Duchenne muscular dystrophy
Duchenne Muscular Dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration and weakness due to a mutation in the DMD gene, located on the X chromosome. This gene is responsible for producing dystrophin, a critical protein that helps maintain muscle cell integrity. The condition predominantly affects male children, with mothers who are carriers having a 50% chance of passing the mutation to their sons. Symptoms typically emerge in early childhood and may include delayed walking, large calf muscles, frequent falls, and difficulty with physical activities. As the disease progresses, individuals may experience muscle contractures, scoliosis, respiratory issues, and cardiomyopathy.
Diagnosis involves a combination of medical history assessments, physical exams, and various tests such as muscle biopsies, CK level measurements, and genetic testing. While there is no cure for DMD, treatment options aim to manage symptoms and improve quality of life. These may include physical therapy, corticosteroids to enhance muscle strength, and surgical interventions for severe symptoms. Ongoing research, such as the application of CRISPR technology, holds promise for future therapies. Despite the challenges associated with this condition, individuals with DMD and their families can seek support and resources to navigate their journey.
Duchenne muscular dystrophy
DEFINITION Duchenne muscular dystrophy (DMD) is a genetic disease that occurs mostly in boys. Symptoms typically appear between the ages of one and four. The main sign of DMD is muscle weakness that worsens over time. Before age five, the muscles in the legs, arms, and trunk begin to weaken. Later in the disease the heart and respiratory muscles weaken.
ALSO KNOWN AS: DMD; pseudohypertrophic muscular dystrophy
Duchenne muscular dystrophy (DMD) is a progressive, serious condition that requires care from a child’s doctor. Parents who suspect their child has this condition should contact the child’s doctor promptly. There are many therapies used to treat the symptoms of this disease, and they should be started as soon as possible.
Risk Factors
Male children and children with a family history of DMD are at risk for the disease. Parents should tell their child’s doctor if their child has any of these risk factors.
Etiology and Genetics
All individuals with Duchenne muscular dystrophy have a mutation in the DMD gene, which is located on the short arm of the X chromosome at position Xp21.2. This is one of the largest human genes known, spanning more than two million base pairs of deoxyribonucleic acid (DNA). Its protein product is called dystrophin, a large molecule found primarily in skeletal muscles and cardiac muscles, but small amounts of the protein are also present in nerve cells in the brain. In muscle cells, dystrophin is the major protein in a complex of proteins that serves to anchor the internal cytoskeleton to the cell membrane and ultimately to the extracellular matrix. It also appears to participate in aspects of cell signaling, since it interacts with other proteins that are known to transmit chemical signals within and between cells. In muscles that lack dystrophin altogether or have a nonfunctioning version, the cell membrane becomes permeable, allowing extracellular matrix elements to enter the cell. The damage to the membrane increases with repeated muscle contractions and relaxations until eventually the cell dies. The resulting immune response can exacerbate the damage. Research suggests the DMD gene is a factor in all major types of cancer.
The inheritance pattern of Duchenne muscular dystrophy is typical of all sex-linked recessive mutations (those found on the X chromosome). Mothers who carry the mutated gene on one of their two X chromosomes face a 50 percent chance of transmitting this disease to each of their male children. Female children have a 50 percent chance of inheriting the gene and becoming carriers like their mothers. Females usually do not exhibit this disorder, since to be affected they would have to inherit the defective gene from both parents. Affected males almost never live to reproduce.
Symptoms
Parents whose child has any of these symptoms should not assume it is due to DMD. These symptoms may be caused by other conditions. Parents should tell their child’s doctor if their child has any of the symptoms.
Children who are late in learning to walk, have larger than normal calf muscles, frequently fall, walk clumsily, have difficulty climbing stairs, have trouble running, walk on their toes or the balls of their feet, have trouble with balance, walk with their shoulders back and belly out, and do not run may have DMD. Additional symptoms include trouble keeping up with friends when playing and using their hands to climb up their bodies when getting up from the floor (Gower’s maneuver). Additional symptoms can occur later in the disease, including muscle contractures (a shortening of the muscle that traps a joint in a contracted position), scoliosis, weakness in respiratory muscles, cardiomyopathy (weakness of heart muscle), and learning disabilities.
Screening and Diagnosis
The doctor will ask about a child’s symptoms and medical history. A physical exam will be done. The doctor will also ask if there is any family history of neuromuscular disease. The exam will focus on the child’s muscles. The doctor will look for signs of weakness. Parents will likely be referred to a specialist.
Tests may include a muscle biopsy, a test that removes a small piece of muscle for examination and is used to detect abnormalities in the muscle; a creatine kinase (CK) level test, a blood test used to measure CK, an enzyme found in damaged muscle; genetic testing, a blood test that identifies the genetic mutation of DMD; and electromyography (EMG), a test that measures how well the nerves and muscles work and is used to detect muscle problems.
Treatment and Therapy
Parents should talk with their child’s doctor about the best plan for their child. The disease worsens over time; a child may need different treatments as the disease progresses.
Options include physical therapy, which plays a large role in treating DMD. A child will work with a therapist to try to keep muscles strong. The disease causes contractures; this is when a muscle shortens, making it difficult to move. The therapist will focus on preventing this with range of motion exercises. Scoliosis is common in DMD. Exercises can help to keep the back as straight as possible.
Braces are used to keep the legs straight and prevent contractures. A walker and wheelchair may be needed later, when the leg muscles become too weak to walk.
The doctor may prescribe a steroid medication like prednisone. This can help to improve muscle strength and slow muscle weakening. Steroids can weaken bones; to keep bones healthy, a child may take vitamin D and calcium supplements. A child who experiences heart problems may be given certain medications to slow the damage. The heart medication eplerenone was found to slow decline in ventricular function in a human trial in 2015 and was approved by the Food and Drug Administration for use in some cases.
As the disease progresses, the muscles that support breathing may weaken. A child may need a ventilator, which will deliver air through a mask, tube, or sometimes through a tracheotomy (a surgical hole in the windpipe).
Surgery is sometimes used to treat symptoms of DMD. For severe contractures, surgery may be performed to release specific tendons. Scoliosis can sometimes interfere with a child’s breathing. In this case, back surgery may be done.
The enzyme-based genome editing tool CRISPR was successfully used to restore dystrophin production in adult mice with DMD in a 2015 study.
Prevention and Outcomes
There are no known guidelines to prevent this progressive muscle disease.
Bibliography
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