Characteristics and relationship between hyperphagia, anxiety, behavioral challenges and caregiver burden in Prader-Willi syndrome

Abstract

Objectives Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by maladaptive behaviors, amongst which hyperphagia is a life-long concern for individuals with PWS and their caregivers. The current study examined the contribution of hyperphagia and other factors to caregiver burden across lifespan, in 204 caregivers of individuals with PWS living in the US, using the Zarit Burden Interview (ZBI) and the hyperphagia questionnaire (HQ-CT). Results We found a strong relationship between ZBI and HQ-CT especially in individuals with PWS older than 4 y and showed that HQ-CT scores of individuals with PWS is positively correlated with ZBI scores of their caregivers. The weight status of individuals with PWS was not associated with HQ-CT and ZBI scores, except for obese individuals who had significantly higher HQ-CT scores when compared to normal weight PWS individuals. We looked at PWS symptoms and care-related issues that impacted individuals and caregivers the most. We found that care-related tasks had the biggest negative impact on caregivers of children aged 0–4 y, whereas anxiety, temper tantrums, and oppositional behaviors of older individuals with PWS had the biggest impact on their caregivers concomitant with their high caregiver burden. Finally, we assessed the variability of HQ-CT and ZBI over 6 months in a subgroup of 83 participants. Overall, neither measure differed between 6 months and baseline. Most individual’s absolute HQ-CT score changes were between 0–2 units, whereas absolute ZBI score changes were between 0–6 points. Changes in the caregiver’s or individual’s life had little or no effect on HQ-CT and ZBI scores. Conclusions This study demonstrates a relationship between hyperphagia and caregiver burden and sheds light on predominant symptoms in children and adolescents that likely underly PWS caregiver burden. The stability and relationship between HQ-CT and ZBI support ZBI as an additional outcome measure in PWS clinical trials.

The Hyperphagia Questionnaire: Insights From a Multicentric Validation Study in Individuals With Prader Willi Syndrome

“…Nevertheless, we did not find a mitigation of hyperphagia in the adult group, since a further increase of the levels of hyperphagia occurred, especially of the Hyperphagic Behavior. Despite the great audience received in the literature about the assumption that hyperphagia decreases and becomes more treatable in the adult age ( 12 ), other recent studies did not find differences in hyperphagia among age groups ( 11 , 38 , 39 ). Similarly, also Dykens et al ( 15 ) even differently grouping participants by age, did not find a decrease of hyperphagia in older age.…”

“…Our findings evidenced that hyperphagia is more pronounced in individuals with PWS with higher weight status even accounting for the age-group. This result may seem obvious, since weight status is a direct effect of hyperphagia, but it should be noted that within each age-group obesity is variably distributed, suggesting again that individual responses to the syndrome can be highly variable ( 38 ).…”

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

“…Unfortunately, caregiver burden remains high, and, in some estimates, exceeds that of caregivers for persons with dementia, Alzheimer’s, and traumatic brain injury. 11 , 12 Recent work has focused on therapeutics that can regulate food intake and EE through mechanisms targeting the hypothalamic leptin-POMC pathway. Melanotan II (MT-II) and setmelanotide are MC4R agonists that have known roles in food intake reduction.…”

“… 8 Management of individuals with PWS is otherwise largely supportive and results in high levels of caregiver burden. 9 , 10 , 11 , 12 …”

Development of an International Database for a Rare Genetic Disorder: The MECP2 Duplication Database (MDBase)

“…Similarly, the research goal of the Global PWS Registry was to collect health-related data to better characterise and study the natural history of this disorder [ 28 ]. Research output stemming from the Global PWS Registry on issues such as weight problems, caregiver burden, suicidality, neuropsychiatric features, thrombosis risk and strabismus in PWS has been published, in the form of either retrospective studies from clinical and patient data collected via surveys (the largest of which featured data from 908 individuals) or prospective, observational studies recruiting individuals from the registry [ 30 , 31 , 32 , 33 , 34 , 35 ]. Such research output has been supported by funding from the Foundation for Prader–Willi Research [ 28 ].…”