Neurogenetics Flashcards
Epidemiology of Duchennes Muscular Dystrophy
X Linked Recessive
1/3000 boys
1/3 affected have a new mutation
What are the general disease milestones for a child with duchenes muscular dystrophy
Hip and Shoulder girdle weakness - 3/4 years
Wheelchair bound - 10-12 years
Death in 20’s
What are the common causes of death in a child with duchennes muscular dystrophy?
Respiratory and Cardiac muscles are affected so respiratory or cardiac failure.
What gene is affected in Duchennes?
Dystrophin gene located on the X chromosome which encodes for the dystrophin protein.
What are some clinical signs off Duchennes?
Tip toe walking
Lumbar lordosis
Calf hypertrophy
Gowers sign
What is gowers sign
When getting up from lying down. The child shimmies his hands along the floor to his feet then uses his hand to push off of his legs like an old man in order to straighten up.
Think Jungle Book
What is used to diagnose Duchennes?
Raised Serum Creatine Kinase - Not very specific
Eclectromyography
Muscle Biopsy
Molecular Genetic Testing
What would be seen on muscle biopsy in Duchennes?
Small irregular muscle cells with no staining for dystrophin.
Describe the types of mutations present in Duchennes?
70% are large scale deletion
30% are point mutations either small insertions or deletions
LIst a rare differential diagnosis for Duchennes.
Autosomal Recessive Limb Girdle Muscular dystrophies.
If a female presents with duchennes like symptoms what is it likely to be?
Autosomal Recessive Limb Girdle Muscular dystrophies.
A mutation in what protein is likely to cause an Autosomal Recessive Limb Girdle Muscular dystrophy.
Sarcoglycan - protein in the same complex as dystrophin.
When is carrier testing used in Duchennes muscular dystrophy?
In the female relatives of an affected male.
Can be offered prenatal testing.
Epidemiology of Huntington’s Disease
Autosomal Dominant trait with an age dependant penetrance
1/10,000 affected
1:1 M:F
What age range does Huntington’s present
30-50 years
From onset of symptoms what is Huntington’s prognosis?
15-20 years
What is the clinical presentation of someone with Huntington’s ?
Rigidity Bradykinesia (difficulty initiating/continuing movement) Severe Chorea ( Uncontrolled movement) Serious Weight loss Inability to walk or speak Swallowing problems - choking
What does the brain of someone with Huntington’s look like?
Caudate Atrophy
Loss of cells from basal ganglia and cerebral cortex
Flattened convex curve of the basal ganglia.
What is the genetic defect in HD?
CAG repeats over >40
CAG codes for Glutamate
Glutamine residues are toxic to cells in brain
What genetic tests can someone undergo for HD?
Pre natal or gestational testing.
What needs to be considered around testing for HD?
Fully inform the patient that a positive test will limit their insurance finances and what they can do for work despite being physically fine for years.
No licensed treatment so diagnosis doesn’t make a difference.
Living with the knowledge has severe impact on mental health.
Spinal Muscular Atrophy Epidemiology.
1 in 50 Carriers
1 in 1000 incidence
Autosomal Recessive
Clinical signs of someone with Spinal Muscular Atrophy
Proximal skeletal and respiratory muscle weakness.
What is the pathology behind spinal Muscular Atrophy?
Loss of the anterior horn due to SMN1 deficiency
Loss of Exon 7 on the SMN1 gene.
What is a treatment used from birth to prevent or delay the progression of Spinal Muscular Atrophy?
Addition of Exon 7 from SMN1 gene onto the SMN2 gene.
Genetic links in Alzhiemers.
5-10% of cases are autosomal dominant
Presenilin 2
Presenilin 1
APP mutation (Linked to Down syndrome)
Which variant of ApoE is linked to longevity?
e2
Which variant of ApoE is linked to clusters of Alzhiemers in families?
e4
