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Back in 1872 George Huntington, a young physician, published the first description of a disease that would one day come to bare his name. Huntington's is a progressive brain disorder which is caused by a "single defective gene of Chromosome 4", one of the 23 human chromosomes that a person's whole genetic code is on. This is a fatal genetic disorder that begins to progressively breakdown the nerve cells in the brain, it will deteriote a person's ability to do physical movements as well slow down their mental abilities during their most prime years.

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Huntington's disease (HD) is a fatal genetic disorder that causes the progressive breakdown of nerve cells in the brain. It deteriorates a person's physical and mental abilities during their prime working years and has no cure. HD is known as the quintessential family disease because every child of a parent with HD has a 50/50 chance of carrying the faulty gene. Today, there are approximately 30,000 symptomatic Americans and more than 200,000 at-risk of inheriting the disease.

Many describe the symptoms of HD as having ALS, Parkinson's and Alzheimer's - simultaneously.

Symptoms usually appear between the ages of 30 to 50, and worsen over a 10 to 25 year period. Ultimately, the weakened individual succumbs to pneumonia, heart failure or other complications. Everyone has the gene that causes HD, but only those that inherit the expansion of the gene will develop HD and perhaps pass it on to each of their children. Every person who inherits the expanded HD gene will eventually develop the disease. Over time, HD affects the individual's ability to reason, walk and speak.

Symptoms Include:

Personality changes, mood swings & depression

Forgetfulness & impaired judgment

Unsteady gait & involuntary movements (chorea)

Slurred speech, difficulty in swallowing & significant weight loss

Stages of HD

Although symptoms of HD vary from person to person, even within the same family, the progression of the disease can be roughly divided into three stages.

Early stage HD usually includes subtle changes in coordination, perhaps some involuntary movements (chorea), difficulty thinking through problems and often a depressed or irritable mood. Medications are often effective in treating depression or other emotional problems. The effects of the disease may make the person less able to work at their customary level and less functional in their regular activities at home.

In the middle stage, the movement disorder may become more of a problem. Medication for chorea may be considered to provide relief from involuntary movements. Occupational and physical therapists may be needed to help maintain control of voluntary movements and to deal with changes in thinking and reasoning abilities. Diminished speech and difficulty swallowing may require help from a speech language pathologist. Ordinary activities will become harder to do.

In the late stage, the person with HD is totally dependent on others for their care. Choking becomes a major concern. Chorea may be severe or it may cease. At this stage, the person with HD can no longer walk and will be unable to speak. However, he or she is generally still able to comprehend language and retains an awareness of family and friends. When a person with HD dies, it is typically from complications of the disease, such as choking or infection and not from the disease itself.

In all stages of HD, weight loss can be an important complication that can correspond with worsening symptoms and should be countered by adjusting the diet and maintaining appetite.

The Scope of HD

Approximately 30,000 Americans have HD, but the devastating effects of the disease touch many more. Within a family, multiple generations may have inherited the disease. Those at-risk may experience tremendous stress from the uncertainty and sense of responsibility. In the community, lack of knowledge about HD may keep friends and neighbors from offering social and emotional support to the family, fostering unnecessary isolation. The Huntington's Disease Society of America has a nationwide network that provides support and referrals for individuals with HD and their families.

HD affects both sexes and all races and ethnic groups around the world.

Who Is At Risk

Every child of a parent with HD has a 50/50 chance of inheriting the expanded gene that causes the disease. If the child has not inherited this expanded gene, he or she will never develop the disease and cannot pass it on to their children.

Genetic Testing & Family Planning

People at-risk for the disease face a difficult choice about genetic testing for HD, given the current absence of an effective treatment or cure. Many people see no benefit in knowing that they will someday develop the disease. Others want an end to uncertainty so that they can make informed choices about the future. The decision whether to test or not is intensely personal and there is no "right" answer.

The Huntington's Disease Society of America recommends that at risk individuals who are considering genetic testing do so at a genetic testing center that follows the HDSA guidelines. Testing procedures at these centers involves sessions with professionals who are knowledgeable about HD and the local services available. It may take several weeks to receive the results once the genetic test is complete.

Genetic testing for children is typically prohibited before the age of 18, as the child may not understand the full implications of testing and may be vulnerable to pressure from others. However, a child under the age of 18 may be tested to confirm a diagnosis of juvenile onset HD after a thorough neurological exam.

