Neurofibromatosis type 1, commonly referred to as NF1 is a genetic disorder that is associated

with the nervous system. The disorder alters the growth and development of nerve cells. As a
result of these changes, benign tumors known as neurofibromas can grow on nerves and skin.
There are two other types of NF (Neurofibromatosis) but are less common. NF2
(Neurofibromatosis Type 2) and Schwannomatosis both occur every 1 in 40000 people.

Allele - An allele is a gene that is passed from parent to child. Genes code for
our visible and underlying characteristics, such as the colour of one's hair or
blood type. There are varying types of alleles for each trait that an individual
possesses, just like how there are different flavours of ice cream. Each parent
passes down half of their genes, meaning a child will inherit one allele from each
parent. The one allele from each parent combine to give the offspring their
unique or similar characteristic or trait.

NF1 has an AUTOSOMAL DOMINANT inheritance pattern meaning

that regardless of which parent the allele comes from, the disorder
will be expressed. In other words the individual would only need one
copy of the mutated gene to express the disease. In 50% of cases of
neurofibromatosis are hereditary, attained through family members, as
shown in the graphic on the left. In the graphic, it displays a
homozygous recessive female (both alleles are normal, i.e. don't carry
the disease) with a heterozygous male (one allele carries the disease
while the other is normal). There is a 50% chance that the mutated
gene could be passed down to offspring since the other allele is
unaffected.
It is important to note the other half of cases show that new
mutations can occur naturally by accident (spontaneous
mutation)
 The NF1 gene is responsible for Neurofibromatosis Type
1. The gene can be found on chromosome 17, specifically on
the long arm of band 11.2, indicated by the yellow arrow in
the image below. The gene is a result of a point mutation. A
point mutation occurs when a cell miscopies a single DNA
base when replicating. DNA bases are the building blocks of
DNA, and when combined together in certain sequences, give
rise to varying genes. A full of deletion of the gene can also
cause the disorder.

The NF1 gene codes for a protein called neurofibromin 1 and its primary purpose is to
stimulate Ras, another type of protein. The function of Ras is that it regulates cell growth
and differentiation through the transmission of signals from the outside of the cell to the
inside. Neurofibromin 1 prevents tumor growth as it turns Ras off when needed. This
prevents uncontrolled division and overgrowth that would typically result in tumours.
When the NF1 gene is mutated the gene produces a version of neurofibromin 1 that is
shortened and unable to control cell differentiation and growth.
This causes the Ras proteins to be on constantly, therefore they are continiously sending
signals even when it is not needed. Due to the over-signaling neurofibromas can form.

In order to diagnose NF1, the individual must have at least 2 of the following symptoms:
 6 cafe au lait spots after puberty that are greater than 15 mm
 At least 2 neurofibromas
 An optic glioma
 At least 2 lisch nodules
 Changes to bone
 A family member with neurofibromatosis of any type (can vary)

Possible Symptom Cause of Symptom Effect of Symptom Graphic

Cafe Au Lait Melanin:  Cafe au lait spots are
Melanin are the cells that harmless. There is no
Spots form the skin’s pigment. pain or irritation of any
sort.
 In NF1 there is an
increased amount  Over time due to sun
of melanin. As a exposure the spots can
result of the get bigger.
increased volume
they group together  These spots can have a
causing the skin to negative impact on
appear darker. emotional and mental
well-being as many
children and adults are
self-conscious about their
appearance.

Neurofibromas Neurofibromin 1:  Neurofibromas are

The failure of benign, meaning not
neurofibromin 1 to control cancerous, but can be
the growth and itchy.
differentiation of cells,
causes rapid overgrowth  If an individual touched
and division. his/her neurofibromas or
got injured, the tumors
 Those would cause pain
compromised  This is due to the
nerve tissues fuse mast cells
with mast cells releasing
(inflammatory white histamine, a
blood cells) and compound
connective tissue correlated with
forming benign immune response.
tumors
(neurofibromas)  The neurofibromas can
under/in skin. become cancerous and
cause extreme pain but
this occurrence is
extremely rare

Plexiform  In some  Plexiform neurofibromas,

circumstances, the the other type of
Neurofibromas inside branches of neurofibromas are less
the nerves become common in NF1 and more
affected, causing serious.
plexiform  Tumors are bigger
neurofibromas and can cause an
increased amount
 of pain compared
to regular
neurofibromas.
 Have an
increased chance
of becoming
cancerous as the
individual gets
older

Lisch Nodules Mutation of NF1 Gene:  Lisch nodules don’t

 The mutation interfere with an
allows benign individual’s vision and
tumors to form causes no known
without regulation complication to the eye.
 Melanocytes (dark  They are difficult to see in
pigment) fuse with most cases without
the tumors forming magnification.
melanocytic
hamartomas
(small, dark
tumors).

