RSPH Neurofibromatosis

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RSPHNeurofibromatosis

• Prepared by Dr Baker I Qaoud
• Supervisor Dr M Abu Nada

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What is Neurofibromatosis?

• The neurofibromatoses are genetic disorders of
  the nervous system that primarily affect the
  development and growth of neural (nerve) cell
  tissues. These disorders cause tumors to grow on
  nerves and produce other abnormalities such as
  skin changes and bone deformities. The
  neurofibromatoses occur in both sexes and in all
  races and ethnic groups. Scientists have
  classified the disorders as neurofibromatosis
  type 1 (NF1) and neurofibromatosis type 2 (NF2).

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What is NF1?

• Most common phacomatosis
• Affects 14000 individuals
• Presents in childhood
• Gene localized to chromosome 17q11
• NB other names
• Von Recklinghausen Disease
• Peripheral NF

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Mode of Inheritance

• NF1 is a genetic disorder, and not a chromosomal
  disorders
• NF1 can be found on the 1st to the 22nd
  chromosome, but not the 23rd (sex chromosome)
• NF1 is a dominant disorder
• NF1 can also be inherited due to spontaneous
  mutation

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Symptoms of NF1

• sex or more light brown skin spots (cafe-au-lait
  macules) measuring more than 5 millimeters in
  diameter in patients under the age of puberty or
  more than 15 millimeters across in adults and
  children over the age of puberty
• two or more neurofibromas (tumors that grow on a
  nerve or nerve tissue, under the skin) or one
  plexiform neurofibroma (involving many nerves)
• freckling in the armpit or groin areas
• benign growths on the iris of the eye (known as
  Lisch nodules or iris hamartomas)

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• a tumor on the optic nerve (optic glioma)
• severe scoliosis (curvature of the spine)
• enlargement or deformation of certain bones other
  than the spine
• a first degree relative (parent. sibling.
  offspring) with NF1 by the above criteria.

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• Café-au-lait spots

Appear during first year of life
Increase in size and number throughout childhood
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• Fibroma moll scum in NF-1

• Appear at puberty
• Pedunculated, flabby nodules consisting of
• neurofibromas or schwannomas

• Increase in number
• throughout life
• Frequently widely distributed

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• Plexiform neurofibroma in NF-1

• Appear during childhood
• Large and ill-defined

• May be associated with
• overgrowth of overlying skin

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• Skeletal defects in NF-1

• Mild head enlargement - uncommon
• Other - scoliosis, short stature, thinning of
• long bones

• Facial hemiatrophy

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• Orbital lesions in NF-1

• Sagittal MRI scan of optic nerve glioma invading
  hypothalamus
• Glioma may be unilateral or bilateral

• Axial CT scan of congenital absence of
• left greater wing of sphenoid bone

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• Eyelid neurofibromas in NF-1

Nodular
Plexiform
May cause mechanical ptosis
May be associated with glaucoma
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• Intraocular lesions in NF-1

Lisch nodules
Very common - eventually present in 95 of cases
Congenital ectropion uveae
Choroidal naevi
Uncommon - may be associated with glaucoma
Common - may be multifocal and bilateral
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Additional Health Problems

• Scoliosis
• Benign tumors with the potential to become
  malignant
• Mental deficiency
• Visual impairment
• Speech impairment
• Early or delayed puberty
• Deformed of enlarged bones
• Headaches
• Large head
• High blood pressure
• Epilepsy (Rare)

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Detection

• The main method of detection for NF1 is by paying
  attention to the signs and symptoms. Some key
  signs are multiple tumors, lots of freckles where
  skin meets skin, and six or more Café-au-lait
  spots.

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Diagnostic Testing

• There are several genetic test that can be done.
  These tests involve testing the DNA and looking
  for mutations or irregularities. The main way to
  diagnosis, however, is by studying the family
  history and observing the symptoms.

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Treatment

• The main form of treatment is to control the
  symptoms. This includes removing tumors and
  repairing bone deformities.

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Genetic Counseling

• Upon visiting a genetic counselor, you will be
  tested to see if you or your spouse are a carrier
  for NF1. If one or both of you are found to be
  carriers, you will be presented with the
  necessary information for planning a future with
  children if you choose to have any. Some
  information that will be told to you is the
  likelihood of having and affect child, between
  25 and 100. You may also discuss alternate
  options for having children, such as adoption.

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Above are some common bone deformities associated
with NF1. Note the curvatures of the long bones.
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Prognosis

• With NF1, most people live a relatively normal
  life. However, they live on average 54-60 years.
• NF1 is primarily treated by controlling the
  symptoms.

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Additional Interesting Facts

• Chromosome 17 is often affected. This chromosome
  contains a tumor suppressor that when affected
  does not function properly.

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What is NF2?

• This less common of the neurofibromatosis affects
  about 1 in 40,000 persons.
• the gene for NF2 is on chromosome 22.
• NF2 is characterized by bilateral (occurring on
  both sides of the body) tumors on the eighth
  cranial nerve.
• It was formerly called bilateral acoustic
  neurofibromatosis or central neurofibromatosis
  because the tumors, which cause progressive
  hearing loss, were thought to grow primarily on
  the auditory nerve.

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• Scientists now know that the tumors typically
  occur on the vestibular nerve, another branch of
  the eighth cranial nerve near the auditory nerve.
  The tumors, called vestibular schwannomas for
  their location and for the type of cells in them,
  cause pressure damage to neighboring nerves. In
  some cases, the damage to nearby vital
  structures, such as other cranial nerves and the
  brainstem, can be life-threatening.

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What are the Symptoms of NF2?

• To determine if an individual has NF2, a
  physician looks for the following
• 1. bilateral eighth nerve tumors,
• 2. a parent, sibling, or child with NF2 and a
  unilateral eighth nerve tumor,
• 3. a parent, sibling, or child with NF2 and any
  two of the following
• glioma,
• meningioma,
• neurofibroma,
• schwannoma, or cataract at an early age.

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• Ocular features of NF-2

Common - combined hamartomas of RPE and retina
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When Do Symptoms of NF2 Appear?

• Affected individuals may notice hearing loss as
  early as the teen years. In addition to changes
  in hearing that may occur in one or both ears,
  other early symptoms may include tinnitus
  (ringing noise in the ear) and poor balance.
  Headache, facial pain, or facial numbness, caused
  by pressure from the tumors, may also occur.

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How is NF2 treated?

• Treatments for NF2 are aimed at controlling the
  symptoms. Improved diagnostic technologies, such
  as MRI (magnetic resonance imaging), can reveal
  tumors as small as a few millimeters in diameter,
  thus allowing early treatment. Surgery to remove
  tumors completely is one option, but may result
  in hearing loss. Other options include partial
  removal of tumors, radiation, and, if the tumors
  are not progressing rapidly, the conservative
  approach of watchful waiting

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Credits

• http//www.ctf.org/
• http//www.nfinc.org/nf1.shtml
• http//www.bcnf.bc.ca/whatis-dc.php
• http//ninds.nih.gov/disorders/neurofibromatosis/n
  eurofibromatosis.htm