Prenatal Testing

For families wishing to have a child who does not have the gene that causes HD, there are a few options. Pre-genetic diagnostic (PGD) testing can be used with In Vitro Fertilization (IVF) to make sure that any fertilized egg implanted does not have the abnormal gene. This can be done without informing the at-risk patient whether or not they have the gene that causes HD. If a woman is already pregnant, she can receive testing for the fetus with a chorionic villus biopsy at 10-11 weeks or via amniocentesis at 14-18 weeks. CLICK HERE TO FIND TESTING CENTERS NEAR YOU.

JHD Overview

In approximately 10% of cases, HD affects children or adolescents. The symptoms of Juvenile HD (JHD) are somewhat different than adult onset HD and may include stiff or awkward walking, increased clumsiness or changes in speech. The ability to learn new information may decline and the child may lose skills they previous had. JHD typically progresses more rapidly than adult onset HD. CLICK HERE FOR MORE INFORMATION

An End To HD?

In 1993, researchers identified the gene that causes HD. Since then, research has moved quickly towards developing treatments and, ultimately, a cure. HDSA supports the goals of clinical and basic research at leading research facilities globally. Clinical and observational trials are an important way you can help to sustain the momentum of HD research and move potential new therapies through the approval process. Visit the Research section of the HDSA website for more information and to find a trial in your area. There are opportunities for all HD family members - gene positive, at-risk, gene negative, and caregivers - to participate.

Where to find help?

With HDSA, no one fights alone. HDSA has developed a nationwide network that includes Chapters, Affiliates, HDSA Centers of Excellence, Support Groups and Social Workers that are ready to assist you with resources in your area.

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Huntington's disease (HD) is a fatal genetic disorder that causes the progressive breakdown of nerve cells in the brain. It deteriorates a person's physical and mental abilities during their prime working years and has no cure. HD is known as the quintessential family disease because every child of a parent with HD has a 50/50 chance of carrying the faulty gene.

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JHD is the form of HD that affects children and teenagers. This is caused by a mutation in the huntingtin gene, this is what we call "CAG repeat expansion." JHD involves a more rapid progression rate than the adult onset. The earlier it happens the faster the disease progresses. JHD death occurs within 10 years compared to the 10-25 years the adults have.

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Juvenile Onset Huntington Disease (JHD) is a form of Huntington disease (HD) that affects children and teenagers. Huntington's disease is a hereditary neurodegenerative disorder that is characterized by progressively worsening motor, cognitive, behavioral, and psychiatric symptoms. JHD is caused by a mutation of the huntingtin gene called a "CAG repeat expansion". The mutation results in gradual neuronal degeneration in the basal ganglia of the brain, which is responsible for coordination of movements, thoughts, and emotions. As JHD progresses, other regions of the brain undergo neuronal degeneration with diffuse and severe brain atrophy that is comparable to late stage Alzheimer disease.

Symptoms

Presentation of JHD includes changes in personality, coordination, behavior, speech or ability to learn. Physical changes include rigidity, leg stiffness, clumsiness, slowness of movement, tremors or myoclonus. In comparison with adult HD, seizures and rigidity are common, and chorea is uncommon.

Predisposition and typical initial symptoms of Juvenile Onset HD include:

Positive family history of HD, usually in the father

Stiffness of the legs

Clumsiness of arms and legs

Decline in cognitive function

Changes in behavior

Seizures

Changes in oral motor function

Chorea in an adolescent

Behavioral disturbances

Onset and Progression

JHD usually has a more rapid progression rate than adult onset HD; the earlier the onset, the faster JHD progresses. Death often occurs within 10 years of JHD onset, as opposed to 10-25 years in adult onset HD.

Treatment

There is no cure or treatment to stop, slow or reverse the progression of JHD. Medications may be prescribed to manage symptoms. A child psychiatrist or behavior management specialist may address behavior disorders. A speech language pathologist may evaluate communication and swallowing problems. A nutritionist may be consulted to address nutritional needs as the disease progresses. Assistive devices such as wheelchairs, helmets, and communication boards may be used for safety, and to improve quality of life.

It is suggested that you contact your closest HDSA Center of Excellence if you have reason to suspect a case of JHD.

