Velammal Education Trust

VELAMMAL VIDYALAYA MEL

AYANAMBAKKAM

ACADEMIC YEAR 2022 – 23

BIOLOGY
INVESTIGATORY
PROJECT

NAME - Arivuselvan.V
ROLL NO
 VELAMMAL EDUCATIONAL TRUST
VELAMMAL
VIDYALAYA MEL AYANAMBAKKAM

NAME: Arivuselvan.V BATCH NO:

CLASS: XII-C REG:

CERTIFICATE
This is to certify that the biology investigatory project on the topic
“CIPA” has been successfully completed by Arivuselvan of class XII
under the guidance of Mrs. Mariam in partial fulfilment of biology
practical in curriculum of AISSCE-CBSE, New Delhi for the academic
year 2022-2023.

Teacher in charge

Signature of external examine Signature of internal examiner

Signature of principal
 ACKNOWLEDGEMENT

I am grateful to almighty for giving me the strength to complete my

project successfully with sustained efforts which many a time oscillate

I am deeply indebted to my biology teacher Ms.MARIAM , whose

constructive feedback, this project would not have been a success. The
valuable advice and suggestion for correction, modification and
improvement did enhance the quality task

I am obliged to Mr. Venkataraman N.S., our principal for providing the

best facilities and environment to bring out innovation and spirit of
inquiry through this venture

I take a special pleasure to acknowledge Ms. Sharmailee for the

willingness in providing us with the necessary lab equipment’s

I am grateful to my parents who helped me in various phases of this

project

CIPA
(Congenital insensitivity to pain with anhidrosis)
Index
 Summary
 Symptoms
 Causes
 Diagnosis
 Treatments
 Lack of Pain
 Case presentation

Summary

Congenital insensitivity to pain with anhidrosis (CIPA) also known as

hereditary sensory and
autonomic neuropathy type IV,
is an inherited disease where
there is an inability to feel pain
and temperature, and
decreased or absent sweating
(anhidrosis).
The inability to feel pain and temperature often leads to repeated,
severe injuries and unintentional self-injury is common. People with
CIPA may also heal slowly from skin and bone injuries, which can lead
to chronic bone infections (osteomyelitis) or a condition called Charcot
joints.
The signs and symptoms of CIPA usually appear at birth or during
infancy. CIPA is caused by changes in the NTRK1 gene. Inheritance is
autosomal recessive.

Symptoms

The most common ages for symptoms of a disease to begin is called

age of onset. Age of onset can vary for different diseases and may be
used by a doctor to determine the diagnosis.

For some diseases, symptoms may begin in a single age range or

several age ranges. For other diseases, symptoms may begin any time
during a person's life.

Most people with congenital insensitivity to pain will show the

following symptoms:

 Pain insensitivity — where

there's no reaction to painful
sensations caused by cuts,
burns, or injections
 Repeated severe injuries and
accidental self-injury — like
severe bite wounds on the
tongue, mouth, and fingers
 Anhidrosis —the reduced ability to sweat
  Anosmia
 No reaction to extreme temperature
 Recurrent high fever — possibly with febrile seizures
 Lack of corneal reflex — which is when you blink as a reflex to
something touching your cornea
 Intellectual disability

CIPA symptoms can vary among people with the condition — you may
see either a few or several of these symptoms in one person with CIPA.

Causes

Mutations in the NTRK1 gene cause CIPA. The NTRK1 gene provides
instructions for making a receptor protein that attaches (binds) to
another protein called NGFβ. The NTRK1 receptor is important for the
survival of nerve cells

The NTRK1 receptor is found on the surface of cells, particularly

neurons that transmit pain, temperature, and touch sensations
(sensory neurons).

When the NGFβ protein binds to the NTRK1 receptor, signals are
transmitted inside the cell that tell the cell to grow and divide, and that
help it survive. Mutations in the NTRK1 gene lead to a protein that
cannot transmit signals. Without the proper signaling, neurons die by a
process of self-destruction called apoptosis.
Loss of sensory neurons leads to the inability to feel pain in people with
CIPA.

In addition, people with CIPA lose the nerves leading to their sweat
glands, which causes the anhidrosis seen in affected individuals.

Inheritance

This condition is inherited in an

autosomal recessive pattern, which
means both copies of the gene in each
cell have mutations.

The parents of an individual with an

autosomal recessive condition each
carry one copy of the mutated gene, but
they typically do not show signs and symptoms of the condition.

Diagnosis
CIP is often diagnosed in early childhood due to a lack of typical pain
response (wincing or crying) during standard medical procedures
like vaccination and treatment for common childhood injuries like falls.
Accidental self-injury is common among young children with CIP — this
includes aggressively biting the mouth, tongue, and fingers to the point
of causing severe damage.

There are not easy tests to identify CIPA, but providers do have a few
tools to help them make the diagnosis.

For example, they can take a small tissue sample and look at it under a
microscope (biopsy) to look for underdeveloped nerves and no sweat
glands.

The most definitive diagnostic test for CIPA is a genetic test to look for
an abnormal TRKA (NTRKI) gene.

Treatments

There is currently no
cure for CIP, so its
treatment mainly
focuses on patient
education — which
includes teaching the patients how to avoid injuries, check themselves
for any injuries, and get treatment for these injuries as quickly as
possible.

