It was generally thought not possible for men or women with PWS to have children. To date, there are no known cases of a man with PWS fathering a child, but around the world, there have been a handful of cases of live births to women with PWS. If fertile, a woman with PWS by deletion has a 50% chance of their baby being born with Angelman syndrome and a woman with PWS by UPD would have every chance of having a healthy baby.

Fertility is unlikely, but current advice is that birth control should be considered for women with PWS who are sexually developed (breast development and menses), even if menstruation is sparse or infrequent. Similarly, males should also be counselled about the possibility of their own fertility if penile length and testicular volume is normal, despite there being no known prior cases.

For hypogonadism (sex hormones) – see H
For puberty – see P

Gastro intestinal issues are very common in PWS and include constipation, poor gastric motility (slow stomach emptying)/ gastroparesis, gastroesophageal reflux, swallowing and choking difficulties, aspiration, acute gastric dilation and a high risk of gastric rupture or necrosis following a binge eating episode. The impaired vomit reflex also contributes to the worsening of serious GI problems. A cause of death survey published in 2016 reported GI issues to be the cause of death in 10% of cases – these included perforation, distention, obstruction and infection. Any instances of abdominal discomfort, pain, bloating /distention (stomach expansion) or vomiting should be carefully evaluated as they may be signs of life-threatening gastric inflammation or necrosis. Due to a high pain threshold, pain may be absent or a person may present with general unwellness rather than localised pain. An xray and endoscopy may be required – for guidance on assessing GI complaints, please see the GI evaluation algorithm chart for medical professionals.

A Comprehensive Overview of GI Issues in PWS – Ann Scheimann, M.D., PWCF News
Acute Gastrointestinal Episodes can be Life-Threatening – Janelee Heinemann, PWSA(USA) from The Gathered View (ISSN 1077-9965)
Recognising Gastric Dilatation and Associated Risks in Prader-Willi Syndrome – Linda M. Gourash, MD and Janice L. Forster, MD, Pittsburgh Partnership
MEDICAL ALERT: Risk of Stomach Necrosis and Rupture – PWSA(USA)
GI Issues in PWS – VIDEO: Dr Anne Scheimann presenting at FPWR conference 2017
Delayed Gastric Emptying in patients with Prader-Willi Syndrome – Arenz T, Schwarzer A, Pfluger T, Koletzko S, Schmidt H., 2010
A descriptive study of Colorectal Function in adults with Prader-Willi syndrome: High Prevalence of Constipation – 2014.
Hidden Gut Issues (Choking & Gastroparesis Concerns) – By Barb Dorn, RN, BSN, Kate Beaver, MSW, Kathy Clark, RN, MSN, PNP, and Margaret Burns, RD

For constipation – see C
For gastroparesis – see G
For choking and swallowing – see C

Gastroparesis is a condition which affects digestion by slowing down or stopping the movement of food from the stomach to the intestine. Food may remain in the stomach for too long which can cause abnormal bacterial growth, a blockage or obstruction. The condition requires a medical diagnosis usually involving image testing.

Perhaps due to hypotonia and vagus nerve dysfunction, it is thought that a significant number of people with PWS have some degree of gastroparesis, although it can be hard to detect as the usual symptoms of nausea, vomiting, abdominal pain and feelings of fullness may not be present. Gastroparesis can lead to life threatening situations, especially if a person with PWS continues to eat whilst their stomach is distended. There is no cure for gastroparesis, but changing the diet to include foods that are easier to digest and eating smaller sized meals can help. Foods high in fat and fibre are harder for the stomach to digest and it is recommended that sufferers avoid them, which differs to the usual advice given for a PWS diet to include high fibre foods to reduce risk of constipation.

Slow stomach emptying can be exacerbated by narcotic pain relievers, high blood sugars and hypothyroidism.