Social Security's Compassionate Allowance
Designation for Juvenile Onset HD (JHD)

Social Security has an obligation to provide benefits quickly to applicants whose medical conditions are so serious that their conditions obviously meet disability standards. Compassionate Allowances are a way of quickly identifying diseases and other medical conditions that invariably qualify under the statutory standard for disability. The Compassionate Allowances program fast-tracks disability decisions to ensure that Americans with the most serious disabilities receive their benefit decisions within days instead of months or years.

Suggested Medical Evidence of Record for Evaluation
A diagnosis of JHD, as well as clinical information documenting neurological or cognitive changes is required to meet the Compassionate Allowance listing.

The preferable sources of this information are the clinical records from the treating primary physician, neurologist, or psychiatrist including:

Treating physician records documenting progression of motor, cognitive, and psychiatric symptoms, family history, and abnormal neurological exam findings consistent with juvenile onset HD

Laboratory testing showing a fully-penetrant CAG repeat expansion in the HD gene (>39 CAG repeats).

Brain imaging providing supporting evidence

Psychological or psychiatric reports including neurocognitive testing

School records providing supporting evidence.

CLICK HERE FOR MORE INFORMATION ON SOCIAL SECURITY'S COMPASSIONATE ALLOWANCES.
Further Information & Assistance

To learn more, click on the links below to download PDF versions of informative and in-depth HDSA publications. To find HDSA resources in your area, CLICK HERE. To speak with someone about JHD contact our Helpline at 800-345-HDSA

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Juvenile Onset Huntington Disease (JHD) is a form of Huntington disease (HD) that affects children and teenagers. Huntington's disease is a hereditary neurodegenerative disorder that is characterized by progressively worsening motor, cognitive, behavioral, and psychiatric symptoms. JHD is caused by a mutation of the huntingtin gene called a "CAG repeat expansion".

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Huntington's is the most commonly inherited neurodegenerative disease dominantly inherited. It is characterized by the excess of motor movements and neuropsychological deficits (Harper 2002; Lund 1860). The fact that the disease is dominant means that if anyone inherits it from a parent will eventually develop the disease themselves. If the disease is passed down from the father to child, not the mother, the disease will begin to show in earlier stages of life; this is know as anticipation. If the parent has the gene but does not pass it down to the chid, the gene will not be passed down to their offspring.

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A Brief History of Huntington's Disease

Huntington's disease (HD) is named after George Huntington, who described it among residents of East Hampton, Long Island in 1872. It is a hereditary neurodegenerative disease. In 1993, a collaborative group of investigators discovered the gene that causes HD. As a result of this discovery it is now possible to diagnose HD with blood or tissue samples.

HD is caused by mutation in a gene located on chromosome 4. This gene is found in every human being, and contains a CAG repeat sequence. We have not yet discovered the gene's normal function. In a case of HD, the gene contains an abnormally large number of CAG repeats. The larger the number of triplet repeats, generally speaking, the earlier in life one will develop HD. Furthermore, when the gene is passed from father to child (but not when passed from mother to child) the gene may lengthen even more, resulting in an earlier age of onset for the disease. This phenomenon is known as .

Genes for diseases can be either dominant or recessive. The gene for HD is dominant. Each child of an affected parent has a 50/50 chance of getting the mutant gene, and therefore has a 50% chance of inheriting the disease. On the other hand, if people with a parent suffering from HD do not inherit the mutant gene, they cannot pass it on to anyone else.

Important Information About HD Testing

It is important to understand that while people are born with the mutated gene for HD, in most cases they will not develop the symptoms until later in life. Therefore someone can be without symptoms or presymptomatic for a number of years. In the past, there was no way to test for the abnormal gene, but now a blood test can determine whether or not an individual carries the gene for HD. This test can be used in cases of suspected HD, to confirm the diagnosis, or it can be used as a predictive test in individuals who are at risk for HD. People who are at risk may want to undergo predictive testing in order to put their minds at ease, to plan for their medical needs, or prior to having children. The decision to have such a test is a momentous one and should not be taken lightly. Most centers that do predictive testing, including ours, require a period of counseling before and after the test.

What Are the Characteristics of HD?

Onset is usually in mid-life, but can occur any time from childhood to old age. The initial signs of this disorder may be subtle. HD is characterized by a movement disorder, dementia, and psychiatric disturbances. Additional characteristics of HD include personality changes, weight loss (probably from a combination of difficulty eating, and calories burned by the involuntary movements), difficulty swallowing, and hard-to-understand speech.

