Prader Willi Syndrome

Question 1

Name 4 mechanisms that may cause Prader Willi Syndrome

Answer 1

Caused by a lack of expression of genes from an imprinted region of the paternally inherited chromosome 15q11-13 near the centromere due to:

1. Paternally inherited chrom 15 micodeletion of PWS region (70%)
2. Maternal uniparental disomy (20%)
3. Imprinting errors
4. Balanced translocation of chromosome 15 (moves genes away from the imprinting centre)

Question 2

True or false; prader willi syndrome is more common in boys.

Answer 2

False! It is equal between males and females.
All ethnicities
and 1/15-25,000

Question 3

What is unique about growth in Prader Willi syndrome depending on age?

Answer 3

At birth FTT, later have central obesity and hyperphagia.

Also short stature.

Question 4

Name 3 GU features seen in Prader Willi

Answer 4

1. Small penis/scrotal hypoplasia
2. Cryptorchidism
3. Hypoplastic labia minora/clitoris

Question 5

Name 5 endocrine features of Prader Willi syndrome

Answer 5

1. Hyperinsulinemia
2. GH deficiency
3. Hypogonadotropic hypogonadism (dt pituitary gland or hypothalamus)
4. DMT2
5. Generalized hypothalamic insufficiency

Question 6

Name 7 neurologic features with PWS

Answer 6

1. Severe neonatal hypotonia that improves w age
2. Poor neonatal suck/swallow
3. Poor gross/fine motor skills
4. LD
5. Seizures
6. GDD
7. Hyperphagia

Question 7

Name 4 Behavioural Features seen in PWS

Answer 7

1. Skin picking
2. Rectal picking
3. Food related stubborn/temper tantrums
4. OCD

Question 8

Name 6 facial features of PWS

Answer 8

1. Narrow bitemporal diameter
2. Almond shaped-eyes
3. Up slanting palpebral fissures
4. Thin upper lip
5. Small-appearing mouth
6. Down turned corners of mouth

Question 9

Name 3 ENT features PWS

Answer 9

1. Hypernasal speech
2. Weak cry
3. Dental crowding/malocclusion

Question 10

Name 5 optho features of PWS

Answer 10

1. Strabismus
2. Nystagmus
3. Retinal hypopigmentation
4. Foveal hypoplasia
5. Refractive errors

Question 11

Name 2 resp features of PWS

Answer 11

1. Hypoventilation

2. Obstructive OR central sleep apnea

Question 12

Name 6 MSK features of PWS

Answer 12

1. Osteoporosis
2. Osteopenia
3. Scoliosis
4. Kyphosis
5. Small hands/feet
6. Clinodactyly

Question 13

Name 3 random other features of PWS

Answer 13

1. Temperature instability
2. High pain threshold
3. Unusual skill with jigsaw puzzles

Question 14

Name 4 proposed criteria that should prompt you to do molecular testing for PWS

Answer 14

Birth-2 years: ++++hypotonia, poor suck, poor weight gain
2-6yo: Congenital hypotonia and GDD
6-12yo: Congenital hypotonia, GDD, hyperphagia with central obesity
13yo+: Cognitive impairment, hyperphagia, hypothalamic hypogonadism, or typical behavioural problems

Question 15

How do you test for PWS?

Answer 15

1. Methylation studies: Confirm absence of paternally imprinted genes in PWS region
2. Karyotype or FISH to assess for deletion/balanced translocation.

Question 16

Name 6 Management strategies for children with PWS

Answer 16

1. Nutritional support in infancy; almost all need NGT for 4-6 mos
2. Caloric restriction in childhood; limit access to food
3. ACTH stim test when well, may need stress dosing when sick
4. Growth hormone deficiency almost universal; good response to tx
5. HCG may help testes descend; consider before surgery
6. Thyroid studies q 2yrs