BBS vs. Prader-Willi syndrome: How to tell the difference
Fact-checked by Bardet-Biedl syndrome (BBS) and Prader-Willi syndrome (PWS) are both rare genetic conditions that lead to extreme hunger and obesity in children. While the two conditions overlap, there are key differences in care and family planning that make the correct diagnosis important.
Why BBS and PWS can look similar
BBS is caused by mutations that interfere with cilia, important structures found throughout the body that help cells sense and respond to their environment. PWS is caused by mutations that render genes on a specific stretch of DNA inactive or absent.
While their specific genetic underpinnings differ, both BBS and PWS ultimately disrupt the function of the hypothalamus, a brain region that regulates hunger, energy expenditure, and hormone production, leading to overlapping symptoms. More widespread impacts on brain development also occur in both.
Symptoms that may overlap
Because of their overlapping effects in the brain, both BBS and PWS can lead to:
- an excessive hunger drive (hyperphagia) and childhood obesity
- reduced sex hormone production (hypogonadism), leading to underdeveloped genitalia, delayed puberty, and fertility issues
- issues with speech, learning, and motor development
- behavioral challenges
- metabolic problems, including type 2 diabetes
These common symptoms can lead to a BBS misdiagnosis if other signs and symptoms are not carefully reviewed.
Signs that point more strongly to BBS
While there is substantial overlap, there are some key ways to distinguish BBS from PWS. Symptoms more common in BBS include:
- being born with extra fingers or toes (polydactyly)
- kidney abnormalities
- vision loss
If a child starts becoming obese in infancy, it is more likely to be BBS. In PWS, low muscle tone and feeding difficulties can actually cause poor weight gain in infancy, followed by hyperphagia and obesity in childhood.
In general, aggressive food-seeking behaviors, extreme food preoccupation, and behavioral issues are more pronounced and difficult to manage in PWS than in BBS, although this can vary.
PWS symptoms not typically seen in BBS include characteristic facial features and light-colored hair, skin, and eyes.
How genetic testing helps clarify the diagnosis
Despite symptom overlap, there is no genetic overlap between BBS and PWS — they have distinct underlying causes. As such, genetic testing is the best way to differentiate them when symptoms look similar. These tests look for disease-causing mutations using cells from a blood, saliva, or cheek swab sample.
More than 20 genes have been associated with BBS. Mutations in any of them can lead to the cilia disruptions that drive disease symptoms. BBS testing panels will screen for these genes and sometimes for genes linked to other rare obesity syndromes. This can capture about 80% of cases.
PWS, on the other hand, is always associated with a loss of paternally inherited genes on a section of chromosome 15, which can happen in a few different ways. A test called a methylation analysis can detect more than 99% of PWS cases.
If these tests come back negative, whole exome sequencing, which examines the protein-coding parts of every gene in the body, may be warranted to establish a genetic obesity diagnosis.
Why the right diagnosis matters for care
Monitoring and care for BBS versus PWS differ, so it’s crucial to reach the correct diagnosis as promptly as possible. A BBS or PWS misdiagnosis can delay access to treatments and interventions that will improve quality of life and prevent complications.
For example, in addition to obesity management, people with BBS need close monitoring for kidney and vision problems, which is not standard in PWS. On the other hand, people with PWS may need more rigid and constant environmental interventions to control food intake and prevent life-threatening complications from excessive eating.
The diagnosis also has family planning implications. While fertility is often impaired with BBS, it is possible for people with the disease to have children. BBS is inherited, so other family members may need to be tested to determine whether they carry a mutation and to understand the risk to future children. PWS nearly universally causes infertility, and the genetic changes associated with it are usually not inherited.
Questions to ask if the diagnosis is still uncertain
If a child shows signs of BBS, PWS, or another form of syndromic obesity, but the diagnosis is still unclear, a few questions families can ask include:
- What additional tests does my child need to establish the diagnosis? Are eye exams or kidney tests needed to look for signs of BBS?
- Should we seek genetic testing? And should we consider broader tests, such as whole-exome sequencing?
- What conditions other than BBS and PWS need to be considered for a rare obesity differential diagnosis?
- What are some additional signs I should look out for that might help us find the right diagnosis?
- While we wait for a diagnosis, are there any treatments or interventions we can start to manage my child’s symptoms?
Rare Obesity News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
