1. Elemente de diagnostic şi
urmarire clinica în PWS,
Conf.Dr. Otilia Mărginean,
UMF Timisoara

2. PWS - History
 1680 - Painting by Juan Carreno
de Miranda
 1887 –Langdon –Down describe
the firt pacient with PWS
 1956 –Prader et col. describe the
specific phenotype
 1981-Ledbetter et col.
Identified the
microdeletion within cr 15

3.  Prader-Willi syndrome is
the consequence due to
a loss of function of
imprinted genes in the
chromosome region
15q11-q13.
In the case of PWS, the absent
contribution to this region is always
paternal, leading to a loss of expression
of paternally transcribed genes.

4. Bienvenu et al. Nature Reviews Genetics 7, 415–426 (June 2006) | doi:10.1038/nrg1878

5. Prader-Willi Syndrome is a congenital condition
(present at birth)
 Children born with Prader-Willi Syndrome may
have early feeding difficulties that lead to tube
feeding, and often have a degree of behavioral
and/or mental problems (some severe).
 The person with Prader-Willi Syndrome has an
insatiable appetite. This can lead to obesity,
stealing, This continuous appetite is caused by a
defect in the hypothalamus; speech impairments,
stunted sexual development, poor muscle tone,
dental problems, diabetes type II.
 The life expectancy of a person with Prader-Willi
Syndrome may be normal if weight is controlled.

6. Newborns with PWS
exhibit nonspecific findings including
 Hypotonia, At birth, babies are usually floppy
 Small ;They may have small hands and feet,
 Poor sucking reflex,
 Giminished or absent cry, and somnolence.
 Boys may have undescended testicles.
 Early developmental milestones are delayed.

7.  Delay of normal development, such as language skills and
walking
 Behavior problems, such as temper tantrums and stubbornness
 After about six months to a year, especially as the child
becomes mobile, they develop an interest in food that may
become an insatiable obsession.
 Weight gain can be rapid, leading to severe obesity that results
in diabetes, strain on the heart, lungs and skeleton, and even
early death.
 Some people have also noticed that children with PWS may be
unusually blonde and blue-eyed.
 Poor muscle tone
 Poor reflexes
 Small to normal size
 Inability to suck well
 A weak, squeaky cry
 Lethargy
As a toddler, new symptoms may include:

8. CHild
 Insatiable hunger, resulting in compulsive eating / obesity
 Continuing behavior problems, such as anger and inflexibility
 Learning disabilities
 Low to normal IQ
 Incomplete sexual development,
 High threshold for pain
 Insensitivity to temperature extremes
 The diagnosis is usually evident based on sympt.
and a characteristic physical appearance:
 Almond-shaped eyes
 Strabismus
 Narrow forehead
 Down-turned mouth / Thin upper lip
 Lighter coloring compared with other family members
 Developmental Issues
 Delay in motor skill development and Cognitive delay or limits
 Delays in physical growth and Incomplete sexual develop. in adol.

9. Adolescent
 Short stature.
 Obesity
 Hypogonadism presents as:
 cryptorchidism, small testes, and decreased scrotal
rugae in males and
 small labia minora and clitoris in females. Puberty
typically is delayed or incomplete.
 Learning disabilities always are present;
however, affected persons may have low-
normal intelligence to moderate mental
retardation.

10. Diagnostic Criteria for Prader-Willi sy.
 Characteristic facial features
(may include almond-
shaped eyes, down-turned
mouth, narrow bifrontal
diameter, strabismus, thin
upper lip;
 Developmental delay
 Feeding problems/failure to
thrive during infancy
 Hypogonadism (may include
cryptorchidism, hypoplastic
scrotum, and small testes in
males; hypoplastic labia
minora and clitoris in
females; and pubertal
deficiency)
 Infantile central hypotonia
 Rapid weight gain between
1 and 6 years of age
 Decreased fetal
movement and infantile
lethargy
 Esotropia, myopia
 Hypopigmentation
 Narrow hands with
straight ulnar border
 Short stature (compared
with family members)
 Skin picking
 Sleep disturbance/sleep
apnea
 Small hands and feet
 Speech articulation
defects
 Thick, viscous saliva
 Typical behavioral
problems
MAJOR CRITERIA MINOR CRITERIA

11. Score
• 1 point for each major criterion and
• 0.5 point for each minor criterion.
A diagnosis of Prader-Willi syndrome should be
suspected in
• children < than three years with a score of at least 5;
• in children >three years and older with a score of at
least 8, (4 points from major criteria).
Supportive criteria (no points) include high pain threshold,
decreased vomiting, temperature control problems,
scoliosis, kyphosis, early adrenarche, osteoporosis,
unusual skill with jigsaw puzzles, and normal
neuromuscular studies.
 The clincal picture must by support by genetic
analises

12. TREATMENT
 The first research on using growth hormone (GH)
with Prader-Willi syndrome (PWS) began in
198I. Two key pioneers in this field were Dr.
Moris Angulo and Dr. Phillip Lee
 In June 2000 growth hormone was the first (and
to date the only) drug approved by the U.S. Food
& Drug Administration (FDA) for the treatment of
Prader-Willi syndrome.

13. The conditions are associated with Prader-Willi
syndrome which require life-long management:
 Scoliosis
 Strabismus
 Osteoporosis
 Dental problems
 Obesity-related
problems, such as:
 Type 2 diabetes
 High blood pressure
 Metabolic syndrom
 Heart failure
 Skin problems
 Skin picking
 Short stature
 COMPLEX TEAM

14. GHITA AURA
 height 140cm (the
height according to
age 150), SDS- 1.5,
weight 88Kg (the
weight according to
the height 54Kg ),
G. AURA
CASE 1 GA
?

15. Scor 8.5
Majore criterias: 5
•caracteristic facial features -1
•hipogonadism-1
•mental retard. -1
•infantile feeding problems -1
•rapid weight gain between 1-6 years - 1
Minor criterias
1. Short stature
2. Skin picking
3. Sleep disturbance/sleep
apnea
4. Small hands and feet
5. Speech articulation defects
6. Thick, viscous saliva
7. Typical behavioral problems

16. G.AURA

17. CASE 2 M.I , 4years old

19. M. IULIA
M. IULIA

20. SCOR 7
Major criterias
 caracteristic facial features -1
 retard mental-1
 infantile feeding problems -1
 rapid weight gain between 1-6
years – 1
 Infantile central hypotonia
Minor criterias:
 Rapid weight gain between 1
and 3 years of age
 Sleep disturbance/sleep apnea
 Small hands and feet
 Speech articulation defects

22. Conclusions
 PWS is underdiagnose
 There is necessary A good information to
general population
 For treatment PWS need a complex team
 In the present is a hope for PWS, children
by use GH