WHAT IS A GENETIC

DISORDER?

A genetic disorder is a genetic problem caused

by one or more abnormalities in the genome,
especially a condition that is present from birth
(congenital). Most genetic disorders are quite rare
and affect one person in every several thousands
or millions.
Genetic disorders may or may not be heritable,
i.e., passed down from the parents' genes. In nonheritable genetic disorders, defects may be caused
by new mutations or changes to the DNA. In such
cases, the defect will only be heritable if it occurs
in the germ line. The same disease, such as some
forms of cancer, may be caused by an inherited
genetic condition in some people, by new
mutations in other people, and mainly by

environmental causes in still other people.

Whether, when and to what extent a person with
the genetic defect or abnormality will actually
suffer from the disease is almost always affected
by the environmental factors and events in the
person's development.

TYPES OF
DISORDERS

SINGLE GENE

A single-gene disorder is the result of a

single mutated gene. Over 4000 human diseases
are caused by single-gene defects. Single-gene
disorders can be passed on to subsequent
generations in several ways.
Genomic imprinting and uniparental disomy,
however, may affect inheritance patterns. The
divisions between recessive and dominant types
are not "hard and fast", although the divisions
between autosomal and X-linked types are (since

the latter types are distinguished purely based on

the chromosomal location of the gene).

AUTOSOMAL DOMINANT

Only one mutated copy of the gene will be

necessary for a person to be affected by an
autosomal dominant disorder. Each affected
person usually has one affected parent.
The chance a child will inherit the mutated gene is
50%.
Autosomal dominant conditions sometimes have
reduced penetrance, which means although only
one mutated copy is needed, not all individuals
who inherit that mutation go on to develop the
disease.

Examples of this type of disorder are Huntington's

disease.

AUTOSOMAL RESSESIVE
Two copies of the gene must be mutated for a
person to be affected by an autosomal recessive
disorder.
An affected person usually has unaffected parents
who each carry a single copy of the mutated gene
(and are referred to as carriers).
Two unaffected people who each carry one copy of
the mutated gene have a 25% risk with each
pregnancy of having a child affected by the
disorder.
Examples of this type of disorder are Albinism,
cystic, sickle-cell disease.

X-LINKED DOMINANCE

X-linked dominant disorders are caused by

mutations in genes on the X chromosome. Only a
few disorders have this inheritance pattern, with a
prime example being X-linked hypophosphatemic
rickets.
Males and females are both affected in these
disorders, with males typically being more severely
affected than females.
Exceptions to this finding are extremely rare cases
in which boys with Klinefelter syndrome (47,XXY)
also inherit an X-linked dominant condition and
exhibit symptoms more similar to those of a
female in terms of disease severity.
The chance of passing on an X-linked dominant
disorder differs between men and women. The
sons of a man with an X-linked dominant disorder
will all be unaffected (since they receive their
father's Y chromosome), and his daughters will all
inherit the condition.
A woman with an X-linked dominant disorder has a
50% chance of having an affected fetus with each
pregnancy.

In addition, although these conditions do not alter

fertility per se, individuals with Rett syndrome or
Aicardi syndrome rarely reproduce.

X-LINKED RESSESIVE
X-linked recessive conditions are also caused by
mutations in genes on the X chromosome. Males
are more frequently affected than females, and the
chance of passing on the disorder differs between
men and women.
The sons of a man with an X-linked recessive
disorder will not be affected, and his daughters will
carry one copy of the mutated gene. A woman who
is a carrier of an X-linked recessive disorder (XRXr)
has a 50% chance of having sons who are affected
and a 50% chance of having daughters who carry
one copy of the mutated gene and are therefore
carriers.
X-linked recessive conditions include the serious
diseases hemophilia A etc. as well as common
and less serious conditions such as male pattern
baldness and red-green color blindness. X-linked
recessive conditions can sometimes manifest in

females due to skewed X-inactivation or monosomy

X (Turner syndrome).

