Patho- Genetic disorders Flashcards
Describe the genetics of Duchenne MD
X-linkes
What is the pathology of DMD?
Dystrophin links actin/myosin to cell membrane. Loss prevents myocytes from renewing.
What are some symptoms of DMD?
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
How do you diagnose DMD?
Clinically
Muscle biopsy: Muscle fibre size variation, Necrosis and Replacement with fat
Genetic testing
Raised CK
What is a mild form of DMD?
Becker’s MD
What is the differential for DMD?
Autosomal recessive limb girdle muscular dystrophies
How do you treat DMD?
No cure
Physio for muscle contractions
Resp support
Describe the genetics of Huntington’s
Autosomal dominant on Ch4
Multiple CAG repeats in Huntington gene
Describe the pathology of Huntington’s
Cerebral atrophy: Loss of caudate nucelus and Loss of putamen
Reduced Ach and GABA synthesis
Raised somatostatin
How do the number of CAG repeats dictate the severity of Huntington’s?
More repeats the worse the disease
How many CAG repeats are considered pathological in Huntington’s?
36
When does Huntington’s tend to start?
30-50
What are some early signs for Huntington’s?
Clumsiness Agitation Irritability Apathy Anxiety Disinhibition Hallucinations
What are some later signs of Huntington’s disease?
Chorea Dystonia Involuntary movements Balance/walking deficits Slow voluntary movements Difficulty initiating movement Loss of control of movement Rigidity
How do you treat Huntington’s?
No treatment
Phenothiazines for chorea
What is multiple sclerosis?
Chronic inflammation of the CNS
What part of the CNS does MS affect?
White matter
What are the symptoms of MS?
Motor weakness Optic neuritis Brainstem demyelination Spinal cord lesion Sensory symptoms Cognitive impairment Epilepsy Fatigue
How does optic neuritis present in MS?
Blurring of vision in one eye
Mild pain
Develops over hours
Recovery in 2 months
How does brainstem demyelination present in MS?
Diplopia Vertigo Nystagmia Facial numbness Dysarthria Dysphagia
How does a spinal cord lesion present in MS?
Spastic paraparesis developing over days or weeks
Lhermitte’s sign- Feels like electrical shock down legs
Lower urinary tract dysfunction
What are the sensory symptoms in MS?Pain
Pain
Parastesia
Loss of proprioception
How do you diagnose MS?
MRI
MacDonald Criteria
Describe the MacDonald Criteria for MS
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)
What is the differential for MS?
Vasculitis
Granulomas
Vascular
Infection
What is the patho of MS?
Multiple demyelination plaques
Increase in inflammatory cells in lesions
Over time axons are damaged
What are the main types of MS?
Relapsing remitting
Primary progressive
Secondary progressive
Describe relapsing remitting MS
Period of symptoms then get better
Describe primary progressive MS
Progressive symptoms without relapse
Describe secondary progressive MS
Relapsing remitting the changes to progressive
How do you treat MS?
Exercise
Stop smoking
Treat exacerbation
Give disease modifiers
How can you treat exacerbations of MS?
Symptomatic treatment
Steroids
Admit and IV steroids
What are some first line disease modifiers in MS?
Beta interferon for RR Glitiramer acetate (copaxone) Tecfidera
What are some second line disease modifiers in MS?
Tysabri- Associated with Progressive multifocal leukoencephalopathy (PML).
Fingolimod
What are some third line disease modifiers in MS?
Mitoxantone- Cardiotoxic
What is cerebral palsy?
Inter-uterine or neonatal brain damage
What are some symptoms of cerebral palsy?
Learning problems- Failure to meet normal milestones
Physical disability- Spastic diplegia
Infantile hemiparesis
Congenital ataxia
What are some causes of cerebral palsy?
Hypoxia Neonatal cerebral haemorrhage and/or infarction Trauma Prolonged seizures Hypoglycemia
What are some Neuroectoderm syndromes?
Neurofibromatosis type 1
Neurofibromatosis type 2
Von Hippel-Lindau syndrome
What is a symptom of Neurofibromatosis type 1 ?
Café-au-lait patches
What can Neurofibromatosis type 2 cause?
Neurotumours
What kind of neurotumors can Neurofibromatosis type 2 cause?
Meningioma Acoustic neuroma (often bilateral) Glioma (including optic nerve glioma) Plexiform neuroma (massive cutaneous overgrowth) Cutaneous neurofibroma
