I was a Conference Virgin

I was 38 years old and still a virgin - a conference virgin, that is.  My third child, diagnosed with PWS, was already 4 years old, but the shock of this diagnosis had not worn off, in fact she was not diagnosed until she was 3, so all our lives were still in a state of flux.  Life was definitely not fair.

In the 80's there was very little information on PWS available in our country then, and certainly no Association or support.  My information came via rather ancient printed copies of the USA "Gathered View" which the only other person I knew who had an older child with PWS had kept stored away in her garage.  Somehow I heard the news that there was to be a conference in Perth, Australia and the speaker was to be a Professor Vanja Holm (known then as the Godmother of PWS in the States).  I was determined to go to a corner of the world I'd never been to before, to listen to people speak on a topic I'd never heard of before, and... fly there.  I hated flying and had loathed it ever since my first flight on an elderly DC3 which shook and bounced its way under and through the clouds and fairly close to the mountain tops.  My mother said she'd come with me. 

Dr. Vanja Holm (front) the first physician to be involved with Prader-Willi syndrome in the United States. Front: Dr. Vanja Holm. In back left to right: Dr. Hans Zellweger, Dr. Gene Deterling and his wife Fausta (founded of the Prader-Willi Syndrome Association-USA), Dr. Andrea Prader and Dr. Sam Beltram, the first Prader-Willi Syndrome Association (USA) president. Taken at the national conference in 1984. Source: Prader-Willi Syndrome Association (USA)

Nervously I boarded the plane.  Confidently, my mother did the same.  She appeared to enjoy the inflight entertainment and certainly enjoyed her meal.  I couldn't eat.  I couldn't concentrate.  I felt every air-pocket for 9 hours.  I was nervous about the conference, I was nervous at leaving the children at home and I was surely nervous about the flight.  We landed, collected our bags and found our way to the hotel.  It overlooked a pedestrian square which was full of people going about their business, shopping, going to work, enjoying the Perth life-style.  Not so confident was their overlooker.

My mother didn't come with me to the conference, so I was completely on my own.  It was like diving off the high dive board into water so deep I couldn't touch the bottom.  I could barely make it to the surface before I sank again into a very watery world full of questions and answers that seemed to float by, but I could never seize.  I went from room to room; I listened to lecture after lecture - delivered by confident specialists who seemed to know what they were talking about.  It seemed so concrete as they imparted fact after genetic fact, rule after rule, warning after warning.  I thought of my small daughter back home, with her smiling face and lovely warm hugs.  I felt her tiny arms around me, saw her own determination to survive in this unforgiving world, and it was only by remembering her boundless love for life that I managed to get through those three days.

After the conference, my mother took me on a bus tour to see the wild flowers of Western Australia.  It wasn't quite the right time of year for it, but I do remember seeing a field of the most vivid purple and exclaimed in delight at what, to me, was beauty and perfection.  The bus-driver overheard my comments and turned on his microphone so that the whole bus could hear..." Yeah, well, that field over there?  That's full of 'Patterson's Curse'.  It's a weed."  He paused for effect, so I felt suitably cowed.  "However," he went on, "it's also known as 'Salvation Jane' as it can be a food crop in the drought."

Under my breath, I said to my Mum, "well, it's probably the prettiest thing I've seen yet".  She firmly agreed.  And I've thought about it often.  How weeds survive.  They're strong.  They don't give up. They are always there, no matter how much you try to weed them out!

Anyway, since that first nervous conference, I've been to many, many more.  I went to the first IPWSO conference in The Netherlands, I've been to places I would never, ever have been to - Taiwan, Romania, South Africa.  I've learned to separate the factual lectures from the child or adult with PWS, because everyone is different.  I've learned to enjoy the company of other parents, and how easy it is to talk freely with them.  I've learned that the knowledge passed on by specialists is something we parents are privileged to share at this level, and I've made good friends with many of our professionals.

First-time conferences are never easy.  I've learned to recognise the lost look on parents' faces, and to sit and talk and share my own experiences.  I've learned to laugh out loud at the things our kids do to try to win the day and have been bent over in hysterics on many an occasion.  I've raised a glass and sung many a good song.  I've also wept and cursed the unfairness of life, but I've learned such a lot about life as well.

If our 9th international PWS conference is going to be your first; be encouraged by what you are going to learn, be uplifted by the friends you are going to make, and, above all, learn to be strong.  To be a 'salvation Jane'.

