Prader-Willi syndrome, also known as PWS is
an uncommon genetic disorder (present at birth) in which seven
genes (or subsets) on chromosome 15 are deleted or unexpressed.
Patients with PWS may have physical, mental and behavioral
problems – the main one being an unrelenting feeling of
hunger.
Individual with Prader-Willi syndrome have
serious problems controlling their body weight, because they
spend much longer eating than other people do – there is a very
strong food compulsion. PWS is the most common genetic cause of
morbid obesity in children.
According to the Prader-Willi Association,
USA, between 1 in 8,000 and 1 in 25,000 people live with the
condition. PWS affects both sexes equally.
Patients with Prader-Willis syndrome often
have low muscle tone, incomplete sexual development, and chronic
(long-term) hunger. They also tend to have a metabolism that
utilizes fewer calories, compared to other people. Many
individuals with PWS have short stature if they do not receive
growth hormone therapy.
A newborn with PWS tends to weigh less than
normal, has weak muscles (hypotonia), and may find sucking
difficult. Between the ages of 2 and 5 years individuals start
developing a voracious appetite. Some, however, may start later.
When hyperphagia begins it tends to persist for life. Hyperphagia
(polyphagia) is an abnormally high appetite for food, and eating
much more food than normal.
Prader-Willi syndrome was first described
in 1956 by Andrea Prader (Switzerland, 1919-2001, pediatrician
and endocrinologist), Heinrich Willi (Switzerland, 1900-1971,
pediatrician), Alexis Labhart (Switzerland, 1916 Prof. Internal
Medicine), and Guido Fanconi (Switzerland, 1892-1979,
Pediatrician).
Prader-Willi syndrome (PWS) is a disorder
caused by a deletion or disruption of genes in the proximal arm
of chromosome 15 or by maternal disomy in the proximal arm of
chromosome 15. Commonly associated characteristics of this
disorder include diminished fetal activity, obesity, hypotonia,
mental retardation, short stature, hypogonadotropic hypogonadism,
strabismus, and small hands and feet.
In 1887, Langdon-Down described the first
patient with Prader-Willi syndrome as an adolescent girl with
mental impairment, short stature, hypogonadism, and obesity and
attributed these symptoms to polysarcia. In 1956, Prader et al
reported a series of patients with similar phenotypes. In 1981,
Ledbetter et al identified microdeletions within chromosome 15
and determined it to be the site for Prader-Willi
syndrome.
According to
Medilexicon"s medical dictionary:
Prader-Willi syndrome is "a congenital
syndrome characterized by short stature, mental retardation,
polyphagia with marked obesity, and sexual infantilism; severe
muscular hypotonia and poor responsiveness to external stimuli
decrease with age; a small deletion is demonstrable in the
paternal-derived chromosome 15q11-13 in many cases; some cases
are due to maternal uniparental disomy (both chromosomes 15 are
derived from the mother)."
What are the signs and symptoms of
Prader-Willi Syndrome?
A symptom is something the patient senses
and describes, while a sign is something other people, such as
the doctor notice. For example, drowsiness may be a symptom while
dilated pupils may be a sign.
Prader-Willi signs and symptoms tend to
occur in two stages, with the first becoming evident during the
first year of an infant"s life, and others occurring between the
ages of 1 and 6 years.
Signs and symptoms in infants (babies
under 1 year of age):
•Hypotonia- poor muscle tone; a
primary sign. The baby may feel floppy when held. Their elbows
and knees may be loosely extended instead of being firmly in
position. Hypotonia improves with age.
•The face- eyes may have an almond
shape. The head may narrow at the temples. The infant"s mouth may
be turned down, with a thin upper lip. The mouth often appears to
be small.
•Failure to thrive- this term refers
to babies and children whose physical growth is less than their
peers". Poor muscle tone may undermine the infant"s ability to
suck properly, making feeding difficult. Babies with Prader-Willi
syndrome commonly gain weight more slowly than other
babies.
•Strabismus- the eyes may not move in
unison. It may appear that an eye wanders, or that the eyes
cross.
•Cry- the infant may have a weak
cry.
•Responsiveness- the infant may not
respond as he/she should to simulation. He/she may seem
tired.
