Topic: Gene Mutation Disorders

and Chromosomal Anomalies

Fathimma Hiba Valiyil Usman

SB23PSY054

I BSc Psychology
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A gene is considered the basic unit of inheritance. Genes are passed from
parents to offspring and contain the information needed to specify physical
and biological traits. Most genes code for specific proteins, or segments of
proteins, which have differing functions within the body. Humans have
approximately 20,000 protein-coding genes.

A mutation is a change in the DNA sequence of an organism. Mutations can

result from errors in DNA replication during cell division, exposure to
mutagens or a viral infection. Mutations are happening in our cells all the time,
but almost none of these affect our health.

There are many reasons that mutations usually don't have major
consequences.

One reason is that our cells have very sophisticated machinery for repairing
mutations very quickly. So there's not enough time for them to cause
problems. Another is that most mutations occur in somatic cells like muscle
cells or skin cells and can only affect the cell where the mutation occurred and
cells that grow from that cell.

Considering the frequency, mutations can be grouped into two:

1. Spontaneous mutation : Naturally occurring; low frequency; more

harmful effects.

2. Induced mutation : Mutation in response to external stimuli collectively

called mutagens; can be in high frequency; more beneficial effects.

Induced mutation has been demonstrated by the use of X-Ray in

Drospohila by H.J.Muller. According to the part of the cell affected by
mutation, it can be classified into three:

1. Chromosomal abnormality, or chromosomal aberration: It is a

disorder characterized by a morphological or numerical alteration in
single or multiple chromosomes, affecting autosomes, sex
chromosomes, or both.
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The four main types of structural chromosomal aberrations are

deletion, duplication, inversion, and translocation.
 Deletions occur when a portion of the chromosome is
deleted, or taken out, which can make that chromosome less
functional.
 In duplication, part of the chromosome is duplicated, resulting
in extra genetic material.
 Inversion of a chromosome happens when the genetic
material is inverted, or flipped in the opposite direction.
 Translocations occur when a piece of one chromosome has
broken off from its original location and attached to another
chromosome.

2. Genomatic mutation: It is the change in the number of

chromosomes from its original chromosome number. It can be
classified as:
 Aneuploidy: It is the presence of an abnormal number of
chromosomes in a cell, for example, a human cell having 45
or 47 chromosomes instead of the usual 46.
 2) Euploidy: It is the gain of one or more complete sets of
chromosomes.

3. Gene mutation: Gene mutations are changes to your DNA

sequence that happen during cell division when your cells make
copies of themselves.

Your DNA tells your body how to form and function. Gene mutations
could lead to genetic conditions like cancer, or they could help humans better
adapt to their environment over time.

A gene mutation is a change in a sequence of your DNA. Your DNA

sequence gives your cells the information they need to perform their functions.
If part of your DNA sequence is in the wrong place, isn’t complete or is
damaged, you might experience symptoms of a gene condition.

 When do gene mutations happen?

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Gene mutations occur during cell division when your cells divide and
replicate. There are two types of cell division:

 Mitosis: The process of making new cells for your body.

 Meiosis: The process of making egg and sperm cells for the next
generation.

 How do genetic mutations happen?

Genetic mutations occur during cell division. When your cells divide, they
hand-write your body’s instruction manual by copying the original document
word for word.

 How do genetic mutations affect other organs?

A genetic mutation changes the information your cells need to form and
function. Your genes are responsible for making proteins that tell your body
what physical characteristics you should have. If you have a genetic mutation,
you could experience symptoms of a genetic condition because your cells are
doing a different job than they should be.

The signs and symptoms you experience could include:

 Physical characteristics like facial abnormalities, a cleft palate,

webbed fingers and toes, or short stature.
 Problems with cognitive (intellectual) function and developmental
delays.
 Vision or hearing loss.
 Breathing problems.
 Increased risk of developing cancer.

GENETIC DISORDERS
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 Genetic disorders occur when a mutation (a harmful change to a gene,

also known as a pathogenic variant) affects your genes or when you
have the wrong amount of genetic material. Genes are made of DNA
(deoxyribonucleic acid), which contain instructions for cell functioning
and the characteristics that make you unique.
 You receive half your genes from each biological parent and may inherit
a gene mutation from one parent or both. Sometimes genes change due
to issues within the DNA (mutations). This can raise your risk of having
a genetic disorder. Some cause symptoms at birth, while others develop
over time. Genetic disorders can be:
 Chromosomal: This type affects the structures that hold your
genes/DNA within each cell (chromosomes). With these conditions,
people are missing or have duplicated chromosome material. Down
Syndrome is an example.
 Complex (multifactorial): These disorders stem from a combination of
gene mutations and other factors. They include chemical exposure, diet,
certain medications and tobacco or alcohol use. Colon cancer is an
example of this condition.
 Single-gene (monogenic) : This group of conditions occurs from a single
gene mutation. Example of this includes Sickle cell anemia.