Once an individual develops signs of HD the course of the disease can last anywhere from ten to thirty years. Typically, the course of HD can be roughly divided into three stages.

Early Stage:
In this stage patients can still perform most of their usual activities. They may still be working and may still be able to drive. Involuntary movements are mild and infrequent, speech is still clear, and dementia, if present at all, is mild.

Middle Stage:
At this stage patients are more disabled and may need assistance with some of their activities of daily living. Falls, weight loss, and swallowing difficulties may become a problem. Dementia is more obvious to the casual observer. Involuntary movements are more pronounced.

Late Stage:
Patients entering this stage of the disease require almost total care and may reside in hospitals or nursing homes, although some remain at home. They may no longer be able to walk or speak. They may be more rigid now and show fewer involuntary movements. Individuals in this stage may or may not be able to swallow food. At this stage most patients do not seem to suffer much as they are apparently unaware of their surroundings. When the patient passes away, the cause of death is usually related to malnutrition, pneumonia, or heart failure.

What Treatments Are Available?

At this time, there is no cure for HD. Researchers are working on a number of treatments that may slow down the progression of the disease. There are a number of interventions available today that improve the quality of life for HD sufferers. In the early and middle stages of the disease, medications can be given in small doses to HD patients to help suppress the involuntary movements. Depression and other psychiatric conditions in people with HD can be quite effectively treated. Proper nutrition, exercise and precautions in the home can help minimize many of the potential consequences of HD such as weight loss, falls, and choking on food. Finally contact with other HD sufferers, family members, and care-providers can be a vital source of support for HD patients and their families.

People with HD should discuss their concerns and wishes about treatments/interventions (e.g. feeding tubes, resuscitation requests) and autopsies with their families and doctors while they are still able to speak for themselves.

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johns hopkins department of psychiatry and behavioral sciences

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huntington's disease center at johns hopkins

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About Huntington's Disease and Related Disorders at The Johns Hopkins Hospital

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Huntington's disease (HD) is named after George Huntington, who described it among residents of East Hampton, Long Island in 1872. It is a hereditary neurodegenerative disease. In 1993, a collaborative group of investigators discovered the gene that causes HD. As a result of this discovery it is now possible to diagnose HD with blood or tissue samples.

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1. Symptoms of Huntington's usually begin to develop and show between the ages of 30-50; in some cases they can begin to appear as early as the age of 2 or as late as the age of 80.

2. The symptom that is typically shown as sign of Huntington's would be the uncontrollable movement of the legs, arms, face, head, and the upper body.

3. With the decline in motor skills there is also the "decline of thinking and reasoning skills, including memory, concentration, judgment and ability to plan and organize (alz.org).

4. Another symptom is the alterations in moods, especially depression, anxiety, anger and irritability. As well there is the development of obsessive-compulsive behavior, which leads the person to the same question or activity they were doing over and over again.

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Currently there is no cure for the disease. there is no way to slow down or stop the brain changes it brings. However, there is treatment that is focused on managing the symptoms it brings. There is strategies that a group of international experts recommend doing when exposed to the most troubling of the symptoms:
Chorea (involuntary movements): Some experts believe beginning treatment with an atypical antipsychotic drug, such as olanzapine, is best. Others start with another type of drug recently approved by the U.S. Food and Drug Administration (FDA) specifically for Huntington’s, called tetrabenazine.
Irritability: For severe anger and threatening behavior, experts agree that an atypical antipsychotic drug is the preferred approach. For less severe, nonthreatening irritability, experts recommend first trying a selective serotonin reuptake inhibitor (SSRI), which is a type of antidepressants.
Obsessive-compulsive thoughts and actions: Experts also recommend SSRIs as the standard treatment for these symptoms.

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Huntington's Disease | Signs, Symptoms, & Diagnosis

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Huntington's disease is a type of dementia, related to Alzheimer's disease. Learn about Huntington's disease causes, genetic aspects, signs and symptoms and treatment and get support resources.

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The disease is caused by a mutation in a gene that is located in chromosome 4, in the region of the first exon of the gene.  This gene is found in every human, it has the CAG repeat sequence. the gene's normal function has yet to be discovered .  When exposed to the disease the gene will contain an abnormally large number of the CAG repeats, the large the number greater the chance the disease will develop earlier in a carrier's life.