Between 1 and 6 years of age – the signs
and symptoms that emerge will tend to persist for the rest of the
child"s life:
•Food craving, body weight- the child
craves for food constantly, and eats lots and often. Consequently
they gain weight. Sometimes the child may hoard food, or eat
things most people would not, such as frozen food before it is
thawed or cooked, or food that has gone off.
•Hypogonadism- the testes or ovaries
do not produce enough sex hormones, resulting in underdeveloped
sex organs. In most cases adults with Prader-Willi syndrome are
infertile. There is poor sexual development during puberty. The
testes of males may not descend, while females may never have
menstrual periods (or very scant ones).
•Growth and strength- individuals with
Prader-Willi syndrome tend to have poor muscle mass, small hands
and feet. Hands may be narrow with straight ulnar border. Adults
with the PWS are usually shorter than average.
•Cognitive abilities- a significant
percentage of people with PWS have mild to moderate mental
retardation. Learning disabilities are common, even among those
without mental retardation.
•Motor skills- coordination
milestones, such being able to sit up or walking are usually
reached later. A baby with PWS may not be able to walk until
he/she is 24 months old. Motor skills refers to movement and
motion.
•Verbal skills- a child with PWS will
start speaking later than other children. Good diction may be
challenging throughout life.
•Behavior and mental disorders- the
child may have temper tantrums, especially when the issue is
food. There is a tendency to be argumentative, oppositional,
rigid, manipulative, possessive and stubborn. Some may develop
OCD (obsessive compulsive disorder), repetitive behaviors,
recurring thoughts, and some other mental disorders.
•Sleep disorders- a higher percentage
of people with PWS have sleep apnea, compared to the rest of the
population. This may be linked to obesity. There may also be
disturbances of the normal sleep cycle.
•Scoliosis (curvature of the spine)- a
significantly higher proportion of children with PWS develop
scoliosis, compared to the rest of the population.
•Skin and hair- the individual"s skin
and/or hair may be fairer compared to parents" and
siblings".
•Pain tolerance- people with PWS tend
to have a high tolerance for pain.
•Eyesight- the individual may have
myopia (short-sightedness).
•Skin picking- repetitive picking of
one"s own skin.
You should see a doctor if your
baby:
Has feeding difficulties
Does not wake up easily
Does not respond to normal stimulation,
such as touch
Feels floppy when held
See a doctor is your child:
Is always hungry
Is constantly foraging for food
Has rapid weight gain
What are the causes of Prader-Willis
Syndrome?
What are genes? Every living organism has
genes. Genes are a set of instructions that decide what the
organism is like, how it survives, and how it behaves in its
environment. The genes lie in long strands of DNA
(deoxyribonucleic acid) called chromosomes. Humans have 23 pairs
of chromosomes – or a total of 46. A donkey has 31 pairs of
chromosomes, a hedgehog has 44, and a fruit fly has just
4.
Prader-Willi syndrome is caused by an error
in a gene (or genes). We are not sure which genes are involved,
but we know the abnormality is in a region of chromosome
15.
All human genes come in pairs, except for
those related to sex characteristics. We get one copy from our
father (paternal gene) and one copy form our mother (maternal
gene). In most types of gene, if one copy is active so is the
other one. Sometimes, however, genes are active on their own –
this is usually normal. A paternal gene may be active while the
maternal one is not (silent). If that paternal active gene is
faulty, genetic information will be missing.
Prader-Willi syndrome may have three
possible causes:
• The paternal genes on chromosome
15 are not present (they are missing)
• The paternal genes on chromosome
15 are faulty
• The offspring has inherited no
chromosome 15 from the father, and two copies form the mother
(and they are both inactive)
This genetic fault results in a disruption
of the normal functions of the hypothalamus. The hypothalamus is
a part of the brain which controls thirst and hunger. It also
releases hormones that trigger the release of chemicals involved
in sexual development and growth.
Put simply- a genetic fault causes a part
of the brain to malfunction, which undermines the person"s
ability to regulate hunger, growth, sexual development, as well
as other functions which result in PWS signs and
symptoms.
