Huntington’s Disease (HD)
“An autosomal dominant disorder characterised by progressive neurodegeneration”
- Adult-onset HD – the most common form, people typically develop symptoms in mid-30s and 40s.
- Early-onset HD – rarely, children or adolescents develop the disease
- If a parent has HD, there is a 50% chance their child will develop it. The longer the CAG repeat, the more likely the person is to be affected.
- For 1-3% of patients, no family history is ever identified
- It is a trinucleotide repeat disorder and is caused by a CAG triplet repetition found on the HTT (Huntingtin) gene located on chromosome 4
- HTT has many functions, including as an anti-apoptotic agent and it also controls the production of brain-derived neurotrophic factor which protects neurones and regulates their creation.
- It is thought that HD is caused by an increase in the toxic function of mutant HTT (mHTT). mHTT protein increases the decay rate of certain types of neurones.
- Early damage is most evident in the striatum but as the disease progresses, other areas of the brain are noticeably affected
- Onset of symptoms is usually in mid-life (30-50 years of age) but can be earlier.
- Early signs symptoms:
- Irritability, behavioural changes, depression, mood swings, trouble driving, trouble learning new things, forgetting facts, trouble making decisions
- Later signs and symptoms include:
- Chorea (an abnormal involuntary movement characterised by brief, abrupt, irregular, unpredictable, non-stereotyped movements)
- Poor coordination
- Jerky eye movements
- Progressive decline in cognition followed by memory deficits, confusion, psychosis, hallucinations, paranoia, and features of parkinsonism (rigidity, bradykinesia and tremors) and progression to dystonia (sustained muscle contraction, causing repetitive, twisting movements)
- Medical diagnosis can be made following the appearance of physical symptoms specific to the disease and confirmed using genetic testing if there is no family history.
- Physical and psychological examination
- can determine whether onset of the disease has begun. Physical symptoms are usually the first symptoms diagnosed whereas cognitive/behavioural symptoms are usually only recognised in hindsight or when they develop further.
- Huntington’s disease rating scale
- a measure of disease progression based on the motor, behavioural, cognitive and functional assessment.
- Blood test and predictive genetic testing
- a blood test can be done to confirm HD, which counts the number of CAG repeats in each of the HTT alleles. The number of CAG repeats is related to the penetrance of the disease.
|Repeat Count||Classification||Disease Status||Risk to Offspring|
|<27||Normal||Will not be affected||None|
|27-35||Intermediate||Will not be affected||Elevate but <50%|
|36-39||Reduced penetrance||May or may not be affected||50%|
|40+||Full penetrance||Will be affected||50%|
- CT or MRI can show atrophy of the caudate nuclei early in the disease process. These changes by themselves are not diagnostic but may aid a clinical diagnosis. Cerebral atrophy may be seen in advanced stages of the disease
- There is no cure for Huntington’s so treatment involves managing symptoms.
- Physical therapy for management of physical symptoms e.g. fall risk assessment and prevention, strengthening, stretching, cardiovascular exercises, breathing exercises, and airway clearance techniques. Walking aids may be prescribed.
- Nutritional management e.g. thickening agents added to fluids, reminders to eat slowly and take smaller pieces of food, and percutaneous endoscopic gastrostomy.
- Medications e.g. benzodiazepines for chorea, antiparkinsonian drugs, valproic acid for myoclonic hyperkinesia, and medication for psychiatric symptoms such as depression and psychosis.
- Education for the patient and their family, especially genetic counselling to update their knowledge, dispel unfounded beliefs, and help them consider future options and plans. Palliative care is also an option for these patients as it aims to improve their quality of life
- Patients have a reduced life expectancy – estimated at 20 years after the onset of symptoms.
- Pneumonia is the largest risk and causes death in 1/3 of those with Huntington’s.
- Heart disease causes almost ¼ of fatalities in those with Huntington’s.
- 7.3% of those with the disease will commit suicide, and up to 27% will attempt to do so