CD-ROM Today (UK) (Spanish) 15/CDRT.iso/dp/0413/04135.txt

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$Unique_ID{BRK04135}
$Pretitle{}
$Title{Prader-Willi Syndrome}
$Subject{Prader-Willi Syndrome Prader-Labhart-Willi Fancone Syndrome
Hypogenital Dystrophy with Diabetic Tendency HHHO
Hypotonia-Hypomentia-Hypogonadism-Obesity Syndrome
Cryptochidism-Dwarfism-Subnormal Mentality Labhart-Willi Syndrome Angelman
Syndrome Cohen Syndrome Alstrom syndrome Laurence-Moon-Biedl Syndrome}
$Volume{}
$Log{}

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

14:
Prader-Willi Syndrome

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

Synonyms

     Prader-Labhart-Willi Fancone Syndrome
     Hypogenital Dystrophy with Diabetic Tendency
     HHHO
     Hypotonia-Hypomentia-Hypogonadism-Obesity Syndrome
     Cryptochidism-Dwarfism-Subnormal Mentality
     Labhart-Willi Syndrome
     Willi-Prader Syndrome

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

     Angelman Syndrome
     Cohen Syndrome
     Alstrm syndrome
     Laurence-Moon-Biedl Syndrome

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.


Prader-Willi syndrome is a complex multisystem disorder diagnosed more
often in males born after a prolonged gestation period (delayed birth), often
in the breech position.  This disorder is characterized by muscular weakness
in the infant (infantile hypotonia), failure to thrive, a decrease in the
efficiency of the testes or ovaries (hypogonadism), short stature and
impaired intellectual and behavioral functioning.  Hyperphagia (eating
excessive amounts of food) leads to severe obesity in early childhood and
adolescence.

Symptoms

Early symptoms of Prader-Willi syndrome include decreased fetal movement, low
birth weight, muscular weakness (hypotonia), sleepiness, a weak cry and poor
sucking ability.  Other characteristics may include unusually small hands and
feet (acromicria), narrow forehead (bifrontal diameter), crossing of the eyes
(strabismus), almond-shaped eyes (palpebral fissures), and developmental
delays relating to head control and the ability to crawl.

A need to eat an extraordinary amount of food (hyperphagia) usually
develops between 1 to 3 years of age.  If left uncontrolled, the obesity of
Prader-Willi Syndrome can lead to life-threatening heart and lung
complications, diabetes, hypertension and to other serious disorders.   The
compulsion to eat is so overwhelming in people with this disorder that if
left unsupervised, they may endanger themselves by eating inedible objects.

The sexual development of children with Prader-Willi syndrome may begin
earlier than normal but generally stops after puberty.  In males the testes
may fail to descend into the scrotum (cryptorchidism) and the penis may be
very small (micropenis).  Unusually small and underdeveloped (hypoplastic)
labia are seen less frequently in girls.  Patients are mentally retarded,
most with IQ's between 40 and 60, but some patients can be only mildly
retarded.  Patients tend to have fair coloring, blue eyes and sun-sensitive
skin.  They may frequently scratch or pick at sores and insect bites.  There
are also behavioral symptoms associated with Prader-Willi Syndrome including
temper tantrams which may become more severe during adolescence.

Causes

Prader-Willi Syndrome is a rare genetic disorder caused most frequently by a
cytogenetic deletion of chromosome 15q11q13.  The deletion always occurs on
the chromosome from the father (paternally derived); these are sporadic (new
and spontaneous or "de novo") deletions, since the father of the child
affected with Prader-Willi syndrome has normal chromosomes.  There is less
than 1:1000 risk of recurrence when a cytogenetic deletion is found.  Prader-
Willi syndrome may be inherited as a dominant gene.

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.)

An identical cytogenetic deletion is seen in patients with Angelman
syndrome, but the chromosome involved is always from the mother (maternal
origin).  These findings suggest that chromosomal imprinting may be critical
in the expression of these two syndromes.   Symptoms of Angelman syndrome are
very different from the symptoms of Prader-Willi syndrome (see the related
disorders section of this report).

Some patients with Prader-Willi syndrome who do not have a cytogenetic
deletion on chromosome 15 have been found (by the testing of genetic material,
DNA markers) to have inherited both of their 15th chromosomes from the
mother (maternal uniparental disomy).   Uniparental disomy is a condition in
which both chromosomes are inherited from the same parent, in this case the
mother.  In genetics, human traits are the product of two genes, one
inherited from the father and one from the mother.  Scientists do not
understand why uniparental disomy occurs in some people.

Additionally, an environmental cause of chromosome 15 abnormality has
been proposed; namely, the prolonged exposure of the father to hydrocarbons
but there is no evidence for chromosomal breakage caused by hydrocarbons.

Affected Population

Prader-Willi syndrome is a rare disorder found more often in males than
females.   Its prevalence is unknown since many patients with Prader-Willi
Syndrome are undiagnosed or misdiagnosed.

Related Disorders

Symptoms of the following disorders can be similar to those of Prader-Willi
syndrome.  Comparisons may be useful for a differential diagnosis:

Angelman Syndrome is a very rare genetic disorder characterized by severe
mental retardation, unusual facial expression and muscular abnormalities.  It
was first described in the medical literature as the "happy puppet syndrome".
Other symptoms usually include a small head (microcephaly), a protruding jaw
(mandible) and an open mouth and visible tongue.  Patients seem to smile
continually and they laugh excessively.  Speech is generally absent.  The
symptoms of Prader-Willi Syndrome are not similar to Angelman Syndrome but
they are both caused by a similar defect on chromosome 15.   (For more
information on this disorder, choose "Angelman Syndrome" as your search term
in the Rare Disease Database).

