Behavioral features in Prader-Willi syndrome (PWS): consensus paper from the International PWS Clinical Trial Consortium

Abstract

Prader-Willi syndrome (PWS) is a rare neurodevelopmental genetic disorder associated with a characteristic behavioral phenotype that includes severe hyperphagia and a variety of other behavioral challenges such as temper outbursts and anxiety. These behaviors have a significant and dramatic impact on the daily functioning and quality of life for the person with PWS and their families. To date, effective therapies addressing these behavioral challenges have proven elusive, but several potential treatments are on the horizon. However, a limiting factor for treatment studies in PWS is the lack of consensus in the field regarding how to best define and measure the complex and interrelated behavioral features of this syndrome. The International PWS Clinical Trials Consortium (PWS-CTC, www.pwsctc.org) includes expert PWS scientists, clinicians, and patient advocacy organization representatives focused on facilitating clinical trials in this rare disease. To address the above gap in the field, members of the PWS-CTC “Behavior Outcomes Working Group” sought to develop a unified understanding of the key behavioral features in PWS and build a consensus regarding their definition and description. The primary focus of this paper is to present consensus definitions and descriptions of key phenotypic PWS behaviors including hyperphagia, temper outbursts, anxiety, obsessive–compulsive behaviors, rigidity, and social cognition deficits. Patient vignettes are provided to illustrate the interrelatedness and impact of these behaviors. We also review some available assessment tools as well as new instruments in development which may be useful in measuring these behavioral features in PWS.

Hypothalamic AAV-BDNF gene therapy improves metabolic function and behavior in the Magel2-null mouse model of Prader-Willi syndrome

“…Patients are highly dependent upon caregivers for maintenance of “food security; restricting of food access and control of food intake occurs through drastic measures such as locks on refrigerators and pantries. 66 To some, surgical methods may seem to be a better alternative to the lock-and-key method. While sleeve gastrectomy was well tolerated in Magel2 -null mice, 67 bariatric procedures in PWS patients result in far greater levels of complications than those observed in non-PWS obese patients 68 and furthermore require patient or caregiver post-surgical compliance to guarantee adequate weight loss.…”

Obsessive Compulsive “Paper Handling”: A Potential Distinctive Behavior in Children and Adolescents with KBG Syndrome

“…The characteristic behavior “paper handling” in KBG syndrome needs to be confirmed by further work using a control group. Indeed, a comparison with a control group (for instance a group of individuals with Prader-Willi syndrome who exhibit ritualistic behaviors as well [ 31 ] or a group of patients with OCD) and a greater understanding of repetitive and stereotyped behaviors are necessary to better clarify the nature of “paper handling” and confirm this evidence. Additionally, the study of the behavior and psychopathology of rare and syndromic diseases is a new frontier to be discovered.…”

Genetic conditions of short stature: A review of three classic examples

“…While fullscale IQ scores are low across PWS subtypes, verbal IQ scores are significantly lower in individuals with deletions than in those with UPD 15 (194,197). Conversely, individuals with UPD 15 are more likely to exhibit signs of ASD or psychotic illness, possibly due to the duplication of several key imprinted and maternally expressed genes in the 15q11-q13 region, including UBE3A and ATP10A (33,36,39,180,196,198). Overall, 12% to 41% of children with PWS have ASD (199).…”

“…Many children exhibit obsessive-compulsive symptoms such as repetitive questioning and checking behaviors. Others exhibit compulsive food-seeking, hoarding, or self-harming behaviors, such as skin-picking (39,195,196,200). Many compulsive behaviors and psychological issues appear to be worse in individuals with chromosome 15q deletions versus those with UPD 15 (Table 4) (193,195).…”

“…Many compulsive behaviors and psychological issues appear to be worse in individuals with chromosome 15q deletions versus those with UPD 15 (Table 4) (193,195). Individuals with PWS often prefer solitary activities and may exhibit signs of anxiety and depression (196).…”