|
GENETICS OF HUNTINGTON'S
DISEASE
Huntington’s disease (HD)
is a genetic disorder of the central nervous system with symptoms usually
appearing in adults within the third or fourth decade of life, although
symptoms can occur in individuals younger or older than this. Within the
same family, the symptoms vary both in their rate of progression and in the
age of onset. Symptoms may include involuntary movement and loss of motor
control. In addition, personality changes may occur, with loss of memory and
decreased mental capacity. Symptoms in individuals, as well as confirmation
of diagnosis in other family members, are used to determine the diagnosis.
Huntington’s disease is inherited as an autosomal dominant condition.
The human body contains 100
trillion cells. A nucleus is inside each human cell (except red blood
cells). Each nucleus contains 46 chromosomes arranged in 23 pairs. One
chromosome of every pair is from each parent. The chromosomes are filled
from each tightly coiled strand of DNA. Genes are segments of DNA that
contain instructions to make protein and other building blocks of life.
Each of us has 46
chromosomes which come in pairs; one member of the pair comes from each
parent. Therefore, 23 chromosomes are from the father. There are two types
of chromosomes: 1) Autosomal chromosomes, which are the first 22 pairs and
2) sex chromosomes, which are the 23rd pair in males consists of
an X-chromosomes and a Y- chromosomes). Since Huntington’s disease is
autosomal dominant, this means the gene involved is on an autosomal
chromosomes (not one of the sex chromosomes) and recently has been
localised on the fourth autosomal chromosome pair (the #4 chromosomes). In
affected individuals, one gene of this gene pair (the HD genes) is not
functioning correctly and expresses itself more strongly or ‘dominates’
the other working gene. Since it is not on one of the sex chromosomes, it
can affect both males and females. Males and females have the same chance of
having affected children.
An affected parent passes
either the HD gene or the other working gene to their offspring. There is
a 50% (1 in 2) chance at each pregnancy that a child of an affected parent
will receive the gene for Huntington’s disease. The age of onset, degree and
type of clinical symptoms, as well as rate of progression varies with HD.
During a clinic visit with a neurologist or geneticist it
may or may not be possible to clinically determine whether an individual has
the HD gene. With increased age and without symptoms the likelihood of
having the risk becomes less than 50%. Therefore the risk for passing the
gene to children decreases. However, if symptoms begin, and a diagnosis is
made, each child of an affected parent has a 50% chance of having the
Huntington’s disease gene. Information about the genetics of HD should be
shared with children prior to their family planning so that they can receive
the most current information.
The gene for Huntington’s disease on the fourth chromosome
has been characterised in recent years. The chromosomes is composed of
genes and each is composed of a string of molecules called nucleotides. The
nucleotides are adenine (A), cytosine (C), guanine (G) and thymine (T). The
gene is made up of a series of three nucleotides which form the structure of
DNA in the gene. Each gene has its own unique sequence of base pairs. In Huntington’s
disease, the DNA sequence, CAG (cytosine – adenine – guanine) is part of
this sequence. This sequence may be duplicated many times in individuals up
to 26 times in the general population. The duplication of this segment is
called a “ trinucleotide repeat
in which these three nucleotides (CAG pattern) are repeated
over and over again. Individuals with Huntington disease may have
from 40 to over 100 repeated CAG segments. Specific laboratory and clinic
evaluations are needed to interpret other repeat levels, which may be
referred to as indeterminate, intermediate, non penetrant, or reduced
penetrance with meiotic instability. It is not known how this repeated
sequence causes Huntington’s disease but research to develop therapies to
treat Huntington’s disease is ongoing.
GENETIC TESTING
A variety of genetic testing options may be discussed with
the genetics personnel or personnel familiar with genetic testing, during a
clinic visit, depending upon information specific to your family and your
individual situation. These options might include direct detection of the HD
gene on an affected individual and subsequent testing of relatives. The
genetic testing of an individual‘s DNA can be obtained from a blood sample.
Tissue samples that have been stored or donated for research from extended
family members may also be useful in genetic testing. Most genetic testing
and analysis should be done before a family member begins a pregnancy. The
decision by an individual to undergo genetic testing is an intensely
personal decision and can be made only by that person. Friends and family,
no matter how fervent their wishes for the person to be tested, can not make
that decision for that competent adult.
At this time the HDSA, in conjunction with researchers and
clinicians involved in caring for people and families with Huntington’s
disease does not support the testing of minors who are at risk for the
development of Huntington’s disease
TREATMENT
There is no cure for Huntington’s disease. Treatment focuses
on reducing symptoms, preventing complications and providing support and
assistance to the patient and those close to him or her.
MEDICATION
Physicians often prescribe various medications to help
control emotional and movement problems. Antipsychotic (Hallucination,
delusions, violent outbursts): haloperidol, chlorpromazine, olanzapine
(contraindicated if patient has dystonia). Antidepressants (depression,
obsessive- compulsive behaviour
fluoxetine, sertraline hydrochloride, nortriptyline.
Tranquilizers (anxiety, chorea) benzodiazepines, paroxetine,
venlafaxin, beta-blockers.
Mood-stabilizer (mania, bipolar disorder) lithium, valproate,
carbamzepine. Botulinum toxin (dystonia, jaw clenching)
Because most used to treat the symptoms of HD can produce
undesirable side effects ranging from fatigue to restlessness and hyperexcitability, physicians often prescribe the lowest possible dose.
More
|