8th International PWS Conference in Cambridge

8^th International PWS Organisation Conference

Jackie Waters

REVIEW

With grateful thanks to Dr Suzanne B Cassidy for checking and amending the original draft and to Dr June-Anne Gold for her additional comments

PWSA UK had been preparing for three years to host the 8^th International PWS Organisation Conference.  It was not an easy process, not least when the venue we had booked to host the Celebration Supper/Gala Dinner was burned to the ground by arsonists just a year before the conference was due to take place. 

The conference was, however, voted a great success by those who attended. It was split into three programmes: scientific, caregivers (for those working in residential care and supported living), and parents. The parents programme was then split into three for parents of children under 5, 6-16 and 16+. 

The following report gives some of the main highlights from the scientific programme (many of the talks in the parent programme were on similar subjects) but it is impossible to cover all the talks and poster presentations within the context of this article. If you would like to know more, some of the presentations and the abstract book are available to view online at www.pwsa.co.uk – click on the link on the home page.

You can also order a hard copy of the abstract/programme book (while stocks last) for the cost of postage (£2 in the UK). If you’d like a copy, please contact Maggie Rowley at our office address, or email mrowley@pwsa.co.uk

 

PWS in the wider context

Guest speaker, Stephen O’Rahilly, Professor of Clinical Biochemistry and Medicine at the University of Cambridge Metabolic Research Laboratories, put PWS into the wider context of obesity research, in that much can be learned about how bodies control fat stores and nutrient levels through studying those where these processes have gone awry, such as people with PWS.  He highlighted the fact that, for the first time in human evolution, humanity is consuming surplus energy to that which it is expending, hence the “obesity epidemic”. However, recent studies have shown that up to 70% of the difference between lean and obese people can be traced to genetic or hereditary factors. Most of the genes which have been identified in “normal” obese people are expressed in the hypothalamus. 

Prevalence, birth incidence and mortality rates

There have been many estimates over the years as to the prevalence and birth incidence of PWS. Tess Lionti and her team from Murdoch Children’s Research Institute in Australia looked at 156 Australians with PWS and found a birth incidence of 1:14,000 and a prevalence of between 1:25,000 and 1:29,000. They found that at 35 years of age, 87% of people with PWS were still living, compared with 98% in the general population. They also reported that generally obesity increased with age, and this remains the major cause of early death. Non-obese people had better survival.

Changing clinical perspectives

Daniel J Driscoll, from the University of Florida, USA, spoke about interventions and changing clinical perspectives in PWS. He commented that PWS was the first recognized human disorder related to genomic imprinting (differences in gene expression depending on the parent from whom the gene was inherited). He went on to say that the previous two-stage model of PWS (pre- and post-hyperphagia) had now been replaced by a model, based on longitudinal studies, of 7 distinct nutritional phases (described by Miller at al, Journal of Medical Genetics, 2011), indicating that PWS is more complex than originally thought.

Dr Miller’s published article describes these phases thus:

“Phase 0 occurs in utero, with decreased fetal movements and growth restriction compared to unaffected siblings.

Phase 1 the infant is hypotonic and not obese, with sub-phase 1a characterized by difficulty feeding with or without failure to thrive (ages birth—15 months; median age at completion: 9 months). This phase is followed by sub-phase 1b when the infant grows steadily along a growth curve and weight is increasing at a normal rate (median age of onset: 9 months; age quartiles 5–15 months).

Phase 2 is associated with weight gain—in sub-phase 2a the weight increases without a significant change in appetite or caloric intake (median age of onset 2.08 years; age quartiles 20–31 months;), while in sub-phase 2b the weight gain is associated with a concomitant increased interest in food (median age of onset: 4.5 years; quartiles 3–5.25 years).

Phase 3 is characterized by hyperphagia, typically accompanied by food-seeking and lack of satiety (median age of onset: 8 years; quartiles 5–13 years). Some adults progress to:

Phase 4 which is when an individual who was previously in phase 3 no longer has an insatiable appetite and is able to feel full.”

Dr. Driscoll also described a number of ongoing PWS clinical research and drug trials. 

