From the 2001 HDSA book
"Juvenile HD Handbook -
A Guide For Physicians, Neurologists and Other Professionals"
written and edited by Dr. Martha Nance
See Section 3 on how to order this book from the HDSA
Chapter I - The Diagnosis of HD in A Child
When To Consider HD
The diagnosis of HD in an adult is usually made in a person who has memory or cognitive changes (dementia), and chorea (dance-like movements), often with behavioral or psychiatric problems such as depression, irritability, or mood swings, and usually with a family history of HD in a parent. The presenting symptoms may be a little different in a child, particularly a child under 10 years
While there is no symptoms or group of symptoms that are absolutely required for the diagnosis of juvenile HD, most affected children have several of these features at the time that the diagnosis is made. Chorea is uncommon in children developing HD within the first decade, but may be one of the first symptoms in a teenager. Severe behavioral disturbances may be the first symptom in an adolescent.
Typical initial symptoms of juvenile HD:
- 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
- Changes in oral motor function
- Family History
For reasons that only became clear after the gene responsible for HD was discovered in 1993, individuals with a very early onset of HD are far less likely to have an affected father than an affected mother. It is very unlikely for HD to appear in a child whose parent was not also affected with HD. If this situation
appears to be present, the physician should consider diagnosis other than HD.
Occasionally an HD-affected child without an affected parent can be explained by the early death of a parent (before the parent's symptoms were evident), misdiagnosis or lack of diagnosis in a parent who was affected, non-paternity (a biological father who is not the same as the apparent father), onset of symptoms in the child before the parent's onset, or adoption.
Documenting the diagnosis of HD in other relatives can be helpful to the physician as the child is evaluated for HD. A parent who suspects that his or her child has juvenile HD can help the physician by assembling information about the family history.
If the family history is missing because the child was adopted, it may still be possible to obtain the missing information if it is important to the child's diagnosis. Adoption agencies and county or regional social services departments, when given an understanding of the serious nature of HD and its hereditary pattern, may be able to contact the birth parents to obtain more information.
Similarly, a mother or family who becomes aware of the family history of HD should be honest and open with the adoption agency, so the adopting parents are aware of the child's genetic risks and are able to plan appropriately.
Declining Cognitive Function
HD is a degenerative condition, which means that children who are symptomatic will begin to lose skills that they have had previously gained.
In a school-aged child, this is often noticed first as
an overall decline in grades or other measures of
school performance. Attention and concentration
In a younger child, increasing difficulty with previously
attained cognitive or motor skills, such as speech,
reading, throwing a ball, or riding a bicycle, might be
In a young child, declining school performance,
accompanied by worsening motor skills, would be
much more suggestive of HD than a change in
In an adolescent, many other common causes of
poor school performance must be considered,
including depression, drug or alcohol use, or
disruptions of family or social life. Detailed
information from teachers and school counselors
may help the physician to pinpoint the different
kids and causes of dysfunction at school.
Behavioral disturbances are common in children with HD. Behavioral disturbances, depression, and attention deficit disorder/hyperactivity are also common in children without HD. The families of children at-risk for HD are often under significant financial and social stress, which increases the chance of social or behavioral problems in the children.
In adolescents, behavior disturbance may be the first
and only presenting symptomof HD. Behavior problems
in these children are often very severe, leading to
psychiatric hospitalization, suspension from school, or
sexual promiscuity, physical or sexual abuse of younger
siblings, severe drug or alcohol abuse, and depression
with suicide attempts.
While adults with HD usually have involuntary movements, and only develop rigidity and dystonia (abnormal stiff postures) much later in the disease, children are likely to have stiffness of the legs, walking on the toes, or scissoring of the gait as initial or early symptoms. Clumsiness of hand and arm movements, thickness of speech, drooling and poor oral motor control are also likely, particularly in very young children.
The earlier the symptoms begin, the less likely the child is to have chorea at any point in the course of the disease. On the other hand, the older the child, the more likely he or she is to have chorea as a presenting symptoms.
