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)(11

UNDER SUPERVISION OF :
PROF.DR:
MARIAM ABO SHADY
ASSISSTENT PROF:
SHIMAA MOUSTAFA

NEUROCUTANEOUS DISORDERS

Definition
Neurocutaneous syndromes in children represent a
large group of neurologic disorders that affect the
central nervous system (brain and spinal cord) and the
peripheral nervous system (nerves that branch out
from the spinal cord to the rest of the body).
Neurocutaneous syndromes are congenital (present at
birth) but not always diagnosed at birth.
(Puttegen.,2015)

It is marked by tumor growth in the brain, spinal


cord, organs, bones and/or skin (skin being the
most common in children), neurocutaneous
syndromes are complex, lifelong conditions that
change and manifest differently during a childs
growth and develpement.

(Puttegen.,2015)

classification
Neurocutaneous Disorders Inheritance
Autosomal Dominant
Autosomal Recessive
X-linked Recessive
SporadicNeurocutaneous Diseases
(Diaconu et al.,2012)

Autosomal Dominant Inheritance

Neurofibromatosis
Tuberous Sclerosis
Von Hippel-Lindau Disease
Lentiginosis-Deafness-Cardiopathy Synd
Hypomelanosis of Ito
PeutzJeghers syndrome
(Diaconu et al.,2012)

Autosomal Ressive Inheritane


Ataxia-Telangiectasia

Xeroderma Pigmentosum
Cockaynes Syndrome
Rothmund-Thomson Syndrome
Sjogren-Larsson Syndrome
Neuroichthyosis
Werner Syndrome and Progeria
(Diaconu et al.,2012)

X-Linked Inheritance
Incontinentia Pigmenti

Sporadic Congenital
andAngiomatoses
Neurocutaneous Melanosis
Linear Sebaceous Nevus
Sturge-Weber Syndrome
Klippel-Trenaunay Syndrome
)Diaconu et al.,2012(

Neurofibromatosis
Neurofibromatosis is a genetic disorder that causes
tumors in the nervous system. Tumors develop in
the nerves or the tissue that surrounds the nerves,
called myelin sheath. . Neurofibromatosis is divided
into three types:

Neurofibromatosistype1(NF1)
Neurofibromatosis type 2(NF2)
Schwannomatosis.
(Wendelin andKitzmller
.,2012)

1. Neurofibromatosis type 1 (NF1).


It is autosomal dominantly inherited, characterized
bymultiple pigmentation (caf-au-lait spots) at birth
and soft tumors (neurofibromas) after infancy.
Surgical removal and laser therapy are conducted.
( Afridi et al.,2015)

Pathology
Neurofibroma is formed by Schwann cells and
intraneural
fibroblasts, with thin undulating collagen fibers
in the middle. Schwann cells test positive for
S-100 protein antibodies.
( Epstein et al., 2015)

Pathogenesis
The gene involved in NF1 is on
chromosome 17 (17q11.2). It produces
neurofibromin, a tumor suppressor. In
NF1, gene mutation in 17q11.2 is
thought to increase proliferation of cells
(the penetration rate of NF1 is 100%).
(Milani et al.,2015)

Clincal picture
characterized by multiple pigmentation (caf-au-lait
spots) at birth and soft tumors (neurofibromas) after
infancy.
Caf-au-lait spot

This is a flat, oval eruption of the color of coffee


with cream or darker brown. It varies in size and
appears on the trunk and extremities.
(Caf-au-lait spots are present in 70% of all
newborns. After infancy, the number of spots
does not increase.
(Varan et al.,2015)
.

Caf-au-lait spots
(Andrade .,2015)

Neurofibroma

A neurofibroma is a soft tumor of normal skin


color or light brownish-pink of various sizes .
It may be produced on any site of skin. It
may be elevated and dome-shaped or
papillary, or flat and palpable.
( Zhou et al.,2015)

(Smith.,2015)

3_Other symptoms of NF1

Central nervous symptoms include


**
**
**
**

neurofibroma in the brain and spiral nerves


meningioma
convulsive seizure
mental retardation or learning impairment.

Bone abnormality, including scoliosis,


deformity or bone defect in the thorax, occurs
in about half of all cases.
( Palazzuoli

et al.,2015)

Diagnosis
NF1 is easily diagnosed by caf-au-lait spots
and neurofibroma.
Although NF1 in childhood is difficult to
diagnose because a few caf-au-lait spots are
the only symptom, the likelihood of NF1 is high
when there are six or more caf-au-lait spots
(the 6-spot criterion) .
(Smith and Santoreneos;2015)

The diagnosis is generally made based on


history, symptoms, and the physical exam.
An MRI scan may be done to create images of
the nerves and brain to look for tumors.
Samples of tumors may also be removed and
sent for a biopsy.
Genetic testing may be recommended for
families with a history of neurofibromatosis.
Prenatal diagnosis may also be possible with
amniocentesis or chorionic villus sampling.
(Wang et
al.,2012)

Treatment
Symptomatic therapy is the main
treatment.
Caf-au-lait spots are treated by laser
therapy and dermabrasion; nevertheless,
they tend to recur.
Neurofibromas on highly visible areas such
as the face on extremities are surgically
removed.
As NF1 is a progressive disease, numerous
neurofibromas may occur on the whole body
after middle age.

