HUNTINGTONS

DISEASE
Dhakal, Gerbabuena, Jittwatanatakool,
Jordan, Karn

A 45 year-old male patient

presented himself with a history of
abnormal movements of hands and
face for the last one and a half
years, and some accounts of
insomnia. In addition, his family and
close friends told his that he had
behavioural changes in this
duration.

CASE

 abnormal movements are aggravated during

outbursts of anger, disturbances in mood, and were

absent during sleep
There was no weakness in any of limbs, but patient

was unable to perform his regular household

activities properly
There was NO history of drug intake such as

phenytoin, oral contraceptives, phenothiazines,

haloperidol, L-dopa, lithium, isoniazid,
amphetamines, tricyclic antidepressants etc.
There was NO history of chest pain, breathlessness,

or joint pain

HISTORY

FAMILY HISTORY
Father died with a neurological disorder at 60 years old

 Mild pallor
Normotensive
Cardiovascular system, abdomen, and respiratory system

essentially normal.
Memory was intact and showed normal orientation in time, space,

and person.
Normal power in all four limbs
The deep tendon reflexes in all four limbs were normal and plantars were
bilaterally flexor
Sensory and cerebellar systems normal
HOWEVER patient could not fix his gaze at one point for more than

30 seconds, with repetitive blinking movements, and was not able

to protrude her tongue out for more than 30 seconds.

PERTINENT PE

Peripheral blood smear

Hb of 7.9 gm%
normocytic hypochromic picture, without any abnormal cells

Spiral CT of head
Prominence of lateral ventricles
Flattening of wall of frontal horn i.e atrophy of caudate nucleus.
Bicaudate distance between ventricles was also increased.
GENETIC TESTING POSITIVE

DIAGNOSTICS

Huntingtons
Disease /
Huntingtons Chorea
DIAGNOSIS

HUNTINGTONS
CHOREA

HUNTINGTONS DISEASE
a progressive, fatal, highly penetrant autosomal dominant

neurodegenerative disorder characterized by motor,

behavioral, and cognitive dysfunction
It is due to an abnormal expansion of IT-15 gene on

chromosome 4 which encodes for the protein huntingtin

characterized by rapid, non-patterned, semi-purposeful,

involuntary choreiform movements

The disease is named after George Huntington

DISCUSSION

 This condition is inherited in an autosomal

dominant pattern, which means one copy of the

altered gene in each cell is sufficient to cause the
disorder
An offspring of an affected parent has 50% chance

of acquiring the disease

In rare cases, an individual with Huntingtons

disease does not have a parent with the disorder

 Mutations in the HTT gene cause Huntingtons disease

The huntingtin gene is located on 4p16.3 (CHROMOSOME 4)
The HTT gene provides instructions for making a protein called

huntingtin
Although the function of this protein is unknown, it appears to play an

important role in nerve cells (neurons) in the brain.

The HTT mutation that causes Huntingtons disease involves a DNA

segment known as a CAG trinucleotide (cytosine, adenine,

guanosine) repeat
Normal CAG segment is repeated 10 to 35 times. In people with

Huntingtons disease, the CAG segment is repeated 36 to more than

120 times
People with 40 or more repeats develop the disorder

ETIOLOGY

 An increase in the size of the CAG segment leads to the

production of an abnormally long version of the huntingtin

protein
The elongated protein is cut into smaller, toxic

fragments that bind together and accumulate in

neurons, disrupting the normal functions of these
cells
The dysfunction and eventual death of neurons in certain

areas of the brain underlie the signs and symptoms of

Huntington disease

 MACROSCOPIC EXAMINATION
Striking atrophy of the CAUDATE NUCLEUS and PUTAMEN
GLOBUS PALLIDUS atrophied secondarily
LATERAL and THIRD VENTRICLES are dilated
Atrophy is frequently seen in FRONTAL LOBE, less in PARIETAL LOBE, and

occasionally in the ENTIRE CORTEX

MICROSCOPIC EXAMINATION
Severe loss of STRIATAL NEURONS
Changes in CAUDATE NUCLEUS (TAIL and PORTIONS NEAR THE VENTRICLE)

