Huntington's Chorea / Huntington Disease
Physicians George Huntington (1872) and William Osler (1893) first described this hereditary form of chorea. Huntington Disease (HD) is a progressive disorder of motor, cognitive, and psychiatric disturbances.
The mean age of onset is 35 to 44 years (modified by repeat length, epigenetic influences, and possibly environmental influences) and the median survival time is 15 to 18 years after onset. Chorea, an involuntary movement disorder consisting of nonrepetitive, non-periodic jerking of limb, face, or trunk, is the major sign of the disease.
In the early stages, manifestations include subtle changes in coordination, minor involuntary movements, difficulty in mental planning, and often a depressed or irritable mood. In the next stage, chorea becomes more prominent with increasing difficulty with voluntary activity and worsening dysarthria and dysphagia. In late stages of HD, behavior problems are gradually lessened; motor disability becomes severe and the individual is often totally dependent, mute, and incontinent.
25% of individuals with HD have their first symptoms after age 50, some even after age 70, with a more benign course than typical. 5-10% of individuals with HD have juvenile HD with onset before age 21 years. Symptoms are similar but more severe, and seizures are common.
This disease occurs in 3-7 per 100,000 in populations of western European descent.
Criteria for diagnosing an affected individual generally include the following:
*Lack of a positive family history should not prevent a neurologist from considering this diagnosis. The asymptomatic father of an affected individual may have an intermediate allele, or either asymptomatic parent may have a reduced penetrance allele, or the disease may not have manifested itself in the parent yet (late onset).
Predictive testing is used for adults in the absence of definite symptoms of the disease. (It is recommended to confirm a mutation in a known affected relative to be sure it is HD in the family before providing predictive testing). The chance that an at-risk person is affected decreases with age.
A standard multidisciplinary protocol, such as the HDSA Testing Guidelines [http://www.hdny.org/genetic_testing_guidelines.htm], are highly recommended. In fact, many labs won't accept samples without using a similar protocol. They should include:
Predictive testing during childhood is consistently discouraged, but requests should be met with sensitive and understanding counseling. Arguments against this testing include taking away the child's right to decide whether or not they want to know; it raises the possibility of stigmatization within the family and in other social settings, and it could have serious educational and career implications. [See also the National Society of Genetic Counselors resolution on genetic testing of children and the American Society of Human Genetics and American College of Medical Genetics points to consider: ethical, legal, psychosocial implications of genetic testing in children and adolescents].
DNA banking (storing DNA) could be considered if there appear to be limitations to currently available testing for a specific family. Future improvements in testing methodologies may then be able to shed light on the recurrence risks and other issues.
Family planning The optimal time for determination of genetic risks and testing options is before a pregnancy has been conceived.
Prenatal testing can be performed for pregnancies at 50% risk by Chorionic villus sampling (CVS) or Amniocentesis. (The presence of an HD mutation in the family should be confirmed prior to achieving pregnancy.) This test is very rarely requested.
Pre-implantation Genetic Diagnosis is another option for those wanting to avoid passing on HD to the next generation. Diagnostic or exclusion testing could be performed on embryos after IVF, and only those either with a normal HD allele by diagnostic methods, or with a “close to zero” risk by exclusion testing, are implanted in the uterus.
“Exclusion testing” can be done prenatally by CVS or Amniocentesis, or Pre-implantation Genetic Diagnosis (PGD), using linkage analysis:
Ethical issues for Exclusion testing:
There is no cure for HD at this time. However, several areas of research are in the areas of neural and stem cell transplantation, apoptosis inhibitors, and inhibition of polyglutamine-induced protein aggregation.
Symptoms can be treated, including neuroleptics or benzodiazepines for chorea, and anti-parkinsonian agents for hypkinesia and rigidity, but L-dopa-containing compounds may increase chorea. Mental illness may be successfully treated by anti-depressants or anti-epileptic meds. There is no treatment for the cognitive impairment.
Supportive care with attention to nursing, diet, special equipment, and eligibility for state and federal benefits is very important for individuals with HD and their families. Local HD support groups can be extremely helpful.
Questions for students:
Lists testing centers and is an excellent resource for supporting patients and their families through testing, diagnosis and treatment.