Optic Glioma Neurofibromin 1:  Optic gliomas mainly

 Optic gliomas cause vision complication
(benign tumors) but can also cause
form on the optic headaches and dizziness,
nerves through the which leads to vomiting.
absence or defect  This is due to the
of the pressure that is
neurofibromin 1 being put on the
protein. optic nerve by the
tumor.

Scoliosis Neurofibromas:  Scoliosis is usually

 Scoliosis occurs harmless when it first
because of forms
neurofibromas that  As the spine grows
grow on the spine. continuously, it can
 This causes the produce immense pain
bone to curve over  As an individual gets
a period of time. older, scoliosis can cause
degeneration
Learning Neurofibromas: Since there are multiple learning
 Various learning disabilities associated with NF1,
Disabilities disabilities can the impact of health can range.
(ADHD)
occur due to
tumors The effects on health are mental
(neurofibromas) rather than physical.
growing on an  Some effects include
individual’s nerves, inability to read body
causing a language and social cues,
dysfunction in their reverse letters and
brain difficulty with organizing
and processing
information.

 Boys with NF1 also have

trouble communicating
due to their motor output
and language.

 ADHD (attention deficit

hyperactivity disorder) is
extremely common in
individuals with NF1. This
disorder corresponds to
the limited control
individuals have with their
impulses.

Macrocephaly Fluid Pressure:  Macrocephaly doesn’t

 Macrocephaly,
other known as an
abnormally large
head size is
caused the
increased amount
of pressure of fluid
in the brain. This
results in an
increased brain
volume.
have any physical impact
on health, but can
interfere with an
individual’s well-being.
 Having a large
head size could
result in emotional
discomfort and
anxiety.

Short Stature Neurofibroma:  Short stature does not

 Short stature is negatively impact one’s
caused by a tumor physical health, but does
(neurofibroma) affect their psychological
growing on the well-being.
hypothalamus,  Studies show that
which is a portion happiness as well
of the brain. as self-esteem is
  The tumor causes gained through
a deficiency in the increased height.
growth hormone,
resulting in an
individual’s short
height.

While NF1 cannot be cured, the symptoms that are involved can be treated

Possible Treatment Benefits Involved Risks Involved

Symptoms

Benefits: Risks:
 This  Some risks of
Surgery (Plastic or treatment can treating regular
Neurofibro Laser): alleviate pain neurofibromas
and correct with surgery
mas  Neurosurgeons the nerves includes thick
can operate on that have scarring and
patients with been affected wounds that may
both cancerous  Patients take a while to
and benign rehabilitate at heal.
tumors a faster rate,  Wound infection
throughout their allowing them
body. to complete
 The daily tasks
surgery with minimal
involves difficulty
cutting
the
neurofibr
omas out
the body,
followed
by
resealing
the skin

Benefits: Risks:
 Rehabilitation  Surgery for
is faster plexiform
 Surgery for neurofibromas
plexiform could result in
Plexiform neurofibromas,  Weight loss damage to an
where tumors and easy individual’s
Neurofibro form in branches management nerves, which
mas of nerves is  This leads to more
more could serious
convoluted, but howev complications
can still be done. er such as the loss
beco of sensation in
me a parts of the
risk, body.
depen
ding
on the
individ
ual