COLOR BLINDNESS
Color blindness, or color vision deficiency, is
the inability or decreased ability to see color, or
perceive color differences, under normal lighting
conditions. Color blindness affects a significant
percentage of the population. There is no actual
blindness but there is a deficiency of color vision.
The most usual cause is a fault in the development
of one or more sets of retinal cones that perceive
color in light and transmit that information to the
optic nerve. This type of color blindness is usually
a sex-linked condition.
The genes that produce photo pigments are
carried on the X chromosome; if some of these
genes are missing or damaged, color blindness will
be expressed in males with a higher probability
than in females because males only have one X
chromosome, whereas females have two and a
functional gene on only one of the X chromosomes
is sufficient to yield the necessary photopigmens.

Color blindness can also be produced by physical

or chemical damage to the eye, the optic nerve, or
parts of the brain. For example, people with
achromatopsia suffer from a completely different
disorder, but are nevertheless unable to see colors.
Color blindness is usually classified as a mild
disability. There are occasional circumstances
where it is an advantage: some studies conclude
that color blind people are better at penetrating
certain color camouflages. Such findings may give
an evolutionary reason for the high prevalence of
redgreen color blindness.

CAUSE
Color blindness can be inherited. It is most
commonly inherited from mutations on the X
chromosome but the mapping of the human
genome has shown there are many causative
mutationsmutations capable of causing color
blindness originate from at least 19 different
chromosomes and 56 different
Most common inherited forms of color blindness
are protanopia and deuteranopia.
Inherited color blindness can be congenital (from
birth), or it can commence in childhood or

adulthood. Depending on the mutation, it can be

stationary, that is, remain the same throughout a
person's lifetime, or progressive. As progressive
phenotypes involve deterioration of the retina and
other parts of the eye, certain forms of color
blindness can progress to legal blindness, i.e., an
acuity of 6/60 (20/200) or worse, and often leave a
person with complete blindness

DIAGNOSIS
The Ishihara color test, which consists of a series of
pictures of colored spots, is the test most often
used to diagnose redgreen color deficiencies.

CYSTIC FIBROSIS

Cystic fibrosis (CF), also known as

mucoviscidosis, is a genetic disorder that affects
mostly the lungs but also the pancreas, liver,
kidneys, and intestine. Long-term issues include
difficulty breathing and coughing up mucus as a
result of frequent lung infections.
Other signs and symptoms include sinus
infections, poor growth, fatty stool, clubbing of the
fingers and toes, and infertility in males among
others. Different people may have different
degrees of symptoms.

CAUSE
CF is inherited in an autosomal recessive manner.
It is caused by the presence of mutations in both
copies of the gene

Those with a single working copy are carriers and

otherwise mostly normal.CFTR is involved in
production of sweat, digestive fluids, and mucus.
When CFTR is not functional, secretions which are
usually thin instead become thick.

DIAGNOSIS

The condition is diagnosed by a sweat test and

genetic testing. Screening of infants at birth takes
place in some areas of the world.
There is no cure for cystic fibrosis. Lung infections
are treated with antibiotics which may be given
intravenously, inhaled, or by mouth.
Lung transplantation may be an option if lung
function continues to worsen.
The average life expectancy is between 42 and 50
years in the developed world. Lung problems are
responsible for death in 80% of people with cystic
fibrosis.

DOWN SYNDROME

In every cell in the human body there is a nucleus,

where genetic material is stored in genes. Genes
carry the codes responsible for all of our inherited
traits and are grouped along rod-like structures
called chromosomes. Typically, the nucleus of
each cell contains 23 pairs of chromosomes, half of
which are inherited from each parent. Down
syndrome occurs when an individual has a full or
partial extra copy of chromosome 21.
This additional genetic material alters the course
of development and causes the characteristics
associated with Down syndrome. A few of the
common physical traits of Down syndrome are low
muscle tone, small stature, an upward slant to the

eyes, and a single deep crease across the center of

the palm - although each person with Down
syndrome is a unique individual and may
possess these characteristics to different degrees,
or not at all.

