CD-ROM Today 1996 January/CD-ROM Today 1996 January.iso/dp/0404/04042.txt

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$Unique_ID{BRK04042}
$Pretitle{}
$Title{Neurofibromatosis}
$Subject{Bilateral Acoustic Neurofibromatosis (NF 2) Central Neurofibromatosis
(NF 2) Intestinal Neurofibromatosis Elephant Man Disease Mixed central and
Peripheral Neurofibromas Neurofibroma, multiple
Neurofibromatosis-pheochromocytoma-duodenal carcinoid syndrome NF NF 1
Recklinghausen's Phakomatosis also known as Phakomatosis Recklinghausen RF 1
Von Recklinghausen Disease, also known as Recklinghausen's I and
Recklinghausen Disease}
$Volume{}
$Log{}

Copyright (C) 1984, 1985, 1986, 1987, 1988, 1989, 1990, 1991, 1992, 1993
National Organization for Rare Disorders, Inc.

3:
Neurofibromatosis

** IMPORTANT **
It is possible the main title of the article (Neurofibromatosis) is not
the name you expected.  Please check the SYNONYMS listing on the next page to
find alternate names and disorder subdivisions covered by this article.

Synonyms

     Bilateral Acoustic Neurofibromatosis (NF 2)
     Central Neurofibromatosis (NF 2)
     Intestinal Neurofibromatosis
     Elephant Man Disease
     Mixed central and Peripheral Neurofibromas
     Neurofibroma, multiple
     Neurofibromatosis-pheochromocytoma-duodenal carcinoid syndrome
     NF
     NF 1
     Recklinghausen's Phakomatosis also known as Phakomatosis Recklinghausen
     (RF 1) Von Recklinghausen Disease, also known as Recklinghausen's I and
Recklinghausen Disease

DISORDER SUBDIVISIONS

     NF 1
     NF 2

Information on the following diseases can be found in the Related
Disorders section of this report:

     Acoustic Neuroma
     McCune-Albright Syndrome
     Proteus Syndrome
     Tuberous Sclerosis

General Discussion

** REMINDER **
The Information contained in the Rare Disease Database is provided for
educational purposes only.  It should not be used for diagnostic or treatment
purposes.  If you wish to obtain more information about this disorder, please
contact your personal physician and/or the agencies listed in the "Resources"
section of this report.


Neurofibromatosis is a term used to describe what are now known to be two
distinctly different disorders:  The more common type 1 neurofibromatosis (NF
1), and the less common type 2 (NF 2).  Both disorders are inherited through
autosomal dominant genes, but the genes involved are on separate chromosomes.
Major symptoms include numerous benign tumors (neurofibromas) and discolored
spots on the skin.  NF 2 causes hearing impairment as well as other symptoms.

Symptoms

Both types of Neurofibromatosis are characterized by the occurrence of
multiple benign (noncancerous) tumors, arising most frequently from the
peripheral nervous system.  These tumors (neurofibromas) appear on or under
the skin or in deeper areas within the body.

Symptoms of NF 1 usually appear during childhood.  The disease is progressive
and tends to become more active at puberty and during pregnancy, although the
course and symptoms of NF vary and are unpredictable.  Brown spots
(cafe-au-lait) on the skin are usually the first sign.  These spots measure
approximately 0.5 cm in diameter in children and grow to 1.5 cm in diameter
in adults.  Six or more cafe-au-lait spots (macules) and two or more
neurofibromas (tumors) are diagnostic in a child.  Freckling under the arm
(axillary) or in the area of the groin (inguinal), or two or more small
grayish neuromas in the iris of the eye (Lisch nodules) are important
diagnostic criteria.

Tumors (neurofibromas) occur in NF 1 and can form under the skin or in
deeper areas in the body.  Pain may or may not occur.  Tumors can produce
disfigurement and orthopedic problems, including curvature in the spine
(scoliosis) and bone loss on the weight bearing long bones of the body
(pseudoarthrosis).  This can result in the bending or even the fracture of
these bones.  Sexual development may be delayed or early (precocious) and
learning disabilities may occur.  Optic tumors (glioma), local or widespread
benign tumor-like nodules (hamartomas), and other central nervous system
lesions are common.

NF 2 develops later than NF 1, usually during the teens or 20's.  Fewer
cafe-au-lait spots and skin (cutaneous) neurofibromas develop.  NF 2 is
characterized by progressively enlarging benign tumors in both auditory
canals (bilateral acoustic neuromas).  It may also be associated with brain
and spinal cord tumors.  Buzzing and ringing in the ears and eventual loss of
hearing occur as result of these neuromas.

