Projects Archive - Foundation for Prader-Willi Research | Clinical Issues

In previous research, Dr. Hall has found that altered internal bodily cues (interoceptive processes), such as pain, itch, and sensual touch, may be involved in skin picking behavior in PWS. Here, he will employ a sophisticated brain imaging method called functional near-infrared spectroscopy (fNIRS), which allows brain activity to be measured...

Currently, hyperphagia is often assessed by proxy informants on the Hyperphagia Questionnaires. Leveraging insights from previous research -- and with input from a PWS Advisory Board, PWS focus groups and our own experience in developing other PWS-specific measures—this project will develop a self-report measure of hyperphagic symptoms for...

Dr. Kelleher and her group have been developing telehealth-based interventions to improve the mental wellness of those caring for individuals with neurodevelopmental disorders. Here, they will expand an existing caregiver support program (Well-CAST) to families with PWS and another disorder (Williams Syndrome, WS). They will evaluate different...

Prader-Willi syndrome individuals show impaired social behaviors and altered oxytocin levels in the brain, but the reason for this remains unknown. Here we will test whether changes in the gut bacterial content in PWS could perturb social behaviors and related changes in oxytocin. In addition, we will examine whether a probiotic bacteria strain...

Social isolation and impaired social cognition underpins loneliness, depression and anxiety, contributes to poor health and reduced longevity. They also are associated with such cognitive consequences as impaired executive functioning, cognitive decline, a bias towards negative, depressive thinking, and oversensitivity to perceived social...

Neuropsychological studies have detailed several cognitive deficits in Prader-Willi Syndrome (PWS), among which the observation of altered social interactions, with notable difficulty in interpreting and responding to social information. The integration of the information from the face and the voice is important for our social communication as...

For Year 1, our project aims were: 1) to characterize the social, cognitive, and affective processes in preschoolers with PWS (by genetic subtype), in comparison to preschoolers with ASD and typically developing children, and 2) to pilot a remotely delivered parent education program to determine if it would be feasible and effective for families...

Orthopedic anomalies are common in patients with Prader-Willi syndrome (“PWS”). Surveys suggest that roughly 19% of individuals with PWS may be diagnosed with knock knees, 10% with hip dysplasia, 7% with patellofemoral instability, and 3% with bowlegs. Yet, there is little consensus among orthopedists about how best to address these issues in...

Temper outbursts are one of the most commonly reported behavior problems of children, adolescents and adults with PWS. Outbursts cause increased stress for families and costs for the community. Despite this, there is currently no known treatment. Meditation on the Soles of the Feet (SoF) is a mindfulness-based intervention designed specifically to...

Recent studies with oxytocin treatment in PWS have yielded inconsistent results. Intranasal administration of oxytocin by the Toulouse group decreased disruptive behaviors in patients with PWS, but a recent randomized trial in Australia of adolescents and adults of intranasal oxytocin (IN-OT) found no effect on syndrome-specific behavior in...

Hyperphagia is one of the distinctive features of Prader-Willi syndrome (PWS), and when not carefully monitored or controlled, can be life threatening. It emerges in early childhood and remains a life-long challenge for individuals with PWS and their caregivers. To effectively manage and, in the future, treat hyperphagia, it is important to be...

Hyperphagia (extreme overeating) is the most significant factor contributing to obesity in Prader-Willi syndrome (PWS) and considered a cardinal feature. PWS is recognized as the most common syndromic cause of life-threating obesity, but no medications are currently available to decrease appetite or lessen obesity in PWS.

The hypothesis set out in our original application is that t-VNS given over time and following a protocol established for its use in epilepsy, will prevent the prolonged and debilitating temper outbursts and associated emotional dysregulation that characteristically affect people with PWS. We further propose that any improvements in behavior are...

Dr. Tucci’s group has shown that mice with the SNORD116 deletion have sleep abnormalities and increased body temperature. They hypothesize that environmental temperature may play a crucial role in the pathophysiology of PWS symptoms including sleep and obesity. They will use PWS mice that will be maintained under different temperature regimens and...

People with intellectual or developmental disabilities, including Prader-Willi syndrome (PWS), are at heightened risk for social exclusion and isolation. This underpins loneliness, depression and anxiety, contributes to poor health and reduced longevity. This project will recruit 50 young adults with PWS into an intensive, 10-week group...

Prader-Willi syndrome (PWS) is a genetically and clinically complex disorder. From a molecular standpoint, a major question has been the contribution of individual genes within the Prader-Willi domain on chromosome 15 to the overall clinical phenotype. Many animal models have attempted to address this question, but have not been able to fully...