Optic Chemotherapy And Chemotherapy And Chemotherapy And

Corticosteroids: Corticosteroids: Corticosteroids:
Glioma  To begin with,
frequent eye Benefits: Risks:
examinations  Tumor is Using chemotherapy is
would be gone highly disruptive to one’s
required to completely lifestyle as there are a
determine the and will not number of drawbacks.
size and effect of grow back
the tumor on the  Impacts of  Some of this risks
nerve. the optic include nausea,
 If treatment is glioma on vomiting, hair
necessary, then loss, diarrhea,
chemotherapy the individuals health fever, fatigue, and
can reduce the (headaches) are loss of appetite.
tumour size. either eradicated or These risks would
Chemotherapy is reduced drastically affect
particularly used the life of children,
if the tumors youth, and adults
have spread to Surgery:
other parts of the  As a result
brain Benefits: of these
 In order to  Any medical risks,
reduce the conditions public
swelling of the associated environme
skull, with the optic nts, such
corticosteroids glioma would as school
are taken heal and work
would
Surgery:  Faster cause
 Surgery is done process individuals
if the entire  Less stress and
tumor can be disruptive to anxiety
removed one’s lifestyle
 If parts of as there are  There are also
the tumor not constantly long-term effects
cannot worrying of undergoing
be about side chemotherapy
removed, effects that such as heart
then may appear problems and
surgery due to damage to lung
can still surgery tissue.
be done  As opposed
to reduce to Surgery:
the chemotherap
amount y, where all Risks:
of cells in the  The main risk with
pressure targeted area surgery is that
on the are tumors can
skull destroyed, regrow after a
even healthy period of time.
ones, surgery  Studies
Radiation Therapy: only involves show that
 Before surgery is the removal patients
done, radiation of the tumour with NF1
therapy helps to itself are twice
reduce the size as likely to
of the tumour, have a
thus making it Radiation Therapy: recoccura
easier for nce
surgeons Benefits:  5% risk of nerve
 High energy rays  Little to no damage
are targeted at impact/disrup
the tumour tions of
lifestyle Radiation Therapy:
 Rather than
surgery and Risks:
chemotherap  It is proven that
y in some individuals with
cases, NF1 are less likely
radiation to have their
therapy tumours shrink
doesn’t  Risk of brain
require disorders
individuals to  18% risk of
go to the Moyamoya
hospital, syndrome which
which can is where arteries
result in
 emotional are blocked in the
comfort brain
 Sessions only
take 15-60
min

Cafe Au Laser Treatment: Laser Treatment: Laser Treatment:

Although cafe au lait
Lait Spots spots are harmless, Benefits: Risks:
many try to use laser  Cafe au lait  The risks involved
treatment to rid of them spots can be with using laser
removed if treatment is that it
Make-Up: there are only will not be
If the patches are a few effective if there
affecting one’s mental  Skin will not are a number of
and emotional health, wrinkle and spots
make-up can cover the will have a
unwanted spots smooth tone
 Youthful Make-Up:
looking skin
Risks:
 Make-up has
Make-Up: close to no risks
involved as it only
Benefits: requires
 Spots are camouflage
covered make-up that can
easily in a easily be found at
matter of pharmacies.
minutes  The only risk
saving time associated is
and money using the product
on open wounds

Lisch No Treatment: Benefits: Risks:

 Currently there  There is no  There are no risks
Nodules are no treatment record of involved
for lisch nodules lisch nodules
as there is no being harmful
need for it. Due
to the small size  Not even the
of the benign individual will
tumors that don’t be able to
affect one’s see nodules
vision or eye easily so
there would
be no
 discomfort
about
appearance

Scoliosis Treatment for scoliosis No Treatment: No Treatment:

can vary depending on
the curvature of the Benefits: Risks:
spine.  No effort is  A risk involved
required with not treating
 If there is a minimal curves of
minimal curve, the spine is that
then treatment Back Brace: there is a
isn’t necessary possibility that the
as over time the Benefits: body will not be
spine will fix  Cheap able to correct
itself. costing itself.
 Back braces can  Rid of back
be used for pain Back Brace:
individual with  Non-invasive
more severe as opposed Risks:
scoliosis and to surgery  The problem with
can be used to using back braces
correct their . is that in many
spine over a cases it is unable
period of time. Surgery: to mend the
 The harshest spine, it just
condition of Benefits: prevents further
scoliosis, can be  Thoroughly damage
treated with corrects the
surgery. spine and
prevents any Surgery:
future
damage Risks:
 For surgery of the
spine, there are
multiple risks
involving
bleeding, failure of
the rods as well
as damage to
nerves.

 For
individuals
that are
older,
(adults to
seniors)
 the
rehabilitati
on
required
could be
too hard of
a
challenge,
resulting in
the
individual
being
confined to
a
wheelchair
until
he/she is
able to
muster the
willpower
and
strength.

