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$Unique_ID{BRK04327}
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$Title{Werdnig-Hoffman Disease}
$Subject{Werdnig-Hoffman Disease Infantile Spinal Muscular Atrophy
Werdnig-Hoffman Paralysis Spinal Muscular Atrophy Type I SMA I SMA, Infantile
Acute Form Muscular Dystrophy, Batten Turner Leukodystrophy, Canavan
Olivopontocerebellar Atrophy (OPCA) Benign Congenital Hypotonia }
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Copyright (C) 1985, 1986, 1987, 1988, 1989, 1992 National Organization
for Rare Disorders, Inc.

36:
Werdnig-Hoffman Disease

** IMPORTANT **
It is possible that the main title of the article (Werdnig-Hoffman)
Disease) is not the name you expected.  Please check the SYNONYMS listing to
find the alternate name and disorder subdivisions covered by this article.

Synonyms

     Infantile Spinal Muscular Atrophy
     Werdnig-Hoffman Paralysis
     Spinal Muscular Atrophy Type I
     SMA I
     SMA, Infantile Acute Form

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

     Muscular Dystrophy, Batten Turner
     Leukodystrophy, Canavan
     Olivopontocerebellar Atrophy (OPCA)
     Benign Congenital Hypotonia

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.


Werdnig-Hoffmann Disease is a rare inherited neuromuscular disorder of
children.  It is characterized by degenerative changes in the spinal cord
(the ventral horn cells).  This results in generalized muscle weakness and
the progressive wasting away (atrophy) of the muscles of the trunk and
extremities.

Symptoms

Werdnig-Hoffman Disease is a rare disorder that may begin in the developing
fetus (in utero) or before 2 years of age.  The earlier the onset, the more
serious the outcome usually is.  The early signs include a generalized muscle
weakness (hypotonia) and hypermobility of joints; absent tendon reflexes;
twitching (fasciculations) of the tongue; and a frog-like position with the
hips moved apart (abducted) and knees bent or flexed.  Mental development is
usually normal.  Typically, the child does not gain head control, cannot turn
over and is unable to sit or stand.

The rate of progression of Werdnig-Hoffman Disease varies.  In the form
that begins in utero, generalized muscle atrophy and weakness tend to
progress rapidly.  Within a few months, breathing (respiratory) and excretory
difficulties may develop.  The infant may be unable to swallow.  Respiratory
failure may occur or food inhaled into the lungs (aspiration) may cause
choking.

The form of Werdnig-Hoffman Disease that begins during the first few
months of life may have a more slowly progressive course, even extending into
adult life.  In rare cases, the disease may become arrested.

Causes

Werdnig-Hoffmann Disease is a rare disorder usually inherited as an autosomal
recessive trait.  In rare instances this disorder may be inherited as an
autosomal dominant trait.

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

In recessive disorders, the condition does not appear unless a person
inherits the same defective gene for the same trait from each parent.  If one
receives one normal gene and one gene for the disease, the person will be a
carrier for the disease, but usually will not show symptoms.  The risk of
transmitting the disease to the children of a couple, both of whom are
carriers for a recessive disorder, is twenty-five percent.  Fifty percent of
their children will be carriers, but healthy as described above.  Twenty-five
percent of their children will receive both normal genes, one from each
parent, and will be genetically normal.

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

The gene that causes the most common recessive form of Werdnig-Hoffman
Disease has been located on the long arm of chromosome 5.

Affected Population

Werdnig-Hoffman Disease is a very rare disorder that affects males and
females in equal numbers.  There may be no known family history of the
disease, since the genetic defect is recessive in most cases.  This disorder
occurs in an estimated 1 in 1,000,000 live births per year.

Related Disorders

Symptoms of the following disorders can be similar to those of Werdnig-
Hoffman Disease.  Comparisons may be useful for a differential diagnosis:

Batten Turner Muscular Dystrophy is a form of muscular dystrophy that is
present at birth.  The initial symptoms of this disorder in the infant may be
a generalized "floppiness" and lack of muscle tone (hypotonia).  Later
muscular weakness may make the child prone to falling and stumbling.  Early
motor development and milestone achievements may be minimally delayed.  As a
rule, walking becomes normal later in life, but physical activities may be
hampered.  (For more information on this disorder, choose "Batten Turner
Muscular Dystrophy" as your search term in the Rare Disease Database).

Canavan Leukodystrophy is a rare inherited disorder that is characterized
by the progressive degeneration of the central nervous system.  The early
symptoms of this disorder include a general lack of energy, floppiness, and
the loss of previously acquired motor skills.  (For more information on this
disorder, choose "Canavan Leukodystrophy" as your search term in the Rare
Disease Database).

