Huntington’s disease is an autosomal dominant neurodegenerative disorder (therefore each child of an affected parent has a 50% chance of developing the disease) due to an abnormal expansion of IT-15 gene on chromosome 4 which encodes for the protein huntingtin. Most people develop Huntington’s disease between 30-54 years old but it can manifest as early as 4 years old and as late as 80 years. Huntington’s disease is clinically characterized by a triad of motor, cognitive and psychiatric symptoms. Motor features include: impairment of involuntary (chorea) and voluntary movements; reduced manual dexterity, slurred speech, swallowing difficulties, balance problems and falls. It may also present with parkinsonism and dystonia in the young (termed the Westphal variant). Cognitive features are characterized initially by loss of speed and flexibility in thinking, but later become more global. Psychiatric features may include: depression (most common), mania, obsessive-compulsive disorder, irritability, anxiety, agitation, impulsivity, apathy, and social withdrawal.
What Causes Huntington’s Disease?
Huntington’s disease is caused by a faulty gene on chromosome 4. The gene, which produces a protein called Huntingtin(HAP-1), was discovered in 1993. In some way - which is not yet understood - the faulty gene leads to a damage of the nerve cells in areas of the brain, including the the basal ganglia and cerebral cortex. This leads to gradual physical, mental and emotional changes. Each person whose parent has Huntington’s disease is born with a 50-50 chance of inheriting the faulty gene. Anyone who inherits the faulty gene will, at some stage, develop the disease. A genetic test is available from Regional Genetic Clinics throughout the country. This test will usually be able to show whether someone has inherited the faulty gene, but it will not indicate the age at which they will develop the disease.
The clinical features of Huntington disease (HD) include a movement disorder, a cognitive disorder, and a behavioral disorder. Patients may present with one or all disorders in varying degrees.
(derived from the Greek word meaning to dance) is the most common movement disorder seen in HD.
- Initially, mild chorea may pass for fidgetiness. Severe chorea may appear as uncontrollable flailing of the extremities (ie, ballism), which interferes with function.
- As the disease progresses, chorea coexists with and gradually is replaced by dystonia and parkinsonian features, such as bradykinesia, rigidity, and postural instability, which are usually more disabling than the choreic syndrome per se.
- In advanced disease, patients develop an akinetic-rigid syndrome, with minimal or no chorea. Other late features are spasticity, clonus, and extensor plantar responses.
- Dysarthria and dysphagia are common. Abnormal eye movements may be seen early in the disease. Other movement disorders, such as tics and myoclonus, may be seen in patients with HD.
- Juvenile HD (Westphal variant), defined as having an age of onset of younger than 20 years, is characterized by parkinsonian features, dystonia, long-tract signs, dementia, epilepsy, and mild or even absent chorea.
is characteristic of HD, but the rate of progression among individual patients can vary considerably. Dementia and the psychiatric features of HD are perhaps the earliest and most important indicators of functional impairment.
- The dementia syndrome associated with HD includes early onset behavioral changes, such as irritability, untidiness, and loss of interest. Slowing of cognition, impairment of intellectual function, and memory disturbances are seen later. This pattern corresponds well to the syndrome of subcortical dementia, and it has been suggested to reflect dysfunction of frontal-subcortical neuronal circuitry. (The so-called cortical dementias primarily involve the cerebral cortex and are associated with aphasia, agnosia, apraxia, and severe amnesia.)
- Early stages of HD are characterized by deficits in short-term memory, followed by motor dysfunction and a variety of cognitive changes in the intermediate stages of dementia. These deficits include diminished verbal fluency, problems with attention, executive function, visuospatial processing, and abstract reasoning. Language skills become affected in the final stages of the illness, resulting in a marked word-retrieval deficit.
The behavioral disorder of HD is represented most commonly by affective illness.
- Depression is more prevalent, with a small percentage of patients experiencing episodic bouts of mania characteristic of bipolar disorder.
- Patients with HD and persons at risk for HD may have an increased rate of suicide.
- Patients with HD also can develop psychosis, obsessive-compulsive symptoms, sexual and sleep disorders, and changes in personality.
Is there any treatment?
Huntington’s disease is incurable. There is no current treatment that can reverse its progression or slow it down.
Scientists at UT Southwestern Medical Center found that man-made molecules that selectively interfere with protein production can stop human cells from making the abnormal molecules that cause Huntington’s disease. They added that “The work has been done only in cultured cells, and it will take years before the effectiveness of this process can be tested in patients.”
Physicians prescribe a number of medications to help control emotional and movement problems associated with HD. In August 2008 the U.S. Food and Drug Administration approved tetrabenazine to treat Huntington’s chorea (the involuntary writhing movements), making it the first drug approved for use in the United States to treat the disease. Most drugs used to treat the symptoms of HD have side effects such as fatigue, restlessness, or hyperexcitability. It is extremely important for people with HD to maintain physical fitness as much as possible, as individuals who exercise and keep active tend to do better than those who do not.
What is the prognosis?
At this time, there is no way to stop or reverse the course of HD. Now that the HD gene has been located, investigators are continuing to study the HD gene with an eye toward understanding how it causes disease in the human body.
What research is being done?
Scientific investigations using electronic and other technologies enable scientists to see what the defective gene does to various structures in the brain and how it affects the body’s chemistry and metabolism. Laboratory animals are being bred in the hope of duplicating the clinical features of HD so that researchers can learn more about the symptoms and progression of HD. Investigators are implanting fetal tissue in rodents and nonhuman primates with the hope of understanding, restoring, or replacing functions typically lost by neuronal degeneration in individuals with HD. Related areas of investigation include excitotoxicity (over-stimulation of cells by natural chemicals found in the brain), defective energy metabolism (a defect in the mitochondria), oxidative stress (normal metabolic activity in the brain that produces toxic compounds called free radicals), tropic factors (natural chemical substances found in the human body that may protect against cell death).