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The nature of the genetic defect in the HD gene explains many of the genetic features of the disorder, including the variability in age at onset, the tendency for juvenile disease to be inherited from fathers, and the sporadic appearance of new mutations to HD. The gene is located on chromosome 4p16.3 and the genetic alteration which causes the disease is an increase of the number of repetitions of three nucleic acids (C, A, and G) in the coding region of the first exon of the HD gene. This CAG "triplet" is normally repeated about 20 times, but an approximate doubling in the number of repeats to 40 or more results in the expression of the disease., shows the distribution of normal repeats, from 10 to 26, and of HD repeats, from 40 to about 80. Repeats between 27 and 35 can be meiotically unstable in paternal transmission. Descendents of men with repeats in this range have been known to inherit disease-associated repeats of 40 or more. In a sample of 1260 persons ascertained from HD families studied in the New England Huntington's Disease Research Center Without Walls (Boston, MA), repeats between 27 and 35, represented about 3.2% of all repeats. Because few of these repeats have been observed, and their frequency in a non-HD sample has not been adequately established, the frequency with which these expansions occur is difficult to estimate. An estimates of 6% has been offered., Repeats between 36 and 39 are also rare (2.7% in this series), and are associated with reduced penetrance, whereby some with repeats in this range develop HD and others do not. Again the estimates of penetrance are poor because of the small numbers of observations and because most of those observed are among persons who develop HD whereas those who do not manifest symptoms may escape detection.

Modification of disease expression by repeat size

HD is a disorder with highly variable clinical expression, as exemplified by the wide variation in onset age. The strong inverse relationship between age at onset and number of CAG repeats is unequivocal. For the 1165 HD cases depicted in , the correlation between repeat size and onset age is r = −0.81 and accounts for about 66% of the variance in onset age. Much of the strength of this correlation derives from the small sample of persons (about 5% of the sample) who have very large repeat sizes and very young onset ages. Thus, although the correlation between repeat size and onset age is strong, it is widely acknowledged that the repeat size is a poor predictor of onset age. The predictive shortcomings can be appreciated by examining the range of onset age for persons with a particular number of repeats. For example, persons represented in with 44 CAG repeats exhibit onset ages as young as 31 and as old as 66 years of age. The 34-year span in onset demonstrates not only the poor predictive power for onset of the repeat size, but also the substantial variation in onset age that is not explained by the HD repeat. It is important therefore to recognize that predictive HD gene testing will not reveal meaningful information about when an individual is likely to develop symptoms of the illness and this should be made clear in pretest counseling.

Sex of the affected parent

Merritt et al. first observed that a disproportionate number of cases with onset before the age of 21 had inherited the HD gene from affected fathers. The observation of earlier ages at onset in successive generations, termed "anticipation", is seen in several of the trinucleotide repeat disorders. Meiotic instability of the HD repeat in paternal transmission explains the observation of anticipation in HD. Although meiotic instability may occur in both maternal and paternal transmission, in paternal transmission there is a propensity toward larger repeat expansion. For maternal transmission, nearly equal numbers of expansions and contractions are seen, and the shifts are small, ranging from 1 to 3 repeats. The observation that paternally transmitted repeats are prone to large increases in size,, explains why most juvenile onset HD is inherited through the male germline.

Genetic modifiers of HD expression

Significant familial aggregation for the age at onset in HD has been reported., Using onset ages adjusted for the size of the HD repeat mutation, pairs of affected siblings were found to have remarkably similar onset ages independent of the size of the HD repeat. Estimates of heritability of onset age after adjustment for the repeat size range from 56% to 65%., Thus 56% to 65% of the variation in onset age, which is not attributable to the repeat size, can be attributed to modifier genes. In addition to the familial aggregation in onset age, Djoussé et al. also found that the size of the normal repeat influenced onset age. Although the effect is small and explains about 1% of the variation in onset age, it is noteworthy that in contrast to the HD repeat itself, larger normal repeats are associated with later onset.

The evidence for strong heritability for the repeat-adjusted onset age led to a genome scan to identify loci that may influence the expression of HD. Suggestive evidence for linkage was found at 4p16 (LOD = 1.93), 6p21-23 (LOD = 2.29), and 6q24-26 (LOD = 2.28), which may be useful for the investigation of genes that modify age at onset of HD. Li et al. noted evidence for a genetic modifier at the HD locus itself. The further investigation of genes that modify disease expression may lead to novel therapeutic interventions to delay the onset of disease.