(NF2)
It is autosomal dominant neurocutaneous
disorder ( phakomatosis) manifesting as
development of multiple CNS tumours.
Unlikeneurofibromatosis type 1 (NF1), it is
not associated with neurofibromas.
Instead, patients with this disease have:
intracranialschwannoma(s):mostlyvestib
ular schwannoma(s)
intracranial and spinalmeningioma(s)
intraspinal-intramedullaryependymoma(s)
)Gutmann et al.,2010(

CAUSES OF NEUROFIBROMATOSIS TYPE 2


Neurofibromatosis type 2 (NF2) is caused by a
genetic mutation in a gene called NF2.
Normally, the NF2 gene produces a protein
called merlin . This protein plays an important
role in regulating the growth of nerve tissue.
In patients with NF2, this gene is faulty.
This results in the cells producing an incomplete
protein, or no protein at all. Without an effective
merlin protein.

(Hriss et al.,2015)

CLINCAL PICTURE
Most of the problems are caused by non
cancerous (benign) tumours, which grow in
various part of the body:
1_ear problems.
2_cataract.
3_skin problems.
4_pripheral neuropathy.
5_Brain problems.
6_spinal cord problems.

EAR PROBLEMS_1
vestibular schwannomas.
Vestibular schwannomas can cause ear
problems such as:
gradualhearing loss
tinnitus

Less common symptoms of vestibular


schwannomas can include (vertigo),
( nausea )and (vomiting).
(Aboukais and Bonne.,2015)

.CATARACT_2

These are cloudy patches in the lens .


Cataracts can make a vision blurred or
misty.

(Miyanaga etal; 2015

SKIN PROBLEMS_3

NF2 develops benign tumours on or underneath


the surface of their skin. These are called
schwannomas.
These often take the form of skin plaques. These
are small, coloured, raised patches of skin that
are usually less than 2cm across.

Some patients with NF2 also develop one or two


caf au lait spots. However, having caf au lait
spots is usually a sign of neurofibromatosis type
1.
(Hriss et al.,2015)

PRIPHERAL NEUROPATHY_4
pins and needles in the affected body part
numbness and a reduced ability to feel
pain or temperature changes particularly
in your feet.

a burning pain usually in the feet and


legs, followed by the hands and arms as
the neuropathy progresses
(Slattery.,2015)

.BRAIN PROBLEMS_5

Benign tumour (meningiomas )and lead to


symptoms of increased intracranial tention

The tumours can also disrupt certain brain


functions. this may cause:
personality changes
weakness or numbness in one side of the body
difficulty speaking, understanding words, writing
and reading (aphasia).
loss of co-ordination and difficultt walking,
speaking and swallowing.
( Slattery;2015)

.SPINALCORD PROBLEMS_6
benign tumours inside spinal cord. These
are known as ependymomas.
Manifested with:
back pain.
muscle weaknes.
numbeness and tingling.
(Spyra et al.,2015)

DIAGNOSING NEUROFIBROMATOSIS
TYPE 2
A family history of NF2 will also be taken into _1
account when diagnosing the condition.
2_By the clinical picture
3_Tests
(Heineman and Evans, 2015)

Tests:
MRI.
Hearing and eye tests.
Blood tests.
Pre implantation genetic diagnosis:
to help ensure a pregnancy is unaffected by
NF2.
5)Tests during pregnancy:

chorionic villous sampling.

amniocentesis.

(Heineman and Evans, 2015)

TREATING NEUROFIBROMATOSIS TYPE


2
The

treatment focuses on regular monitoring and,


if possible, treating any problems caused by
tumours.

Monitoring:

annual MRI scans


annual eye tests to check for the presence
of cataracts
annual hearing tests to check the extent of
any hearing impairment.
(Naghshineh et al., 2014)

Treating tumours:
The growth of tumours is one of the main problems
associated with NF2 and it's not always obvious
what the best treatment is.
Surgery
It's possible to surgically remove sometumours,
but the risks involved can often outweigh the
benefits.
Radiotherapy
For smaller tumours, a type of radiotherapy known
as the gamma knife may be an option.
(Naghshineh et al., 2014)

Tuberous Sclerosis
Definition
Tuberous sclerosis complex (TSC) is a genetic
disorder affecting cellular differentiation, proliferation,
and migration early in development, resulting in a
variety of hamartomatous lesions that may affect
virtually every organ system of the body.

