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Questions and Answers
What does Gowers' sign specifically describe?
What does Gowers' sign specifically describe?
Which of the following characteristics is associated with the gait seen in Duchenne Muscular Dystrophy (DMD)?
Which of the following characteristics is associated with the gait seen in Duchenne Muscular Dystrophy (DMD)?
At what age is loss of ambulation typically observed in children with Duchenne Muscular Dystrophy?
At what age is loss of ambulation typically observed in children with Duchenne Muscular Dystrophy?
What muscle group tends to show weakness earlier in the progression of Duchenne Muscular Dystrophy?
What muscle group tends to show weakness earlier in the progression of Duchenne Muscular Dystrophy?
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Which sign indicates weakness in the hip abductors observed in children with DMD?
Which sign indicates weakness in the hip abductors observed in children with DMD?
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Which statement best describes the typical gait of a child with DMD?
Which statement best describes the typical gait of a child with DMD?
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At what stage does a child with DMD typically begin to walk with braces?
At what stage does a child with DMD typically begin to walk with braces?
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What physical change is typically observed in DMD patients as they progress to ages 12-14?
What physical change is typically observed in DMD patients as they progress to ages 12-14?
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What is the standard medical treatment for individuals with Duchenne Muscular Dystrophy (DMD)?
What is the standard medical treatment for individuals with Duchenne Muscular Dystrophy (DMD)?
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Which of the following is a side effect of corticosteroid therapy in individuals with DMD?
Which of the following is a side effect of corticosteroid therapy in individuals with DMD?
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Which drug is known to be used in corticosteroid therapy for DMD?
Which drug is known to be used in corticosteroid therapy for DMD?
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What is the primary mechanism of exon-skipping therapies for DMD?
What is the primary mechanism of exon-skipping therapies for DMD?
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Which of the following FDA-approved drugs utilizes exon-skipping therapy for DMD?
Which of the following FDA-approved drugs utilizes exon-skipping therapy for DMD?
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What is the first gene therapy approved for treating Duchenne Muscular Dystrophy (DMD)?
What is the first gene therapy approved for treating Duchenne Muscular Dystrophy (DMD)?
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What is a common behavioral side effect of corticosteroid therapy during the initial treatment period?
What is a common behavioral side effect of corticosteroid therapy during the initial treatment period?
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What is the effect of corticosteroid therapy on muscle strength in children with DMD?
What is the effect of corticosteroid therapy on muscle strength in children with DMD?
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What is the most common form of muscular dystrophy?
What is the most common form of muscular dystrophy?
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Among which age range do symptoms of Duchenne Muscular Dystrophy typically start to become noticeable?
Among which age range do symptoms of Duchenne Muscular Dystrophy typically start to become noticeable?
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What genetic inheritance pattern is associated with Duchenne Muscular Dystrophy?
What genetic inheritance pattern is associated with Duchenne Muscular Dystrophy?
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Which characteristic symptom is most indicative of Duchenne Muscular Dystrophy?
Which characteristic symptom is most indicative of Duchenne Muscular Dystrophy?
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What is the consequence of the absence of dystrophin in muscle cells?
What is the consequence of the absence of dystrophin in muscle cells?
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At what age do children with Duchenne Muscular Dystrophy typically experience difficulty getting up from the floor?
At what age do children with Duchenne Muscular Dystrophy typically experience difficulty getting up from the floor?
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Which type of muscle weakness pattern is most commonly seen in Duchenne Muscular Dystrophy?
Which type of muscle weakness pattern is most commonly seen in Duchenne Muscular Dystrophy?
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What often replaces muscle tissue in individuals with advanced Duchenne Muscular Dystrophy?
What often replaces muscle tissue in individuals with advanced Duchenne Muscular Dystrophy?
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What is one common early clinical feature of Duchenne Muscular Dystrophy?
What is one common early clinical feature of Duchenne Muscular Dystrophy?
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What typically occurs to the deep tendon reflexes in individuals with Duchenne Muscular Dystrophy?
What typically occurs to the deep tendon reflexes in individuals with Duchenne Muscular Dystrophy?
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What is a common consequence of muscle weakness and imbalance in DMD patients?
What is a common consequence of muscle weakness and imbalance in DMD patients?
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At what spinal curve degree is spinal fusion considered for DMD patients with scoliosis?
At what spinal curve degree is spinal fusion considered for DMD patients with scoliosis?