CAUSE
Regardless of the type of Down syndrome a person
may have, all people with Down syndrome have an
extra, critical portion of chromosome 21 present in
all or some of their cells. This additional genetic
material alters the course of development and
causes the characteristics associated with Down
syndrome.
The cause of the extra full or partial chromosome
is still unknown. Maternal age is the only factor
that has been linked to an increased chance of
having a baby with Down syndrome resulting from
nondisjunction or mosaicism. However, due to
higher birth rates in younger women, 80% of
children with Down syndrome are born to women
under 35 years of age.

The additional partial or full copy of the 21st

chromosome which causes Down syndrome can
originate from either the father or the mother.
Approximately 5% of the cases have been traced
to the father.

DIAGNOSIS
There are two categories of tests for Down
syndrome that can be performed before a baby is
born: screening tests and diagnostic tests. Prenatal
screens estimate the chance of the fetus having
Down syndrome. These tests do not tell you for
sure whether your fetus has Down syndrome; they
only provide a probability.
By examining the karyotype, doctors can diagnose
Down syndrome. Another genetic test called FISH
can apply similar principles and confirm a
diagnosis in a shorter amount of time.

HAEMOPHILIA
Hemophilia, is a group of hereditary genetic
disorders that impairs the body's ability to
control blood clotting, which is used to stop
bleeding when a blood vessel is broken.
People with hemophilia have lower clotting
factor level of blood plasma or impaired activity of
the coagulation factors needed for a normal
clotting process. Thus when a blood vessel is
injured, a temporary scab does form, but the

missing coagulation factors prevent fibrin

formation, which is necessary to maintain the
blood clot. A hemophiliac does not bleed more
intensely than a person without it, but can bleed
for a much longer time.
In severe haemophiliacs even a minor injury can
result in blood loss lasting days or weeks, or even
never healing completely. In areas such as the
brain or inside joints, this can be fatal or
permanently debilitating

CAUSES
.
Female carriers can inherit the defective gene from
either their mother or father, or it may be a new
mutation. Although it is not impossible for a female
to have hemophilia, it is unusual: daughters which
are the product of both a male with hemophilia A
or B and a female carrier will have hemophilia.

KLINEFELTER SYNDROME
Klinefelter syndrome is a genetic disorder that
affects males. Klinefelter syndrome occurs when a
boy is born with one or more extra
X chromosomes. Most males have one Y and one X
chromosome. Having extra X chromosomes can

cause a male to have some physical traits unusual

for males.
Many men with an extra X chromosome are not
aware that they have it, and they lead normal
lives. Klinefelter syndrome occurs in about 1 out of
1,000 males.

CAUSE
The presence of an extra X chromosome in males
most often occurs when the genetic material in the
egg splits unevenly. But it can also occur when the
genetic material in the sperm splits unevenly. Even
though Klinefelter syndrome is a genetic disorder,
it is not passed down through families. So, parents
who have a child with Klinefelter syndrome are not
any more likely than other couples to have another
child with the condition.

DIAGNOSIS

Klinefelter syndrome usually is not diagnosed until the

time of puberty. At this point, the boy's testicles fail to grow
normally and you may start to notice other symptoms.
Klinefelter syndrome can be detected before birth
(prenatally) through genetic tests on cells collected from
amniocentesis or chorionic villus sampling (CVS).

SICKLE CELL ANAEMIA

The term sickle cell disease (SCD) describes a
group of inherited red blood cell disorders. People
with SCD have abnormal hemoglobin,

called hemoglobin S or sickle hemoglobin, in their

red blood cells.
Hemoglobin is a protein in red blood cells that
carries oxygen throughout the body.
Inherited means that the disease is passed by
genes from parents to their children. SCD is not
contagious. A person cannot catch it, like a cold or
infection, from someone else.
People who have SCD inherit two abnormal
hemoglobin genes, one from each parent. In all
forms of SCD, at least one of the two abnormal
genes causes a persons body to make hemoglobin
S. When a person has two hemoglobin S genes,
Hemoglobin SS, the disease is called sickle cell
anemia. This is the most common and often most
severe kind of SCD.
Hemoglobin SC disease and hemoglobin S
thalassemia are two other common forms of SCD.

