Name: Areeba Khan

ID: 19008231-018
Department: Biotechnology
Semester: 6th
Batch: 8th
Course: Molecular Biology-II
Assignment: 3
Submitted to: Miss Tahoor Khalid
Topic: Diseases related to Epigenetics
Epigenetics:
Epigenetics is the study of heritable changes in gene expression that occur without a change in
DNA sequence. It is basically a stable alteration in gene expression pattern that play a key role in
normal cell growth and differentiation.

Disorders associated with Epigenetics:

Fragile X syndrome:

Fragile X syndrome is a genetic condition that causes a range of developmental problems including
learning disabilities and cognitive impairment. Usually, males are more severely affected by this
disorder than females.

Symptoms:

Symptoms of fragile X syndrome include chromosome instability and intellectual disabilities.

Causes:

Mutations in the FMR1 gene cause fragile X syndrome. The FMR1 gene provides instructions for
making a protein called FMRP. This protein helps regulate the production of other proteins and
plays a role in the development of synapses, which are specialized connections between nerve
cells. Synapses are critical for relaying nerve impulses.

Nearly all cases of fragile X syndrome are caused by a mutation in which a DNA segment, known
as the CGG triplet repeat, is expanded within the FMR1 gene. Normally, this DNA segment is
repeated from 5 to about 40 times. In people with fragile X syndrome, however, the CGG segment
is repeated more than 200 times. The abnormally expanded CGG segment silences the FMR1 gene,
which prevents the gene from producing FMRP. Loss or a shortage of this protein disrupts nervous
system functions and leads to the signs and symptoms of fragile X syndrome.
Diagnosis:

Fragile X syndrome can be diagnosed by testing a person's DNA from a blood test. A doctor or
genetic counselor can order the test. Testing also can be done to find changes in the FMR1 gene
that can lead to fragile X-associated disorders.

Other diseases associated with Fragile X syndrome:

Affected individuals usually have delayed development of speech and language by age 2. Most
males with fragile X syndrome have mild to moderate intellectual disability, while about one-
third of affected females are intellectually disabled. Children with fragile X syndrome may also
have anxiety and hyperactive behavior such as fidgeting or impulsive actions. They may have
attention deficit disorder (ADD), which includes an impaired ability to maintain attention and
difficulty focusing on specific tasks. About one-third of individuals with fragile X syndrome have
features of autism spectrum disorder that affect communication and social interaction. Seizures
occur in about 15 percent of males and about 5 percent of females with fragile X syndrome. Most
males and about half of females with fragile X syndrome have characteristic physical features that
become more apparent with age.

Treatment:

There is no cure for FXS. However, treatment services can help people learn important skills.
Services can include therapy to learn to talk, walk, and interact with others. In addition, medicine
can be used to help control some issues, such as behavior problems. To develop the best treatment
plan, people with Fragile X syndrome, parents, and health care providers should work closely with
one another, and with everyone involved in treatment and support, which may include teachers,
childcare providers, coaches, therapists, and other family members. Taking advantage of all the
resources available will help guide success.

Rett syndrome:

Rett syndrome is a rare genetic neurological and developmental disorder that affects the way the
brain develops, causing a progressive loss of motor skills and speech. This disorder primarily
affects girls.
Symptoms:

Slowed growth:

The brain doesn’t grow properly, and the head is usually small (doctors call this microcephaly).
This stunted growth becomes clearer as the child gets older.

Problems with hand movements:

Most children with Rett syndrome lose the use of their hands. They tend to wring or rub their hands
together.

No language skills:

Between ages 1 to 4, social and language skills start to decline. Children with Rett syndrome stop
talking and can have extreme social anxiety. They may stay away from or not be interested in other
people, toys, and their surroundings.

Trouble with breathing:

A child with Rett may have uncoordinated breathing and seizures, including very fast breathing
(hyperventilation), forceful exhaling of air or saliva, and swallowing air.

Children with Rett syndrome also tend to become tense and irritable as they get older. They may
cry or scream for long periods of time, or have long fits of laughter.

Causes:

Most children with Rett syndrome have a mutation on the X chromosome. Exactly what this gene
does, or how its mutation leads to Rett syndrome, isn’t clear. Researchers believe that the single
gene may influence many other genes involved in development. Although Rett syndrome is
genetic, children almost never inherit the faulty gene from their parents. Rather, it’s a chance
mutation that happens in DNA. When boys develop the Rett syndrome mutation, they rarely live
past birth. Males have only one X chromosome (instead of the two girls have), so the effects of
the disease are much more serious, and almost always fatal.
Diagnosis:

A diagnosis of Rett syndrome is based on a girl’s pattern of symptoms and behavior. Doctors can
make the diagnosis based on these observations alone and by talking to the girl’s parents about
things like when the symptoms started. Because Rett syndrome is rare, doctors will first rule out
other conditions, including autism spectrum disorder, cerebral palsy, metabolic disorders, and
prenatal brain disorders. Genetic testing can help confirm the diagnosis in 80 percent of girls
with suspected Rett syndrome. These tests may also predict how severe it will be.

