Muscular Dystrophies and Myopathies — MCQs
What will be the likely cause of death in a 4-year-old boy who tires easily, exhibits weakness in the pelvic and shoulder girdles, and calf muscle enlargement, with elevated serum creatine kinase levels, and a biopsy showing marked variation in muscle fiber size and shape, muscle fiber necrosis, myophagocytosis, regenerating fibers, and fibrosis?
A 4-year-old boy is brought to the physician by his parents due to frequent falls, inability to jump, and easy fatigue. Physical examination reveals weakness in the pelvic and shoulder girdles, as well as enlargement of the child's calf muscles. The serum level of creatine kinase is elevated. A biopsy of calf muscle reveals marked variation in size and shape of muscle fibers, with foci of muscle fiber necrosis, myophagocytosis, regenerating fibers, and fibrosis. Molecular diagnostic assays performed on muscle biopsy from the patient would show alterations in the length of the primary transcript for which muscle-associated protein?
All are congenital myopathies except
Muscle biopsy shows ragged red fibers on modified Gomori trichrome stain. Which enzyme defect is most likely?
Which is NOT a feature of polymyositis?
Perifascicular atrophy of muscle fibers is seen in?
Variation in size and shape of muscle fibers, combined with degenerative changes and intramysial fibrosis, is typical of
A Thirty five year old female has proximal weakness of muscles, ptosis and easy fatigability. The most sensitive test to suggest the diagnosis is -
Which of the following is not a chromosome breakage disorder?
An electron microscopy of muscle biopsy shows 'parking lot' appearance. Which additional finding would confirm myotonic dystrophy?
Muscular Dystrophies and Myopathies Indian Medical PG Practice Questions and MCQs
Question 1: What will be the likely cause of death in a 4-year-old boy who tires easily, exhibits weakness in the pelvic and shoulder girdles, and calf muscle enlargement, with elevated serum creatine kinase levels, and a biopsy showing marked variation in muscle fiber size and shape, muscle fiber necrosis, myophagocytosis, regenerating fibers, and fibrosis?
- A. Respiratory failure/complications (Correct Answer)
- B. Cerebrovascular complications
- C. Chronic kidney disease
- D. Pulmonary embolism
Explanation: ***Cardiomyopathy*** - In boys with **Duchenne muscular dystrophy (DMD)**, cardiomyopathy is a significant complication leading to **heart failure** and death. - The muscle biopsy findings support **muscular dystrophy** [1], and the patient's symptoms indicate weakening of the heart muscle over time. *End-stage renal disease* - Typically results from **chronic kidney conditions**, which are not indicated by the case presented. - The symptoms described, including **muscle weakness** and **fibrosis**, are not directly related to renal dysfunction. *Cerebrovascular disease* - Generally manifests as a sudden neurological deficit and is uncommon in **pediatric muscular conditions**. - There is no indication of **neurological symptoms** in this patient's presentation. *Pulmonary saddle embolism* - This condition typically presents with sudden **shortness of breath** or **chest pain**, neither of which is mentioned here. - The findings focus more on **muscle degeneration** rather than any acute pulmonary events. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Peripheral Nerves and Skeletal Muscles, pp. 1244-1245.
Question 2: A 4-year-old boy is brought to the physician by his parents due to frequent falls, inability to jump, and easy fatigue. Physical examination reveals weakness in the pelvic and shoulder girdles, as well as enlargement of the child's calf muscles. The serum level of creatine kinase is elevated. A biopsy of calf muscle reveals marked variation in size and shape of muscle fibers, with foci of muscle fiber necrosis, myophagocytosis, regenerating fibers, and fibrosis. Molecular diagnostic assays performed on muscle biopsy from the patient would show alterations in the length of the primary transcript for which muscle-associated protein?