Children with Prader-Willi syndrome suffer from very low muscle tone, growth delay, short stature, developmental delay, muscle weakness and exercise intolerance. Studies have suggested that there is a problem with energy metabolism in PWS but what kind of problem this is and how this leads to PWS is not clear at the present time. Many PWS patients...

There is increasing evidence that Prader-Willi Syndrome is associated with high rates of psychosis, a serious mental disorder that profoundly disrupts thought and emotion. However, little is known about the early or ‘prodromal’ phase of illness and the risk factors that predict the emergence of psychosis in PWS patients. This is a critical gap in...

This proposed proof of concept study follows an earlier trial of vagus nerve stimulation, using a surgically implanted medical device, in three people with PWS to investigate whether such treatment might reduce the over-eating behaviour characteristic of people with PWS. Whilst the effects on eating were equivocal, two of the three participants,...

Study one: There is a reduction in the number of neurons that produce oxytocin in people with PWS. This, along with a range of other evidence supports the likelihood that abnormalities in the oxytocin system are key to the problems of PWS. However, studies examining the levels of oxytocin in PWS as well as clinical trials evaluating the effect...

Paying attention to communicative faces is essential for our understanding of the social world. Indeed, faces provide observers rich and complex information about the identity (gender, age, etc), the socio-emotional state (eye-brows movements, eye-gaze) and the linguistic message (auditory speech sounds/mouth movements) of our social partners. The...

Temper outbursts are commonly shown by people with Prader-Willi syndrome (PWS) and can cause great problems for people with the syndrome, their family members and caregivers. One common reason for temper outbursts is that people with PWS find changes to routines or to plans very difficult. This difficulty with change is linked to impairment in a...

Prader-Willi Syndrome (PWS) is a complex genetic disorder characterized by an insatiable feeling of hunger and an irrepressible urge to overeat. If left uncontrolled, hunger and overeating can lead to morbid obesity, diabetes, cardiovascular disease and premature death. Why PWS causes hunger is an important question that must be answered in we...

A remarkable clinical resemblance between Prader-Willi syndrome (PWS) and hypotonia-cystinuria syndrome (HCS) was observed in our multidisciplinary clinic for PWS in our center. All HCS patients were initially referred for genetic analysis of PWS. Patients with either syndrome suffer from weakness and poor sucking in the newborn period. This...

In Prader-Willi syndrome (PWS) the progression from poor appetite and failure-to-thrive (FTT) to obesity and voracious appetite is complex and takes several years. We have recently shown that there are 6 distinct post-natal nutritional phases in PWS. By looking at the end products of cellular processes in individuals with PWS before and after the...

Hyperphagia (extreme overeating) is the most significant factor contributing to obesity in Prader-Willi syndrome (PWS) and considered a cardinal feature. PWS is recognized as the most common syndromic cause of life-threating obesity, but no medications are currently available to decrease appetite or lessen obesity in PWS. Preliminary studies have...

Prader-willi syndrome is a genetic disorder caused by loss of a portion of a copy of chromosome 15. Common features include early problems with muscle weakness and feeding followed by occult weight gain without an increase in food consumption beginning during late infancy/early toddler period prior to the onset of hyperphagia. Recent research has...

The MAGEL2 gene appears as one of the main genes involved in feeding and behavioral (autistic like behavior) alterations observed in Prader-Willi Syndrome. We showed that, in mouse, the deficiency of Magel2 results in a phenotype similar to the clinical description of patients with mutations in MAGEL2. Indeed, we showed that Magel2-deficient mice...

Once Prader-Willi patients reach the stage where hyperphagia is a dominant characteristic of the disease, the progression to obesity, morbid obesity and diabetes and their complications reduces the quality of life of the patient and increases their risk of death from a number of causes. The constant food seeking and food obsession combined with...

Prader-Willi Syndrome (PWS) is a neurodevelopmental disorder caused by lack of inherited genes from fathers on chromosome 15. PWS is characterized by intellectual disabilities, repetitive and compulsive behaviors, social cognition deficits, increased eating and obesity. These individuals typically consume up to three times the normal caloric...

The vagus nerve is a major route of communication between the brain and the gut. Vagus nerve stimulation (VNS) is a procedure whereby a small implanted device placed under the skin on a patient’s chest delivers an intermittent electrical impulse to the vagus nerve, which will travel up and down the nerve and into the brain and to the gut. VNS has...

Dr. Jennifer Miller is assisting FPWR in identifying opportunities for clinical trials in PWS and developing recommendations for the conduct of such clinical trials. Among the issues to be addressed are target population, identification of informative surrogate endpoints, and assessment of recruitment challenges. In addition, she is providing...