Olivopontocerebellar Atrophy (OPCA) is a rare neurological disorder that
is characterized by the degeneration of the cerebellar cortex.  This disorder
usually affects adults but it may occur in infants.  In cases affecting
children the disorder is inherited as an autosomal recessive trait.  Symptoms
include floppiness (severe hypotonia) and generalized muscle weakness, the
lack of deep reflexes and a general failure to thrive.  There may also be an
enlargement of the heart, respiratory complications and dislocation of the
hips.  (For more information on this disorder, choose "Olivopontocerebellar
Atrophy" as your search term in the Rare Disease Database).

Benign Congenital Hypotonia is a nonprogressive neuromuscular disorder
which occurs at birth.  The disorder is characterized by a generalized muscle
weakness or "floppiness" (hypotonia).  Infants with Benign Congenital
Hypotonia also appear weak and listless.  In many cases the symptoms improve
as the child ages and the central nervous system matures.  (For more
information on this disorder, choose "Benign Congenital Hypotonia" as your
search term in the Rare Disease Database).

For more information on disorders that cause muscle weakness, type
"neuromuscular" as your search term in the Rare Disease Database.

Therapies:  Standard

Treatment of Werdnig-Hoffman Disease is symptomatic and supportive.  Physical
therapy, respiratory care, and aggressive treatment of respiratory infections
are used.  Orthopedic devices may be helpful when the condition is relatively
stable.

Genetic counseling will be of benefit for patients and their families.

Therapies:  Investigational

Scientists have been investigating the possibility that nerve cells contain
nourishing (trophic) substances essential to the maintenance of health in the
muscle cells that they stimulate.  Researchers are trying to develop
treatments that may replace these substances in muscles.

The orphan drug Ciliary Neutrotrophic Factor, Recombinant Human, is being
tested as a possible treatment for spinal muscular atrophies.  The drug is
manufactured by Syntex-Synergen Neuroscience, 1885 33rd Street, Boulder, CO,
80301.

The Muscular Dystrophy Association (MDA) supports basic and applied
studies on nerve and muscle metabolism in the hope that these will lead to a
better understanding of the biological processes that give rise to
neuromuscular diseases such as Werdnig-Hoffmann disease.

Research on genetic defects and their causes is ongoing.  The National
Institutes of Health (NIH) is sponsoring the Human Genome Project that is
aimed at mapping every gene in the human body and learning why they sometimes
malfunction.  It is hoped that this new knowledge will lead to prevention and
treatment of genetic disorders in the future.

This disease entry is based upon medical information available through
October 1992.  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 Werdnig-Hoffman disease, please contact:

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

     Families of Spinal Muscular Atrophy
     P.O. Box 1465
     Highland Park, IL  60035
     [phone]

     Muscular Dystrophy Association, National Office
     3300 E. Sunrise Dr.
     Tucson, AZ  85718
     [phone]

     NIH/National Institute of Neurological Disorders & Stroke (NINDS)
     9000 Rockville Pike
     Bethesda, MD  20892
     [phone]
     [phone]

     Muscular Dystrophy Group of Great Britain and Northern Ireland
     Nattrass House
     35 Macaulay Road
     London, England SW4 OQP
     01-720-8055

For Genetic Information and Genetic Counseling Referrals:

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

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

References

MENDELIAN INHERITANCE IN MAN, 10th Ed.:  Victor A. McKusick, Editor:  Johns
Hopkins University Press, 1992.  Pp. 1563-1564.

CECIL TEXTBOOK OF MEDICINE, 19th Ed.:  James B. Wyngaarden, and Lloyd H.
Smith, Jr., Editors; W.B. Saunders Co., 1990.  P. 2140.

BIRTH DEFECTS ENCYCLOPEDIA, Mary Louise Buyse, M.D., Editor-In-Chief;
Blackwell Scientific Publications, 1990.  Pp. 1576-1577.

PRINCIPLES OF NEUROLOGY, 4th Ed.; Raymond D. Adams, M.D. and Maurice
Victor, M.D., Editors; McGraw-Hill Information Services Company, 1989.  Pp.
1146-1147.

EMG EVALUATION OF THE FLOPPY INFANT:  DIFFERENTIAL DIAGNOSIS AND TECHNICAL
ASPECTS.  H.R. Jones Jr.; Muscle Nerve (April 1990; 13(4)):  Pp. 338-347.