Cohen Syndrome is a rare genetic disorder characterized by multiple
facial, mouth and eye abnormalities, muscle weakness, obesity and mental
retardation.  Children who have Cohen syndrome usually have a low birth
weight and delayed growth.  Other symptoms of this disorder may include an
usually small head (microcephaly), a high nasal bridge, an open mouth,
prominent lips and large ears.  The jaw may develop abnormally and there may
be a mild down-slant to the eyes.  (For more information on this disorder,
choose "Cohen Syndrome" as your search term in the Rare Disease Database).

Alstrm Syndrome is a rare inherited disorder characterized by retinitis
pigmentosa (degeneration of the retina in the eyes) and childhood obesity.
There is usually degeneration of the retina leading to visual impairment.
Involuntary rhythmic movements of the eyes and the loss of central vision
occur.  The child generally develops hearing loss and diabetes mellitus after
the age of ten.   (For more information on this disorder, choose "Alstrm
Syndrome" as your search term in the Rare Disease Database).

Laurence-Moon-Biedl Syndrome is a rare inherited disorder characterized
by a decrease in the efficiency of the testes or ovaries (hypogonadism),
retinitis pigmentosa (degeneration of the retina in the eyes), mental
retardation, more than the normal number of fingers or toes (polydactyly),
and obesity.  Obesity is one of the earliest signs of this disorder.  (For
more information on this disorder, choose "Laurence-Moon-Biedl Syndrome" as
your search term in the Rare Disease Database).

Therapies:  Standard

The treatment for Prader-Willi syndrome is symptomatic and supportive.  High
resolution prometaphase chromosome analysis is recommended to identify the
specific genetic defect.

Physical therapy may be necessary to help develop a proper walking
pattern, and improve muscle size and tone.  Exercise programs can be helpful
for weight control.

The development of a proper diet, good nutrition, and a good exercise
program are necessary to deal with the life-threatening insatiable appetite
of Prader-Willi patients.  A highly structured residential program is usually
necessary, keeping food out of reach of the patient.  Meals must be calorie
controlled containing approximately 60 percent less calories than would
normally be expected.

Therapies:  Investigational

Prader-Willi Syndrome is the subject of ongoing medical research including
studies in the area of obesity and chromosomal abnormalities.  Specific
diets, studying behavior, daily hormone cycles and brain scans are also the
subject of studies.  For further information contact:

     NIH/National Institute of Child Health and Human Development (NICHD)
     9000 Rockville Pike
     Bethesda, MD  20892
     Att:  Dr. Sidbury
     [phone]

Prader-Willi syndrome and its association with diabetes and nutrition are
also under investigation.  For further information contact:

     USC Medical Center
     2025 Zonal Avenue, Rm. 252
     Los Angeles, CA
     [phone]
     Att:  George Bray, M. D.

The Prader-Willi Syndrome Association is funding a study on the molecular
genetics of Prader-Willi patients.  Interested parties may get more
information by contacting:

     Drs. Suzanne Cassidy or Robert Erickson
     Dept. of Pediatrics
     University of Arizona
     Tucson, AZ

Scientists are studying the use of Human Growth Hormone (hGH) in Prader-
Willi Syndrome in the hope that the drug may decrease fat and build muscle.
However, the drug is very expensive ($10,000 to $40,000 per yer) and some
insurors will not pay for it unless there is proof that the patient has an
actual deficiency of growth hormone.

This disease entry is based upon medical information available through
September 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 Prader-Willi Syndrome, please contact:

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

     Prader-Willi Syndrome Association
     1821 University Ave., N-356
     St. Paul, MN  55104
     [phone]
     [phone]
     FAX [phone]

     NIH/National Institute of Child Health and Human Development (NICHD)
     9000 Rockville Pike
     Bethesda, MD  20892
     [phone]

     Association for Retarded Citizens of the United States
     P.O. Box 6109
     Arlington, TX  76005
     [phone]
     [phone]

For information on genetics and genetic counseling referrals, please
contact:

     March of Dimes Birth Defects Foundation
     1275 Mamaroneck Ave.
     White Plains, NY  10603
     [phone]

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

References

SMITH'S RECOGNIZABLE PATTERNS OF HUMAN MALFORMATION, 4th ed., Kenneth L.
Jones, M.D., W.B. Saunders, Co. 1988.  Pp. 170-3.

MENDELIAN INHERITANCE IN MAN, 10th Ed.:  Victor A. McKusick, Editor:
Johns Hopkins University Press, 1992.  Pp. 912-916.

CECIL TEXTBOOK OF MEDICINE, 19th Ed.:  James B. Wyngaarden, and Lloyd H.
Smith, Jr., Editors; W.B. Saunders Co., 1990.  Pp. 1146.

BIRTH DEFECTS ENCYCLOPEDIA, Mary Louise Buyse, M.D., Editor-In-Chief;
Blackwell Scientific Publications, 1990.  Pp. 1408-1411.

LOCALIZATION OF THE GENE ENCODING THE GABAA RECEPTOR BETA 3 SUBUNIT TO
THE ANGELMAN/PRADER-WILLI REGION OF HUMAN CHROMOSOME 15, J. Wagstaff et al.;
Am J Hum Gen (Aug 1991; 49(2)):  Pp. 330-337.

PRADER-WILLI SYNDROME:  CURRENT UNDERSTANDING OF CAUSE AND DIAGNOSIS, M.G.
Butler; Am J Med Genet (Mar 1990; 35(3)).  Pp. 319-332.