- A. Creatine kinase
- B. Desmin
- C. Dystrophin (Correct Answer)
- D. Glycogen phosphorylase
Explanation: ***Dystrophin*** - The clinical features, including muscle weakness, calf muscle hypertrophy, and elevated **creatine kinase**, indicate a muscular dystrophy, most characteristically associated with **dystrophin** deficiency [1]. - **Muscle biopsy results** showing variation in muscle fiber size and necrosis further support the diagnosis of **Duchenne muscular dystrophy**, where dystrophin mutations are commonly identified [1]. *Desmin* - Although desmin is a muscle protein, it is primarily involved in **muscle fiber structure** and not directly associated with the symptoms or findings noted in this case. - Conditions linked to desmin abnormalities usually involve **myofibrillar myopathies**, which present differently than the scenario described here. *Glycogen phosphorylase* - Glycogen phosphorylase is crucial in **glycogen metabolism**, and its deficiency typically leads to metabolic myopathies presenting with **exercise intolerance** rather than the distinct symptoms of muscle necrosis seen here. - The muscle pathology observed (necrosis and regeneration) does not correlate with typical presentations seen in glycogen storage diseases. *Creatine kinase* - While creatine kinase levels are elevated in many muscle disorders, including dystrophies, it is not a structural protein and thus does not fit the question's focus on **primary transcript alterations** [2]. - Measuring creatine kinase assists in diagnosing muscle damage but does not indicate a molecular defect like **dystrophin**. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Peripheral Nerves and Skeletal Muscles, pp. 1244-1245. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Peripheral Nerves and Skeletal Muscles, pp. 1245-1246.
Question 3: All are congenital myopathies except
- A. Polymyositis (Correct Answer)
- B. Central Core myopathy
- C. Centronuclear myopathy
- D. Nemaline myopathy
Explanation: ***Polymyositis*** - This is an **acquired inflammatory myopathy** characterized by **autoimmune muscle inflammation** and weakness, typically presenting in adulthood [1]. - It is not a genetic or congenital condition but rather an **immune-mediated disorder** [1]. *Nemaline myopathy* - This is a **congenital myopathy** characterized by the presence of **rod-like inclusions (nemaline bodies)** in muscle fibers. - Symptoms often begin in infancy or childhood, including **muscle weakness** and **feeding difficulties**. *Central Core myopathy* - This is a **congenital myopathy** associated with mutations in the **RYR1 gene**, leading to abnormalities in muscle fibers characterized by **central cores**. - It is often linked to **malignant hyperthermia susceptibility** and presents with early-onset **proximal muscle weakness**. *Centronuclear myopathy* - This is a **congenital myopathy** where muscle fibers have an **abnormal central placement of nuclei** that normally reside at the periphery. - It typically presents at birth or in early childhood with **muscle weakness** and **hypotonia**. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Peripheral Nerves and Skeletal Muscles, pp. 1240-1242.
Question 4: Muscle biopsy shows ragged red fibers on modified Gomori trichrome stain. Which enzyme defect is most likely?
- A. Complex IV
- B. Complex II
- C. Complex III
- D. Complex I (Correct Answer)
Explanation: ***Complex I*** - **Ragged red fibers** on modified Gomori trichrome stain are the pathological hallmark of **mitochondrial myopathies** [1] - **Complex I (NADH-CoQ reductase) deficiency** is the **most common cause** of mitochondrial disease, accounting for approximately 30-40% of all cases - Complex I deficiency is the **most frequent cause of ragged red fibers** in muscle biopsies - Associated clinical features include progressive muscle weakness, exercise intolerance, lactic acidosis, and encephalomyopathy (Leigh syndrome) [1] - The ragged red appearance results from subsarcolemmal accumulation of abnormal mitochondria attempting to compensate for defective oxidative phosphorylation *Complex II* - **Complex II (succinate dehydrogenase) deficiency** is a relatively rare cause of mitochondrial myopathy - More commonly associated with hereditary paraganglioma-pheochromocytoma syndromes and certain cancers - Can cause ragged red fibers but is much less common than Complex I deficiency - The only complex entirely encoded by nuclear DNA (not mitochondrial DNA) *Complex III* - **Complex III (ubiquinol-cytochrome c reductase) deficiency** is a rare cause of mitochondrial disease - Can present with myopathy and ragged red fibers, but accounts for only a small percentage of mitochondrial disorders - Associated with exercise intolerance and multisystem involvement when present *Complex IV* - **Complex IV (cytochrome c oxidase, COX) deficiency** can cause mitochondrial myopathy with ragged red fibers [1] - However, it is **less common than Complex I deficiency** as a cause of ragged red fibers - COX-deficient fibers can be identified using specific COX histochemical staining [1] - Associated with Leigh syndrome and other encephalomyopathies, but not the **most likely** cause when ragged red fibers are present **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Central Nervous System, pp. 1305-1306.