Abnormalities develop in a MEDIAL-TO-LATERAL DIRECTION in CAUDATE

DORSAL-TO- VENTRAL in PUTAMEN

MEDIUM SIZED NEURONS GABA --- inhibitory nerve impulses

MORPHOLOGY

 Mutant huntingtin undergoes N-terminal cleavage resulting in polyglutamine

fragments
The N-terminal fragments, oligomers of these fragments, and the fully formed

inclusions have been implicated in the toxicity of HD

Mutant huntingtin adversely affects a multitude of intracellular processes and

causes widespread disruption, including

Mitochondrial dysfunction
Transcriptional dysregulation of various genes
Altered axonal transport of critical factors
Disrupted calcium signalling
Abnormal protein interactions
Alterations in proteosomal function
Autophagy

The overall effects of mutant huntingtin expression are cell loss and gliosis in the

brain, with the striatum being most affected by the disease

PATHOPHYSIOLOGY

 The age onset is most commonly in the 4 th and 5th decades and is

related to the length of CAG repeat in HD gene

MOTOR symptom often precede COGNITIVE IMPAIRMENT

The movement disorder of HD is CHOREIFORM

HD patients have an increased risk of suicide, with INTERCURENT

INFECTION being the most common natural cause of death

CLINICAL FEATURES

Hallmark symptoms of Huntington's disease

Uncontrolled movement of the arms, legs, head, face

and upper body

Decline in thinking and reasoning skills, including

memory, concentration, judgment and ability to plan

and organize
Alterations in mood, especially depression, anxiety,

and uncharacteristic anger and irritability

obsessive-compulsive behavior

SIGNS AND SYMPTOMS

 Jerky, involuntary, or sudden movement of head, arms or

legs
In severe chorea, development of uncontrolled flinging (or

flailing) of arms or legs (ballism) can interfere with ones

ability to move around
Patient is more likely to fall and have difficulty in feeding or

dressing up

CHOREA

 This tends to gradually replace chorea

Shoulder, neck, arm, and leg muscle spasm
Leads to twisting movements, repetitive movements, or abnormal

postures
BRADYKINESIA stiffness of limbs and slowed of movements
Swallowing and choking problems are common (i.e. dysphagia)
Slurred speech
Eye movements may also be affected, causing problems looking from

side to side, or up and down

DYSTONIA

 The first noticeable symptoms that may appear are

problems with short-term memory

Lack of concentration, short-term memory lapses

and problems with orientation are common

Learning new skills can become difficult.
The slow decline in cognition in HD is similar to a

dementia-type problem

PROBLEMS WITH
COGNITION

 Behavioural changes can be one of the first signs of HD

The patient may experience irritability, agitation and losing of interest to

things that one has previously enjoyed

People related to the patient may notice lost of interest in self care
Judgement about things can become affected
Patient may become aggressive towards people and can sometimes lose

his/her inhibitions, leading to embarrassing behaviour in social situations

Behavioural changes and anti-social behaviour can put a strain on ones

relationships
The patient may find it difficult to accept that his/her behaviour may be a

problem

MOOD AND BEHAVIORAL

PROBLEMS

GENETIC TESTING

ANGELINA EFFECT

The test can confirm that the defective gene

for huntingtin protein is the cause of

symptoms in people with suspected
Huntington's disease and can detect the
defective gene in people who don't yet have
symptoms but are at risk because a parent
has Huntington's

DIAGNOSTIC TESTS

 Dopamine-blocking agents (HALOPERIDOL) control the

chorea
Irritability

For severe anger and threatening behaviour atypical

antipsychotic drug
For less severe, nonthreatening irritabilityrecommend first
trying a selective serotonin reuptake inhibitor (SSRI), which is a
type of antidepressant.
Obsessive-compulsive thoughts and actions Experts also

recommended SSRIs as the front-line treatment

Psychosis with atypical neuroleptics such as clozapine (50600

mg/d), quetiapine (50600 mg/d), and risperidone (28 mg/d)

TREATMENT /
MANAGEMENT