The cloning of the HD gene in 1993 led to important advances in the understanding of the mechanisms for gene expression. One important aspect of HD, which is not addressed in this chapter, is the use of transgenic mice for study of therapeutic intervention and for understanding of the pathogenesis of the disease. Fortunately these have recently been described in other reviews. ⁻

Genetic test utilization

Cost and accuracy.

Genetic testing is both cost-efficient and diagnostically precise. Nevertheless, it is important to establish that HD is present in the family via genetic test confirmation because some other illnesses may be misdiagnosed as HD. Unfortunately, in some instances there are no living relatives for whom such a test can be performed. The expense of the laboratory procedure for DNA testing is $250 to $300.

Confirmation of diagnosis.

Confirmation genetic testing is appropriate for persons with a suspected diagnosis of HD. Such confirmations are particularly helpful when there is no known family history because of the early death of a parent, adoption, non-paternity or a possible new mutation. Recent studies suggest that the frequency of new mutation to HD may be substantially higher than previously suspected. Almqvist et al. estimate that 24% of new diagnoses of HD represent individuals who have no family history of the illness. These studies suggest that the mutation rate may be as high as 6.9 per million, which is double previous estimates. Thus the use of HD testing is valuable in the absence of family history. Importantly, the confirmation of disease assists in establishing proper care of the individual and in revealing genetic risk for relatives. The recognition of de novo HD by genetic testing often brings with it implications for the children, siblings, and other relatives of the individual with the illness. It is important to arrange for this information to be imparted to those relatives now recognized to be at risk for the disease.

In some instances the "confirmation" genetic test does not apply. When the individual has an unequivocal family history of HD, but equivocal symptoms and a clinical diagnosis of HD cannot be made, the test is more appropriately considered "presymptomatic." Although the genetic test can reveal whether or not a person carries the HD gene, it cannot establish the presence of symptoms of disease. Persons at risk for HD may develop other diseases, which should not be overlooked by a gene-positive test result.

Presymptomatic testing of persons at risk.

The presymptomatic direct genetic test includes counseling, neurological examination, and the DNA assay and may cost ∼$1000. Many persons choose to pay out of pocket to maintain a higher degree of confidentiality, particularly in light of concerns for access to health insurance, and potential for employment discrimination. Consequently, confidentiality is a primary concern for testing and many test programs implement additional procedure protocols for protection of medical records and storage of test results. In some instances individuals may seek testing anonymously or by using a pseudonym, with the view that confidentiality may be more highly guarded in this scenario. Anonymous tests raises additional concerns because there may be no means to contact the individual if a false address and telephone number are provided. Furthermore, no legal document of the test result exists and the individual may need to seek a second test under his or her legal name to document proof of a gene-negative result. Finally, next of kin cannot access the information if the individual dies, nor can a valid record be shared with medical professionals. The possible disadvantages of anonymous testing should be discussed with those who request it.

The primary consideration in presymptomatic test counseling is to increase the opportunity for the individual to make an informed choice concerning the risks, benefits and alternatives to testing. Individuals may seek testing with either an inflated or deflated view of their genetic risk. Some believe treatment options are more successful than they have proven to be to date. Some individuals are not informed about options other than testing. Finally, some individuals enter the testing protocol with the view that they are obliged to be tested or that if everyone at risk for HD were tested and all those proven to be gene-positive opted not to have children, the disease could be eliminated in a single generation. Unfortunately, the relatively substantial mutation rate to HD demonstrates that although testing may reduce the prevalence of the disease it will never eliminate it altogether.

The consensus among HD testing programs is that counseling information is delivered in two sessions, with the blood sample drawn on the second visit. This practice permits the individual to assimilate information about the test, and to fully consider the implications of testing before the decision to test is made. Once blood is drawn, there appears to be an increased commitment to following through with a test that has been ordered. Thus by drawing blood at the second visit, the individual is given the opportunity to change his or her mind. In our program, about one-third of those seen do not return for a second visit.

The individual is strongly encouraged to bring a friend or, if married, the spouse, to the counseling sessions. This companion offers a second perspective for interpreting the information about genetic risk, intermediate repeats and other complex factors important to making an informed choice. The companion gives the individual someone to talk to about this important decision. Further, this individual may provide an additional emotional support resource after the test.

