Prader-Willi Syndrome Research Update (January 2021)

Below is a summary of some recently published PWS-related research.  

Source: Foundation for Prader-Willi Research

Genetic research 

PWS is caused by the absence of paternally expressed gene products from a small section of chromosome 15 (hence 15 for 15).  A recently published article describes efforts to activate the normally silent maternal section of chromosome 15 without negatively affecting other functions.  The approach was successful suggesting that activation of the maternal section of chromosome 15 might have potential as a therapeutic strategy for those with PWS.  There is still a long way to go with this work but it is an encouraging step forward. 

Another recent work gives a good general overview of PWS, the role of genetics in clinical presentation and potential treatments for those with the condition. 

Biology of PWS 

Those with PWS are understood to have impaired hypothalamic endocrine (hormone) function but the reason for this is not clear.  A recent study by Victor Chen et al. has shown that deficits in secretory granules, which store chemicals known as neuropeptides for release into the blood.  The paper postulates that the lower numbers of secretory granules could be one of the reasons for the clinical characteristics of those with PWS.  The authors suggest that these findings suggest unanticipated approaches for therapeutic intervention (treatment), thus alleviating several pathogenic processes in those with PWS.  Again, there is still much work to be done but the results are promising. 

A study from the laboratories of Dr Golder and colleagues recently published an article in Translational Psychiatry on the relationship between 2 PWS-related genes and autism. Increased UBE3A mRNA levels were correlated with developmental functioning scores in the deletion group, and increased autism features in the non-deletion PWS group. 

Zhang-Molina, Schmit and Cai have modelled a biochemical mechanism that is consistent with feeding behaviours seen in those with PWS.  They found that activating a chemical called PKC-d and inhibiting another called Htr2a suppresses feeding whereas the opposite is true for increasing feeding.  If both chemicals are activated feeding is also suppressed.  This could be significant in treatment and therapy options for those with PWS. 

Pace et al. relate decreased expression of the SNORD116 gene (one that is made in the region where PWS defects are seen) to abnormal sleep patterns, food intake and temperature regulation. 

Clinical research  

A study of weight Body Mass Index (BMI) change over by Theresa Strong et al. of 165 adolescents and adults with PWS has shown a relatively small increase in weight and BMI over a 6-month period.  Significantly, those individuals on growth hormone started with lower BMIs and were more likely not to show weight increases according to the study. 

Drs. Pascal Barone and Maithe Tauber and their teams at the University of Toulouse in France have been working to understand how those with PWS process facial cues and sounds, including voices.  They found that  

“deficits in voice and non-voice recognition (sounds that aren’t voices), difficulty distinguishing voices from environmental sounds, slower processing times and poor emotional recognition means that individuals with PWS may be at a disadvantage compared to their typical peers in staying attuned to social cues. All individuals with PWS are impacted, but those with PWS by Uniparental Disomy (UPD) are more likely to have a harder time. The development of tailored PWS interventions, based on an understanding of the specific weaknesses exhibited by those with PWS, may lead to more fulfilling social interactions for individuals with PWS and their social group.”  


Although hip dysplasia is far more prevalent in those with PWS than the general population (8 to 30 times higher) Dr Harold van Bosse and collaborators have released new guidance on treatment of the condition in babies and infants with PWS.  Based on a decade-long study of outpatients from hospitals in the United States that reviewed 9.4 million patients who received hip or knee replacements, only 65 were diagnosed with PWS, indicating that the increased prevalence of hip dysplasia in those with PWS does not lead to increased likelihood of hip and knee replacements. The new guidance suggests observation rather than surgical intervention for those with stable or improving hips. 

Measuring hyperphagia in those with PWS is usually assessed through a survey response.  To try to find a more accurate and definitive measure of hyperphagia researchers have been evaluating eye tracking.  The study compared how children between the ages of 3 and 11 years looked pictures of food, animals and household items.  They found there wasn’t a significant difference between those with PWS and those without PWS but found those with more advanced food-seeking behaviours looked at pictures of food for longer periods.  The researchers concluded that, based on this finding research into eye tracking should continue. 

Please note that the Prader-Willi Syndrome Association of Victoria provides this information to report to its members – not to impose any particular treatment options.  Any decisions about treatment options should be made in consultation with your own medical team

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Article By Nick Burke

Nick Burke is the father to Amelia, a 14 year old with Prader-Willi Syndrome and her brother Sean, 12. He is a current board member of the PWSA Vic and has been an active member for many years. He is passionate about supporting those with Prader-Willi Syndrome and their families and has taken a keen interest in research that stands to benefit the PWS community.