Gastroparesis: The Newest Threat – Lisa Graziano, M.A., Janalee Heinemann, M.S. and Ann Scheimann, M.D., M.B.A., Gastroenterologist, from The Gathered View (ISSN 1077-9965) by PWSA(USA)
Delayed Gastric Emptying in patients with Prader-Willi Syndrome – Arenz T, Schwarzer A, Pfluger T, Koletzko S, Schmidt H., 2010

Reduced GH secretion in PWS is well documented and reduced GH responses have been recorded in 58 – 100% of people affected by PWS. Characteristic symptoms of PWS resemble those seen in association with GH deficiency (GHD), i.e. reduced muscle strength, altered body composition, low energy expenditure, fatigue and reduced growth, even in the presence of obesity.
Before the availability of growth hormone treatment, short stature with small hands and feet were common features of PWS. The lack of a pubertal growth spurt and GH insufficiency resulted in an average final height of 155-160 cm for males and 148-150 cm for females. GH therapy was initially provided for PWS patients based on growth data to increase height, but has since been indicated as a treatment for PWS for its effects on body composition. In addition to improving body composition, GH treatment is known to have other beneficial effects on respiratory function, mobility, physical performance, cognition, speech, bone mineral density, mental health and quality of life for adults.

Growth Charts for Non-Growth Hormone Treated Prader-Willi Syndrome – Butler MG et al, 2015
Consensus Guidelines for Recombinant Human Growth Hormone Therapy in Prader-Willi Syndrome – Growth Hormone Research Society Workshop Summary
VIDEO: Growth Hormone for Adults with PWS – Dr Jennifer Miller, FPWRC Conference 2009

Individuals with PWS have an increased appetite from around age 4.5yrs and become hyperphagic from around age 8. They may rarely feel full and may be consistently hungry or preoccupied with food. Supervision around food is necessary. If unsupervised access to food is gained they may quickly ingest large quantities leading to rapid weight gain and a risk of choking, gastric necrosis or rupture. Weight is quickly and easily gained due to the altered body composition of reduced muscle mass and increased fat mass. Reduced energy expenditure and the challenges involved in exercise make any weight gained very difficult to lose. Storing food securely out of sight and mind is recommended. Please see the Dietary Management page for tips on using the ‘Food Security’ model to manage hyperphagia.

fMRI Studies of Food Motivation in Prader-Willi Syndrome

The prevalence of hypertension (abnormally high blood pressure) in PWS is unknown but it is thought it could be present in approximately 1/3 of adults with PWS, but it is uncommon in children. Risk increases with weight gain and inactivity. The type of hypertension seen in PWS is usually pulmonary hypertension, which affects the arteries in the lungs and the right side of the heart.

Hypogonadism in PWS is due to a combination of hypothalamic and primary gonadal deficiencies. It occurs in both sexes and is a failure of the gonads (testes in men and ovaries in women) to function properly, resulting in diminished or disrupted production of sex hormones, such as testesterone and oestrogen. In nearly all people with PWS, hypogonadism is characterised by underdeveloped genitalia, incomplete puberty and infertility.

The affects of hypogonadism on genitalia are evident from birth, although they may be overlooked in females. In boys, the penis may be small and the scrotum underdeveloped with small testes. Cryptorchidism (undescended testes) is typical in the vast majority of male infants and a procedure called orchidopexy to bring testes down may be necessary (usually done between 6-15mths old.)

The reduced or disrupted sex hormone levels in PWS often cause puberty to be delayed, progress slowly and remain incomplete.

For puberty – see P
For fertility – see F
For premature adrenarche – see A

All individuals are at risk for hypothermia which is associated with impaired peripheral somatosensory and central thermoregulation in PWS. Certain medications may also increase risk. Some individuals may be more susceptible to episodes of sustained hypothermia, particularly in middle age. Hypothermia can be life threatening if untreated so preventative measures and close monitoring during exposure to cold temperatures are required.

