Patho- Genetic disorders

Question 1

Describe the genetics of Duchenne MD

Answer 1

X-linkes

Question 2

What is the pathology of DMD?

Answer 2

Dystrophin links actin/myosin to cell membrane. Loss prevents myocytes from renewing.

Question 3

What are some symptoms of DMD?

Answer 3

Delayed motor development
Pelvic and pectorial girdle weakness at 3-4YO: Gives accentuated lumbar lordosis and Gower’s sign
Calf hypertrophy- Toe walking
Death by resp muscle failure

Question 4

How do you diagnose DMD?

Answer 4

Clinically
Muscle biopsy: Muscle fibre size variation, Necrosis and Replacement with fat
Genetic testing
Raised CK

Question 5

What is a mild form of DMD?

Answer 5

Becker’s MD

Question 6

What is the differential for DMD?

Answer 6

Autosomal recessive limb girdle muscular dystrophies

Question 7

How do you treat DMD?

Answer 7

No cure
Physio for muscle contractions
Resp support

Question 8

Describe the genetics of Huntington’s

Answer 8

Autosomal dominant on Ch4

Multiple CAG repeats in Huntington gene

Question 9

Describe the pathology of Huntington’s

Answer 9

Cerebral atrophy: Loss of caudate nucelus and Loss of putamen
Reduced Ach and GABA synthesis
Raised somatostatin

Question 10

How do the number of CAG repeats dictate the severity of Huntington’s?

Answer 10

More repeats the worse the disease

Question 11

How many CAG repeats are considered pathological in Huntington’s?

Answer 11

36

Question 12

When does Huntington’s tend to start?

Answer 12

30-50

Question 13

What are some early signs for Huntington’s?

Answer 13

Clumsiness
Agitation
Irritability
Apathy
Anxiety
Disinhibition
Hallucinations

Question 14

What are some later signs of Huntington’s disease?

Answer 14

Chorea
Dystonia
Involuntary movements
Balance/walking deficits
Slow voluntary movements
Difficulty initiating movement
Loss of control of movement
Rigidity

Question 15

How do you treat Huntington’s?

Answer 15

No treatment

Phenothiazines for chorea

Question 16

What is multiple sclerosis?

Answer 16

Chronic inflammation of the CNS

Question 17

What part of the CNS does MS affect?

Answer 17

White matter

Question 18

What are the symptoms of MS?

Answer 18

Motor weakness
Optic neuritis
Brainstem demyelination
Spinal cord lesion
Sensory symptoms
Cognitive impairment
Epilepsy
Fatigue

Question 19

How does optic neuritis present in MS?

Answer 19

Blurring of vision in one eye
Mild pain
Develops over hours
Recovery in 2 months

Question 20

How does brainstem demyelination present in MS?

Answer 20

Diplopia
Vertigo
Nystagmia
Facial numbness
Dysarthria
Dysphagia

Question 21

How does a spinal cord lesion present in MS?

Answer 21

Spastic paraparesis developing over days or weeks
Lhermitte’s sign- Feels like electrical shock down legs
Lower urinary tract dysfunction

Question 22

What are the sensory symptoms in MS?Pain

Answer 22

Pain
Parastesia
Loss of proprioception

Question 23

How do you diagnose MS?

Answer 23

MRI

MacDonald Criteria

Question 24

Describe the MacDonald Criteria for MS

Answer 24

2 or more attacks (relapses)/2 or more objective clinical lesions -> None
2 or more attacks/ 1 objective clinical lesion
1 attack/ 2 or more objective clinical lesions
1 attack/ 1 objective clinical lesion (clinically isolated syndrome)  Dissemination in space and time
Insidious neurological progression suggestive of MS (primary progressive MS)

Question 25

What is the differential for MS?

Answer 25

Vasculitis Granulomas Vascular Infection

Question 26

What is the patho of MS?

Answer 26

Multiple demyelination plaques Increase in inflammatory cells in lesions Over time axons are damaged

Question 27

What are the main types of MS?

Answer 27

Relapsing remitting Primary progressive Secondary progressive

Question 28

Describe relapsing remitting MS

Answer 28

Period of symptoms then get better

Question 29

Describe primary progressive MS

Answer 29

Progressive symptoms without relapse

Question 30

Describe secondary progressive MS

Answer 30

Relapsing remitting the changes to progressive

Question 31

How do you treat MS?

Answer 31

Exercise Stop smoking Treat exacerbation Give disease modifiers

Question 32

How can you treat exacerbations of MS?

Answer 32

Symptomatic treatment Steroids Admit and IV steroids

Question 33

What are some first line disease modifiers in MS?

Answer 33

``` Beta interferon for RR Glitiramer acetate (copaxone) Tecfidera ```

Question 34

What are some second line disease modifiers in MS?

Answer 34

Tysabri- Associated with Progressive multifocal leukoencephalopathy (PML). Fingolimod

Question 35

What are some third line disease modifiers in MS?

Answer 35

Mitoxantone- Cardiotoxic

Question 36

What is cerebral palsy?

Answer 36

Inter-uterine or neonatal brain damage

Question 37

What are some symptoms of cerebral palsy?

Answer 37

Learning problems- Failure to meet normal milestones Physical disability- Spastic diplegia Infantile hemiparesis Congenital ataxia

Question 38

What are some causes of cerebral palsy?

Answer 38

``` Hypoxia Neonatal cerebral haemorrhage and/or infarction Trauma Prolonged seizures Hypoglycemia ```

Question 39

What are some Neuroectoderm syndromes?

Answer 39

Neurofibromatosis type 1 Neurofibromatosis type 2 Von Hippel-Lindau syndrome

Question 40

What is a symptom of Neurofibromatosis type 1 ?

Answer 40

Café-au-lait patches

Question 41

What can Neurofibromatosis type 2 cause?

Answer 41

Neurotumours

Question 42

What kind of neurotumors can Neurofibromatosis type 2 cause?

Answer 42

``` Meningioma Acoustic neuroma (often bilateral) Glioma (including optic nerve glioma) Plexiform neuroma (massive cutaneous overgrowth) Cutaneous neurofibroma ```