CAUSE AND DIAGNOSIS

Cells in tissues need a steady supply of oxygen to

work well. Normally, hemoglobin in red blood cells
takes up oxygen in the lungs and carries it to all
the tissues of the body.
Red blood cells that contain normal hemoglobin
are disc shaped (like a doughnut without a hole).
This shape allows the cells to be flexible so that
they can move through large and small blood
vessels to deliver oxygen.
Sickle hemoglobin is not like normal hemoglobin. It
can form stiff rods within the red cell, changing it
into a crescent, or sickle shape.
Sickle-shaped cells are not flexible and can stick to
vessel walls, causing a blockage that slows or
stops the flow of blood. When .
The lack of tissue oxygen can cause attacks of
sudden, severe pain, called pain crisis. These pain
attacks can occur without warning, and a person
often needs to go to the hospital for effective
treatment this happens, oxygen cant reach nearby
tissues.

.
Most children with SCD are pain free between
painful crises, but adolescents and adults may also
suffer with chronic ongoing pain.
The red cell sickling and poor oxygen delivery can
also cause organ damage. Over a lifetime, SCD can

harm a persons spleen, brain, eyes, lungs, liver,

heart, kidneys, penis, joints, bones, or skin.
Sickle cells cant change shape easily, so they tend
to burst apart or hemolyze. Normal red blood cells
live about 90 to 120 days, but sickle cells last only
10 to 20 days.
The body is always making new red blood cells to
replace the old cells; however, in SCD the body
may have trouble keeping up with how fast the
cells are being destroyed. Because of this, the
number of red blood cells is usually lower than
normal. This condition, called anemia, can make a
person have less energy.

TURNER SYNDROME
Turner syndrome is a chromosomal condition that
alters development in females. Women with this
condition tend to be shorter than average and are
usually unable to conceive a child (infertile)
because of an absence of ovarian function. Other
features of this condition that can vary among
women who have Turner syndrome include: extra
skin on the neck (webbed neck), puffiness or
swelling (lymphedema) of the hands and feet,
skeletal abnormalities, heart defects and kidney
problems.
This condition occurs in about 1 in 2,500 female
births worldwide, but is much more common
among pregnancies that do not survive to term
(miscarriages and stillbirths).
Turner syndrome is a chromosomal condition
related to the X chromosome.

CAUSE

Turner syndrome is not usually inherited in

families. Turner syndrome occurs when one of the
two X chromosomes normally found in women is
missing or incomplete. Although the exact cause of
Turner syndrome is not known, it appears to occur
as a result of a random error during the formation
of either the eggs or sperm.
Humans have 46 chromosomes, which contain all
of a person's genes and DNA. Two of these
chromosomes, the sex chromosomes, determine a
person's gender. Both of the sex chromosomes in
females are called X chromosomes. (This is written
as XX.) Males have an X and a Y chromosome
(written as XY). The two sex chromosomes help a
person develop fertility and the sexual
characteristics of their gender.
In Turner syndrome, the girl does not have the
usual pair of two complete X chromosomes. The
most common scenario is that the girl has only one
X chromosome in her cells. Some girls with Turner
syndrome do have two X chromosomes, but one of
the X chromosomes is incomplete. In another
scenario, the girl has some cells in her body with
two X chromosomes, but other cells have only one.
This is called mosaicism.

DIAGNOSIS
A diagnosis of Turner syndrome may be suspected
when there are a number of typical physical
features observed such as webbed neck, a broad
chest and widely spaced nipples. Sometimes
diagnosis is made at birth because of heart
problems, an unusually wide neck or swelling of
the hands and feet.
The two main clinical features of Turner syndrome
are short stature and the lack of the development
of the ovaries.
Many girls are diagnosed in early childhood when a
slow growth rate and other features are identified.
Diagnosis sometimes takes place later when
puberty does not occur.
Turner syndrome may be suspected in pregnancy
during an ultrasound test. This can be confirmed
by prenatal testing - chorionic villous sampling or
amniocentesis - to obtain cells from the unborn
baby for chromosomal analysis. If a diagnosis is
confirmed prenatally, the baby may be under the
care of a specialist pediatrician immediately after
birth.

Diagnosis is confirmed by a blood test, called a

karyotype. This is used to analyze the
chromosomal composition of the female.