Hypothermia and Prader-Willi Syndrome – An Overview – Barb Dorn, RN, BSN for The Gathered View (ISSN 1077-9965), published by PWSA(USA)
Winter Warning on Hypothermia in PWS – Janalee Heinemann, PWSA (USA) Director of Research & Medical Affairs
Hyperthermia Prevention: Cold Weather Tips – Kathy Clark RN MSN Medical Coordinator, PWSA(USA)

Hypothyroidism is when a person has low thyroid levels which is an important hormone involved in maintaining metabolism, energy levels and body temperature. The thyroid gland is controlled by the pituitary gland and regulated by the hypothalamus, so this process can be disrupted by hypothalamic dysfunction in PWS.

Central hypothyroidism has been documented in up to 25% of individuals with PWS, with a mean age of diagnosis and treatment of 2 yrs. Children on GH treatment will have regular checks of thyroid levels and hypothyroidism can easily be treated with thyroid medication.

The following information sheet explains about the different types of hypothyroidism and the testing of TSH levels: Thyroid Issues in PWS – Kathy Clark M.S.N, R.N., P.N.P. Medical Director

Hypermobile joints have an unusually large range of movement and in PWS they may be attributed to weak muscles around the joint.

Joint hypermobility in PWS can add to postural and balance issues, causing wobbles and stumbles. Motor skills are also likely to be affected. Using orthotic supports and building muscle strength are the recommended, traditional treatments. However, providing sensory, vestibular input may also provide information to the brain receptors that are not receiving appropriate stimulation from the muscles around the hypermobile joints.

Feet may roll inwards and ankle supports are usually required for young children learning to walk, with orthotic insoles often permanently required.

For orthopaedic issues – see O

Possibly due to metabolism differences, unusual reactions to some medications may occur and side effects may be more likely. Medications that may cause sedation, suppress breathing or slow digestion (i.e. pain meds, anaesthetics and psychotropic meds) should be used with caution. Medications may remain in the system of someone with PWS longer than usual which can result in a prolonged and exaggerated response to narcotics/ sedatives. Furthermore, combinations of medications have the potential to fatally impair breathing in PWS, particularly after surgery when pain meds are used. As a high pain threshold can be experienced in PWS, a reduced dose of pain medication may suffice. Providing a lower than standard dosage of other medications may also be required to reduce risk of side effects, particularly with SSRI’s and neuroleptics.

The increased risk for disrupted temperature regulation or hyperglycaemia /diabetes mellitus in PWS should be considered with some medications.

Water intoxication has occurred in relation to some medications with antidiuretic effects (including some neurotropic drugs.)

MEDICAL ALERT: Warning – Medication combinations may fatally impair breathing in PWS – by PWSA(USA), reviewed by Scientific and Clinical Advisory Boards
Medical Alert on Antidiuretic Hormone – Linda Keder, The Gathered View, 1997

For water intoxication – see W

Anxiety is a common problem and central to many of the behavioural challenges of PWS, but it is usually stress dependent and can be avoided or reduced if managed correctly. However, when anxiety disorder becomes severe, expert behavioural support or medications may be required. Compulsive and repetitive behaviours such as skin picking, hoarding and concerns with exactness and ordering are also typical in PWS, but do not mean a person has obsessive compulsive disorder, although there is a risk of developing OCD. There are also increased rates of oppositionality, aggression and impulsivity in PWS. Sometimes these issues and inattentiveness lead to a separate diagnosis of ADHD.

There is an increased rate for ‘thought’ problems in children and adults with PWS (seeing things /hearing voices /strange ideas), and in some cases, behavioural episodes can become more extreme and an evaluation may be needed for psychotic disorders.

Individuals with PWS are more susceptible to mood issues or depression, particularly during adolescence and early adulthood. The prevalence of mental illness in adults with PWS is high (17 – 28% in PWS by deletion and 64 – 65% in PWS by UPD.) Non-psychotic depressive illness and depressive illness with psychotic symptoms are the major cause of illness in those with PWS by deletion, but in PWS by UPD, almost all individuals diagnosed with mental illness suffered psychotic symptoms, with a frequent diagnosis of bipolar illness.