Learning Therapies: Benefits: Risks:

 Various forms  While there are no
Disabilities of therapy all physical risks
For treating learning
difficulties, various ultimately involved with
forms of therapy can develop and therapy, an
help individuals of all strengthen individual’s overall
ages. skills such as well-being could
reading and be corrupted for a
 Such therapies speech period of time.
include language  Teaches
and speech individuals to  Therapy usually
therapy as well not be held involves changing
as occupational down by their one’s lifestyle,
therapy. disabilities and in many
 These cases, individuals
forms of feel that they do
treatment not have control
could be over their
beneficial personal lives,
as it causing emotional
would distress.
allow the  However,
individual this a
s to short-term
control risk and as
their the
 learning therapy
disabilitie progresse
s and s, their
adapt to mental
the and
environm emotional
ent well-being
around will be
them. healthy.
 People with
ADHD, which is
the main
learning
disability that
people with NF1
have, often have
trouble carrying
out daily
activities and are
prone to
aggressive
and/or emotional
outbursts.
 Behavior
al
therapy
could
help
hone and
improve
their self-
control.

Macroceph  There is no Benefits: Risks:

treatment for  No treatment  The risk of having
aly (Large macrocephaly as means no no treatment for
Head Size) there are no disruption or this symptom is
danger changes to that the individual
associated with lifestyle or could feel
this symptom. quality of life insecure with
 Pediatricians themselves
and family resulting in stress
doctors monitor and anxiety
the growth and
development of
the individual.

Short  Treatment is not Benefits: Risks:

always needed  There is an  There are major
Stature for individuals immediate risks involved with
 with short result when taking growth
stature. the injections hormones, most
 are first taken notably chronic
However, causing the kidney disease.
if the individual to  Disorders such as
symptom feel an turner’s
is increase in syndrome, which
affecting appetite affects the growth
the and development
emotiona of females, is a
l and frequent side
mental effect.
wellbeing  Physical
and/or is complications
affecting includes muscle
his/her and joint aches,
body headaches, and
develop swelling of hands
ment, and/or feet
then
short
stature
can be
treated.

 Growth
hormones are
most commonly
taken to
increase one’s
height. Children
and adults can
take injections 3-
6 times a week.

Patient Medical Case History File #616M4L

Personal Data
Sex: Male
Age: 19
 The patient recently left his pediatrician and is now seeing a family doctor in
the medical centre. In the patient’s last appointment he had a concern
Patient’s regarding his lack of focus in his studies. The patient has had trouble
concentrating in university due to his Attention-Deficit Hyperactivity Disorder
Initial (ADHD). The patient also mentioned how his father was diagnosed with
Concern neurofibromatosis 1 over a year ago and was worried about the disease
passing down to himself.

PEDIGREE

Patient:
The patient is in good health, but is not physically active. He
has recently started his post-secondary education and has
admitted to his diet suffering.
Figure
Patient’s Father: 1
The patient’s father was recently diagnosed with NF1 after
consulting a neurologist about having multiple cafe au lait
spots spread throughout his body. The father had these spots
for decades but didn’t not believe it to be a health concern as
it did not cause any pain. However, he noted that he was self-
Medical conscious about his appearance. An MRI of the father brain
History displayed a benign neurofibroma indicated by the yellow
Provided By arrows in Figure 1.
Patient And Patient’s Grandmother:
Family The patient’s grandmother died from brain cancer when the
patient was an infant. She was confined to a wheelchair
beginning in her 40’s as she was diagnosed with severe
scoliosis. The patient’s grandmother was also mentioned to
be short and had a abnormally large head size.

Patient’s Sister:
The patient’s sister is in perfect health as she is physically
active in elementary school.

Patient’s Mother:
 The patient’s mother is also in perfect health with no genetic
disease and has no family history of genetic disorder.

Medical exam indicates that the patient is in Figure

moderate health 2

Test 1 - MRI Scan:

MRI scans showed 3 benign tumors in the patient's
legs, 2 on his back and 1 on his arm as well as over
6 cafe au lait spots spread throughout the body.

Test 2 - Ophthalmologic Slit Lamp Exam;

Results Of Medical The exam indicates that the patient has lisch nodules
Examination And on left and right eye. The lisch nodules have been
Consultation previously gone undiagnosed due to their light
appearance (Figure 2).

Test 3 - X-Ray:
X-ray results show that the patient has mild scoliosis
(Figure 3)
 Figure
3

Additional The grandmother was also illustrated to have a glioma on her optic
nerve when she was alive and the patient’s grandfather currently has
Comments dementia and is living in a long-term care facility