Diagnostic Criteria, Presentation
Name two hallmark early-life features of PWS.
hypotonia, feeding difficulties, distinct facial features, hypogonadism
What is the most common genetic cause of PWS?
Paternal deletion of 15q11-q13 (70%)
Hyperphagia typically begins around what age or stage of life?
early childhood, between 2-6 ish
What is the first-line genetic test used to diagnose PWS?
DNA methylation analysis
Explain the role of the imprinting control region (ICR) in regulating PWS and AS gene expression.
ICR regulates expression by silencing one parent’s allele depending on methylation
What is the main eating-related symptom that defines PWS?
hyperphagia
What are the other two main causes?
(maternal uniparental disomy (25%), imprinting defects (1-3%))
What early life muscle condition is typical in PWS?
Hypotonia
This test is required to confirm chromosomal deletions in PWS.
FISH
What is the process describing when both copies of a chromosome are inherited from the same parent, disrupting imprinting.
uniparental disomy (UPD)
What intellectual and behavioral characteristics are commonly seen in PWS
Mild to moderate intellectual disability; temper outbursts, compulsive behaviors
What is the estimated prevalence of PWS?
1 in every 20,000 to 30,000 births
What brain region's dysfunction underlies many symptoms of PWS, including appetite dysregulation?
hypothalamus
What hormone therapy is commonly used to improve growth and muscle tone in PWS?
growth hormone therapy
Explain how UPD and methylation errors can both lead to PWS.
UPD - no paternal genes. Methylation errors - genes silenced
T or F: More than 70% of children and adolescents with PWS have a high risk of developing autism spectrum disorder.
T
How do methylation defects cause PWS?
Methylation defects silence the paternal allele, leading to loss of gene expression.
Describe the typical progression of appetite and weight changes from infancy to childhood in PWS.
Infancy: poor feeding and failure to thrive; Childhood: insatiable appetite, rapid weight gain
Discuss the role of multidisciplinary care in PWS management.
Coordinated care involving endocrinology, nutritionists, behavioral therapists, and genetic counselors.
What physical features (dysmorphisms) help identify PWS?
Almond-shaped eyes, narrow forehead, small hands/feet, thin upper lip.
T or F: Generally, there are no consistent significant differences in PWS prevalence when it comes to gender or race.
T
What sleep abnormalities are caused by hypothalamic and brainstem dysfunction in PWS?
Central and obstructive sleep apnea, excessive daytime sleepiness, and altered REM sleep patterns
Why is traditional karyotyping typically not sufficient to diagnose Prader-Willi Syndrome?
PWS is usually caused changes too small or subtle for standard karyotyping to detect