Causes

NF 1 and NF 2 are inherited as autosomal dominant traits; however, about half
of all cases are due to new mutations that are not inherited from parents.

Human traits including the classic genetic diseases, are the product of
the interaction of two genes for that condition, one received from the father
and one from the mother.

In dominant disorders, a single copy of the disease gene (received from
either the mother or father) will be expressed "dominating" the normal gene
and resulting in appearance of the disease.  The risk of transmitting the
disorder from affected parent to offspring is 50% for each pregnancy
regardless of the sex of the resulting child.

The gene for NF 1 is on chromosome 17 (17q11.2).  The gene for NF 2 is on
chromosome 22 (22q).  The NF2 gene is a new type of tumor suppressor gene
that has been associated with the non-inherited as well as inherited forms of
cancer.  Neurofibromatosis 2 results when the gene is activated.  This same
gene is also implicated in approximately thirty percent of brain tumors that
occur sporadically.  The NF2 gene produces a protein termed "merlin" that is
an acronym for moesin-ezrin-radaxin-like-protein.  These proteins are thought
to act like links between proteins in the cell membrane, that hold cells
together, and the cytoskeleton, a lattice-work of tiny filaments that act to
support the cell.

A localized form of neurofibromatosis appears to be caused by a somatic
mutation, with little risk of recurrence in offspring.

Affected Population

Neurofibromatosis affects approximately 100,000 Americans, both male and
female.  It is estimated that NF 1 affects 1:4,000 individuals; NF 2 affects
1:50,000.

Related Disorders

Symptoms of the following disorders can be similar to those of
Neurofibromatosis.  Comparisons may be useful for a differential diagnosis:

Acoustic Neuroma is a benign tumor (neuroma) of the 8th cranial nerve.
This nerve lies within the internal auditory canal.  Symptoms of this
disorder include ringing in the ears (tinnitus), hearing loss, or both.  The
tumor may grow in the direction of the brain stem.  Increasing pressure
inside the brain may led to personality changes and impaired thinking.  As
pressure increases on the facial nerve, facial twitching can occur.  (For more
information on this disorder, choose "Acoustic Neuroma" as your search term
in the Rare Disease Database).

McCune-Albright Syndrome is a multi-system disorder primarily
characterized by abnormal fibrous tissue development (dysplasia) in one or
more bones, abnormally early puberty, and brown (cafe-au-lait) spots on the
skin.  Other symptoms may include an overactive thyroid gland
(hyperthyroidism), other endocrine abnormalities, and a variety of bone and
soft-tissue tumors.  (For more information on this disorder, choose "McCune-
Albright" as your search term in the Rare Disease Database).

Proteus syndrome is a rare hereditary disorder characterized by abnormal
and asymmetric growth.  Diverse abnormalities of the skin, face, eyes, ears,
lungs, muscles and nerves are present.  The symptoms of this disorder become
apparent during the first year of life.  Skin lesions may occur as well as
hemangiomas, lipomas and lymphangiomas.  Abnormal growths in the abdominal
cavity may occur as well.  It was once believed that the broadway show, "The
Elephant Man", was based on a person with neurofibromatosis, but it was later
discovered that this patient actually had Proteus syndrome.  (For more
information on this disorder, choose "Proteus Syndrome" as your search term
in the Rare Disease Database).

Tuberous Sclerosis is a rare disorder characterized by seizures, mental
retardation, developmental delay, lesions of the eyes and skin and brain
tumors.  Seizures, which occur in 90 percent of patients, are often the first
symptoms.  Abnormalities may be seen on an electroencephalograph (EEG).
Approximately 60 to 90 percent of infants have brownish skin spots
(hypomelanotic macules) at birth.  Fibromas may present on the area around or
under the nails (periungual or subungual).  (For more information on this
disorder, choose "Tuberous Sclerosis" as your search term in the Rare Disease
Database).

Therapies:  Standard

Surgical removal of troublesome Neurofibromatosis tumors may be beneficial
when they cause discomfort.  Physical therapy is occasionally useful and
orthopedic devices can improve disabilities in some cases.  Other treatment
is symptomatic and supportive.

Therapies:  Investigational

Neurofibromatosis research is ongoing in numerous areas including recombinant
DNA and nerve growth factor to understand the formation of neurofibromas.
Recent genetic studies have led to the development of genetic tests.  Once
the gene that causes NF 1 and NF 2 can be cloned, research on prevention and
new treatments will be pursued.