Seizures are said to occur in about 25% of children with juvenile HD, and may be a presenting symptom. They may be of any type, and they may or may not be severe. The physician should never simply assume that seizures are caused by HD; any child with a seizure should have cerebral imaging studies and an electroencephalogram (EEG), as well as appropriate laboratory studies to rule out metabolic causes such as lowblood sugar or poison ingestion.
This brief overview only describes the most typical presenting symptoms of HD; ach child is unique and may have additional symptoms or symptoms that differ rom the typical features described. It may take several visits to the physician or everal neurological examinations before mild or intermittent symptoms are recognized y the physician as being due to HD.
Seeing The Physician
In many health care systems in the United States, a patient must first see a family physician or pediatrician to obtain a referral to a pediatric neurologist or HD specialist. The diagnosis of juvenile HD can be challenging, and it is appropriate to request such a referral. In some localities, an adult neurologist specializing in movement disorders or HD may be more helpful than a pediatric neurologist who is unfamiliar with the condition; a telephone call from the referring pediatrician to the specialist can help the family to avoid unnecessary appointments. A parent should understand that diagnosis of juvenile HD is unlikely to be made immediately at the first visit, and should be prepared to work with the physician through the process of diagnosis.
The physician will first take a medical and neurological history, a family history,
and a development history, and perform a neurological examination. It is
helpful for the parent to bring records to review, including any previous
neurological examinations, psychological evaluations or school testing records.
It is important for the physician to review the neurological, behavioral, and
functional problems before considering an HD gene test. If cognitive changes
are present, a formal neuropsychological assessment (tests of memory, development skills, and intelligence) can document areas of strength and weakness, suggest strategies of management, and serve as a baseline for comparison later.
Either behavioral changes or changes in school performance in a child at-risk for HD should prompt the physician to evaluate the child's psychosocial situation and to make appropriate referrals for individual or family counseling, county child protection services, school-based programs, or social services. Physical, occupational, and speech therapist can perform baseline assessments of motor with an emphasis on how the child is able to function in school and at home.
Children in HD families are not immune from having developmental delay, attention deficit disorder, mental retardation, or other medical or neurological conditions entirely unrelated to HD, and both parents and physicians should consider these possibilities as they go through the diagnostic process.
Brain imaging, by computerized tomography (CT) or magnetic resonance imaging (MRI), is often normal early in the course of HD, and may help to rule out other conditions. Similarly, routine blood tests, while not helpful in securing a diagnosis of HD, can help to rule out other diseases that can cause abnormal movements, such as hyper- or hypothyroidism, toxin or drug ingestion, systemic lupus erythematosus, or recent streptrococcal infection (Sydenham's chorea).
When the history, examinations, and initial laboratory evaluations are strongly suggestive of HD, a genetic test may be the most efficient and accurate way to confirm the diagnostic impression. If the diagnosis is not evident from the examination, then it is not appropriate to have genetic testing performed immediately, as the presence of the abnormal HD gene does not resolve the problem at hand, which is whether the person's symptoms are due to HD.
It is extremely important to limit diagnostic testing of the HD gene to children who clearly have clinical symptoms and a course that is consistent with HD. Often it is recommended that a child be evaluated by the neurologist or other clinician twice, six to twelve months apart, to determine whether the initial symptoms have remained or progressed despite appropriate management, before the HD gene test is performed.
This strategy makes it less likely that a child with temporary or nonprogressive symptoms would be tested prematurely. The table shows some of the risks of identifying a child as an HD gene carrier prematurely.
Potential risks of premature gene testing in a child
- Incorrect attribution of symptoms to HD
- Failure to make the correct diagnosis
- Stigmatizing the child
- Psychological effects on the child
- Social effects on the child
Diagnostic Genetic Testing In Children
The ability to detect changes in the HD gene itself has made confirmation of the diagnosis of HD much simpler. The HD gene can be isolated from a blood sample, and examined chemically; the abnormality in the gene that causes HD is called a "CAG repeat expansion." The HD gene normally has a variable number of "CAG repeats" - any number up to 35 repeats is normal.