Genetics

In his talk Bernhard Horsthemke, from the Institut für Humagenetik in Germamy, described how finding a microdeletion affecting the SNORD116 snoRNA gene cluster in a few patients pointed to a major role of this gene in PWS. This is one of the genes located in the region of chromosome 15 relevant to the cause of PWS. But he also warned that, despite many years research, it is still unclear how or what roles this gene actually plays in causing the features of PWS. Although mouse models have been used extensively in trying to understand PWS, they are not an exact or ideal match. For instance, human lipid metabolism and obesity is not replicated in mouse models, their immune system is different, and they do not have cholesterol. There is still no mouse model of PWS which is obese.

SNORD116 and the regulation of energy homeostasis in PWS

More research into SNORD116 was included in a poster presentation by a team at the Garvan Institute of Medical Research in Australia. They generated mouse models which were lacking in the SNORD116 gene and investigated their metabolic physiology. They found that these mice suffered growth deficiency from birth, with reduced body weight, bone mass and length, compared with healthy mice. They also showed increased food intake and an impairment in the growth hormone pathway.

Marc Lalande, from University of Connecticut, presented work on the development and use of pluripotent stem cells to study the mechanism of silencing and re-activating of the maternally inherited genes related to PWS, especially SNORD116. Once this is understood, there is the potential for future treatments by reactivating these genes.

Françoise Muscatelli presented work from researchers in France that showed a small amount of residual expression from imprinted genes, especially NDN, in the PWS region, and they were able to show better outcomes in mice with higher residual function. Re-activating imprinted genes to improve outcomes in PWS may be able to be exploited. 

Endocrinology and hyperphagia

A talk by Anthony Goldstone, of Imperial College London, outlined the extensive role that neuroendocrine factors have in PWS. These include underdeveloped genitalia, childhood development of obesity and hyperphagia (excessive eating), growth hormone deficiency, delayed puberty and infertility (in most), developmental delay and learning disabilities, and abnormal sleep patterns. Dr Goldstone reported that people with PWS have normal fasting and post-prandial (after meal) plasma levels of several anorexigenic (appetite suppressing) hormones (leptin, PYY, GLP-1 and CCK). However, fasting and post-prandial levels of the anorexigenic hormone pancreatic polypeptide (PP) are reduced in PWS, and this appears to be present from early childhood. As with genetics, there is still much research to be done. The cause for the delayed development of hyperphagia remains unknown and, in addition to hormonal abnormalities, there are likely to be overriding hypothalamic brain defects which also contribute to the appetite problems. 

Indian cactus caralluma fimbriata – effect on hyperphagia

A small scale study of the use of caralluma fimbriata extract (CFE), a cactus extract, was performed by Joanne Griggs and her team at the Victoria University College of Health Biomedicine in Australia. Nine children and adolescents aged between 5 and 17 years were given powdered CFE or a placebo. Interim results suggested that supplementation with CFE decreases appetite behaviour in some children and adolescents with PWS and some decrease in behaviours relating to distraction and distress. They are now hoping to extend their research into a worldwide population to see if these results are replicated in a larger sample of patients. CFE is licensed for use as “Slimaluma”. There was no monitoring of liver function tests during this study.

Vagus nerve stimulation in PWS: effects on eating and behaviour

A team from the Department of Psychiatry at the University of Cambridge presented a poster about three individuals with PWS who underwent surgery to implant a vagus nerve stimulation (VNS) device. This device is used to control epilepsy, but it had been noted that these patients with epilepsy also lost weight.  The team wanted to test the theory that this would also occur with PWS patients.  Effects on weight were equivocal, with one person putting on weight and others showing some improvement in eating behaviour.  However, unexpectedly, two of the three participants reported marked improvements in their behaviour and asked for the VNS to continue at the end of the study.

Thyroid function in children and adolescents with PWS

In a poster presentation, a team from Italy had conducted thyroid function tests on 299 children and adolescents with genetically confirmed PWS, and found thyroid axis dysfunction in 10.7% of their patients – more than is in the general population. They conclude that thyroid function should be carefully evaluated in PWS patients to identify those who may require hormonal replacement therapy.

Assessment of adrenal function

A poster presentation by a Japanese team from Dokkyo Medical University set out to assess adrenal function in 36 children and adolescents with PWS by insulin tolerance test. Central adrenal insufficiency (CAI) due to hypothalamic dysfunction had previously been suggested as a possible cause of death by other researchers, particularly in association with infection-related stress. This study results suggest that basal and peak levels of cortisol are within the normal range in PWS patients, while peak responses of cortisol to insulin stimulation are delayed in most patients. The researchers state that it is likely that hypothalamic dysfunction alters secretion patterns of cortisol in PWS, but say that further studies are necessary to clarify the possible association between the altered response of cortisol to hypoglycaemia and unexplained deaths in PWS.