Research Projects:

Families with one or more members who have central Neurofibromatosis (NF
II) with Bilateral Acoustic Neuromas are being sought for a clinical research
study at the National Institute of Neurological Disorders and Stroke (NINDS)
in Bethesda, MD.  The goal of the study is to establish methods for early
detection and diagnosis of this type of Neurofibromatosis.  Doctors who wish
to refer potential candidates or obtain additional information should
contact:

     Dr. Donald Wright
     Surgical Neurology Branch
     NINCDS, Bldg. 10A, Rm. 3E68
     Bethesda, MD  20892
     [phone]

Researchers are studying learning disabilities and neurological changes
in NF children aged birth to eighteen years.  A controlled study is underway
among children with NF along with siblings who do not have the disorder.
Testing is being performed in conjunction with Children's Hospital,
Washington, DC.

     Neurofibromatosis Clinic
     Children's Hospital
     111 Michigan Avenue, NW
     Washington, DC  20010
     [phone]

Ongoing research is directed toward understanding the genetic changes in
tumor formation in Neurofibromatosis.  Tissue is requested from any known or
suspected malignancy.  Samples of neurofibromas from female patients is also
requested.  Understanding of the genetic basis of tumor formation represents
a major step toward a improved diagnosis and treatment of this disorder.
Patients undergoing such surgery should contact:

     Dr. Gary R. Skuse or Dr. Peter T. Rowley
     University of Rochester Medical Center
     Division of Genetics
     Box 641
     601 Elmwood Ave.
     Rochester, NY  14642
     [phone]

This disease entry is based upon medical information available through
May 1993.  Since NORD's resources are limited, it is not possible to keep
every entry in the Rare Disease Database completely current and accurate.
Please check with the agencies listed in the Resources section for the most
current information about this disorder.

Resources

For more information on Neurofibromatosis, please contact:

     National Organization for Rare Disorders (NORD)
     P.O. Box 8923
     New Fairfield, CT  06812-1783
     [phone]

     Neurofibromatosis, Inc.
     3401 Woodridge Ct.
     Mitchellville, MD  20716
     [phone]

     National Neurofibromatosis Foundation, Inc.
     141 Fifth Ave.
     New York, NY  10010
     [phone]

     NIH/National Institute of Neurological Disorders & Stroke (NINDS)
     9000 Rockville Pike
     Bethesda, MD  20892
     [phone]
     [phone]
For information on genetics and genetic counseling referrals, please
contact:

     Alliance of Genetic Support Groups
     35 Wisconsin Circle, Suite 440
     Chevy Chase, MD 20815
     (800) 336-GENE
     [phone]

     March of Dimes Birth Defects Foundation
     1275 Mamaroneck Ave.
     White Plains, NY  10605
     [phone]

CLINICAL FACILITIES

     Massachusetts General Hospital
     Neurofibromatosis Clinic
     Department of Neurosurgery
     15 Parkman St., Room 312
     Boston, MA
     [phone]
     Att:  Robert Marthuza, MD

     Children's Hospital
     Neurofibromatosis Clinic
     111 Michigan Avenue, NW
     Washington, DC  20010
     [phone]
     Att:  Kenneth Rosenbaum, MD

     Children's Hospital
     Neurofibromatosis Clinic
     34th and Civic Center Blvd., Room 9028
     Philadelphia, PA
     [phone]
     Att:  Anna Meadows, MD

     Baylor College of Medicine
     Neurofibromatosis Clinic
     1 Baylor Plaza
     Houston, Texas  77030
     [phone]
     Att:  Vincent Riccardi, MD

     Mount Sinai School of Medicine
     Neurofibromatosis Clinic
     100th St. and Madison Ave.
     New York, NY
     [phone]
     Att:  Alan Rubinstein, MD

References

BIRTH DEFECTS ENCYCLOPEDIA, Mary Louise Buyse, M.D., Editor-In-Chief;
Blackwell Scientific Publications, 1990.  Pp. 1233-34.

CLINICAL REVIEW OF NEUROFIBROMATOSIS, J. Rosner; J Am Optom Assoc
(August, 1990, Issue 61 (8)).  Pp. 613-618.

LISCH NODULES IN NEUROFIBROMATOSIS TYPE I, Marie-Louise E. Lubs, et al.;
N Eng J. Med., (May 2, 1991, issue 324 (24)).  Pp. 1264-1266.