Dr. Tauber is leading a European effort to collect blood samples on infants and children with PWS to monitor changes in hormones over time. This funding will support a blood bank recruitment coordinator, who will work to collect clinical data on birth, growth, endocrine functions and feeding behavior in newly diagnosed patients with PWS.

Prader-Willi Syndrome (PWS) is a complex genetic disorder associated with varied clinical findings, neurocognitive delay, and endocrine abnormalities. Clinically, individuals with PWS progress along a path marked by different nutritional stages. In infancy, children with PWS have hypotonia, poor feeding, excessive daytime sleepiness, and...

Prader-Willi syndrome is a multisystem disorder due to absence of paternally expressed imprinted genes at 15q11.2-q13. Diminished bone mineral density (BMD) and osteoporosis are common in PWS individuals, especially in adolescence and adulthood. The reasons for the increased prevalence of osteoporosis in PWS are not totally clear, but decreased...

: Prader-Willi Syndrome (PWS) is a genetic disease characterized by failure to thrive and low muscle tone during infancy, followed by food-seeking, insatiable appetite and progressive obesity in childhood. The resulting increases in total body fat and decreases in muscle mass lead to metabolic problems such as diabetes and heart disease.

Early in infancy, babies with Prader-Willi syndrome (PWS) have no interest in feeding manifested by lack of crying for food and failure-to-thrive requiring assisted feeding with a G-tube, NG tube, or cross-cutting of bottle nipple (phase 1a). There is then a series of transition through five nutritional phases, ending in the classic PWS...

Prader-Willi syndrome (PWS) is a rare multisystem genetic disease leading to severe disabilities such as morbid obesity, as well as behavioral and socialization problems. We are greatly lacking in information on the natural history of this complex disease and the factors involved in its progression and outcome. Early diagnosis and a...

Many people with Prader-Willi Syndrome (PWS) frequently engage in severe skin picking behavior, often causing open wounds and sores that can become infected. Why do people with PWS do this? How often and under what circumstances does it occur? Are people with PWS more likely to exhibit skin picking when they are bored or anxious? Does the skin...

Background: Hypogonadism (impaired sex hormone production) is a major feature of PWS, although the clinical expression is variable. Nevertheless, early onset of puberty has been seen in both sexes, and pregnancies have been documented in some PWS women. The causes of hypogonadism in PWS are heterogeneous, encompassing a spectrum which includes...

Hypogonadism (decreased production of testicular or ovarian hormones resulting in incomplete sexual development) is considered to be a cardinal feature of Prader-Willi syndrome, however, the clinical expression is variable. Most, but not all PWS males have unilateral or bilateral undescended testes. Arrested pubertal development leads to...

Prader Willi Syndrome is characterized by a range of well-recognised symptoms including overeating and other food obsessions, rage attacks or tantrums, skin-picking, obsessions, abnormalities of sleep breathing and body temperature, and diificulties in learning and understanding social cues. These difficulties have serious impacts on the health of...

Prader-Willi Syndrome (PWS) is a condition characterized by growth hormone deficiency, hypogonadism, various behavioral disturbances, an insatiable hunger drive (hyperphagia) and excessive eating leading to life-threatening obesity. The specific causes of the disturbed eating behavior in persons with PWS remain unknown. More importantly, effective...

Individuals with Prader-Willi Syndrome (PWS) have been described by parents and clinicians as having difficulty with regulation of sensory stimuli from the environment. It is suspected that this problem may be related to other symptoms of PWS such as poor satiety recognition, decreased sensitivity to pain, tendency to self-injure and sleep issues....

This study examines the effect of growth hormone replacement therapy (GHRT) on physical and behavioral sexual maturation in males and females with Prader-Willi syndrome (PWS). Previously, sexual maturity among affected individuals has been largely ignored due in part to the assumed universality of underdeveloped/immature genitals, lack of sex...

Alzheimer's disease (AD) is well-known as a condition of old age, prevalence rising with age from about 70 years. However, some groups appear to be at risk from a much earlier age, for example people with Down's syndrome. Recently, in pathological studies of people with Prader-Willi syndrome (PWS) who died aged over 40 years, signs of AD have been...

This is Year 2 of a study to examine the effect of growth hormone replacement therapy (GHRT) on physical and behavioral sexual maturation in males and females with Prader-Willi syndrome (PWS). Previously, sexual maturity among affected individuals has been largely ignored due in part to the assumed universality of underdeveloped/immature genitals,...

An insatiable appetite (hyperphagia), in conjunction with a low metabolic rate, means that obesity and all of its associated health risks are common in people with Prader-Willi syndrome. Overeating is one of the main barriers to independent living I adults with Prader-Willi syndrome. Moreover, attempts to control their food intake often lead to...