Huntington Disease (HD) and Chorea

What is chorea?

In medical terms, chorea means involuntary movements of different areas of body that are random, purposeless, unpredictable, brief, and abrupt. When happening, they seem to spread from one body part to another.

What is Huntington disease or HD?

HD is the most common cause of genetic based chorea.  

What other conditions may look like chorea?

Tic, tremor, myoclonus, dyskinesia, and dystonia are some of those conditions.

What are different causes of chorea?

1. Structural causes: For example, stroke, demyelinating disease, or tumor.
2. Degenerative causes: Affecting basal ganglia or cerebellum.
3. Infectious: For example, Sydenham chorea, HIV disease, prion disease, viral encephalitis.
4. Autoimmune: For example, SLE, Sjogren syndrome, Behcet disease, celiac disease, antiphospholipid syndrome, autoimmune encephalitis.
5. Paraneoplastic: For example, associated with anti-Hu, anti-Ma, P/Q type VGCC, LGI1, CRMP-5, CASPR2 antibodies.
6. Metabolic and endocrine: Hyperthyroidism, hypernatremia, hyponatremia, hyperglycemia, hypomagnesemia, uremia, hypocalcemia, vitamin B12 or B1 def, liver failure, kernicterus.
7. Hematologic: Thrombocytopenia, polycythemia vera
8. Pharmacologic: Tardive dyskinesia
9. Miscellaneous: Hypoxic brain injury, carbon monoxide poisoning, chorea gravidarum.
10. Psychological: Functional disorder.

What drugs may cause chorea?

Many drugs are known to trigger chorea, especially in high doses. Following are some examples:

1. Dopamine agonists: Like levodopa.
2. Dopamine antagonists: Like anti-psychotic meds, or metoclopramide.
3. Epilepsy meds: Phenytoin, carbamazepine, lamotrigine, zonisamide, valproic acid, gabapentin.
4. Antidepressants: SSRIs, tricyclics.
5. Stimulants: Cocaine, amphetamine.
6. Others: Steroids, baclofen, methadone, digoxin, calcium channel blockers, oral contraceptives, fluoroquinolones.

 How is the diagnosis of chorea made?

It is made on clinical observation and examination of the patient.

How is the diagnosis of Huntington disease is made?

In some cases where there already is family history of HD, clinical exam is enough and further testing may not be needed. Testing on the other hand, may provide useful insight about its progression and prognosis. HD is definitively diagnosed by a gene test done on a blood sample.

What is the gene defect in HD?

HD is an autosomal dominant disorder. This means that if one parent has the disease, chances of a child having it is at least 50%. The abnormal gene is on chromosome 4. Like most of the genes, this gene or the code is for a protein, but the function of this protein is not fully understood. Having this gene results in degeneration of neurons of different areas of brain, especially in the basal ganglia. There is a DNA pattern called CAG repeats. For this gene, normal CAG repeat is 26 or less. Any higher number may result in minimal, mild, moderate or severe disease based upon the number of CAG repeats. Age of onset of disease may also depends upon the number of repeats. Individuals with 40-60 or more repeats have full blown disease, and with 60 or more repeats it may appear in childhood. For this reason, age of onset may vary from 2 to late 80s.

What are pros and cons of genetic testing for HD?

Any genetic test requires careful consideration of its risks and benefits—including the potential risks of undergoing the test itself, regardless of the result. For most genetic disorders, such as Huntington’s disease (HD), there is no specific treatment. The primary benefit of genetic testing is diagnostic confirmation, which in many cases may not significantly alter management. As noted above, testing may also help with prognostication.

Learning that one carries a disabling or fatal genetic condition can carry a substantial psychological burden and may increase the risk of depression, self-harm, or suicide. For asymptomatic family members, I generally discourage predictive genetic testing, as the disease may not manifest for many years or even decades. Knowing that one carries a disease-causing gene in the absence of symptoms can have a profound negative impact on psychological well-being.

In patients with early or mild symptoms, genetic testing may have greater value, particularly when there is no known family history. Genetic counseling is essential for anyone considering this type of testing. Genetic testing may also be valuable for couples with the disease or a family history of the condition when making decisions about future pregnancies. In such cases, prenatal genetic testing can be performed using amniotic fluid from the unborn child.

What are initial symptoms of HD?

Chorea or involuntary movements is the most typical initial symptom in adult populations. Younger patients may present with Parkinson disease like picture. As the disease progresses, more symptoms appear, including behavioral or psychiatric, and dementia. Chorea may be subtle in initial stages. It may lead to severe disability with inability to safely walk or function.

What if I have HD type clinical features but the gene test for HD is negative?

In that case, non-genetic causes must be explored. If that is not the case, there are many genetic disorders that share features of HD. Some examples are spinocerebellar ataxia or dentatorubral pallidolusysian atrophy, and some others. And then there are other genetic causes of chorea like neuroacanthocytosis.

How is HD treated?

There is no specific treatment to slow down, halt or reverse the process. Symptoms are managed by different meds, and some are as follows:

1. Chorea: Tetraabenazine (Xenazine), deutetrabenazine (Austedo), valbenazine (Ingrezza).
2. Behavioral symptoms: SSRIs and anti-psychotics.
3. Dementia: No specific med but memantine and donepezil can be tried.
4. Others: Valproic acid, carbamazepine, amantadine.

Where may I get more information about HD or chorea?

American Academy of Neurology

International Parkinson and Movement Disorder Society

Center for Disease Control