Circumstances of concern for presymptomatic HD testing.

Some test circumstances are recognized to be associated with risk for adverse reactions. Occasionally, individuals request testing with a substantial investment in finding that they are not gene carriers. For example, an at-risk individual who seeks testing after becoming engaged to be married but who has not informed the fiancé of his or her risk status may not fully acknowledge the potential adverse consequences of a gene-positive test result. In these instances, there is a possibility for a heightened negative reaction from persons who are influenced by the results of the test, but may feel that critical information was withheld or hidden from them. We encourage individuals who are directly influenced by the test outcome to participate in test counseling.

Persons who have only recently learned that they are at risk for inheriting HD are a second special consideration in testing. This may occur when a parent is newly diagnosed in the absence of a family history, when an ancestor died young of other causes, or when divorce has caused the presence of the disease to be hidden from the family. Some at-risk individuals who grow up with a gradually increasing awareness of their risk develop an acceptance of the presence of the HD threat and testing can be scheduled at a time when other pressures are minimal. Adults who learn of their HD risk unexpectedly may find the sudden introduction of the threat of a severely disabling and ultimately fatal illness unbearable. The prospect of the illness can be overwhelmingly frightening and the desire to return to "the way things were" may compel them to seek testing immediately, regardless of the consequences or of concurrent events in their lives. This may be magnified when they already have children and the worry for their well-being can be paramount in the desire to remove the risk immediately. It is advisable that persons who have recently discovering their HD risk proceed cautiously when contemplating an HD test. When the desire to make the threat "go away" is so compelling that the individual cannot imagine or plan for the possible gene-positive result, he or she may be entering the test unprepared for its outcome. Because there is no medical urgency for intervention, it is possible for individuals to take advantage of the time it takes to adjust to and assimilate information in evaluating the available testing options, including the option to postpone the test or to not be tested.

Contraindications for genetic testing.

For adult-onset diseases such as HD, genetic testing of children is rarely considered appropriate, and some have argued that appropriate informed consent is not possible for minors. Many intelligent and insightful individuals at risk for HD opt never to be tested after a careful consideration of its risks and benefits. It is widely accepted that minors be given the opportunity to grow up, learn about the associated risks and benefits for themselves and make their own choice for or against testing. The testing of minors takes that choice away from them. Furthermore, the decision for testing today is in the context of limited treatment options. If the child is found to be a gene carrier, the emotional burden on the parent may also produce an adverse impact on the psychological well-being of the child. If a treatment is found in the next 10 or 20 years, minors who may not develop the disease for 30 or 40 years might unnecessarily experience life-changing and irreversible trauma. Testing for minors is to be avoided.

In some instances, persons may be in litigation for divorce, child custody, or criminal complaints. Although a gene-negative test result may be viewed as providing an advantageous position for these circumstances, it is important that the individual also consider the possible negative consequences of a gene-positive test. It may be necessary to assist adults who are in litigation and do not wish to be tested to prevent such tests from being mandated. Adults should not be tested against their wishes or if they (or appropriate family members) cannot provide consent due to psychiatric, cognitive, or other impairment.,

Prenatal testing.

Prenatal testing is not frequently requested for persons at risk for HD. About one-half of 1% of all HD tests involve a prenatal test. One apparent reason for the low frequency of prenatal testing is that many at-risk individuals seek predictive testing before becoming pregnant. The majority of those who test gene-positive opt not to have children rather than undergo prenatal testing. Prenatal test counseling follows a similar course to that defined for presymptomatic testing, but there are additional concerns for this procedure.

Unfortunately, many of those who seek prenatal testing are already pregnant when they contact the testing program. Because these individuals will not have undergone presymptomatic testing they request simultaneous presymptomatic and prenatal testing. When both the parent and the fetus are found to be HD gene carriers, the emotional impact is very profound. When an individual learns that he or she is a gene carrier and shortly thereafter learns that their unborn child is as well, the despair can challenge the emotional stability of both members of the couple. Intense grieving may occur with the loss of the anticipated healthy baby but also the loss of one's prospect for a healthy life. Unfortunately, the time constraint imposed for prenatal testing means that there is little time to prepare couples for the potential adversities that they may encounter. Consequently, prenatal testing may be the most challenging HD test situation.

