Genetics of Ataxia and Dystrophies - week 23

Question 1

What is Duchenne muscular dystrophy?

Answer 1

genetics disease causing progressive weakness and loss of muscle mass

Question 2

Epidemiology of Duchenne muscular dystrophy?

Answer 2

3-5 yrs
more likely to affect boys
most common form of MD

Question 3

Pathophys of Duchenne muscular dystrophy?

Answer 3

X-linked recessive
Frame shift DMD gene = deletion
DMD gene = dystrophin

Question 4

What is the function of dystrophin?

Answer 4

Stabilizes muscle membrane in contraction and relaxation

Question 5

Presentation of Duchenne muscular dystrophy?

Answer 5

Delay in walking/falls
muscle weakness
muscle wasting
muscle pseudohypertrophy
scoliosis

Question 6

What important clincial sign is an indicator of Duchenne muscular dystrophy?

Answer 6

Gowers sign - use hands and arms to walk up their own body due to reduced strength in hips and thighs

Question 7

Investigation for Duchenne muscular dystrophy?

Answer 7

Elevated creatine kinase
Antibody testing to rule our differentials
DNA test
electromyography

Question 8

Prognosis Duchenne muscular dystrophy?

Answer 8

Premature death common to resp or cardiac failure

Question 9

What is Becker muscular dystrophy?

Answer 9

Progressive wasting of muscles, genetics

milder form than DMD

Question 10

Epidemiology of Becker muscular dystrophy?

Answer 10

male
onset after 7yrs, average 11

Question 11

Pathophys of Becker muscular dystrophy?

Answer 11

In frame DMD mutation
Dystrophin is partially functional, muscle degeneration is slower than DMD

x-linked recessive

Question 12

Presentation of Becker muscular dystrophy?

Answer 12

Gait problems
Gower’s sign
Proximal muscle weakness -
Calf pseudohypertrophy
Systemic features - Cardiomyopathy, Respiratory muscle involvement, Scoliosis.
Severity correlates to muscle Dystrophin levels

Question 13

What is the presentation of myotonic dystrophy?

Answer 13

in adulthood

Progressive muscle weakness
Prolonged muscle contractions
Cataracts
Cardiac arrhythmias

Autosomal dominant - CTG expansion (anticipation)

Question 14

Presentation of Facioscapulohumeral Muscular Dystrophy?

Answer 14

childhood

Weakness face, shoulders, arms

sleeping eyes open and weakness is pursing lips

cannot blow cheeks out without air leaking from mouth

Autosomal dominant

Question 15

Presentation of Oculopharyngeal Muscular Dystrophy?

Answer 15

late adulthood

ocular muscles and pharynx

bilateral ptosis, restricted eye movement and swallowing problems

Muscles around the limb girdles are also affected

Question 16

What is Limb-girdle Muscular Dystrophy?

Answer 16

teenage years

progressive weakness limb girdles

Question 17

What is Emery-Dreifuss Muscular Dystrophy?

Answer 17

childhood

contractures - commonly elbows and ankles

Progressive weakness and muscle wasting

Question 18

What are two types of ataxia?

Answer 18

cerebellar (wide-based gait/intention limb/speech slurred)

sensory (unsteady high-stepping gait/ worse in dark)

Question 19

What is ataxia?

Answer 19

Disurbance of coordination, gait or speech

Question 20

Causes of cerebellar ataxia?

Answer 20

Acquired (vascular/drugs/inflammatory/hypothyroidism/deficiency/neoplastic)

Hereditary (autosomal recessive/dominant/mitochondrial)

Question 21

What is Friedreich’s ataxia?

Answer 21

Commonest familial ataxia
Disturbance in coordination/gait/speech

Question 22

Presentation of Friedreich’s ataxia?

Answer 22

Gait and limp ataxia
pes cavus (high arch)
absence of reflexes
pyramidal reflexes
hypertrophic cardiomyopathy

Question 23

Pathophys of Friedreich’s ataxia?

Answer 23

Expansion of GAA trinucleotide repeat
X25 gene - codes for frataxin

NO ANTICIPATION

Question 24

What is autosomal dominant cerebellar ataxias?

Answer 24

adult onset
27 subtypes
some CAG repeat expansion
very variable phenotype (cerebellar features)