Treatment:

Although there is no cure for Rett syndrome, there are treatments that can improve symptoms. And
children should continue these treatments for their entire life. Experts believe that therapy can help
girls with Rett syndrome and their parents such as physical therapy, speech therapy,
occupational therapy, behavioral therapy. Some girls may be able to go to school and learn
better social interaction. Medicines can treat some of the problems with movement in Rett
syndrome. Medication can also help control seizures. Many girls with Rett syndrome can live at
least into middle age. Researchers are studying women with the disease, which was only widely
recognized in the last 20 years. Good nutrition is also necessary to treat a Rett syndrome.

ATR X syndrome:

Alpha thalassemia X-linked intellectual disability (ATR-X) syndrome is a rare genetic disorder
affecting multiple organ systems of the body. Alpha thalassemia, a condition where there is a
defect in the production of the oxygen-carrying pigments of red blood cells (hemoglobin), is not
seen in every case. Additional abnormalities are usually present in most cases. ATR-X syndrome
is inherited as an X-linked recessive genetic condition.

Symptoms:

ATR-X syndrome is characterized by intellectual disability, characteristic facial features,

abnormalities of the genitourinary tract, and alpha thalassemia. Additional symptoms include an
abnormally large, protruding tongue, improper positioning of the teeth of the upper jaw in relation
to those of the lower jaw (malocclusion), and abnormal configuration of the outer, visible portions
of the ears.

Causes:

ATR-X syndrome is inherited as an X-linked recessive genetic condition. X-linked genetic

disorders are conditions caused by an abnormal gene on the X chromosome and manifest mostly
in males. Females that have a defective gene present on one of their X chromosomes are carriers
for that disorder. Males have one X chromosome that is inherited from their mother and if a male
inherits an X chromosome that contains a defective gene, he will develop the disease.

Female carriers of an X-linked disorder have a 25 percent chance with each pregnancy to have a
carrier daughter like themselves, a 25 percent chance to have a non-carrier daughter, a 25 percent
chance to have a son affected with the disease and a 25 percent chance to have an unaffected son.
Females who carry the mutated ATRX gene are intellectually normal and do not have clinical
symptoms because of a process known as marked skewing of X chromosome inactivation. In this
process, early during fetal development, one of a female’s two X chromosomes is inactivated.
With rare exceptions, the X chromosome carrying the mutated ATRX gene is inactivated.

If a male with X-linked disorders is able to reproduce, he will pass the defective gene to all of his
daughters who will be carriers. A male cannot pass an X-linked gene to his sons because males
always pass their Y chromosome instead of their X chromosome to male offspring. No male with
ATR-X is known to have reproduced.

Diagnosis:

ATR-X syndrome may be suspected at birth or during infancy based upon a thorough clinical
evaluation and identification of characteristic findings e.g., intellectual disability, distinctive facial
features, genitourinary abnormalities. Blood tests e.g., brilliant cresyl blue stain that demonstrate
the presence of hemoglobin H inclusion bodies in red blood cells may assist in diagnosis. HbH is
a variable finding in ATR-X syndrome and failure to detect HbH inclusion bodies does not rule
out ATR-X syndrome. A diagnosis of ATR-X syndrome may be confirmed by molecular genetic
testing that identifies a mutation of the ATR-X gene.
Other disorders associated with ALTR-X syndrome:

Smith-Fineman-Myers syndrome is a rare genetic disorder characterized by intellectual

disability, diminished muscle tone (hypotonia), characteristic facial features, short stature and
additional abnormalities. Smith-Fineman-Myers syndrome is inherited as an X-linked recessive
genetic condition. One family diagnosed as Smith-Fineman-Myers syndrome had a mutation in
ALTR-X gene, but the original family has not been studied at a molecular level.

Alpha thalassemia/intellectual disability chromosome 16 (ATR-16) syndrome is an extremely

rare disorder characterized by intellectual disability, which is milder than in ATR-X syndrome,
and alpha thalassemia, which is more severe than in ATR-X syndrome. ATR-16 syndrome occurs
due to deletion of genes at the end of chromosome 16.

Coffin-Lowry syndrome is a rare genetic disorder characterized by intellectual disability;

abnormalities of the head and facial area, large, soft hands with short tapered fingers, short stature,
and various skeletal abnormalities. It is caused by mutations in the RPS6KA3 gene and is inherited
as an X-linked dominant genetic condition. Males are usually more severely affected than females.

Treatment:

The treatment of ATR-X syndrome is directed toward the specific symptoms that are apparent in
each individual. Treatment may require the coordinated efforts of a team of specialists.
Pediatricians, surgeons, dental specialists, speech pathologists, eye specialists, and specialists
in treating skeletal disorders (orthopedists), and other healthcare professionals may need to
systematically and comprehensively plan an affected child’s treatment. Genetic counseling will
be of benefit to the families of affected individuals. Other treatment for ATR-X syndrome is
symptomatic and supportive.