Acquired Prader-Willi Syndrome- if there is
damage to the hypothalamus during a person"s life, PSW-like signs
and symptoms may develop – may be acquired. This could be caused
by aHead injury, a tumor, or surgery to remove a tumor. In such
cases the patient does not have the genetic faults or physical
characteristics of PWS, but may acquire some of the behavioral
problems linked to the syndrome, such as a constant craving for
food.
Treatment used for patients with congenital
PSW can be effective for those with acquired PSW.
Diagnosing Prader-Willi Syndrome
Prader-Willi syndrome used to be diagnosed
by clinical presentation – if the signs and symptoms were
present. Today diagnosis is done through genetic
testing.
Genetic testing is recommended:(Source:
Prader-Willi Syndrome Assoc. USA)
•Infants- if an infant has pronounced
hypotonia (poor muscle tone) with poor suck.
•Children aged 2 to 6 years- if the
child has a history of poor suck, as well as general
developmental delays.
•Children aged 6 to 12 years- if the
child has a history of poor muscle tone, poor suck, general
developmental delays, constant hunger and overeating (with
central obesity if uncontrolled).
•Everybody aged 13 years or more- if
there are signs of mild mental retardation, constant hunger and
overeating (with central obesity if uncontrolled), hypogonadism,
temper tantrums, and obsessive compulsive behaviors.
Genetic testing involves a DNA-based
methylation test to detect the absence of the paternally
contributed PSQ region on chromosome 15q11-q13. This test will
detect 97% of patients with PSW. The test is important to confirm
the diagnosis of PWS in all patients, but especially those who
are too young to have enough evident signs and symptoms. Early
diagnosis of PWS allows for early intervention as well as the
early prescription of growth hormone.
A significant number of patients with PWS
are undiagnosed, or misdiagnosed asDown syndrome. Experts say
this is mainly because many in the medical community are
unfamiliar with Prader-Willi syndrome.
What are the treatment options for
Prader-Willi Syndrome?
There is no cure for Prader-Willi syndrome,
however, several treatments are available which help to lessen
the signs and symptoms of the condition, including infant/child
nutrition, growth hormone therapy, sex hormone therapy, physical
therapy, speech therapy, occupational therapy, and developmental
therapy . The best treatment involves a team of different health
care professionals who will be involved in the care of the
patient for most of his/her life.
•Infant/child nutrition- if the infant
has feeding difficulties a high-calorie formula may be
recommended. Doctors will carefully monitor the child"s weight
and growth. Later on a nutritionist may help the child develop a
healthy, low-calorie diet to keep his/her weight under
control.
•Growth hormone treatment- growth
hormone treatment has been shown in studies to help increase
growth and lower body fat in children with Prader-Willi syndrome.
However, we do not know what the long-term effects might be. An
endocrinologist will help determine whether the child is suitable
for growth hormone treatment.
•Sex hormone treatment- HRT (hormone
replacement therapy) may be recommended for children with
Prader-Willi syndrome. HRT would involve testosterone for boys
and progesterone for girls to top up low levels of sex hormones.
Apart from helping their sexual development, HRT may also reduce
the risk of osteoporosis (thinning of bones).
Put simply– HRT hormone therapy
can increase stature, decrease obesity, and increase muscle
mass.
•General development- a range of
therapies may help the child, including:
oDevelopmental therapy- to acquire social
and interpersonal skills appropriate for the child"s
age.
oOccupational therapy- to help with
everyday tasks.
oPhysical therapy- to improve strength and
movement.
oSpeech therapy- to help with diction and
oral communication.
•Mental health- if the child has
symptoms of obsessive-compulsive disorder, a mood disorder or
some behavioral problems, a psychologist or psychiatrist may help
provide the appropriate therapies.
•Adulthood- the majority of
individuals with Prader-Willi syndrome require supervision and
specialized care for the rest of their lives.
If obesity can be prevented and
complications controlled properly, the life expectancy for a
person with PWS is normal or near-normal.
Non-stop food restriction and behavior
management is often demanding and stressful for family members.
Various Prader-Willi organizations around the world can provide
information and support for families as well as health care
providers. Sometimes, family counseling may help.