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What percentage of boys with DMD are reported to have cardiomyopathy?
What percentage of boys with DMD are reported to have cardiomyopathy?
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Which of the following is an early sign of respiratory impairment in DMD?
Which of the following is an early sign of respiratory impairment in DMD?
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Which diagnostic test is specifically used to identify the absence of dystrophin in muscle tissue in DMD patients?
Which diagnostic test is specifically used to identify the absence of dystrophin in muscle tissue in DMD patients?
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What condition is commonly associated with gastrointestinal dysfunction in DMD due to muscle deterioration?
What condition is commonly associated with gastrointestinal dysfunction in DMD due to muscle deterioration?
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What is the average IQ reported for boys diagnosed with DMD?
What is the average IQ reported for boys diagnosed with DMD?
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What is the leading cause of death in patients with DMD?
What is the leading cause of death in patients with DMD?
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What is the primary aim of the gene therapy administered as a one-time IV infusion for DMD patients?
What is the primary aim of the gene therapy administered as a one-time IV infusion for DMD patients?
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What significant milestone did Givinostat (Duvyzat) achieve in March 2024?
What significant milestone did Givinostat (Duvyzat) achieve in March 2024?
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How does the research into utrophin aim to assist DMD patients?
How does the research into utrophin aim to assist DMD patients?
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Which of the following surgical interventions is specifically mentioned for individuals with DMD?
Which of the following surgical interventions is specifically mentioned for individuals with DMD?
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What is the typical life expectancy for individuals with Duchenne muscular dystrophy historically?
What is the typical life expectancy for individuals with Duchenne muscular dystrophy historically?
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Which characteristic differentiates Becker's Muscular Dystrophy from Duchenne's MD?
Which characteristic differentiates Becker's Muscular Dystrophy from Duchenne's MD?
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What approach is recommended for supportive treatment of DMD?
What approach is recommended for supportive treatment of DMD?
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What is the primary purpose of reassessments in the rehabilitation of DMD patients?
What is the primary purpose of reassessments in the rehabilitation of DMD patients?
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What does the research into myostatin inhibitors aim to achieve for DMD patients?
What does the research into myostatin inhibitors aim to achieve for DMD patients?
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What was a key finding in the drug trials for Givinostat over 18 months?
What was a key finding in the drug trials for Givinostat over 18 months?
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What is the earliest symptom typically associated with Becker Muscular Dystrophy (BMD)?
What is the earliest symptom typically associated with Becker Muscular Dystrophy (BMD)?
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Which muscles are primarily affected in Becker Muscular Dystrophy?
Which muscles are primarily affected in Becker Muscular Dystrophy?
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What gait characteristic is commonly seen in Becker Muscular Dystrophy as the condition progresses?
What gait characteristic is commonly seen in Becker Muscular Dystrophy as the condition progresses?
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What is a common complication associated with Limb-Girdle Muscular Dystrophy (LGMD)?
What is a common complication associated with Limb-Girdle Muscular Dystrophy (LGMD)?
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What distinct symptom is often seen in Facioscapulohumeral Dystrophy (FSHD)?
What distinct symptom is often seen in Facioscapulohumeral Dystrophy (FSHD)?
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What is the primary cause of respiratory dysfunction in Becker Muscular Dystrophy?
What is the primary cause of respiratory dysfunction in Becker Muscular Dystrophy?
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What age range is typical for the onset of Limb-Girdle Muscular Dystrophy?
What age range is typical for the onset of Limb-Girdle Muscular Dystrophy?
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Which feature is NOT typically associated with Myotonic Dystrophy?
Which feature is NOT typically associated with Myotonic Dystrophy?
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What is the inheritance pattern for Congenital Muscular Dystrophy?
What is the inheritance pattern for Congenital Muscular Dystrophy?
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In Facioscapulohumeral Dystrophy, which symptom typically occurs last?
In Facioscapulohumeral Dystrophy, which symptom typically occurs last?
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What complication is less severe and less frequent in Becker Muscular Dystrophy compared to Duchenne Muscular Dystrophy?
What complication is less severe and less frequent in Becker Muscular Dystrophy compared to Duchenne Muscular Dystrophy?
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What is a common manifestation of Myotonic Dystrophy?
What is a common manifestation of Myotonic Dystrophy?
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What is the typical lifespan expectancy for those with Becker Muscular Dystrophy?
What is the typical lifespan expectancy for those with Becker Muscular Dystrophy?