A second concern is raised when persons are uncertain about their views on the termination of a pregnancy. When a couple chooses not to terminate the pregnancy after learning that the fetus is an HD gene carrier, there may be significant implications for the unborn child later in life. These concerns may include emotional burdens already alluded to but also possible health insurance or career discrimination that is difficult to anticipate. Couples who are uncertain about terminating the pregnancy may want to consider whether prenatal testing is a wise choice.

Preimplantation genetic diagnosis.

The development of the technology to perform Preimplantation Genetic Diagnosis (PDG) offers a new option for couples seeking to have children who are known to be gene-negative and avoids ethical issues associated with terminating a pregnancy. Most often PGD tests are performed on single cells biopsied at the eight-cell embryo (day 3 of development). The genetic analysis for monogenic disorders such as HD takes advantage of PCR to amplify the DNA and for detection of the repeat sizes for each chromosome. The main concern for PCR in single-cell amplification is for allele drop-out or for one of the two chromosomes to not amplify. Eggs are harvested, fertilized in vitro, tested, and those testing gene-negative are implanted. The main impediments to PGD are its expense, which can run $14,000 and the low efficiency of in vitro fertilization (IVF), with only 20% to 30% of couples achieving pregnancy per IVF cycle. Pickering et al. report their experience in the first 100 PDG cycles performed at the Guy's and St. Thomas' Center in London. The overall pregnancy rate was 24% per cycle started, 29% per egg collection, 38% per transfer, and 40% per couple treated. Thus the success rate, even among experienced programs, does not lead to the majority of couples achieving their goal. Nevertheless, this option is known within the lay community and should be considered for some couples.

Some programs offer PDG for couples who do not wish to undergo HD presymptomatic testing. In this circumstance, parental gene status is not revealed to the parent during the protocol.

Genetic test protocols for Huntington's disease

The goals of counseling are: (1) to inform the individual of his or her options about testing or other alternatives, depending upon personal circumstances, (2) to ensure that the individual is aware of the risks and possible adverse consequences of his or her specific testing circumstances, and (3) to inform the individual of the limitations and level of accuracy of the procedure. Counseling does not try to exclude or discourage persons but tries to insure that the individual is making an informed choice. The protocol used in our New England HD testing program includes telephone intake, two counseling visits, a neurological examination, and in-person delivery of test results.

Information about the family history of the person is gathered to confirm the presence of HD in the family and also to assess the current risk status of the individual. Cases that warrant the inclusion of other family members in the testing process should be identified and options for how to include those people should be discussed. This includes any tests which will reveal risk information about another individual. Occasionally individuals seek testing when the genetic status of their parent is unknown. This may happen when the parent died before the appearance of symptoms, or because the parent has not yet reached the age of disease onset. A positive result in this case would indicate that the parent is a gene carrier and would increase the risk for all descendants of this individual. If the parent is living, he or she must be informed before testing that a test is being done, and an understanding of how the result will be delivered should be determined. In both situations, the manner by which the siblings of the person being tested will be alerted to this information should be addressed before the test is performed. If an identical twin is seeking testing, implications for the co-twin must be considered and the co-twin must be counseled and involved in the decision to proceed with testing.

Neurological examination.

Many programs include a neurological evaluation as part of the pretest evaluation. Many at-risk persons seek testing in the context of concerns for having exhibited symptoms of HD, and the neurological evaluation will answer the question of whether the individual has symptoms of the illness. Not uncommonly, persons who learn that they do not have symptoms decide to postpone the genetic test, because their primary worry for the onset of the disease has been addressed. For those persons who may be symptomatic and who may be diagnosed in the course of the genetic test evaluation, it is important to recognize that the test is no longer presymptomatic and to initiate treatment associated with the onset of the illness.

With appropriate consideration for the associated risks, HD testing can be implemented in a variety of circumstances. The procedures to minimize risk for adverse consequences of the test are recognized and can be readily implemented in testing programs. By anticipating discussion and preparation for the unique concerns of the individual seeking testing, one can enhance the likelihood of a successful adjustment to the test result.

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The nature of the genetic defect in the HD gene explains many of the genetic features of the disorder, including the variability in age at onset, the tendency for juvenile disease to be inherited from fathers, and the sporadic appearance of new mutations to HD.