History and exam
Key diagnostic factors
common
positive family history of Huntington's disease
May not be available in about 5% to 8% of cases.
Sometimes the affected parent is misdiagnosed as having Alzheimer's disease or a psychiatric disorder; sometimes suicide or alcoholism pre-empts a diagnosis of emerging Huntington's disease.
False paternity, divorce, or denial may also occur.
Occasionally an affected parent dies before symptoms become manifest, or they have a CAG repeat length that expanded into the symptomatic range in the affected patient.
known expansion of the CAG repeat length at the N-terminal end of the huntingtin gene
The patient may have had pre-symptomatic genetic testing.
Huntington's disease occurs with expansions of the CAG repeat length at the N-terminal end of the huntingtin gene.
All patients with ≥40 CAG repeat lengths develop Huntington's disease if they live a normal lifespan, and the longer the repeat length, the earlier that symptoms tend to appear.[11]
Patients with repeats in the 36 to 39 range may develop symptoms of Huntington's disease or may remain asymptomatic.[11]
The tendency for expansion of the CAG repeat in successive generations (anticipation) puts offspring at risk for earlier onset of the disease than their parents.
impaired work or school performance
Descriptions of work, hobbies, and outside interests and careful attention to spousal signals or input may be helpful.
There may be increased errors in complex functions or an assumption of responsibilities by colleagues or family members.
Patients may be uncomfortable with open discussion of apparent failings, so individual discussions with family members may be informative.
personality change
Personality changes manifest in different ways.
Irritability or temper outbursts are common.
Family members may describe only a gradual loss of enthusiasm or involvement in previously engaging activities.
irritability and impulsivity
When questioned, families may describe unusual purchases, snap decisions, gambling, or changes in sex drive.[23]
chorea
Mild chorea, if not previously encountered, is easily overlooked.
Random movements of fingers and toes, with occasional peculiar postures of hands, trunk, or limbs, and odd facial expressions are typical of early Huntington's disease.
Patients without the condition should be able to recite serial 7s seated, with eyes closed, without adventitious movements of fingers or toes.
Involuntary movements are often partially suppressible, so observation during the interview coupled with at least several minutes of formal testing for chorea is appropriate.
Patients with juvenile Huntington's disease may not have chorea but may be rigid or parkinsonian.
twitching or restlessness
Patients may be unaware of symptoms or may explain them away as nervousness.
Family member input is often helpful.
Spouses sometimes report difficulty sleeping with a restless patient or may see a resemblance to a previously affected family member.
loss of coordination
This may manifest as dropping things, stumbling, or motor vehicle accidents.
deficit in fine motor coordination
Finger tapping (index finger on thumb) should normally be rapid, regular, and of equivalent speed to the examiner (25 taps in 5 seconds); slowing and irregular tempo are characteristically seen in Huntington's disease.
Similar changes may be noted in the voice or with rapid tongue movements.
Rapid alternating movements of the hands, a form of gross motor coordination, may be relatively normal.
slowed rapid (saccadic) eye movements
Saccade speed is slowed.[33]
To test this, the patient is asked to shift gaze from the examiner's right thumb to the left index finger when held shoulder width apart in front of the patient.
Slow saccades are often most prominent in juvenile patients, even early in the course of the disease.
Insuppressible head turning or eye blinking is evidence of impairment.
motor impersistence
To test for motor impersistence, subjects are requested to protrude the tongue or close the eyes tightly for at least 10 seconds.
Patients often have trouble maintaining maximal protrusion or lid closure.
More advanced patients may show a 'milkmaid's grip', with variation in the intensity of a requested squeeze.[1][34]
impaired tandem walking
Tandem walking may bring out chorea, imbalance, or other problems.
Patients who appear slightly unsteady need to be tested close to a wall to minimise the risk of falling.
Other diagnostic factors
common
concentration impairment/task anxiety or apathy
Early cognitive changes are subtle and may be denied.[23]
Patients may be more comfortable acknowledging a change in their ability to concentrate than impaired judgement or slowed thinking.
Loss of executive function may manifest as heightened anxiety over tasks previously handled without difficulty.
Slips, misjudgements, or motor vehicle accidents may occur.
cognitive decline relative to spouse/siblings
Although not considered a typical aspect of the physical examination, comparing patients with spouses or siblings well matched for education or IQ is often informative.
changes in personal habits/hygiene
A reluctance to bathe or lack of attention to appearance may occur.
Asking about daily routines is a good introduction to this issue.
disinhibition or unusually anxious behaviour
Patients tend to make inappropriate comments or be less or more concerned about issues than they should.[23]
Often their behaviour is in contrast to that of a spouse, who may act more in a parental or carer role.
Risk factors
strong
expansion of the CAG repeat length at the N-terminal end of the huntingtin gene
Huntington's disease occurs with expansions of the CAG repeat length at the N-terminal end of the huntingtin gene.
All patients with ≥40 CAG repeat lengths develop Huntington's disease if they live a normal lifespan; the longer the repeat length, the earlier that symptoms tend to appear.[11]
Patients with repeats in the 36 to 39 range may develop symptoms of Huntington's disease or may remain asymptomatic.[11]
The tendency for expansion of the CAG repeat in successive generations (anticipation) puts offspring at risk for earlier onset of the disease than their parents.
family history
May not be available in about 5% to 8% of cases.
Sometimes the affected parent is misdiagnosed as having Alzheimer's disease or a psychiatric disorder; sometimes suicide or alcoholism pre-empts a diagnosis of emerging Huntington's disease.
Divorce, denial, or false paternity may also occur.
Occasionally, an affected parent dies before symptoms become manifest.
Alternatively, an asymptomatic parent has a CAG length that is inherited in an expanded form, producing symptoms in the affected child.
weak
other genetic factors
A variety of genes may have a small influence on the age of onset of patients with Huntington's disease.[22]
None of these genes are routinely screened for or used for managing clinical cases.
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