Oxytocin

In her talk on New Perspectives for Prader-Willi Syndrome, Maithé Tauber, of the Centre de Référence du Syndrome de Prader-Willi in France, acknowledged that the cure for PWS remains the foremost issue for persons with PWS and their families and carers. She described how her team’s research into oxytocin administered to 24 adult patients with PWS showed a positive effect on trust in others and on disruptive behaviour, with a trend towards decreased food intake. In PWS mouse models, they demonstrated that a single injection of oxytocin in the first five hours of life completely rescued the newborn mice from early death by recovering normal suckling abilities. They are now testing this treatment with 5 babies with PWS, and long term effects are currently being analysed, with the hope that this may offer positive treatment early in life.

However, a different result of treatment with oxytocin was reported by Ellie Smith, University of Sydney, Australia, who described her team’s research in administering oxytocin or a placebo as a nasal spray to 31 people with PWS aged between 12 and 30 years. Behaviours such as hyperphagia, temper outbursts, skin-picking, obsessive behaviours, and under-reaction to pain were evaluated daily by primary carers. The outcomes were disappointing in that there were no significant differences between those who received oxytocin and those who received the placebo.

Growth hormone treatment in children

Nienke Bakker, from the Dutch Growth Research Foundation in Rotterdam, reported on 8 years of growth hormone (GH) treatment in 60 children with PWS. The Dutch team found that during this time lean body mass improved, fat percentage and body mass index remained stable, while height and head circumference had completely normalised. They conclude that GH is a potent force for counteracting the clinical course of obesity in PWS. 

Growth hormone and face shape

Using dense surface modelling and shape signature techniques, Peter Hammond and teams from University College London and the University of Catania, Italy, demonstrated that growth hormone therapy in PWS has a corrective effect on vertical facial growth, but not more generally on face shape.

Effect of growth hormone on bone fragility and effect on BMI and adipose tissue of stopping growth hormone

In a poster presentation, a team from the Dokkyo Medical University, Japan, investigated 148 patients (112 treated with GH and 36 untreated) between 2 and 47 years of age to assess bone mineral density (BMD) in the lumbar spine (L2-4). They also looked at scoliosis, which was present in 45 treated and 19 untreated patients. They found that 33.8% of the patients had BMD below the normal range (osteoporosis), and 27.7% had low normal BMD (osteopenia). The difference in BMD between those with and without scoliosis did not reach statistical significance.  Treatment with GH did improve BMD. They suggest that GH may be a useful treatment for reducing the frequency of bone fractures and surgical complications caused by osteoporosis.

In a separate poster, this research team also looked at 14 patients with PWS before and after the cessation of GH treatment. They discovered that body mass index (BMI) significantly increased after cessation, though subcutaneous and visceral adipose tissue was not significantly affected. They conclude that to maintain good body composition and prevent complications of obesity, long-term use of GH in adult patients with PWS may be advisable. 

Growth hormone therapy and respiratory disorders: long-term follow-up in PWS children

In another poster presentation, a team from Italy looked at the effects of long-term growth hormone therapy on sleep-disordered breathing and adenotonsillar hypertrophy in 50 children with PWS.  They observed an increase of apnoea hypopnoea and a decrease of central apnoea events, leading to an overall decrease of the respiratory disturbance index.  However, the percentage of patients with severe adenotonsillar hypertrophy increased significantly after two and three years of growth hormone treatment. They recommend annual overnight polysomnography checks and adenotonsillar evaluation.

Another poster presentation on this topic was from a Scandinavian collaborative group. These authors conducted a placebo controlled study of GH in 46 adults with PWS that respiratory polysomnography did not change over time with GH treatment, and therefore that GH in PWS is not associated with increased risk of sleep apnea.

Sex hormone deficiency

The Hypothalamic-Pituitory –Gonadal (HPG) Axis is Active in Prader-Willi syndrome infants

Harry Hirsch, of The Hebrew University, Israel, reported on research his team had conducted into hypogonadism (immature sexual development) in infants with PWS. As nearly all adult men with PWS have abnormally low testosterone levels and adult females have low Inhibin B levels (a hormone produced by ovarian follicles), it might be expected to find abnormally low levels of these reproductive hormones in infants with PWS. Normal infants have an increase in the HPG axis from birth to 4 months often referred to as “minipuberty”. However, of the 9 male and 6 female infants with PWS the Israeli team studied, all of the boys and some of the girls had normal reproductive hormone levels for age. These results show that most infants with PWS are not born with deficiencies in sex hormone production, and that further studies are needed to determine why gonadal function becomes abnormal in PWS adolescents and adults and why genitalia are small starting at birth.

