Prader Willi Syndrome, Klinefelters Flashcards
What is Prader Willi Syndrome (PWS)?
The PWS chromosomal region is found at 15q11-13 (i.e. bands 11 to 13 on the long arm of chromosome 15) - dysfunctional paternal copy of this gene (maternal gene silenced but is the important)
How is Angelman’s syndrome related?
A mutation to the same region of genes on the maternal chromosome can affect a gene called UBE3A which is only expressed on the maternal chromosome and imprinted on the paternal chromosome
o If this happens, it leads to Angelman syndrome – severe intellectual disability, seizures, ataxia
What are the clinical features of PWS in a newborn?
Hypotonia (floppy)
o Poor suckling reflex (can make feeding difficult)
o Failure to thrive
What are the clinical features of PWS in an infant?
Eating improves and then turns into overeating
Dysfunction of hypothalamus means that they feel hunger even with a full stomach
Can become morbidly obese → can lead to T2DM, obstructive sleep apnoea
etc
Developmental delay
Low IQ
Short stature
Hypogonadism
Characteristic facies
What investigations do you do for PWS?
Genetic testing
What is the management of PWS?
Must restrict food intake e.g. lock fridge
Giving GH can improve height and lean body mass
What is Klinefelter’s syndrome and how common is it?
A chromosomal disorder involving an extra X chromosome in phenotypic males
Incidence: 1-2 per 1000 live birth males
What is the aetiology of Klinefelter’s syndrome?
• Having an extra X chromosome makes the testicular cells generate less testosterone
o The normal function of Sertoli and Leydig cells is interrupted
Sertoli and Leydig cells do
not produce inhibin or testosterone respectively
o In response, LH and FSH levels increase
o Less testosterone suppresses testes maturation and sperm production, and
development of secondary male characteristics
What are the clinical features of Klinefelters?
• Features are most apparent around time of puberty – lack of secondary sexual characteristics
• Infertility: most common presentation
• Hypogonadism with small, firm testes and penis
• Pubertal development may appear normal
• Less muscle mass, less facial and body hair, weaker bones, lower energy levels
• Gynaecomastia in adolescence
• Tall stature with long legs and short stature
• Intelligence usually in the normal range (but some have educational and psychological
problems)
• Increased risk of breast cancer and osteoporosis
What investigations do you use in klinefelters?
• Karyotyping
o CVS or amniocentesis before birth
o Blood test after birth
• After puberty, low levels of testosterone and high levels of LH/FSH
What is the management of Klinefelters?
Hormone therapy to replace testosterone