Experts say that teenagers and adults with
Prader-Willi syndrome can function well in group and supported
living programs if there is proper nutritional control and a
structured environment.
Reactions to medications–
individuals with Prader-Willi syndrome may react differently to
standard dosages of medications. Doctors are advised to be
extremely cautious when administering sedatives, as prolonged and
exaggerated responses are possible.
Pain tolerance– people with PWS
tend to have a high tolerance for pain. A patient may not
complain about discomfort or pain until an infection or condition
is severe.
Vomiting– people with PWS rarely
vomit. If an individual with PWS vomits he/she may have something
much more serious than others may think. Hyperphagia (abnormally
increased appetite for and consumption of food) may result in the
consumption of unhealthy foods, such as uncooked or spoiled
foods. A gastrointestinal complication, such as a stomach
infection would result in vomiting much earlier in people who
don"t have PWS.
Anesthesia– children with PWS are
at higher risk of developing a complication from anesthesia,
compared to other children. Many infants and children undergo
surgical procedures for obstructive sleep apnea – the medical
team should be aware of the possible complications.
What are the possible complications of
Prader-Willi syndrome?
Obesity – individuals with PWS have a
significantly higher risk of becoming obese for two main
reasons:
•Hyperphagia- there is an abnormally
high appetite for food, and an abnormally high consumption of
food.
•Muscle mass- muscle mass is usually
lower than other people"s, so a person with PWS generally
requires fewer calories than other people of the same
weight.
Hyperphagia combined with low muscle mass
make the patient much more likely to become obese. Medical
complications related to obesity include:
•Type II diabetes– the body either
does not produce enough insulin or the insulin is not working
properly (insulin resistance). In the case of insulin resistance,
the body is producing the insulin, but insulin sensitivity is
reduced and it does not do the job as well as it should do. The
glucose is not entering the body"s cells properly, causing two
problems: 1. A build-up of glucose in the blood. 2. The cells are
not getting the glucose they need for energy and
growth.
In the early stages of Type 2 insulin
sensitivity is the main abnormality – also there are elevated
levels of insulin in the blood. There are medications which can
improve insulin sensitivity and reduce glucose production by the
liver. As the disease progresses the production of insulin is
undermined, and the patient will often need to be given
replacement insulin.
•Heart disease/stroke- obese
individuals are at significantly higher risk of developing
hypertension (High Blood Pressure), hardened arteries, and
elevated blood cholesterol levels – all of which contribute to a
higher risk of stroke orheart disease.
•Osteoarthritis- cartilage loses its
elasticity. If the cartilage is stiff it becomes damaged more
easily. The cartilage, which acts as a shock absorber, will
gradually wear away in some areas. As the cartilage becomes
damaged tendons and ligaments become stretched, causing pain.
Eventually the bones may rub against each other causing very
severe pain.
•Obstructive sleep apnea(OSA)- a
condition which causes interruptions in breathing during sleep.
It is a potentially serious sleep disorder in which breathing
repeatedly stops and starts during sleep as the throat muscles
intermittently relax and block the airway. In obstructive sleep
apnea, breathing is interrupted by a physical block to airflow,
despite the effort to breathe. The most noticeable sign of
obstructive sleep apnea is snoring. However, not everyone who has
OSA snores.
Hypogonadism– sexual growth and
development is poor because the gonads (ovaries or testes) are
not producing enough hormones (estrogen, progesterone, and
testosterone). This can lead to:
•Infertility- most people with PWS
cannot have children. Cases of females with PWS who became
mothers are extremely rare.
•Osteoporosis- bones become thin and
weak (brittle).
Observations
And to think that many, so-called
"experts", treating obesity do not know what
Félix E. F. Larocca MD
Médico psiquiatra de adultos y
de niños. Psicoanalista de adultos y de niños. Ex
oficial médico de la US Navy. Especialista en las
enfermedades del comer (disorexias). Ex miembro de las facultades
de Washington University y de Saint Louis University en Saint
Louis, MO. Ex miembro de la Facultad de Educación
Extensiva del Saint Louis Psychoanalytical
Institute.
Punta Cana, Provincia de la Altagracia,
República Dominicana
Autor:
Félix E. F. Larocca
MD