 What are the types of gene mutation disorders?

There are many types. They include:

1. Albinism
2. Phenylketonuria
3. Alkaptonuria
4. Galactosemia
5. Brachydactyly
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ALBINISM

Albinism is a rare genetic disorder where you aren’t born with the usual
amount of melanin pigment. Melanin is a chemical in your body that
determines the color of your skin, hair and eyes. Most people with albinism
have very pale skin, hair and eyes. They are prone to sunburn and skin
cancer. Melanin also is involved in optical nerve development, so you may
have vision problems.

 Symptoms and Causes:

Albinism is caused by mutations in specific genes that are responsible for

melanin production.

What are the symptoms of albinism?

People with albinism may experience the following symptoms:

 Very pale skin, hair and eyes.

 Patches of missing skin pigment.
 Crossed eyes (strabismus).
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 Patches of missing skin pigment.

 Vision problems.
 Light sensitivity (photophobia).

 Diagnosis and Tests:

Your healthcare provider may do a physical exam and examine your skin, hair
and eyes. However, a genetic test will provide the most accurate results and
help determine which gene is mutated. This DNA test will help determine
which type of albinism you have.

 Management and Treatment:

There is no cure for albinism. You must manage the condition by being
vigilant about sun protection. You can protect your skin, hair and eyes by:

 Staying out of the sun.

 Wearing sunglasses.
 Covering up with sun-protective clothing.
 Applying sunscreen regularly.
 Wearing hats.

If you have crossed eyes (strabismus), a surgeon may be able to correct the
issue with surgery.

PHENYLKETONURIA

Phenylketonuria (PKU) is a genetic condition that causes elevated levels of a

substance called phenylalanine to build up in your body. Phenylalanine is
found in the body as part of normal biochemical pathways, but problems arise
when levels are persistently higher than normal.
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Phenylalanine is an amino acid. Amino acids are molecules that form proteins.
Many of the foods you eat that contain protein and the artificial sweetener
aspartame have phenylalanine. If this condition isn't treated, buildup of
phenylalanine in your body causes symptoms including challenges with
cognitive development (intellectual disability).

 Who does phenylketonuria (PKU) affect?

Phenylketonuria (PKU) can affect anyone who has mutations in both copies of
the PAH gene.

 Symptoms and Causes:

Since diagnosis and treatment of phenylketonuria (PKU) most often occur

shortly after birth due to an abnormal newborn screen, noticeable symptoms
are very rare. Symptoms affect those with undiagnosed or untreated cases.

Symptoms of untreated PKU include:

 Eczema
 Skin and/or hair discoloration (lighter compared to other members of
their family).
 Small head size (microcephaly).
 A musty odor to their breath, skin or urine.

Severe symptoms of untreated PKU include:

 Behavioral problems.
 Developmental delays.
 Behavioral problems.
 Seizures (rare).

Children and adults with mild hyperphenylalaninemia are at a much lower risk
for intellectual disabilities in the absence of treatment.
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 What causes phenylketonuria (PKU)?

Mutations in both copies of the PAH gene causes phenylketonuria (PKU). The
PAH gene gives your body instructions to make an enzyme (phenylalanine
hydroxylase) that's responsible for converting amino acids into components
(proteins) that your body can use. When your body can’t process the amino
acids that you eat in your diet, they build up in your blood and tissues. Your
body is sensitive to phenylalanine. Too much phenylalanine in your body
damages your brain.

 Is phenylketonuria (PKU) dominant or recessive?

Phenylketonuria (PKU) is a genetic condition that passes to children from their

parents in an autosomal recessive pattern. This means that babies receive
one copy of the mutated gene that causes PKU from each parent during
conception.

 Management and Treatment:

Treatment for PKU is lifelong. It may include a special diet or medication.

Treatment could include:

 Eating a special diet low in phenylalanine but full of nutrients.

 Taking vitamins, minerals and supplements.
 Adding a supplemental medication called sapropterin dihydrochloride to
break down phenylalanine in your body.

 What foods contain phenylalanine?

 Milk.
 Eggs.
 Cheese.
 Nuts.
 Fish.
 Chicken.
 Beef.
 Beans.
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ALKAPTONURIA
Alkaptonuria is a rare inherited disorder. It occurs when your body can’t
produce enough of an enzyme called homogentisic dioxygenase (HGD). This
enzyme is used to break down a toxic substance called homogentisic acid.

