Introduction
Duchenne Muscular Dystrophy(DMD) is a rare muscle disorder characterized by progressive degeneration and wasting (atrophy) of the body muscles. However, it is a frequent genetic disorder that affects one in every 3500 male children born globally.
Dystrophinopathies include a group of muscle disorders caused due to alteration in the dystrophin gene. DMD occurs due to a mutation of the DMD gene that codes for the protein dystrophin which plays an important role in the stability of muscle cells membrane.
A mild form of DMD with reduced dystrophin occurs in Becker Muscular Dystrophy. DMD is characterized by a complete lack of dystrophin. The condition first affects the pelvic muscles and later progresses to involve the shoulder, forearm, trunk, and other muscles of the body. In advanced stages, heart and gut muscles are affected.
What Are the Causes?
DMD is an X-linked disorder (a condition that occurs due to an abnormal gene on the X-chromosome). Males are affected more than females. Females with one of the defective gene act as carriers. Human sex chromosomes are designated as X and Y. Males have one X and one Y chromosome while females have two X chromosomes.
If the X chromosome inherited from the mother is defective and if the child is male he will be affected. Females who are carriers of the condition have a 25 % chance of passing this condition to a male child. There is also a 25 % chance for the female child to become a carrier if the mother is a carrier for DMD. There is a 25 % chance that the carrier female will have an unaffected son.
If the affected male (having defective X chromosome) has children, then all the female offsprings will be carriers for the condition. A male parent only passes the Y chromosome to the son, so the defective X chromosome is not passed to the male child.
What Are the Signs and Symptoms?
DMD is usually recognized in early childhood (3 to 6 years of age). By teenage, the condition becomes advanced and the patient may even require wheelchair assistance.
The signs and symptoms include the following:
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Delay reaching developmental milestones like sitting, walking, standing, etc.
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Abnormal gait or waddling manner of walking and frequent falling.
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Gower’s sign or difficulty while rising from a sitting position and while climbing stairs.
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Wasting of the thigh and pectoral muscles.
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Toe walking (walking on toes).
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Short stature.
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By age 8 to 9 years, the affected may require leg braces.
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By their teenage, the affected may require wheelchair assistance.
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Hypertrophy (increase in size) of calf muscles.
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The curvature of the spine (Scoliosis).
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Delay in speech.
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Learning disabilities.
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Fatigue.
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Cognitive impairment.
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By teenage the condition becomes advanced and other complications occur like cardiomyopathy (heart muscle deterioration). Cardiomyopathy results in irregular heartbeat, the inability of the heart to pump blood, and eventually heart failure.
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As DMD affects the muscles of the ribcage, it can result in an increased risk of respiratory infections and even respiratory failure.
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Involvement of gut muscles results in dysmotility (a condition in which food passage through the digestive tract slows down), which leads to diarrhea and constipation.
How Is the Condition Diagnosed?
Diagnosis is made based on patient history, clinical examination, molecular genetic test, and biopsy. A biopsy of the affected muscle is done in cases where the molecular genetics test is not informative.
The diagnostic tests done include:
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Molecular Genetic Test: Molecular genetic testing helps in the identification of the mutation of chromosomes. Blood samples or muscle cells are used for investigation. A prenatal (before birth) analysis is also possible.
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Blood Tests: Increased levels of creatine kinase (CK) indicate muscle damage.
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Biopsy: A biopsy is done by surgically removing a small piece of the affected muscle.
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Electrocardiogram (EKG): EKG is done to check the status of the heart as it gets affected due to DMD.
How Is the Condition Managed?
As DMD is a genetic disorder complete cure is not possible. Symptomatic treatment is done to improve the quality of life of the affected.
The management of the condition involves the following:
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Corticosteroid Therapy:
Corticosteroids can slow the progression of muscle weakness. It can delay the loss of ambulation(walking) by two to three years. Prednisone and deflazacort are commonly used for DMD. Deflazacort was approved by the FDA (Food and Drug Administration) in 2017 to treat DMD patients 5 years and older.
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Eteplirsen:
Eteplirsen (brand name Exondys 51), an antisense oligonucleotide, is approved by the FDA to treat DMD in patients whose dystrophin gene mutation is amenable to exon 51 skipping.
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Casimersen:
Casimersen (Amondys 45) is used to treat DMD patients with dystrophin gene mutation amenable to exon 45 skipping.
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Golodirsen and Viltepso:
Golodirsen and Viltepso are used in DMD patients with dystrophic gene mutation amenable to exon 53 skipping.
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Physiotherapy:
Physical therapy and exercises (active and passive) are suggested to build muscle strength and prevent contracture.
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Mechanical Aids:
Braces are used to prevent contracture development. As the condition reaches the advanced stage mechanical aids like wheelchairs, canes, braces, etc are needed to aid in walking.
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Spinal Surgery:
In the case of patients with scoliosis spine surgery is carried out.
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Continuous Monitoring:
The affected individual should be regularly monitored for the involvement of heart muscles and respiratory distress. In case of severe respiratory distress, ventilators are used to assist breathing.
What Are the Preventive Measures?
Genetic counseling should be given to the affected. Genetic tests which are done during pregnancy help in determining DMD.
What Is the Life Expectancy for Patients With DMD?
Before the development of medical science, DMD patients hardly made it to their teens. With advancements in medical science and proper supportive care, life expectancy has reached the early thirties. Nowadays, the quality of life of the affected individuals can be greatly improved and lead a normal life in most cases.
Conclusion
DMD is a rare muscle disorder genetically inherited in most cases though can occur de novo (new occurrence). DMD causes progressive muscular deterioration that get worsened with increasing age. With advancements in medical science and proper supportive care, the life expectancy and quality of the affected can greatly be improved.