Pregnancy in PWS

Two new cases of women with deletion-type PWS becoming pregnant were described by Suzanne Cassidy, from the University of California. One case was a 27 year old woman who had a normal son, delivered by Caesarean section. She had had no psychotropic medications. The other case was a 31 year old woman who took Citalopram for two years before pregnancy. Her daughter had Angelman syndrome. There have been two previously reported cases of successful pregnancy to women with PWS. Dr Cassidy concluded that fertility in a few women with PWS probably reflects variability in hypogonadism and absence of opportunity in others who are potentially fertile, and recommends that sex education and contraception should be part of the management of women with PWS.

Treatment of Hypogonadism in Females

In a poster, Talia Eldar-Geva presented the Israeli group’s approach to treating hypogonadism in adolescent and adult females with PWS. Their approach is individualized, using contraception and hormone replacement based on bone density, hormonal profiles and personal and family wishes.

Scoliosis

The topic of scoliosis and other spinal deformities in PWS was addressed by Harold van Bosse, of the Shriners Hospital for Children, Pennsylvania. He said that 40-90% of children with PWS have spinal deformities, and that 15% of all children will require treatment. There are two main peaks in incidence of scoliosis 0-24 months representing initial hypotonia and the second being idiopathic. His data did not support discontinuing growth hormone treatment, and in fact indicated that its use correlated with decreased risk for spine surgery.

In a poster presentation, Dr van Bosse discussed the prevention of surgical complications in PWS scoliosis surgery. Previous studies had reported frequent serious complications after spinal procedures, with rates as high as 56%. He and his team developed a protocol for pre-operative work-up and peri-operative care to minimize complications. The pre-operative protocol included pulmonary function tests, sleep studies, and assessments for behavioural risks. Surgical planning avoided anterior approached, and paid special attention to the characteristic osteopenia and cervicothoracic kyphosis of PWS. Post surgery, extubation was delayed, followed by BiPAP or CPAP. Oral intake was delayed. He concludes that scoliosis surgery can be performed safely in children with PWS, as long as there is careful attention to their special physiological and emotional characteristics. 

General anaesthesia

The topic of general anaesthetics has always been one of concern to parents and Graziano Grugni, of S Andrea Hospital, Vercelli, Italy, described his team’s survey of 49 patients with PWS who had, in total, 101 surgical episodes, programmed in 95 cases, and as an emergency in 6. Of these, only four patients reported problems after general anaesthesia, two with respiratory insufficiency and two with psychomotor agitation. The researchers concluded that no complication leading to lasting disability or death had been observed.

Nutrition in children with PWS

Chris Smith, who is the dietitian attached to the PWS Multidisciplinary Clinic at Brighton and Sussex University Hospitals Trust, reported on an analysis of food diaries kept by 11 parents of children with PWS over 10 years. His team found that PWS children on average have 30% less calorific intake, compared to other children of the same age. The proportions of % energy from fat, carbohydrate and protein (compared to UK recommendations) were 25% (35%), 59% (50%) and 16% (15%) respectively. The lower fat intake meant that children were at increased risk of inadequate intake of polyunsaturated fats, but there appeared to be little detrimental effect on micronutrient intake overall. 

Post-prandial metabolic profile in adults with PWS

This study by Louise Purtell and her team at The Children’s Hospital, Sydney, Australia, set out to investigate the basis behind the development of obesity in PWS, and especially why even those who are on a closely controlled calorie-restricted diet still become obese. They hypothesized that this may be due to the way people with PWS metabolise energy after eating a meal, but their study found there were no differences in measures of meal metabolism between those with PWS and non-PWS obese people when the amount of lean body mass was taken into account. The study did not detect an intrinsic metabolic problem in people with PWS and suggested that the development of obesity in PWS, even on a strict diet, may be due to other factors.

A poster presentation by Elena Borgova from Russia showed significantly higher levels of Brain Derived Neurotrophic Factor (BDBF) over two control groups of non-PWS obese individuals and lean controls. Brain-derived neurotrophic factor (BDNF) is a neurotrophin, known to affect neuron maintenance or function, and it also contributes to the central control of food intake. 

