months.
Excessive daytime sleepiness can be caused by central sleep apnea or obstructive sleep apnea, and these individuals should get a sleep study. If there is an anomaly, non-invasive ventilation may be used. Cardiac problems are the second biggest cause of mortality in people with myotonic dystrophy type 1, and they may occur without warning. All afflicted people should get an ECG once a year or twice a year. Assistive devices such as canes, neck braces, walkers, and wheelchairs are used to enable safe navigation.
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Medications:
To treat myotonia symptoms, the doctor may prescribe Mexiletine. To treat myotonic dystrophy-related pain, the doctor may prescribe over-the-counter drugs. Nonsteroidal anti-inflammatory medications, Gabapentin, Mexiletine, and low-dose glucocorticoids, such as oral prednisone, are also possible candidates. Warm baths, massages, and heating pads can be used in addition to medication. Anti-diabetic medications are used to control blood sugar levels and treat mild diabetes symptoms.
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Rehabilitative Therapy:
It is a type of treatment that is used to help muscle weakness and myotonia. Speech therapy for problems with swallowing and pronouncing words and behavioral and psychological difficulties are treated by psychiatric therapy, and support for learning difficulties and cognitive deficits are provided on an individual basis.
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Surgery:
Contractors and orthopedic surgery for gait issues, removal of cataracts, and droopy eyelids can be corrected by eyelid surgery. Surgery, on the other hand, is often utilized as a last option treatment for myotonic dystrophy patients due to the increased risk of complications associated with anesthesia.
A deep understanding of the molecular pathophysiology of myotonic dystrophy type 1 and the examination of numerous proof-of-concept therapeutic options have resulted in a potential myotonic dystrophy type 1 drug development which is in the pipeline.
Gene editing, which could be built to connect to RNA instead of DNA in human cells, was the first to show that gene therapy could be used to supply RNA-binding proteins to cells. This novel method, RNA-directed Cas9, was first used to cure the rare hereditary condition of myotonic dystrophy type 1.
Conclusion:
Individuals with classic myotonic dystrophy type one or congenital myotonic dystrophy type one have a shorter life expectancy. The disease may be different if myotonic dystrophy type one occurs before adolescence. Symptoms of congenital-onset myotonic dystrophy type one normally improve once a child survives it. They may, however, have cognitive impairments, delayed speech, eating and drinking problems, and other developmental challenges. Myotonic dystrophy type two usually has a better prognosis than type one. The symptoms are usually milder, and they progress more slowly.
