Muscle disorders Flashcards
What are congenital myopathies?
A group of genetic muscle disorders characterized by hypotonia and weakness from birth, with a static or slowly progressive course.
What are common clinical features of congenital myopathies?
Hypotonia, weakness, feeding and respiratory difficulties, slow improvement over time.
What causes congenital myopathies?
Mutations in genes encoding proteins important for muscle fiber contraction and relaxation.
How many genetic causes of congenital myopathies exist?
Approximately 30, all related to protein coding for muscle function.
How are congenital myopathies diagnosed?
muscle biopsy, genetic testing, and sometimes EMG (electromyography).
What gene is affected in nemaline myopathy?
The nemaline gene, which encodes a structural protein that holds actin together in muscle.
What is the hallmark pathological feature of nemaline myopathy?
Presence of small rod-like inclusions (nemaline rods) in muscle fibers.
What are the main symptoms of nemaline myopathy?
Generalized muscle weakness, facial weakness, hypotonia, hyporeflexia, respiratory involvement, scoliosis, joint contractures.
What is the defining feature of core myopathies?
Lack of mitochondria.
What are the main symptoms of core myopathies?
Proximal muscle weakness, facial weakness, contractures, respiratory and cardiac involvement, slow progression
What is the key feature of centronuclear myopathies?
Nuclei are abnormally positioned in the center of muscle cells and appear larger with a vesicular structure.
What are the symptoms of centronuclear myopathies?
Proximal muscle weakness, facial weakness, hypotonia, scoliosis, joint contractures, respiratory issues, cardiomyopathy.
What are congenital muscular dystrophies (CMDs)?
Genetic muscle disorders causing muscle weakness, delayed motor development, and respiratory issues due to mutations affecting the sarcolemma.
How is CMD diagnosed?
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
What is the primary pathophysiology of CMDs?
Mutations affect proteins that maintain the muscle cell membrane (sarcolemma), leading to membrane fragility and muscle damage.
What enzyme is elevated in CMDs?
Creatine kinase (CK), due to sarcolemma damage.
What are common clinical features of CMDs?
Muscle weakness, motor milestone delays, respiratory difficulties, progression to contractures and joint deformities.
What protein is affected in collagen VI-related muscular dystrophy?
Collagen VI, which maintains muscle fiber integrity.
What are key symptoms of collagen VI-related muscular dystrophy?
Proximal muscle weakness, hypermobile distal joints, skin rash (hypokeratosis pilaris), scoliosis, respiratory issues, joint fractures.
What protein is affected in alpha-2 laminin deficiency?
Alpha-2 laminin, which stabilizes the muscle cell membrane.
What are key features of alpha-2 laminin deficiency?
Cardiac conduction defects, early-onset muscle weakness, brain white matter changes, respiratory and swallowing difficulties.
What causes SEPN1-related muscular dystrophy (Rigid Spine Syndrome)?
Mutations in the SEPN1 gene.
What are key symptoms of SEPN1-related muscular dystrophy?
Rigid spine, progressive muscle weakness, respiratory issues.
What gene mutation causes LAMA2-related muscular dystrophy?
Mutations in the LAMA2 gene.
Which populations have a higher prevalence of LAMA2-related muscular dystrophy?
Traveller community and certain Asian populations.
Q: What are the key symptoms of LAMA2-related muscular dystrophy?
A: Progressive muscle weakness, motor delays, contractures, severe respiratory and swallowing difficulties.
Q: What causes myotonic dystrophy?
A: Abnormal expansion of the DMPK gene.
What systems does myotonic dystrophy affect?
Multisystem disease: cardiac, endocrine, GI, CNS
Q: How is myotonic dystrophy inherited?
A: Autosomal dominant (50% chance of passing it on).
Q: What is genetic anticipation in myotonic dystrophy?
A: Symptoms become more severe in successive generations.
Q: What are the clinical features of myotonic dystrophy?
A: Muscle weakness, myotonia, cardiac issues, cataracts, respiratory problems, GI and endocrine dysfunctions.
Cognitive effects of congenital myotonic dystrophy?
learning disabilities, ASD traits, and low IQ (40-80 range).
Q: What are prenatal signs of congenital myotonic dystrophy?
A: Polyhydramnios (excess amniotic fluid) and reduced fetal movements.
Q: What are key symptoms at birth for congenital myotonic dystrophy?
A: Hypotonia, talipes (clubfoot), feeding/swallowing difficulties, developmental delays, hypernasal speech.
Q: What is the long-term prognosis of congenital myotonic dystrophy?
A: Many children achieve walking, and feeding/swallowing difficulties improve, though speech and coordination remain challenging.
Q: What is Duchenne muscular dystrophy (DMD)?
A: A severe, X-linked muscular dystrophy caused by mutations in the dystrophin gene.
Q: What protein is affected in DMD?
A: Dystrophin, a muscle shock absorber.
Q: How is DMD inherited?
A: X-linked recessive (affects males, carrier females may have symptoms).
Q: What are the early signs of DMD?
A: Delayed walking (>18 months), frequent falls, waddling gait, difficulty standing up (Gower’s maneuver).
What is calf pseudohypertrophy in DMD
enlarged calves due to fat and fibrous tissue replacing muscle
Q: What are the key progressive symptoms of DMD?
A: Muscle weakness, loss of ambulation (by 9-12 years), contractures, scoliosis, respiratory and cardiac failure.
Q: What speech and cognitive issues are associated with DMD?
A: Speech delay, phonological processing issues, cognitive delay, ASD/ADHD (30%).
Q: What percentage of DMD patients experience dysphagia?
A: 70%, with solid foods being harder to swallow than liquids.
Q: What test is used to confirm DMD?
A: Elevated creatine kinase (CK) levels.
Q: What treatments help manage DMD?
A: Corticosteroids (prednisone, deflazacort), non-invasive ventilation, ACE inhibitors for heart function.
Q: What is the prognosis for DMD?
A: Life expectancy has improved to the 30s with treatment.
What is the major cause of death in DMD?
Dilated cardiomyopathy
Impact of DMD on respiration?
Progressive respiratory failure—may require BiPAP or tracheostomy.
Gene therapy research in DMD
Experimental treatments (e.g., exon-skipping drugs like eteplirsen) are being tested to slow disease progression
