Muscle disorders

Question 1

What are congenital myopathies?

Answer 1

A group of genetic muscle disorders characterized by hypotonia and weakness from birth, with a static or slowly progressive course.

Question 2

What are common clinical features of congenital myopathies?

Answer 2

Hypotonia, weakness, feeding and respiratory difficulties, slow improvement over time.

Question 3

What causes congenital myopathies?

Answer 3

Mutations in genes encoding proteins important for muscle fiber contraction and relaxation.

Question 4

How many genetic causes of congenital myopathies exist?

Answer 4

Approximately 30, all related to protein coding for muscle function.

Question 5

How are congenital myopathies diagnosed?

Answer 5

muscle biopsy, genetic testing, and sometimes EMG (electromyography).

Question 6

What gene is affected in nemaline myopathy?

Answer 6

The nemaline gene, which encodes a structural protein that holds actin together in muscle.

Question 7

What is the hallmark pathological feature of nemaline myopathy?

Answer 7

Presence of small rod-like inclusions (nemaline rods) in muscle fibers.

Question 8

What are the main symptoms of nemaline myopathy?

Answer 8

Generalized muscle weakness, facial weakness, hypotonia, hyporeflexia, respiratory involvement, scoliosis, joint contractures.

Question 9

What is the defining feature of core myopathies?

Answer 9

Lack of mitochondria.

Question 10

What are the main symptoms of core myopathies?

Answer 10

Proximal muscle weakness, facial weakness, contractures, respiratory and cardiac involvement, slow progression

Question 11

What is the key feature of centronuclear myopathies?

Answer 11

Nuclei are abnormally positioned in the center of muscle cells and appear larger with a vesicular structure.

Question 12

What are the symptoms of centronuclear myopathies?

Answer 12

Proximal muscle weakness, facial weakness, hypotonia, scoliosis, joint contractures, respiratory issues, cardiomyopathy.

Question 13

What are congenital muscular dystrophies (CMDs)?

Answer 13

Genetic muscle disorders causing muscle weakness, delayed motor development, and respiratory issues due to mutations affecting the sarcolemma.

Question 14

How is CMD diagnosed?

Answer 14

Elevated CK levels are a key diagnostic marker.

Muscle MRI can show characteristic patterns of muscle involvement.

Genetic testing is the gold standard for diagnosis

Question 15

What is the primary pathophysiology of CMDs?

Answer 15

Mutations affect proteins that maintain the muscle cell membrane (sarcolemma), leading to membrane fragility and muscle damage.

Question 16

What enzyme is elevated in CMDs?

Answer 16

Creatine kinase (CK), due to sarcolemma damage.

Question 17

What are common clinical features of CMDs?

Answer 17

Muscle weakness, motor milestone delays, respiratory difficulties, progression to contractures and joint deformities.

Question 18

What protein is affected in collagen VI-related muscular dystrophy?

Answer 18

Collagen VI, which maintains muscle fiber integrity.

Question 19

What are key symptoms of collagen VI-related muscular dystrophy?

Answer 19

Proximal muscle weakness, hypermobile distal joints, skin rash (hypokeratosis pilaris), scoliosis, respiratory issues, joint fractures.

Question 20

What protein is affected in alpha-2 laminin deficiency?

Answer 20

Alpha-2 laminin, which stabilizes the muscle cell membrane.

Question 21

What are key features of alpha-2 laminin deficiency?

Answer 21

Cardiac conduction defects, early-onset muscle weakness, brain white matter changes, respiratory and swallowing difficulties.

Question 22

What causes SEPN1-related muscular dystrophy (Rigid Spine Syndrome)?

Answer 22

Mutations in the SEPN1 gene.

Question 23

What are key symptoms of SEPN1-related muscular dystrophy?

Answer 23

Rigid spine, progressive muscle weakness, respiratory issues.

Question 24

What gene mutation causes LAMA2-related muscular dystrophy?