Dr Bogova’s study suggests possible resistance to BDNF at its receptor in individuals with PWS. BDNF signaling in PWS needs to be full defined and may lead to new treatment strategies.  

GLP-1 based therapies (Liraglutide and Exenatide) – effect on weight loss and stomach emptying

Anthony Goldstone’s team at Imperial College London looked at the potential for using drugs such as Liraglutide and Exenatide, normally used for treating diabetes, in stimulating insulin release and weight loss in people with PWS. However, there had been theoretical concerns about the safety of using these drugs in PWS because they are known to cause delayed stomach emptying, already known to be a potentially fatal issue in PWS because of the risk of stomach rupture. While Liraglutide improved sugar control, it did not have a major impact on hyperphagia or weight gain other than helping to prevent weight gain related to the use of insulin. The team therefore advises caution in the use of these drugs.

Very similar results were obtain in another study of GLP-1 treatment in PWS presented by the Italian collaborative endocrine group.

Pain and PWS

The Italian collaborative group presented a study investigating the cause of the high pain threshold in PWS in 11 adults with PWS, 3 obese non-diabetic people and 7 age-matched normal weight healthy adults, using nerve conduction and somatosensory evoked potential studies, quantitative sensory testing, quantitative insulin-sensitivity, and a skin biopsy. They found normal electroneurographic studies, but significantly higher thermal and pain thresholds and reduced proximal and distal intraepidermal nerve fibres in PWS. They conclude that altered perceptions of pain in PWS are mainly based on loss of sensory neurons in dorsal root ganglia.

Infection and PWS

In a poster, the Italian collaborative group presented a study that looked at the risk of infection in 116 people with PWS compared with 113 normal subjects matched for age, gender and environment. No difference between the two groups was found despite the fact that there were more surgical procedures in the PWS group. However, the PWS group showed more lower respiratory severe infections, though fewer mild infections, possibly related to high threshold of pain and vomiting.

Cognition – Executive functioning

Johann Chevalere‘s  team from Université Bordeaux, Segalen, France suggested from two studies that executive functioning in PWS is impaired and that the impairment is highly connected with the intellectual disability. Differences were found between the deletion and the m-UPD groups for the two task assessing, planning and mental switching, the m-UPD performing worse than the deletion group. However the deficit on switching and cognitive estimation is not totally attributable to intellectual level, suggesting syndrome-specific association. Executive function seems to vary with the genotype.

Behaviour  

The team from the Cerebra Centre in Birmingham, UK, demonstrated that changing routines triggered more temper behaviours. They found that signalling any potential changes in advance by showing a card to the person with PWS triggered less temper outbursts, and they also recommended more research into increasing the flexibility of routines from an early age as a potential helpful management technique.

A Dutch group studied 66 children with PWS using several different tests of social cognitive functioning and showed a markedly reduced level of social cognitive ability, suggesting that the approach to them should be adjusted accordingly.

Brain abnormalities between different genetic subtypes

Akvile Lukoshe and the team from the Dutch Growth Research Foundation investigated global brain morphology in children with PWS, using MRI imaging and comparing the different genetic subtypes of deletion (DEL) and maternal uniparental disomy (mUPD). They found that both subtypes show signs of impaired brain growth indicated by smaller cortical surface area and smaller global white matter volume. However, children with mUPD also show signs of early brain atrophy and increased cortical thickness, similar to that found in autism. In contrast, children with DEL have a proportionately developed, albeit smaller brain compared to healthy age matched sibling controls. They suggest that the results show divergent neurodevelopmental patterns in children with DEL and mUPD.

Autism spectrum disorders

Symptoms of autism spectrum disorders in children with PWS

In a poster presentation the team from the Dutch Growth Research Foundation and Erasmus University, Rotterdam, tested 66 children aged 7 to 17 years using the Theory of Mind Test-R (ToM) and the Diagnostic Interview for Social Communication Disorders. ToM includes the ability to share feelings of others (empathy). ToM development was related to IQ levels, but not to genetic sub-type, and one third of the children scored positive for Autism Spectrum Disorder. The team highlighted the importance of an adjusted approach to children with PWS. Their impaired empathetic abilities require clear communication such as avoidance of figurative language and naming things precisely.

