USMLE Step 1 · Biochemistry & Genetics

Prader-Willi syndrome vs Angelman syndrome

How to tell Prader-Willi syndrome and Angelman syndrome apart when a board question makes them look alike.

Fastest separator

Prader-Willi is paternal loss with hyperphagia/obesity/hypogonadism; Angelman is maternal loss with seizures/ataxia/happy affect.

Side by side

Prader-Willi syndromeAngelman syndrome

Key clue

Prader-Willi causes neonatal hypotonia, poor feeding followed by hyperphagia, obesity, hypogonadism, intellectual disability, and paternal 15q11-q13 loss or maternal uniparental disomy.

Angelman causes severe intellectual disability, seizures, ataxia, inappropriate laughter/happy demeanor, minimal speech, and maternal 15q11-q13 loss or paternal uniparental disomy.

Mechanism

Loss of paternally expressed genes in the 15q11-q13 imprinted region causes hypothalamic and neurodevelopmental dysfunction.

Loss of maternally expressed UBE3A in neurons disrupts synaptic function and neurodevelopment.

Labs and tests

Hyperphagia, obesity, hypogonadism, and paternal deletion support Prader-Willi.

Seizures, ataxia, happy affect, minimal speech, and maternal deletion support Angelman.

The trap

Both involve chromosome 15 imprinting, so parent-of-origin and behavior/feeding phenotype are decisive.

Watch it explained

60-second lessonPrader-Willi vs Angelman: Imprinting on Chromosome 15 Made Easy (USMLE Step 1)

Quiz yourselfPrader-Willi or Angelman? 6-Second Genetics Pop Quiz (USMLE Step 1)

Test it now

The repair move

For chromosome 15 imprinting, pair paternal loss with Prader-Willi and maternal UBE3A loss with Angelman.

Try a free question

Core

A 2-year-old child was hypotonic with poor feeding as a neonate but now has insatiable hunger (hyperphagia), rapid weight gain with central obesity, almond-shaped eyes, small hands and feet, hypogonadism with cryptorchidism, and mild intellectual disability. Methylation testing reveals a paternal deletion of 15q11-q13. Which condition is most likely?

Show answer and explanation

Answer: A. Prader-Willi syndrome. Prader-Willi syndrome results from loss of paternally expressed genes in the 15q11-q13 imprinted region (paternal deletion or maternal uniparental disomy). Features: neonatal hypotonia and poor feeding, transitioning to hyperphagia and obesity, hypogonadism, small hands/feet, mild intellectual disability.

Why the other choices are tempting

B. Angelman syndrome is the OPPOSITE imprinting defect (maternal loss) with severe intellectual disability, seizures, and happy demeanor, not hyperphagia with obesity.
C. Bardet-Biedl syndrome features obesity, retinitis pigmentosa, polydactyly, and renal anomalies, not the PWS 15q11 imprinting pattern.
D. Cohen syndrome features microcephaly, intellectual disability, and central obesity but not the PWS imprinting pattern.
E. Cushing syndrome features cortisol excess with central obesity and hypertension, not the PWS imprinting/hypotonia pattern.

Flashcards

Tap a card to flip it.

What clue supports Prader-Willi syndrome?

Choose Prader-Willi syndrome when the stem gives this pattern: Prader-Willi causes neonatal hypotonia, poor feeding followed by hyperphagia, obesity, hypogonadism, intellectual disability, and paternal 15q11-q13 loss or maternal uniparental disomy.

What clue supports Angelman syndrome?

Choose Angelman syndrome when the stem gives this contrasting pattern: Angelman causes severe intellectual disability, seizures, ataxia, inappropriate laughter/happy demeanor, minimal speech, and maternal 15q11-q13 loss or paternal uniparental disomy.

Quick answers

What is the fastest way to tell Prader-Willi syndrome from Angelman syndrome?