Prader-Willi and Angelman syndrome are both syndromal causes of genetic obesity, with Prader-Willi syndrome (PWS) being the most common. These genetic imprinting syndromes can be expected to appear on the exam, although a general rule of thumb is that the rarer the condition, the less in-depth it will be covered.

Disruptions in gene imprinting can lead to certain genetic medical conditions. PWS and Angelman are both caused by disruptions in parental imprinting that affect the same region of chromosome 15. However, the results vary drastically based on whether the genetic abnormality occurs on the paternal or maternal copy of the chromosome.

PWS occurs due to a paternal chromosome 15q partial deletion (i.e., underexpressed gene) at the 15q11-q13 loci. This leads to the characteristic findings of neurodevelopmental delays and intellectual disability with excessive weight gain and hyperphagia, with obesity commonly occurring between 2-5 years of age. However, they are often smaller at birth, with bitemporal narrowing of the head, hypotonia, and characteristic “floppiness.” Notorious physical examination findings include short stature, thin upper lips, and almond-shaped eyes.

PWS leads to high ghrelin levels and low pancreatic polypeptide levels. Treatment includes calorie restriction and behavioral therapy, with growth and sex hormone replacement at puberty. The ABOM will likely require an ability to recognize the condition based on the characteristic findings and determine the genetic abnormality leading to this condition.

Reminder: Syndromic obesity refers to obesity that is part of a broader syndrome or medical condition. These conditions can include genetic disorders such as Prader-Willi syndrome (most common) or Bardet-Biedl syndrome. In these cases, obesity is just one symptom of the underlying condition. The findings associated with each condition may also be expressed to different extents among individuals.

Now, let’s jump to the less common imprinting error. Although it is on the same chromosome and gene as PWS (15q11-q13), Angelman syndrome is caused by a genetic abnormality corresponding to the ubiquitin protein ligase E3A (UBE3A), which is normally inherited from the mother (maternal imprinting), whereas the paternal gene is normally silenced. If the mother’s gene is missing or defective, this causes Angelman syndrome, which often occurs de novo. In other words, it is not inherited.

Patients with Angelman syndrome also have some unique characteristics:

  • A very happy personality with frequent smiling and laughing
  • Development milestone delays, including walking
  • Minimal talking early on (often babbling)
  • Seizures between 2-3 years of age
  • Spastic and jerky movements with microcephaly
  • Sleep disorders, including insomnia

In addition, these patients may have increased appetites leading to obesity (one-third of patients), which is why it may show up on test day.

The fact that PWS and Angelman syndrome are caused by the disruption of the same chromosomal region but in a parent-specific manner highlights the role of genetic imprinting in these conditions. The different expression patterns of imprinted genes on chromosome 15 from the paternal and maternal copies significantly impact the clinical features and development of individuals with PWS and Angelman syndrome. Be familiar with both of their characteristic clinical findings and the genetic abnormality leading to the condition.

Update: Diazoxide choline extended-release (VYKAT® XR) was approved in 2025 and is indicated for the treatment of hyperphagia in adults and pediatric patients 4 years of age and older with Prader–Willi syndrome.

Sample Question

A 3-year-old boy is brought into the pediatric office, as the mother has recently noticed increased weight gain and an insatiable appetite that was not previously present. After reviewing the growth chart, it is noted that his height has maintained the 60th percentile. However, his weight has increased from the 50th percentile to the 90th percentile in the past 1.5 years. A speech therapist has seen him for delayed speech and he is scheduled to see a therapist for late motor development. Which of the following would most likely be seen on physical examination?

A. Short 4th and 5th metacarpals

B. Hepatosplenomegaly

C. Polydactyly

D. Macroglossia

E. Almond-shaped eyes

Next Week: Monthly Knowledge Check. This is a review checklist of must-know items for ABOM exams based on the previous four blog topics (Meal-terminating anorexigenic hormones, Aspire Assist® device, body fat measurements (calipers vs. DXA, etc), and Prader-Willi vs. Angelman). In addition, this will include a brief explanation of the correct answers to previous sample questions.

Upcoming: Motivational interviewing, lap band, idiopathic intracranial hypertension (i.e., pseudotumor cerebri), cortisol levels/weight gain with no sleep.

For more practice questions, check out the following:

  • Obesity Medicine Board Review Questions (2026): Qs 79 and 115.
  • Obesity Medicine Practice Tests (2026): Qs 87, 200, 221, 259, 382, 410, and 418.

(Copyright 2026) Obesity Medicine Board Review Questions, LLC: obesitymedicinereview.com

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