In some cases, doctors may suggest preventative medical procedures,

like the removal of primary teeth, to prevent young patients from
injuring themselves before they can learn how to protect themselves.

An opioid antagonist called Naloxone has been explored as a treatment

option for channelopathy-associated congenital insensitivity to pain
and has shown partial success in some cases.

Lack of Pain

Pain is the body’s alarm system. Without it, you may not know that you
have injuries—even if they’re serious. You may re-injure yourself
regularly because there’s no pain to signal to help you avoid doing so.

For example, without pain as a cue, you might not you’re doing too
much on a broken leg that’s trying to heal
If you have CIPA, it’s important to learn how to prevent injuries and to
monitor any injuries you do get carefully so they don’t become
infected or more damaged.

When children have CIPA, it’s up to their caregivers to keep an eye on

injuries. It’s also important that kids with CIPA learn strategies for
staying safe.

COPING WITH CIPA: -

Good medical care and lifestyle changes are key ways to live safely with
CIPA. These strategies should be implemented as soon as the diagnosis
is made and adjusted as needed throughout a child’s life.

CIPA is a rare disorder, making it challenging for families to cope.

Joining a support group—especially one for uncommon disorders that
most people don’t know about or understand—can be a relief and
make you feel less alone. These resources can also help you find
practical ways to make living with CIPA easier.

Since CIPA is an inherited disorder, adults with the condition will want
to discuss it with their partners and providers if they’re thinking about
planning for a family
 Case presentation

A 2.5-year-old boy was referred to the pediatrics clinic with severe self-
mutilating injuries to his hands, feet, tongue and oral mucosa caused
by unconscious biting.

(Ulcerative lesions of the fingers due to self-biting and palmar keratosis)

He is the second child of cousin parents and the product of a term,

normal vaginal delivery with a birth weight of 3300 gr. At two-months
of age, he was admitted to the hospital as a result of fever and
convulsion.
The patient continued to have fever throughout his hospital stay and
evaluation for the etiology of prolonged fever was done and abnormal
results were not seen in any of the diagnostic tests including blood
culture, CSF analysis and culture, urine analysis and culture,
echocardiography, blood smear, bone marrow aspiration and culture,
Wright and Vidal test, abdominal sonography 7 and brain CT scan.
Finally, he was discharged from the hospital on phenobarbital
medication, but episodes of hyperthermia and unexplained fever
recurred.
He is the second child of cousin parents and the product of a term,
normal vaginal delivery with
a birth weight of 3300 gr.
At two-months of age, he was admitted to the hospital as a result of
fever and convulsion. The
patient continued to have fever throughout his hospital stay and
evaluation for the etiology of prolonged fever was done and abnormal
results were not seen in any of the diagnostic tests
including blood culture, CSF analysis and culture, urine analysis and
culture, echocardiography,
blood smear, bone marrow aspiration and culture, Wright and Vidal
test, abdominal sonography

and brain CT scan. Finally, he was discharged from the hospital on

phenobarbital medication, but episodes of hyperthermia and
unexplained fever recurred.

His parents found him never sweating after birth and he did not
tolerate warm weather or sun exposure and he was irritable and cried
with appropriate tearing in such situations. The parents also
complained that the child showed no response to any kind of injury
including pinpricking, burning, hitting and cutting. The boy had never
complained of painful sensation and his hands or feet were burned by
heater flame or hot water repeatedly.
He had a right third metatarsal fracture without reason when he was
2.5 years old that was managed on an outpatient basis and caused
edema and deformity in his right foot.
Teething had started at seven months of age, but because of biting and
ulcerative lesions in the gums, his teeth had started to shed at 1.5
years of age.
On examination, he had 12 kilograms weight (10th percentile), 92-
centimetre height (75thpercentile) and 48 centimetre head
circumference (10th percentile) and a normal blood pressure without
orthostatic hypotension. Ulcerative lesions were seen in his fingers,
toes and mouth that were caused by self-biting
Fungiform papillae on the tongue were present. In addition, keratosis
and thick and dry skin in the palms of his hands and soles of feet were
visible. He had red eyes and corneal ulcer. The deformity as Charcot
joint (neuropathic osteoarthropathy) was observed in the right ankle
due to repeated trauma.
 (Charcot joint in the right ankle)

Neurologic examination revealed normal function of the cranial nerves.

The light response of
pupils and deep tendon reflexes (DTR) were normal and plantar reflex
was flexor bilaterally. He
could not cooperate with the sensory exam. The child had
neurodevelopmental delay based on
Denver Developmental Screening Test-II. His parents and brother were
healthy with normal
intelligence. Family history was also negative and they had no sign of
hereditary disease. The
result of CBC, uric acid, serum glucose, liver, renal and thyroid function
tests, serum lactate,
ammonia, creatinine phosphokinase level and chromatography of amino
acids were normal.
Nerve conduction velocity (NCV) was normal and brain MRI showed
mild brain atrophy.
Electron microscopic study of nerve biopsy and genetic tests were not
available in our centre

Bibliography

https://medlineplus.gov
https://www.webmd.com/
https://rarediseases.info.nih.gov