There is a relationship between the repeat numbers and the age that HD symptoms begin, so that higher repeat numbers are associated with younger ages of onset.
Most adults with HD have between 40-50 CAG repeats in their abnormal HD gene. Usually, juvenile HD is associated with CAG repeat numbers of 50 or higher, although it is not possible to define rigid boundaries. Very young age of onset are associated with very high CAG repeat numbers; children with HD onset at age 2-3 years and with over 100 CAG repeats have been reported.
The gene test is close to 100% accurate. If the tests show two normal HD genes, the child will never develop HD and is not at-risk for passing HD on to his children.
If the test shows an abnormal HD gene, the child will someday develop HD. The gene test, however, cannot predict when a particular person's symptoms will begin.
Occasionally, individuals will have a CAG repeat length in the 36-39 range, which may or may not be associated with the development of HD symptoms during a normal life span. Results in this "intermediate range" are not usually a factor when testing children for possible symptomatic HD.
And rarely, very high CAG repeat numbers (over 100 CAG repeats) are not detected by the standard gene test. If HD is strongly suspected in a very young child who has a normal gene test results, the physician may want to contact the laboratory or a genetic counselor to discuss the possibility of a special analysis to look for very large CAG repeat numbers.
The potential risks of testing a child for the HD gene inappropriately or prematurely cannot be emphasized enough. Individuals who develop HD have the CAG repeat expansion in one of their HD genes from the moment of conception - years or decades before their symptoms begin.
There are two ways in which a premature gene test can be misleading or damaging to a child's care. First, an abnormal gene test result may incorrectly be assumed to "explain" a child's symptoms, when in fact the symptoms are not clearly related to HD. For example, an adult whose gene test was felt to "explain" his blurry vision and headaches was incorrectly diagnosed as having HD and, as a result, the diagnosis of his pituitary tumor was delayed.
Secondly, it is possible that a gene test will show a small CAG repeat expansion, one that is likely to be associated with adult-onset HD but not
juvenile onset HD. This is equivalent to a predictive gene test and does not help to explain the child's current symptoms.
Due to the very sensitive nature of the gene test results, it is important for
counseling to occur before the results are given, so there are no mis-understandings about their significance. If the physician is unable or does not have the time to explain the gene test in details, a genetic counselor may be asked to help with this part of the process.
Testing Children Who Do Not Have Symptoms
When one child has been diagnosed with HD, parents may want to have their other children tested as well. Testing of a person who does not have symptoms of HD is called predictive testing, in order to distinguish it from diagnostic testing for a person who has symptoms suggestive of HD.
Although, at first thought, it may seem reassuring for parents to find out that their other children do not carry the HD gene, it is very important to consider the complex potential effects of the tests results on the entire family, as well as on the individual or individuals being tested.
The risks of premature genetic diagnosis of HD have already been discussed and genetic testing experts believe that predictive tests should be reserved for individuals who are able to understand the potential risks and benefits of the test and who are able to give informed consent.
Experience in the United States has shown that most adults at-risk for HD do not choose to undergo predictive genetic testing, so a parent who requests predictive testing for a child is most likely doing something that the child would not want if he or she were able to make the choice.
In addition, at this time, there is no medical advantage to knowing that someone carries the HD gene - treatments that prevent or delay the disease have not been developed yet.
For all these reasons, most genetic professionals in North American decline parental requests for predictive tests on their asymptomatic children. Occasional exceptions might be made for adolescents in adult situations, such as an "emancipated minor" or a married teenager.
In the United States, potential adoption is not usually felt to be an appropriate indication for HD predictive testing, because of the potential for social, financial, educational, insurance and employment discrimination based on the test results and the lack of medical treatment or care to balance the potential social harms. Other countries may have different practices.
Steps in the diagnosis of juvenile HD