When you don’t produce enough HGD, homogentisic acid builds up in your
body. The buildup of homogentisic acid causes your bones and cartilage to
become discolored and brittle. This typically leads to osteoarthritis, especially
in your spine and large joints.

People with alkaptonuria also have urine that turns dark brown or black when
it’s exposed to air.

 Symptoms and causes

What are the symptoms of alkaptonuria?

 Dark stains on a baby’s diaper are one of the earliest signs of

alkaptonuria. There are few other symptoms during childhood.
Symptoms become more obvious as you age.
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 Your urine may turn dark brown or black when it’s exposed to air. By the
time you reach your 20s or 30s, you may notice signs of early-onset
osteoarthritis.

Other symptoms of alkaptonuria include:

 Dark spots in the sclera (white part) of your eyes.

 Thickened and darkened cartilage in your eyes.
 Blue speckled discoloration of your skin, particularly around sweat
glands.
 Dark colored sweat or sweat stains.
 Kidney stones and prostrate stones.
 Arthritis.

Alkaptonuria can also lead to heart problems. The buildup of homogentisic

acid causes your heart valves to harden. This can keep them from closing
properly, resulting in aortic and mitral valve disorders.

 What causes alkaptonuria?

Alkaptonuria is caused by a mutation on your homogentisate 1,2-dioxygenase

(HGD) gene. It’s an autosomally recessive condition.

 How is alkaptonuria treated?

There’s no specific treatment for alkaptonuria. Instead, treatment is focused

largely on managing symptoms. However, The National Institutes of Health
warns that long-term use of vitamin C can sometimes increase the production
of kidney stones and has generally proven ineffective for long-term treatment
of this condition. Other treatments for alkaptonuria are focused on preventing
and relieving possible complications, such as arthritis, heart diseases and
kidney stones.
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GALACTOSEMIA
Galactosemia is an inherited metabolic disorder that makes your body unable
to process a sugar called galactose. Galactosemia can be a problem for
newborns because galactose is present in both breast milk and most baby
formulas. With early diagnosis and a lactose-restricted diet, people with
galactosemia can go on to lead relatively normal lives.

 How does this condition affect my child’s body?

When your child is unable to break down the galactose in their food, it begins
to build up in their blood. Galactosemia literally means “galactose in the
blood.” As it builds up, it overflows into places it shouldn’t go. An enzyme that
is not supposed to be involved with galactose converts it to galactitol, an
alcohol derivative that is toxic to the body. As toxic galactitol accumulates in
your child’s organs and tissues, it can cause serious damage. If left untreated,
galactosemia leads to a cascade of side effects, including:

 Cataracts.
 Developmental delays.
 Intellectual disabilities.
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 Speech difficulties.
 Fine and gross motor difficulties.
 Neurological impairments.
 Kidney disease.
 Premature ovarian insufficiency.

 Who does galactosemia affect?

Galactosemia is a genetic disorder. It can affect anyone who inherits the

mutated genes (one from each parent). If both of your parents are carriers of
the mutated gene, you have a 25% chance of inheriting galactosemia. This
condition happens around the world, in all ethnic groups.

 Symptoms and Causes:

In newborns, signs of classic galactosemia begin to appear after a few days of

feeding. Symptoms can be mild or severe and may include:

 Loss of appetite.
 Lethargy.
 Vomiting.
 Diarrhea.
 Severe weight loss.
 Weakness.
 Failure to thrive.
 Jaundice.
 Enlarged liver.

These symptoms require immediate medical attention. After a healthcare

provider diagnoses galactosemia and you remove galactose from your baby’s
diet, these symptoms should improve.

 What causes galactosemia?

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Galactosemia happens because of a gene mutation. You have to inherit it

from both parents to get it. Each parent provides one copy of the mutated
gene. But unless both copies of their galactosemia genes are mutated, the
parents typically won’t have symptoms of the condition themselves, so
symptoms in their baby can come as a surprise.

 Management and Treatment:

The only known way to treat galactosemia is to eliminate galactose from your
diet. This usually means avoiding dairy products. Newborns can receive a
soy-based or elemental formula. Children and adults may need to supplement
their calcium and vitamin D intake to make up for the lack of dairy products in
their diet. Supplementing with calcium and vitamin D helps to maintain bone
density.
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BRACHYDACTYLY
Brachydactyly means “short digits” and is a general term to identify fingers
and toes that are shorter than normal. Brachydactyly is a genetic condition,
and it happens because of a gene mutation that affects bone growth.

 Symptoms and Causes:

The major symptom of brachydactyly is short bones in your hands and feet
that cause your fingers and toes to appear shorter than normal in proportion to
the rest of your body.

A genetic mutation causes brachydactyly. Different genes cause different

types of brachydactyly.

