imprinted genes have only a maternal methylation pattern.
If
Figure C-38 A 12-month-old girl with Prader-Willi syndrome. Note her
fair coloring, narrow bifrontal diameter, almond-shaped eyes. and down-turned
mouth. The hyperphagia. with resulting central obesity, generally does not begin
until the age of 2 to 6 years. See Sources & Acknowledgments.
non-insulin-dependent (type 2) diabetes mellitus. Longevity
can be nearly normal if obesity is avoided.
Most children with PWS have delayed motor and language
development as well as mild intellectual disability (mean IQ,
60 to 80). They also have behavioral problems, including
temper tantrums, obsessive-compulsive disorders, and poor
adaptation to changes in routine. These behavioral problems
continue into adulthood and remain disabling. Approximately
5% to 10% of patients also develop psychoses during early
adulthood.
Other anomalies associated with PWS include short stature,
scoliosis, osteoporosis, and dysmorphism. Dysmorphic fea­
tures include a narrow bifrontal diameter, almond-shaped
eyes, triangular mouth, and small hands and feet (Fig. C-38).
Also, many patients have hypopigmentation of the hair, eyes,
and skin.
Management
Although it is often suspected on the basis of history and
physical features, a diagnosis of PWS is defined by the absence
of a paternally imprinted 15ql1-q13. Loss of the paternal
imprint is detected by DNA analyses showing that the
the DNA studies confirm PWS, genetic counseling requires a
subsequent karyotype and FISH for 15ql1-q13 to determine
whether PWS arose from inheritance of a chromosomal
translocation.
No medications are currently available to treat the hyper­
phagia; a very low-calorie and restrictive diet and exercise
remain the mainstays for controlling the obesity. Growth
hormone replacement can normalize height and improve lean
body mass. Sex hormone replacement promotes secondary
sexual features but frequently worsens behavioral problems in
males and increases the risk for stroke in females. Behavioral
management and serotonin reuptake inhibitors are the most
effective therapies currently available for the behavioral dis­
order_ Adult patients usually perform best in sheltered living
(group homes) and employment environments.
INHERITANCE RISK
The risk for recurrence of PWS in future children of parents
is related to the molecular cause. For imprinting defects, the
risk can be as high as 50%, whereas for either deletion of
15q11-q13 or maternal uniparental disomy, the recurrence
risk is less than 1%. The risk for recurrence if a parent carries
a balanced translocation depends on the nature of the trans­
location but can be as high as 25%; in contrast, all PWS
patients reported to date with an unbalanced translocation
have had a de novo chromosomal rearrangement.
REFERENCES
Cassidy SB, Schwartz S, Miller JL. et al: Prader-Willi syndrome. Genet Med 14:10-
26. 2012.
Driscoll OJ, Miller JL. Schwartz S, et al: Prader-Willi syndrome. Available from:
http://www.ncbi.nlm.nih.gov/boolcs/NBK1330/.