(Saxena and Sampson .,2015)

Clinical presentation
Tuberous sclerosis was classically described
as presenting in childhood with a triad (Vogt
triad) of:
seizures: absent in one-quarterof
individuals
mental retardation: up to half have
normal intelligence
adenoma sebaceum: only present in
about three-quartersof patients.
(Schwichtenberg,
Malowk.,2015)

Other features of tuberous sclerosis


Neurological
1 _subependymal hamartomas
o 88% are associated with

calcification, although calcification


absent in early childhood
o visible within the first 6 months of
age
2 _white matter abnormalities
variable appearance, with nodular, illdefined, cystic and band like lesions

(Wataya-Kaneda.,2015)

Musculoskeletal
sclerotic bone lesions: 40-66%
hyperostosis of inner table of calvaria
periosteal new bone
scoliosis

Skin
Cutaneous lesions are present in ~95% of cases :
hypopigmented macules : seen in 90% patients
( Gupta et al.,2015)

Treatment and prognosis


Treatment of seizures is essential and
depending on the degree of intellectual
disability, supportive care may be
required
Dermabrasion, excision, cryotherapy and
laser therapy are conducted on the
cutaneous lesions for cosmetic reasons
There is no treatment for the
progressive mental retardation.
( DiMario and Sahin.,2015)

Peutz-Jeghers syndrome
Peutz-Jeghers syndrome (PJS) is a disorder
passed down through families
(inherited) in which the person
developsintestinal
(Ruiz, Gamallo
.,2014)
polyps.A person with PJShas
ahigh risk
developing
certain cancers.

Symptoms
Brownish or bluish-gray pigmented spots
on the
lips, gums, inner lining of the mouth, and
skin

Clubbed fingers or toes

Cramping pain in the belly area

pigmented spots on the


lips and gums

intestinal polyps

(Krishnan et al .,2015 )

Diagnosis
*. A colonoscopy will show colon polyps.
* The small intestine is evaluated with either a
barium x-ray (small bowel series) or a small
camera
that is swallowed and then take multiple
pictures as
it travels through small

Laboratory tests may include:

Complete blood count -- may


revealanemia
Genetic testing

Total iron-binding capacity(TIBC) - may be


associated with iron-deficiency anemia
( Kimura,etal.,2015)

Treatment
Surgery may be needed to remove polyps
that
cause long-term problems.
Iron supplements help counteract blood
loss.

Persons with this condition should be


monitored

Incontinentia pigmenti
Incontinentia pigmenti is skin condition passed
down
through families. It leads to unusual blistering
and
changes in skin color.
(Chatterjee and Mason.,

Causes
Incontinentia pigmenti (IP) is caused by anxlinked dominantgenetic defect.
The condition is most often seen in females.
When it occurs in males, it is lethal.
Most babies born with IP develop discolored
skin within the first 2 weeks. The discolored
skin occurs when a substance called melanin
builds up under the skin. Melanin gives skin
its color.
(Godambe et
al.,2011)

Symptoms
Infants with IP are born with
streaky,blisteringareas. When the areas heal,
they turn into rough bumps. Eventually, these
bumps go away, but leave behind darkened
skin, calledhyperpigmentation.
IP is associated withcentral
nervousystemproblems, including:

Delayed development

Loss of movement (paralysis)

Intellectual disability

Muscle spasms

Incontinentia pigmenti on the leg

(Landy .,2011)

Possible Complications

Delayed development

Infections of blistered skin

Intellectual disability
Muscle spasticity
Paralysis
Seizures
Walking difficulty
Vision problems
(Pereira et al.,
2012)

Treatment
There is no specific treatment for IP.
Treatment is aimed at the individual
symptoms. For example, glasses may be
needed to improve vision. Medicine may be
prescribed to help control seizures or
muscle spasms.
(Landy et al.,2010)

Sturge-Weber syndrome
Sturge-Weber syndrome is a rare disorder
that is present at birth. A child with this
condition will have aport-wine
stainbirthmark (usually on the face) and
may have nervous system problems.
(Limotai et al.,2015)

Causes
The cause of Sturge-Weber is unknown. It is
not thought to be passed down (inherited)
through families.
(Kavanaugh,etal.,2013)
Symptoms

Port-wine stain (more common on the face


than the body)
Seizures
Paralysisor weakness on one side
Learning disabilities
(Quan et
al.,2015)

Sturge-Weber syndrome - soles of feet


This picture shows the soles of two feet
involved with port wine stain. Port wine
stains in the area of the ophthalmic branch
of the trigeminal nerve, with ipsilateral
vascular anomalies constitute the SturgeWeber syndrome. Glaucoma, retinal
detachment, calcification of the outer layers
of the cerebral cortex, and seizures
may
(Limotai et
al .,2015)

Possible Complications
Abnormal blood vessel growth in the
skull
Continued growth of the port-wine stain
Developmental delays
Emotional and behavioral problems
Glaucoma, which may lead to blindness
Paralysis
(Tripathi et
al.,2015)

Treatment
Treatment is based on the patient's signs
and symptoms, and may include:

Anticonvulsant medicines for seizures

Eye drops or surgery to treat glaucoma

Laser therapyfor port-wine stains


Physical therapy for paralysis or
weakness
Possible brain surgery to prevent
seizures
(Ahmed and Prayson.,2015)

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