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PREFACE

Neurofibromatoses genetic disorders

of the nervous system.
Mainly affect the growth and
development of nerve cell tissue.
The disorders are known as:
neurofibromatosis type 1 (NF1) and
neurofibromatosis type 2 (NF2).
NF1 is the more common type of
neurofibromatosis.

Embriology
Neural crest cells (primitive cells which exist
during fetal development) eventually turn
into:
cells which form nerves throughout the
brain, spinal cord, and body.
Nerves sheath
pigment cells
the meninges
cells which ultimately develop into the
bony structures of the head and neck,

What causes neurofibromatosis?

NF1 and NF2 occur as a result of defects in

different genes .
Neurofibromatosis is a genetic disorder that
may be associated with multiple neurofibromas.
This disease is transmitted through an
autosomal dominant mutant gene.
The mutated gene can be inherited from a
parent who has NF or in some cases of a
spontaneously mutated gene.
A parent with NF has a 50% chance of passing
the gene on to each of their children.

Neurofibromatosis type 1 (NF1)

The NF1 gene is a large gene (60 exons)
localized on chromosome 17 and
mutations are scattered over the gene.
The NF1 gene is a tumor suppressor gene
and its gene product neurofibromin
negatively regulates p21 ras.
In a small subset of NF1 patients (5%) a
NF1 microdeletion can be demonstrated.
NF1 patients with a microdeletion show
more neurofibromas at a younger age,
have a lower average IQ and a higher risk
of developing MPNST.

Neurofibromatosis type 2 (NF2)

less frequent than NF1 and has a
birth incidence of 1 in 30 000-40 000.
It is caused by a dominant mutation
in the NF2 gene which is located on
chromosome 22.
The NF2 gene codes for the protein
Merlin/Schwannomin.
The hallmarks of NF2 are the bilateral
vestibular schwannomas (formerly
called acoustic neuromas).

In neurofibromatosis, a genetic
defect causes these neural crest cells
to develop abnormally. This results in
numerous tumors and malformations
of the nerves, bones, and skin.

Neurofibromatosis occurs in about

one of every 4,000 births. Two types
of NF exist, NF-1 (90% of all cases),
and NF-2 (10% of all cases).

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Neurofibromatosis is diagnosed using a number

of tests, including:
Medical history
Family history
Physical examination
X-rays
Computerized tomography (CT) scans
Magnetic resonance imaging (MRI)
Biopsy of neurofibromas
Eye tests
Tests for particular symptoms, such as hearing or
balance tests
Genetic testing (available for families with
documented cases of NF1 and NF2)

NF-1 has a number of possible signs

and can be diagnosed if any two of
the following are present:

The presence of caf-au-lait (French for

coffee-with-milk) spots.
These are patches of tan or light brown
skin, usually about 5-15 mm in diameter.
Nearly all patients with NF-1 will display
these spots.
Multiple freckles in the armpit or groin
area.
Lisch nodules in the iris (colored area) of
the eye.

Neurofibromas. These soft tumors are the

hallmark of NF-1. They occur under the skin,
often located along nerves or within the
gastrointestinal tract. Neurofibromas are
small and rubbery, and the skin overlying
them may be somewhat purple in color.
Skeletal deformities, twisted spine
(scoliosis), curved spine (humpback), or
bowed legs.
Tumors along the optic nerve, vision
disturbance in about 20% of patients.
The presence of NF-1
in a patient's parent, child, or sibling.

Caf-au-lait mark

Neurofibroma

Freckling in the armpit

Neurofibromas

Plexiform neurofibroma

Clinical manifestations of NF1:

Scoliosis, pseudarthrosis, bowing, optic pathway glioma.

There are basically types of

neurofibromas found in NF1:
1. Cutaneous:
superficial, soft
button like tumors
with no malignant
potential

2. Subcutaneous:
tumors in the dermis
that may cause
localized pain or
tenderness

There are basically types of

neurofibromas found in NF1:
3. plexiform:
large network of tumours
involving the dorsal
nerve roots . invasive
tumours that may involve
all layers of skin, muscle,
bone and blood vessels

NEUROFIBROMA, PLEXIFORM

Characteristic symptoms of NF-2 are due to

tumors along the acoustic nerve.
loss of hearing
causing weakness of the muscles of the
face
headache, dizziness, poor balance, and
uncoordinated walking.
cataracts
As in NF-1, the chance of brain
tumors developing is unusually high.

Management

There is no cure for

neurofibromatosis.
Treatments for both types of
neurofibromatosis focus on controlling
symptoms.
There is no standard treatment for NF
and many symptoms, such as caf au
lait spots, do not need treatment.

When treatment is necessary, options may include:

Surgery to remove problematic growths or tumors
chemotherapy or radiation if a tumor has turned
malignant or cancerous
Surgery may also help some bone problems, like
scoliosis
Therapy (including physical therapy, counseling or
support groups)
Cataract removal surgery
Aggressive treatment of associated pain

Indication of surgery:

Biopsy: to determine the type of

mass
Pain
Cosmetic consideration
Progressive neurological
deterioration
Compression of adjacent tissues
Suspicion of malignant tumor

Monitoring the progression of

neurofibromatosis involves careful testing
of vision and hearing.
X-ray studies the development of
deformities.
CT scans and MRI scans track the
development/progression of tumors in the
brain and along the nerves.
Auditory evoked potentials determine
involvement of the acoustic nerve
EEG patients with suspected seizures.