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Study Notes
Muscular Dystrophies Overview
- Muscular dystrophies (MDs) are a group of genetic disorders causing progressive muscle weakness and degeneration.
- They typically cause symmetric muscle wasting, increasing deformity, and disability.
- Hereditary myopathies are variations of MDs, each with unique genetic and phenotypic characteristics.
- MDs are the most frequent inherited progressive neuromuscular disorders in childhood, affecting approximately 250,000 people in the U.S.
- Symptoms can emerge at any point in a person's lifespan.
Objectives for Studying Muscular Dystrophies
- Understand the etiology, pathophysiology, and signs/symptoms of different types of MDs.
- Learn about various MD forms and compare/contrast their characteristics and symptoms.
- Identify diagnostic tests/parameters used to identify MD.
- Describe the general course and prognosis of different MD types.
- Discuss medical and/or surgical management options.
- Learn important rehabilitation considerations for individuals with MDs.
Duchenne Muscular Dystrophy (DMD)
- DMD is the most common and severe form of the dystrophic disorder, appearing in early childhood.
- It’s characterized by rapid progression of weakness and disability/loss of walking.
- Early childhood onset leads to premature death in the 20s/30s.
- Incidence: 1 in 3500 live male births worldwide.
- X-linked inheritance pattern suggests males inherit the disease from their asymptomatic mothers.
- The gene "dystrophin," located on the short arm of the X chromosome (Xp21), is affected.
- 70% of cases result from deletions/duplications, and 30% from mutations (one in 10,000).
- There is no familial history in 70% of cases.
- Dystrophin maintains the muscle membrane integrity, so lack of the protein results in damage to the membrane during contraction cycles. This leads to calcium influx, activating a proteinase, causing cell destruction and muscle replacement by fatty and connective tissues.
DMD - Clinical Picture
- Signs noticeable in utero and neonatal muscles, but symptoms often go unnoticed until early childhood (ages 2-4).
- Symptoms may include delayed motor development, delayed walking, inability to walk by 18 months in 50% of individuals.
- Other features: difficulty getting up from the floor, climbing stairs, running, tendency to fall, increased lumbar lordosis.
- Characteristic gait, clumsiness, falls, and possible complications (scoliosis, contractures).
- Progressive muscle weakness; calf pseudohypertrophy (enlarged calves due to fat and fibrous tissue buildup, not muscle).
- The onset of weakness develops initially in proximal muscles then progresses to distal muscles. Weakness is evident by ages 3-5.
- Delayed pubertal development.
- Diminished deep tendon reflexes.
- Gowers' sign (using hands to 'walk' up legs to rise from a seated position) is a valuable clinical indicator for DMD.
DMD - Complications
- Contractures (due to weakness and imbalance).
- Scoliosis (spinal curvature).
- Fractures (due to falls and osteoporosis).
DMD - Comorbidities
- Cognitive impairments (average IQ is 85; 1/3 score below 75 with specific reading disorders).
- Cardiomyopathy (affecting cardiac muscle fibers in over 60% of cases).
- Dilated cardiac myopathy.
- Respiratory impairment (weak respiratory muscles, contractures, scoliosis).
- Gastrointestinal dysfunction (smooth muscle deterioration and gastrointestinal tract/gastric dilation).
- Constipation.
- Pseudo-obstruction.
DMD - Diagnosis
- Based on clinical presentation, family history, and diagnostic testing.
- Serum enzyme levels (elevated creatine kinase, CK).
- Muscle ultrasound to assess skeletal muscle damage localization.
- Genetic testing to identify the presence/absence or mutations in the dystrophin gene.
- Electromyography (EMG) to assess muscle function via fibrillation potentials, positive sharp waves, long-duration polyphasic motor units, full recruitment with low force, and low-amplitude MUAPs.
- Nerve conduction velocity (NCV) testing is normal.
- Muscle biopsy for muscle fiber degeneration, variation in muscle fiber size, central nuclei, inflammatory cells, fat and connective tissue, and dystrophin absence.
DMD - Treatment
- No known curative treatment.
- Corticosteroids, such as prednisone, can treat DMD, but include side effects like weight gain, obesity, cushingoid features, acne, and growth retardation.
- Exon-skipping therapies use drug therapy to omit (skip) mutated sections of genes to produce functional dystrophin protein.
- Four drugs, approved by the FDA, use this approach/method: Eteplirsen (Exondys 51), Golodirsen (Vyondys 53), and Viltolarsen (Viltepso).
