Mitochondrial Myopathies and Muscular Dystrophies

Question 1

What is the inheritance pattern of mitochondrial myopathies?

Answer 1

Mitochondrial (maternal) inheritance

Question 2

What histological feature is characteristic of mitochondrial myopathies?

Answer 2

Ragged red fibers on muscle biopsy

Question 3

Why do mitochondrial myopathies show maternal inheritance?

Answer 3

Mitochondria are inherited exclusively from the mother

Question 4

What is the cause of mitochondrial myopathies at the cellular level?

Answer 4

Mutations in mitochondrial DNA (mtDNA) affecting oxidative phosphorylation

Question 5

What is heteroplasmy in mitochondrial diseases?

Answer 5

The presence of both normal and mutated mtDNA within a cell, leading to variable expression of disease

Question 6

What is the hallmark triad of Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes (MELAS)?

Answer 6

Stroke-like episodes, Lactic acidosis, Myopathy

Question 7

What genetic mutation is associated with MELAS?

Answer 7

mtDNA mutations in tRNA genes (e.g., MT-TL1)

Question 8

What metabolic abnormality is commonly seen in mitochondrial myopathies?

Answer 8

Lactic acidosis due to impaired oxidative phosphorylation

Question 9

What are the key features of Myoclonic Epilepsy with Ragged Red Fibers (MERRF)?

Answer 9

Myoclonus, Seizures, Ataxia, Ragged red fibers on muscle biopsy

Question 10

What mutation is associated with MERRF?

Answer 10

mtDNA mutation in MT-TK (tRNA-lysine gene)

Question 11

What are the clinical features of Leber Hereditary Optic Neuropathy (LHON)?

Answer 11

Painless bilateral vision loss (optic atrophy), typically in young males

Question 12

What mutation is associated with LHON?

Answer 12

mtDNA mutations affecting complex I of the electron transport chain

Question 13

What is the primary affected organ system in mitochondrial myopathies?

Answer 13

Muscles (myopathy), Brain (encephalopathy), and sometimes eyes (optic neuropathy)

Question 14

Why do mitochondrial myopathies cause exercise intolerance?

Answer 14

Impaired ATP production leads to muscle fatigue and weakness

Question 15

What is the role of the electron transport chain in mitochondrial myopathies?

Answer 15

Defective oxidative phosphorylation leads to decreased ATP production and increased lactic acid

Question 16

What is the treatment for mitochondrial myopathies?

Answer 16

Supportive care (exercise, vitamins, coenzyme Q10, L-arginine for stroke-like episodes in MELAS)

Question 17

What is the inheritance pattern of mitochondrial DNA deletion syndromes like Kearns-Sayre syndrome?

Answer 17

Sporadic (not inherited maternally)

Question 18

What are the key features of Kearns-Sayre syndrome?

Answer 18

Progressive external ophthalmoplegia, Pigmentary retinopathy, Heart block

Question 19

What is a key difference between MELAS and MERRF?

Answer 19

MELAS presents with stroke-like episodes, whereas MERRF is characterized by myoclonus and seizures

Question 20

What laboratory finding is common in mitochondrial myopathies?

Answer 20

Elevated serum lactate (due to defective oxidative phosphorylation)

Question 21

What gene is mutated in Duchenne and Becker muscular dystrophy?

Answer 21

DMD gene (dystrophin)

Question 22

What is the inheritance pattern of Duchenne and Becker muscular dystrophy?

Answer 22

X-linked recessive

Question 23

What type of mutation causes Duchenne muscular dystrophy (DMD)?

Answer 23

Frameshift or nonsense mutation in the DMD gene

Question 24

What is the key difference in mutation type between Duchenne and Becker muscular dystrophy?

Answer 24

Duchenne = frameshift/nonsense (nonfunctional dystrophin), Becker = in-frame mutation (partially functional dystrophin)

Question 25

At what age does Duchenne muscular dystrophy typically present?

Answer 25

Early childhood (before age 5)

Question 26

What is the hallmark clinical sign of Duchenne muscular dystrophy?

Answer 26

Gower sign (using hands to push up from the floor)

Question 27

What muscles are first affected in Duchenne muscular dystrophy?

Answer 27

Proximal muscles, especially pelvic girdle

Question 28

What serious complication is associated with Duchenne muscular dystrophy?

Answer 28

Dilated cardiomyopathy (leading cause of death)

Question 29

What lab finding is elevated in Duchenne muscular dystrophy?

Answer 29

Creatine kinase (CK)

Question 30

What muscle biopsy finding is characteristic of Duchenne muscular dystrophy?

Answer 30

Fibrofatty muscle replacement

Question 31

What mutation causes Becker muscular dystrophy (BMD)?

Answer 31

In-frame mutation in DMD gene leading to partially functional dystrophin

Question 32

How does Becker muscular dystrophy differ from Duchenne muscular dystrophy?

Answer 32

Milder symptoms, later onset (adolescence or early adulthood), slower progression

Question 33

What is the typical age of onset for Becker muscular dystrophy?

Answer 33

Adolescence or early adulthood

Question 34

What is the primary cause of death in Duchenne and Becker muscular dystrophy?

Answer 34

Dilated cardiomyopathy and respiratory failure

Question 35

What genetic mutation causes myotonic dystrophy?

Answer 35

CTG trinucleotide repeat expansion in the DMPK gene (Type 1)

Question 36

What is the inheritance pattern of myotonic dystrophy?

Answer 36

Autosomal dominant

Question 37

What are the characteristic symptoms of myotonic dystrophy?

Answer 37

Myotonia (delayed muscle relaxation), Cataracts, Frontal balding, Testicular atrophy, Arrhythmias

Question 38

What is the key clinical test for myotonia?

Answer 38

Hand grip myotonia (delayed relaxation after squeezing a hand)

Question 39

What systemic features are associated with myotonic dystrophy?

Answer 39

Cardiac conduction defects, Insulin resistance, Cognitive impairment

Question 40

What phenomenon explains worsening severity of myotonic dystrophy in successive generations?

Answer 40

Anticipation (expansion of CTG repeats in subsequent generations)

Question 41

How does myotonic dystrophy differ from Duchenne and Becker muscular dystrophy?

Answer 41

It is autosomal dominant, involves myotonia, and has multisystem involvement

Question 42

What treatment is available for muscular dystrophies?

Answer 42

Supportive care (physical therapy, steroids for Duchenne, cardiac monitoring)

Question 43

What cardiac abnormality is common in myotonic dystrophy?

Answer 43

Conduction defects (risk of arrhythmias)

Question 44

What facial feature is characteristic of myotonic dystrophy?

Answer 44

Hatchet face (due to muscle wasting)