Question 5: Which is NOT a feature of polymyositis?
- A. Proximal muscle weakness
- B. Elevated serum creatine kinase (CK) levels
- C. Ocular muscle involvement (Correct Answer)
- D. Endomysial inflammation on muscle biopsy
Explanation: ***Ocular muscle involvement*** - **Polymyositis** primarily affects **proximal skeletal muscles**, sparing the **ocular** and facial muscles. - Involvement of **ocular muscles** is more characteristic of other neuromuscular disorders, such as **myasthenia gravis**. *Proximal muscle weakness* - This is a hallmark symptom of **polymyositis**, manifesting as difficulty with activities like rising from a chair or lifting objects [1]. - The weakness is typically **symmetric** and progressive, affecting muscles of the **shoulders, hips, and neck** [1]. *Elevated serum creatine kinase (CK) levels* - Elevated **CK levels** are a key laboratory finding in polymyositis, indicating **muscle damage** and inflammation. - The degree of **CK elevation** often correlates with disease activity and muscle breakdown. *Endomysial inflammation on muscle biopsy* - A **muscle biopsy** is crucial for diagnosing polymyositis, revealing characteristic **inflammatory infiltrates** consisting mainly of **CD8+ T cells** surrounding and invading non-necrotic muscle fibers. - This **endomysial inflammation** differentiates polymyositis from other myopathies.
Question 6: Perifascicular atrophy of muscle fibers is seen in?
- A. Myopathy due to corticosteroids
- B. Dermatomyositis (Correct Answer)
- C. Inclusion body myositis
- D. Nemaline myopathy
Explanation: ***Dermatomyositis*** - Characterized by **perifascicular atrophy** of muscle fibers, which is a distinct histological feature seen in dermatomyositis [1]. - Additionally associated with **skin manifestations** such as a heliotrope rash and Gottron's papules. *Inclusion body myositis* - Features **rimmed vacuoles** and **inflammatory infiltrate**, but does not show perifascicular atrophy as seen in dermatomyositis. - Typically affects older adults and has a different clinical presentation compared to dermatomyositis. *Nemaline myopathy* - Characterized by **nemaline bodies** on muscle biopsy, not perifascicular atrophy, which is specific to dermatomyositis. - Generally presents with **congenital muscle weakness**, distinctly different from the autoimmune nature of dermatomyositis. *Steroid myopathy* - Results from **chronic corticosteroid use**, leading to muscle weakness but does not feature perifascicular atrophy. - Primarily affects **proximal muscles** and is linked to medication rather than a specific myopathy like dermatomyositis. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Peripheral Nerves and Skeletal Muscles, pp. 1240-1241.
Question 7: Variation in size and shape of muscle fibers, combined with degenerative changes and intramysial fibrosis, is typical of
- A. Denervation of muscle with reinnervation
- B. Denervation atrophy
- C. Muscular dystrophy (Correct Answer)
- D. Mitochondrial myopathy
Explanation: ***Muscular dystrophy*** - The combination of **variation in muscle fiber size and shape**, **degenerative changes**, and **intramysial fibrosis** is a hallmark of muscular dystrophies [1]. - These conditions are characterized by progressive muscle weakness and degeneration, often with cycles of degeneration and attempted regeneration, leading to fibrosis [1]. *Denervation of muscle with reinnervation* - This typically leads to **fiber type grouping** as reinnervated fibers take on the characteristics of the reinnervating nerve. - While there may be some variation in fiber size, the prominent **degenerative changes** and **intramysial fibrosis** described are less characteristic of this process alone. *Denervation atrophy* - Primarily features widespread **atrophy of muscle fibers**, often angular in shape. - It lacks the prominent combination of **fiber size variation** and **significant degenerative changes with fibrosis**. *Mitochondrial myopathy* - Characterized by the presence of **ragged red fibers** on Gomori trichrome stain and often **lipid accumulation** due to mitochondrial abnormalities. - While there may be some fiber size variation, the description of widespread degenerative changes and intramysial fibrosis isn't the primary defining feature. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Peripheral Nerves and Skeletal Muscles, pp. 1244-1245.
