Signs and symptoms
Huntington’s disease (HD) is a progressive neurological disorder. It is characterised by involuntary movements (chorea), psychiatric disturbance and cognitive impairment.
HD can begin at any age, but usually between the ages of 35 and 50. The disease progresses over 15-20 yrs from onset. Movement disorder is usually the first symptom to be noticed, with patients initially showing a general lack of coordination, unsteady gait and slurring of speech.
Chorea is often prominent in the early stages but as the condition progresses dystonia and bradykinesia also develop. Difficulties in swallowing may lead to aspiration, chest infection and malnutrition. Selective cognitive abilities are progressively impaired including memory impairment. Psychiatric symptoms can be quite variable including anxiety, depression, psychosis and behavioural changes.
Episodic Dyscontrol Syndrome (EDS) is an organically determined aggression condition due to loss of frontal lobe control of anger. Young adults sometimes present with psychiatric symptoms before physical symptoms are recognised.
Pathology
People who carry the mutation in the gene for HD produce a mutant form of the cytoplasmic protein huntingtin. Production of huntingtin increases the rate of neuronal decay in certain types of neurons. Examination of the brain at autopsy shows degeneration of the basal ganglia and the brain is generally smaller.
Genetics
HD is an autosomal dominant condition. The Huntington gene (HTT) is located on chromosome 4 and contains a sequence of the three DNA bases cytosine, adenine and guanine (CAG) repeated multiple times (a trinucleotide repeat). HD is caused by an increased trinucleotide repeat number within the Huntington gene. The affected individual inherits a copy of a gene with an expanded trinucleotide repeat (the mutant allele) from an affected parent.
There is a statistical relationship between an increased number of (CAG) repeats and an earlier age of onset but it is not possible to accurately predict the age of onset of the disease in an individual.
Very large trinucleotide repeat numbers are associated with early onset (Juvenile Huntington’s disease if under age 20). This is an uncommon disease and presents slightly differently to the adult disorder.
The rate of new mutation is not established. Lack of family history can be due to other factors such as non-paternity or early death of at-risk parent.
Diagnosis
Physical and psychological testing can determine if initial symptoms are present. Pre-symptomatic genetic testing is possible in adults but not undertaken in children below age of consent. A pre-symptomatic test is a life changing event and a very personal decision. Predictive testing is only available through a genetic service and involves several counselling sessions following an internationally agreed protocol.
Prenatal and pre-implantation genetic diagnosis is also available through specialist genetic services. DNA analysis may help in confirming or refuting a clinical diagnosis of Huntington’s disease.
Management and prognosis
Drug treatment for chorea and psychiatric symptoms can be helpful (see below).
Because Huntington’s disease is a condition that causes disability, practical aids and adaptations can be helpful, and early referral to Occupational Health and Social Services is recommended.
Nutrition management is important in the disease since weight loss is a common complication. Early referral to Speech and Language Therapy and Dietetics can help reduce this problem. Patients may have a large calorie requirement and high calorie dietary supplements are often used. In later stages of the disease, when swallowing is difficult and the risk of aspiration is great, consideration may be given to the use of parenteral feeding such as a PEG tube.
Death is usually due to the complications of disability, although many Huntington’s disease patients die of unassociated causes such as heart disease or cancer. There is also an increased suicide risk.
Drug Treatment
No treatment has yet been shown to slow down the progression of HD. However, current research suggests that this may be possible in the future. Despite the fact that a cure is not possible, symptoms can be reduced by drug treatments, although drug treatment is a small part of the management of the condition and can be limited due to an increased likelihood of side-effects in HD patients.
Chorea
This should only be treated if the symptom is problematic for an individual since drug side effects are common. Commonly used drugs are dopamine blockers such as sulpiride, risperidone and olanzapine. An alternative is the dopamine depleter tetrabenazine, but sedation can be severe.
Benzodiazepines are not generally useful because of tolerance, but can be useful in the short term, for treating sleep disturbance and to reduce chorea during medical procedures.
Depression
The treatment of depression in Huntington’s Disease is essentially the same as that of depression generally. SSRI are often the best choice. Use of tricyclics is limited because of side effects on cognition and mental state, but can be useful for neuropathic pain.
Hypertonicity
This may be due to the disease or can be a side-effect of neuroleptic drugs used to treat the condition. If neuroleptics are suspected as the cause of the hypertonicity, alternative drugs or dose reduction should be considered. Muscle relaxants such as baclofen and benzodiazepines are sometimes used, and if spasticity is focal, then injections of botulinum toxin may be helpful.
Episodic Dyscontrol Syndrome
The anticonvulsants sodium valproate and carbamazapine have been used to reduce the aggression due to Episodic Dyscontrol Syndrome. Aleternative drugs are low dose antipsychotics, and maximum dose SSRIs.
Information and contacts
Regional Contacts
The Northern Region’s Huntington’s Disease Service is run jointly by the Northern Genetics Service and the Cumbria, Northumberland Tyne and Wear NHS Foundation Trust based at Walkergate Park, Newcastle upon Tyne.
Useful websites
For both clinician and patients:
Huntington's Outreach Project for Education (HOPES)