- Gene therapy (Elevidys) using viral vectors to deliver a functioning dystrophin gene to muscles.
- Non-steroidal drug therapy (Givinostat).
- Research into other therapies like utrophin protein levels, myostatin inhibitors, and phosphodiesterase inhibitors is underway.
- Stem cell transplantation.
- Supportive therapy: maintaining function via complication avoidance (contractures, ulcers, infections); deconditioning avoidance via submaximal exercise, breathing exercises, positioning, and orthotics.
Becker Muscular Dystrophy (BMD)
- BMD is less common than DMD and has a slower progression.
- Similar to DMD but less severe, with later onset and a longer lifespan.
- Symptoms usually emerge between the ages of 5-10.
- Similar symptoms to DMD but slower progression leading to later life expectancy and survival into older adulthood/40's
- Incidence: 5 in 100,000 live male births
- X-linked recessive inheritance and mutation in the dystrophin gene.
Limb-Girdle Muscular Dystrophy (LGMD)
- LGMD has variable types with autosomal recessive or dominant inheritance.
- Signs may not manifest until the 40s.
- The onset of symptoms may occur during late childhood, adolescence, or early adulthood.
- Affects both proximal and distal muscles, causing mild impairment, slow progression, and muscle weakness (upper arm and pelvic muscles.)
- In later stages, possible complications: winging of scapulae, lumbar lordosis, abdominal protrusion, waddling gait, balance problems, and difficulty raising arms overhead.
Facioscapulohumeral Muscular Dystrophy (FSHD)
- FSHD is a relatively mild form of MD with autosomal dominant inheritance.
- 5 in 100,000 live births, with males more often affected than females.
- 10%-30% arise from mutations.
- Onset typically in early adolescence; some cases begin at any age.
- Symptoms of facial weakness, including an expressionless face, difficulty closing eyes, and diffuse facial flattening, are noticeable.
- Other possible symptoms include pouting lower lips, inability to whistle or pucker the mouth, and shoulder girdle weakness causing scapula winging, forward shoulders, and difficulty raising arms.
- Distal leg and hip girdle muscles weakness often develops later
- Wide variability in side-to-side symmetry.
- Frequent hearing loss, retinal disease are other complications.
Congenital Muscular Dystrophy (CMD)
- CMD is an inherited disorder affecting approximately 4.65 in 100,000 people in some populations.
- Characterized by an autosomal recessive pattern.
- Characterized by significant muscle weakness/strength loss and respiratory impairment, which emerges shortly after birth.
- Signs: severe muscle weakness leading to delayed gross motor skills, limited or no ability to ambulate, and needing a wheelchair by age 10.
- Other symptoms: mixed central and peripheral symptoms, cognitive impairments (often severe); distinctive feature is often distal laxity mixed with proximal contractures (e.g. knees.)
- Some cases exhibit rapid progression with death in the first year; others exhibit slower progression.
Myotonic Dystrophy
- Typically appears in adolescence, adulthood, (some in 20s/30s.)
- Autosomal dominant inheritance.
- Characterized by muscle weakness, muscle wasting, delayed relaxation of skeletal muscles, and increased excitability.
- Different types include congenital myotonic dystrophy (most severe form, with weakness and myotonia at birth.)
- Most common characteristic: facial weakness (atrophy and weakness, slurred speech.)
- Other symptoms include: ptosis, sagging jaw, lip drooping, mild limb weakness, generalized disability, and myotonia (prolonged spasms).
- The condition also may affect other systems (e.g., cardiac conduction, respiratory function, hearing loss, hypersomnia, testicular atrophy)
Emery-Dreifuss Muscular Dystrophy (EDMD)
- Most commonly X-linked recessive in inheritance.
- Onset usually occurs in the early 10s and some not until mid-20s.
- Gradually worsening. Progressive symmetric atrophy and weakness, particularly of shoulder and upper/lower arms, as well as the back of the neck muscles and lower legs.
- Contractures in certain joints, such as spine, ankles, knees, and elbows begin early.
- Cardiac issues are frequent.
- Cardiovascular problems warrant monitoring.
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Description
Test your knowledge about Duchenne Muscular Dystrophy (DMD) with this informative quiz. Learn about its associated signs, gait characteristics, and progression of the disease in children. The quiz covers various critical aspects of DMD, perfect for students and healthcare professionals alike.
