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HISTORY OF HUNTINGTON’S DISEASE
In 1872, George Huntington (1850-1916) in Middleport , Ohio
wrote a paper entitled "On Chorea." A short time
later the medical community adopted the eponym "Huntington's
Chorea." The word “chorea” is derived from
the Latin word 'choreus', which means dance and the Greek word
'choros' which means chorus. Chorea has become the hallmark
of the movement aspect of this neurodegenerative disorder.
Although this was George Huntington’s only original contribution
to the medical literature, he beautifully described all the
cardinal features of this disease, including the adult onset,
progressive course and eventually fatal outcome, the choreic
movements combined with mental disorders, and some features
of inheritance.
Although Charles Oscar Waters and George Huntington had recognized
the hereditary nature of HD, it was not until 1908 when the
mendelian dominant inheritance was established in HD. In 1930s
and 1940s, the eugenic movement in Nazi Germany launched an
HD eradication program by sterilizing individuals with this
disease. It should be noted, however, that this approach was
not only inhumane, but also ineffective. New cases of HD pop
up in the general population as results of new mutation events
(See the section of the Genetics of Huntington’s Disease).
The next major breakthrough came with the mapping of the HD
locus to the short arm of chromosome 4 in 1983. (See the section
on Pathogenic Process of Huntington’s Disease). However,
in spite of vigorous search of the gene in this chromosomal
region, it took another 10 years to find the gene. In 1993,
the HD-causing mutation was finally identified in the gene
then known as IT15 (“intriguing transcript 15”),
which is now officially registered as HD in the Genome Database.
Starting in 1993, the progress in research has been remarkable
and rapid enough to raise a cautious optimism for the development
of effective treatments for this devastating disease in the
near future.
SYMPTOMS
AND SIGNS OF HUNTINGTON’S DISEASE
Chorea consists of involuntary, continuous, rapid, abrupt,
brief, unsustained, irregular movements that flow randomly
from one body part to another. Patients are able to partially
and temporarily suppress the chorea with efforts for a limited
time period. Many patients "camouflage" some of the
movements by incorporating them into semipurposeful activities.
This is called parakinesia. Patients also exhibit the inability
to maintain voluntary contractions, which is known as “motor
impersistance” and is exemplified by an inability to
protrude the tongue for an extended period or failure to make
continuous tight manual grip (milk-maid grip). Affected individuals
typically have a peculiar, irregular, and dance-like gait.
Other motor disorders include dysarthria (slurred speech),
dysphagia (swallowing difficulties), postural instability,
ataxia (loss of motor coordination), dystonia (sustained involuntary
postures and/or movements, myoclonus (lightening-like jerky
movements), and tics.
Besides these involuntary movements, there are two other major
components of the disease, i.e., cognitive decline and psychiatric
symptoms. The neurobehavioral symptoms vary but are usually
expressed as personality changes, apathy, social withdrawal,
agitation, impulsiveness, depression, mania, paranoia, delusions,
hostility, hallucinations or psychosis. Cognitive changes are
manifested chiefly by loss of recent memory, poor judgment,
impaired concentration and acquisition. These changes occur
in nearly all patients with HD; but some patients with late-onset
chorea never develop a significant loss of their intellectual
abilities. Cognitive impairments in HD differ from the severe
general loss of intellectual abilities” seen in Alzheimer’s
disease. For example, most HD patients recognize their family
members until very late stage of the disease. In HD, tasks
requiring psychomotor or visuospatial processing are affected
early on and get worse a lot faster than memory loss. Because
of this unique pattern, the cognitive loss in HD often appears
deceivingly mild, and is missed on a casual neurological examination
of the patient by disability-assessing doctors.
About 10% of HD cases start having symptoms or signs of the
disease before age 20, but the usually HD starts at 40 - 50
years of age. Juvenile-onset patients usually inherit the disease
from their father. Juvenile HD (onset of symptoms before 20
years) typically starts with the combination of progressive
parkinsonism (manifestations similar to those seen in Parkinson’s
disease), loss of intellectual ability, ataxia (loss of coordination
and balance), and seizures. In contrast, the clinical diagnosis
of adult HD is usually established when patients have the insidious
onset of clumsiness and involuntary restless movements, which
may be wrongly attributed to simple nervousness. Slowness of
movement (bradykinesia) usually occurs in patients with the
rigid form of HD, but it often coexists with chorea in adult
cases. When this happens it may not be fully appreciated on
a routine examination. Bradykinesia in HD may be caused by
a mechanism different from true Parkinson’s disease,
and this possibly explains why a reduction in chorea with anti-dopaminergic
drugs rarely improves overall motor functioning and indeed
may cause an exacerbation of the motor impairment.
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November 20, 2009