Answer 24

Mutations in the LAMA2 gene.

Question 25

Which populations have a higher prevalence of LAMA2-related muscular dystrophy?

Answer 25

Traveller community and certain Asian populations.

Question 26

Q: What are the key symptoms of LAMA2-related muscular dystrophy?

Answer 26

A: Progressive muscle weakness, motor delays, contractures, severe respiratory and swallowing difficulties.

Question 27

Q: What causes myotonic dystrophy?

Answer 27

A: Abnormal expansion of the DMPK gene.

Question 28

What systems does myotonic dystrophy affect?

Answer 28

Multisystem disease: cardiac, endocrine, GI, CNS

Question 29

Q: How is myotonic dystrophy inherited?

Answer 29

A: Autosomal dominant (50% chance of passing it on).

Question 30

Q: What is genetic anticipation in myotonic dystrophy?

Answer 30

A: Symptoms become more severe in successive generations.

Question 31

Q: What are the clinical features of myotonic dystrophy?

Answer 31

A: Muscle weakness, myotonia, cardiac issues, cataracts, respiratory problems, GI and endocrine dysfunctions.

Question 32

Cognitive effects of congenital myotonic dystrophy?

Answer 32

learning disabilities, ASD traits, and low IQ (40-80 range).

Question 33

Q: What are prenatal signs of congenital myotonic dystrophy?

Answer 33

A: Polyhydramnios (excess amniotic fluid) and reduced fetal movements.

Question 34

Q: What are key symptoms at birth for congenital myotonic dystrophy?

Answer 34

A: Hypotonia, talipes (clubfoot), feeding/swallowing difficulties, developmental delays, hypernasal speech.

Question 35

Q: What is the long-term prognosis of congenital myotonic dystrophy?

Answer 35

A: Many children achieve walking, and feeding/swallowing difficulties improve, though speech and coordination remain challenging.

Question 36

Q: What is Duchenne muscular dystrophy (DMD)?

Answer 36

A: A severe, X-linked muscular dystrophy caused by mutations in the dystrophin gene.

Question 37

Q: What protein is affected in DMD?

Answer 37

A: Dystrophin, a muscle shock absorber.

Question 38

Q: How is DMD inherited?

Answer 38

A: X-linked recessive (affects males, carrier females may have symptoms).

Question 39

Q: What are the early signs of DMD?

Answer 39

A: Delayed walking (>18 months), frequent falls, waddling gait, difficulty standing up (Gower’s maneuver).

Question 40

What is calf pseudohypertrophy in DMD

Answer 40

enlarged calves due to fat and fibrous tissue replacing muscle

Question 41

Q: What are the key progressive symptoms of DMD?

Answer 41

A: Muscle weakness, loss of ambulation (by 9-12 years), contractures, scoliosis, respiratory and cardiac failure.

Question 42

Q: What speech and cognitive issues are associated with DMD?

Answer 42

A: Speech delay, phonological processing issues, cognitive delay, ASD/ADHD (30%).

Question 43

Q: What percentage of DMD patients experience dysphagia?

Answer 43

A: 70%, with solid foods being harder to swallow than liquids.

Question 44

Q: What test is used to confirm DMD?

Answer 44

A: Elevated creatine kinase (CK) levels.

Question 45

Q: What treatments help manage DMD?

Answer 45

A: Corticosteroids (prednisone, deflazacort), non-invasive ventilation, ACE inhibitors for heart function.

Question 46

Q: What is the prognosis for DMD?

Answer 46

A: Life expectancy has improved to the 30s with treatment.

Question 47

What is the major cause of death in DMD?

Answer 47

Dilated cardiomyopathy

Question 48

Impact of DMD on respiration?

Answer 48

Progressive respiratory failure—may require BiPAP or tracheostomy.

Question 49

Gene therapy research in DMD

Answer 49

Experimental treatments (e.g., exon-skipping drugs like eteplirsen) are being tested to slow disease progression