A study contacted by researchers from Dokkyo Medical University, Japan, looked at 45 Japanese individuals with PWS. Their findings were consistent with previous studies on Caucasian patients, and indicated that those with mUPD were more prone to autism spectrum disorders, regardless of ethnicity. These were less apparent in childhood.

Psychotic illness

Researchers at the Maastricht University Medical Centre reviewed literature relating to psychosis in PWS. Overall, in a total of 602 reported individuals, they found that psychotic illness is more prevalent among those with disomy (mUPD) (15.6%) than those with a deletion (8.8%).

In a poster, Denise Thuilleaux presented results from a French-Spanish collaborative psychopathological profile study of 154 adults with PWS. They found basal (49%), impulsive (24%), compulsive (16%) and psychotic profiles. Overall, 11% had psychosis, but those with UPD had a 25% prevalence of psychosis.

Tony Holland, PWSA UK President, from the University of Cambridge proposed a clinical trial to investigate whether psychosis can be prevented in PWS. This was based on the case of an older adult with mUPD who had not become psychotic, but who had been given antipsychotic medication to control behaviour problems earlier in his life. It has also been noted that antipsychotic medication was very effective where cases did occur, and relapse rates appeared to have been less in those who continued the medication after recovery. They proposed to recruit people with mUPD aged 16 to 20 years who had never had a psychotic illness, allocating them to an experimental or a control group. Those in the experimental group would be given low doses of antipsychotic medication. Tony asked if this could be an international study, but also if such a study was appropriate or ethically justified.

Vagus Nerve Stimulation

On looking back through my notes taken at the IPWSO Conference, I want to describe a little further the topic of Vagus Nerve Stimulation and what the study and researchers want to do to take this further.  The reason for the research was to see whether there would be weight loss in PWS, as previously discussed.  This didn't happen, but there were other positive effects.  The slide below summarises:

"Vagus Nerve Stimulation is used in epilepsy and depression.  It is surgically implanted and works for 30 seconds on, and 5 minutes off.  There have been reports of weight loss as a side effect (in other patient groups).
A study was done (in Cambridge, under the guidance of Professor Tony Holland)  for three years from 2009 to 2012 with three participants: Katie, Simon and Jennifer.  They travelled to Cambridge on a regular basis for many different tests and measurements."  One of the participants was able to negotiate the travel by train and bus by herself.

Slide showing where the implant was placed, what it looks like, and a picture of the ward (on right)

: What does the future hold?  The scientists/researchers want to:
"1. Undertake a formal trial involving 12 people with PWS to test:

• Whether VNS reduces the frequency and severity of problem behaviours
• If it results in improvements, how it works;
• Whether any improvement in eating behaviours are secondary to the changes in other behaviours.

2. Outline application to be submitted next week (end of July) for government funding to undertake this research.

3.  Researchers would like to hear from anyone with PWS from age 16 years and over and/or their family if they might be interested in being part of this.  Contact:  Tony Holland  ajh1008@medschl.com.ac.uk "

Conference Day 4

Always at a conference there are one or two things that really stand out for you, and I'd been waiting for this to happen.  My curiosity had been spiked by a talk to be given by Prof Tony Holland about Vagus Nerve Stimulation, something I'd never heard of before.  What happens is that something similar to a pacemaker is inserted just beneath the skin on the chest.  It is designed to release electric impulses which stimulate the vagus nerve in the brain.  This type of treatment is used for patients with epilepsy and, during trials, it was noticed that patients lost weight.  So a trial was set up for 3 adults with PWS.

Presentation of this talk started with a brief introduction from Prof Holland and then each person with PWS spoke about their experiences, and then the parent spoke about the noticeable differences in behaviours, weight loss, appetite suppression etc.  The results were interesting.  Sadly, there was no weight loss, but there were noticeable changes in behaviours cited by both those with PWS and their families.  There was a very noticeable decrease in anxiety and stress, and also a decrease in the interest in food.  Tests were carried out at the beginning of the trial showing a timed session of "all you can eat" and done again after some months of treatment.  In the second "all you can eat" session, the interest in food, and consumption, was lower, although there was no overall weight loss.

What interested me most was hearing from the very articulate three adults who had undergone this treatment.  Each spoke highly of their increased confidence and lessened stress and all recommended this to anyone with PWS!  One lass said that without this measure of self-esteem, she would never have been able to get through what was the happiest day of her life - her marriage!

What more could you ask!