Medications a parent takes during pregnancy, including antiepileptic

medicines to treat epilepsy, could cause brachydactyly. Low blood flow to your
hands and feet during infancy could affect how your bones grow.

 Management and Treatment:

In most cases, brachydactyly doesn’t affect the function of your fingers and
toes on your hands and feet, so no treatment is necessary.

If the shortened bones in your fingers and toes affect movement,

reconstructive surgery will improve your ability to use your hands and feet.
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CHROMOSOMAL
ANOMALIES
A chromosomal abnormality is an extra, missing, or irregular piece of
chromosomal DNA, which makes up part of our genetic material. Many
inherited diseases and specific traits are the result of chromosomal
abnormalities or alterations. Certain chromosomal abnormalities may be
visible or apparent at birth (birth defects) or can give rise to congenital
conditions which develop over the course of time.
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DOWN SYNDROME
This syndrome is a type of trisomy as there is an extra copy of chromosome
21. It is a genital condition where people are born with an extra chromosome.
It is named after the person who discovered this chromosomal disorder –
Langdon Down. The symptoms in a person include the following:

 The person is short and has a small and round head.

 Physical and mental development is retarded.
 Furrowed tongue and partially open mouth.
 Broad palm.
 Dental problems.
 Vision problems.

 Cognitive signs include:

A child’s inability to meet developmental milestones may vary from other

children, including how they walk and move, speak, learn and play.

 Behavioral signs include:

 Strubbornness and tantrums.
 Difficulty paying attention.
 Obsessive or compulsive behaviors.

 Treatment:

There is no single, standard treatment for Down syndrome. Treatments are

based on each individual’s physical and intellectual needs, as well as his or
her personal strengths and limitations. People with Down syndrome can
receive proper care while living at home and in the community. However, they
could include the following:

 Physical therapy.
 Speech-language therapy.
 Occupational therapy.
 Emotional and behavioral therapies.
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KLEINFELTER’S SYNDROME

This genetic disorder arises due to the presence of an additional X

chromosome in males. Most males have 46 chromosomes. Thus, resulting in
a chromosome count of 47 (44 + XXY) instead of 46. This is a congenital
condition. The symptoms include:

 Depression,
 Anxiety,
 ADHD,
 Speech delays as (neurological symptoms)
 Testicular failure,
 Smaller penis,
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 Might experience infertility, meaning they might lose the ability to make
sperm.

 Treatment:

Although there's no way to repair the sex chromosome changes due to

Klinefelter syndrome, treatments can help minimize its effects. The earlier a
diagnosis is made and treatment is started, the greater the benefits. But it's
never too late to get help. However other treatments include:

 Testosterone replacement therapy,

 Breast tissue removal,
 Speech and physical therapy,
 Fertility treatment.
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TURNER’S SYNDROME

Unlike Klinefelter syndrome, in this chromosomal disorder there is the

absence of one X chromosome in females. Hence, decreasing the
chromosomes count to 45 (44 + X0).

 Symptoms include the following:

 Low levels of sex hormones.
 Have smaller than expected expected ovaries that may only function for
a few years or not at all.
 Hypertension.
 Osteoporosis.
 Short stature.
 Fertility issues.

 Treatment:
 Growth hormone therapy.
 Oestrogen and Progesterone replacement therapy.
 Therapy.
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CRI DU CHAT SYNDROME

Cri du chat syndrome is a rare genetic disorder caused by a missing section

on a particular chromosome known as Chromosome 5. Sometimes, material
from another chromosome is missing as well. Around one in every 50,000 or
so babies is diagnosed with this disorder. This estimate is coming down. With
more advanced and frequent genetic testing, and many more milder cases
being diagnosed, it may be as low as one in 25,000. It is not the result of
anything the parents have done or failed to do.

The characteristics of a newborn with cri du chat syndrome include a high-

pitched cry, a small head and a flattened bridge of the nose.

Around a third as many girls as boys are affected. Other names for this
condition include cat-cry syndrome, 5P minus syndrome and Le Jeune’s
syndrome.

 Symptoms of Cri Du Chat Syndrome:

Cri du chat syndrome is often diagnosed at birth. The symptoms in a newborn

baby can include:

 a high-pitched, cat-like cry or weak cry.

 low birth weight.
 a small head
 a rounded face
 a broad, flattened bridge of the nose.
 eyes spaced wide apart.
 folds of skin over the eyelids.

 Treatment for cri du chat syndrome:

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There is no cure for cri du chat syndrome. Treatment aims to stimulate the
child and help them to reach their full potential and can include:

 Physiotherapy to improve poor muscle tone.

 Speech therapy.
 Communication alternatives, such as sign language, since speech is
usually delayed, often severely.
 Occupational therapy to teach coping strategies and new skills.