Genetic Conditions Flashcards
What is Huntington’s disease
A genetic condition that causes progressive neurological dysfunction
What is the inheritance pattern of Huntington’s disease
autosomal dominant
What causes Huntington’s disease
It is a trinucleotide repeat disorder caused by an expanded CAG repeat at the N-terminus of the HTT gene, which codes for the huntingtin protein
What chromosome is the HTT gene located on
Chromosome 4
What protein does CAG code for
Glutamine
Explain the pathophysiology of Huntington’s disease
- Elongated polyglutamine tail is cleaved and toxic fragments are generated
- Aggregates form that resist degradation and interfere with a variety of normal cellular function
What is the primary affected brain region in Huntington’s disease
Striatum
What is the CAG repeat threshold for Huntington’s disease certainty
Individuals with 40 or more CAG repeats are certain to develop Huntington’s disease.
What is the relationship between repeat length and symptom onset in Huntington’s disease
The longer the repeat length, the earlier symptoms tend to appear
What does 36-39 CAG repeats in Huntington’s disease testing indicate
An intermediate result of 36 to 39 repeats implies that the person may or may not develop symptoms of Huntington’s disease during their lifetime.
What does a result of 29-35 CAG repeats indicate in Huntington’s disease testing?
This range represents an expanded CAG repeat that will not cause disease in the patient but could expand enough to cause disease in offspring.
What is considered a normal result range for CAG repeats in Huntington’s disease testing
<28 repeats
Huntington’s disease displays genetic anticipation. Describe this
The tendency for expansion of the CAG repeat in successive generations puts offspring at risk for earlier onset and increased severity of the disease than their parents.
Give 5 clinical manifestations of Huntington’s disease
- Chorea - involuntary, random movements
- Personality change - depression, Irritability and impulsivity
- Cognitive decline
- Deficit in fine motor coordination
- impaired tandem walking
Characteristics of juvenile Huntington’s disease
Patients with juvenile Huntington’s disease may not have chorea but may present with rigidity or parkinsonian symptoms.
How is Huntington’s diagnosed
Diagnoses is clinical and can be confirmed by CAG repeat testing
How is Huntington’s disease managed non-pharmacologically
There are no Tx options for slowing/ stopping disease progression
* Counselling patient and family
* Advanced directive
* Palliative care and MDT
Pharmacological interventions for Huntington’s
- Chorea - 1. tetrabenazine, 2. sulpiride
- Antidepressants - 1. citalopram, 2. Sertraline
Give 3 late manifestations of Huntington’s disease
- Weight loss
- Dysphagia
- Falls
What is the life expectancy for someone with Huntington’s
10-20 years after onset of symptoms
What are 2 common causes of death in Huntington’s disease
- Aspiration pneumonia
- Suicide
What is the inheritance pattern of neurofibromatosis
autosomal dominant fashion
What are the genetic causes of the two types of neurofibromatosis
- NF1 (Neurofibromatosis type 1): Caused by a mutation on chromosome 17; more common.
- NF2 (Neurofibromatosis type 2): Caused by a mutation on chromosome 22
Describe the characteristics of neurofibromatosis 1
- Cafe-au-lait spots (>= 6, 15 mm in diameter)
- Axillary/groin freckles
- Peripheral neurofibromas - skin coloured , raised nodules/ papules
- Iris hamatomas (Lisch nodules) in > 90%, yellow-brown spots on iris
- Scoliosis
- Pheochromocytomas
What are the features of neurofibromatosis 2
- Bilateral vestibular schwannomas
- Multiple intracranial schwannomas, mengiomas and ependymomas
- may have Cafe-au-lait spots
Give 3 complications of neurofibromatosis 1
- malignant peripheral nerve sheath tumours
- GI stromal tumour
- renal artery stenosis
