Prader-Willi Vignette

Question 1

Describe the chromosomal 15 abnormalities associated with Prader-Willi Syndrome (PWS) and how to test for them.

Answer 1

Genetic information from paternal allele of 15q11-q13

region of chromosome 15 is imprinted so that its critical that information frmo both the maternal and paternal alleles are present for a person to be normal

PWS may result from a deletion of the paternal allele, or because of uniparental disomy (2 copies frmo one parents) of the maternal allele, or an imprinting error in how the alleles are marked

deletion of maternal allele causes a different disorder: Angelman syndrome

Testing for PWS: The maternal and paternal alleles are marked by different patterns of methylation, can do methylation testing
other options: if deletion can do FISH test or a microarray

Question 2

2. Describe the role of imprinting in disorders involving chromosome 15.

Answer 2

Information on imprinting is above; but basically you need alleles from both parents for a person to be normal (because they both get imprinted).

Question 3

3. Describe the physical features (Phenotype) seen in a patient with Prader-Willi Syndrome.

Answer 3

Infancy: very, very floppy (hypotonic). Have subtle facial feature differences (almond shaped eyes), males have undescended testicles (in the abdomen), severe feeding problems that necessitate a Gtube. lighter pigmentation than family members.

Toddler/Preschooler: feeding problems completely reverse from 2-4, child will eat ANYTHING without being sated. Generally become really obese unless treated with growth hormone.

Question 4

4. Describe the medical problems seen in patients with Prader-Willi Syndrome.

Answer 4

Eyes: strabismus, nystagmus common

orthopedics: scoliosis
respiratory: obstructive sleep apnea, contraindication to use of growth hormone
developmentally: mild-moderate cognitive disabilities are usually found

Question 5

5. Recognize and describe the developmental and behavioral phenotypes of a patient with Prader-Willi Syndrome.

Answer 5

behavioral: the eating stuff and mental retardation
developmental: see #3

Question 6

6. Describe other common disorders associated with abnormalities on Chromosome 15q.

Answer 6

Angelman Syndrome: Maternal deletion (rather than paternal like in PWS)

IDIC: associated with autism, hypotonia (low muscle tone and flopiness), seizures, ID

maternally inherited interstital duplication: associated with autism, hypotonia, seizures, ID