Question 8: A Thirty five year old female has proximal weakness of muscles, ptosis and easy fatigability. The most sensitive test to suggest the diagnosis is -
- A. CPK levels
- B. Single fiber EMG (Correct Answer)
- C. Muscle Biopsy
- D. Edrophonium test
Explanation: ***Single fiber EMG*** - This patient's symptoms (proximal muscle weakness, ptosis, and easy fatigability) are highly suggestive of **myasthenia gravis**. - **Single fiber EMG (SFEMG)** is the **most sensitive electrophysiological test** for detecting impaired neuromuscular transmission in myasthenia gravis, even in cases with normal routine EMG [1]. *CPK levels* - **Creatine phosphokinase (CPK)** levels are typically elevated in muscle diseases involving **muscle fiber damage**, such as inflammatory myopathies (e.g., polymyositis, dermatomyositis) or muscular dystrophies [1]. - In myasthenia gravis, CPK levels are usually **within normal limits** as it is a disorder of the neuromuscular junction, not muscle fiber integrity. *Muscle Biopsy* - Muscle biopsy is performed to identify **structural abnormalities** of muscle tissue, inflammation, or fiber type changes, often used in diagnosing myopathies. - It is **not the primary diagnostic test** for myasthenia gravis, as there are no specific or consistent pathological changes evident upon muscle biopsy in this condition. *Edrophonium test* - The **Edrophonium (Tensilon) test** involves administering a short-acting acetylcholinesterase inhibitor, leading to a temporary improvement in muscle strength in myasthenia gravis. - While it was historically used for diagnosis, it is **less sensitive** than SFEMG and can have false positives or negatives, thus it is not considered the **most sensitive test** overall.
Question 9: Which of the following is not a chromosome breakage disorder?
- A. Bloom syndrome
- B. Ataxia telangiectasia
- C. Duchenne muscular dystrophy (Correct Answer)
- D. Fanconi anemia
Explanation: ***Duchenne muscular dystrophy*** - Duchenne muscular dystrophy is primarily a **muscle degeneration disorder** caused by mutations in the **dystrophin gene**, not a chromosome breakage disorder. - It does not involve issues with **chromosomal stability** or breakage, unlike the others listed. *Ataxia telangiectasia* - Ataxia telangiectasia is associated with defects in **DNA repair mechanisms**, leading to **chromosome breakage** and instability [1]. - Patients exhibit progressive **ataxia**, **telangiectasia**, and increased sensitivity to radiation. *Fanconi anemia* - Fanconi anemia is characterized by a defect in the **DNA repair pathway**, resulting in increased **chromosome breakage** [1]. - It is associated with **bone marrow failure** and development of various malignancies. *Bloom syndrome* - Bloom syndrome results from defects in the **BLM gene**, leading to **genomic instability** and an increased rate of chromosome breakage [1]. - This condition causes symptoms like **short stature**, **facial lesions**, and a predisposition to cancer. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 322-323.
Question 10: An electron microscopy of muscle biopsy shows 'parking lot' appearance. Which additional finding would confirm myotonic dystrophy?
- A. Ragged red fibers
- B. Ring fibers (Correct Answer)
- C. Central cores
- D. Nemaline rods
Explanation: ***Ring fibers*** - **Ring fibers** are a classic histopathological feature seen in **myotonic dystrophy**, characterized by peripheral myofibrils arranged circularly around a central core [1]. - The "parking lot" appearance on electron microscopy refers to collections of **sarcoplasmic reticulum** and **T-tubules**, which can be seen in various myopathies but are often prominent in myotonic dystrophy, complementing the presence of ring fibers [1]. *Ragged red fibers* - **Ragged red fibers** are characteristic of **mitochondrial myopathies**, indicating abnormal proliferation of mitochondria beneath the sarcolemma. - They are typically identified with **Gomori trichrome stain** and are not a feature of myotonic dystrophy. *Central cores* - **Central cores** are a hallmark of **central core disease**, a congenital myopathy, and are regions within muscle fibers where oxidative enzyme activity is absent. - These are not typically associated with myotonic dystrophy; rather, they suggest a different underlying genetic defect affecting muscle structure. *Nemaline rods* - **Nemaline rods** are rod-like inclusions observed in muscle fibers in **nemaline myopathy**, an inherited disorder often associated with mutations in genes encoding components of the thin filament. - They are distinct from the pathological findings in myotonic dystrophy and point to a specific type of congenital myopathy. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Manifestations Of Central And Peripheral Nervous System Disease, pp. 732-733.
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