Response to medications and dose can be both unique to PWS and can vary in individuals, therefore treatments need to be carefully considered and monitored. Earlier intervention leads to improved mental health outcomes.

The Mental Health of People with Prader-Willi Syndrome – Prof Tony Holland, University of Cambridge, 2017
Mental Health Problems in Children with Prader-Willi Syndrome – Skokauskas N., Gallagher L. et al, 2012
PWS Information for Psychiatrists – Drs Forster and Gourash, The Pittsburgh Partnership, 2018
VIDEO: Behaviour and Mental Health in Prader-Willi Syndrome – PWSAI and IPWSO

For anxiety – see A
For psychiatric concerns – see P
For medications sometimes used – see Other Medicines

The most recent study of mortality in PWS collected data on causes of death in 486 cases between 1973 and 2015. The mean age for these reported deaths was 29.5 ± 16 years (2mo–67yrs), with 70% occurring in adulthood. The age at death increased over time for females, suggesting an increased lifespan due to early diagnosis and medical care. Adult deaths were equally occurring between males and females but deaths in the under 18 category were predominantly male. Males were at increased risk for presumed hyperphagia-related accidents/injuries compared to females and cardiopulmonary factors. The maternal disomy genetic subtype showed an increased risk of death from cardiopulmonary factors compared to the deletion subtype.

Causes of Death: 13 Major Categories – View Diagram
Respiratory failure was the most common cause accounting for 31% of all deaths, followed by cardiac disease/failure (16%), gastrointestinal (GI) related problems such as perforation, distension or obstruction (10%) and infections (9%). Obesity was listed as a cause of death for 7% and pulmonary embolism was also reported for 7%. Additional categories reflected disease-associated behavioural risks from choking, accidents and hypothermia possibly related to food seeking and consumption. Additional morbidity possibly related to food seeking (e.g., accidents, choking) appeared in childhood and adolescence, contributing to approximately one third of all deaths and approximately half of the (predominantly male) deaths under the age of 18 years. The BMI at the time of death was identified for 132 cases with an average of 49±23 kg/m² and range of 14–122. Standardized mean BMIs were well above normal (>90th percentile).

The findings highlighted the heightened vulnerability towards obesity and hyperphagia-related mortality in PWS.

Causes of Death in Prader-Willi Syndrome: Prader-Willi Syndrome Association (USA) 40-Year Mortality Survey – Merlin G. Butler and Ann Manzardo et al, 2017

Motor development may be significantly delayed due hypotonia and decreased muscle mass. As a result, children with PWS reach gross motor skill milestones later than their peers, i.e. rolling, sitting, crawling and walking. However, with the availability of early growth hormone treatment, these delays can be considerably reduced.

In addition to growth hormone, children with PWS need early intervention therapies to help develop motor skills, motor planning, balance, strength and sensory integration processes. These therapies may include physiotherapy (for gross motor skills) and occupational therapy (for fine motor skills.) Therapy exercises for young children revolve around play and ensure that cognitive development is not hindered too much by their physical inability to interact with their environment.

Although muscle tone can improve over time, people with PWS usually have ongoing difficulties with tasks involving motor planning, balance and coordination. Gross motor activities such as jumping, climbing, catching a ball and riding a bike can prove difficult. These motor difficulties are typical of dyspraxia and if tested, people with PWS may receive a dual diagnosis. In PWS, fine motor skills are typically more advanced than gross motor skills. Occupational therapy for fine motor skills may focus on developing hand / eye coordination, hand strength and finger dexterity, and completing tasks such as using scissors, writing and tying shoelaces.

VIDEO: Therapeutic Interventions for the Young Child with PWS – Janice Agarwal CNDT PT
The Young Child with Prader‐Willi Syndrome: Physical and Sensory Issues and Recommendations – Janice M. Agarwal, PT, CNDT, 2014
The Young Child with Prader-Willi Syndrome: a seminar handout – Janice M. Agarwal, physiotherapist
VIDEO: Sensory Motor Issues in PWS – Dr J Forster, presenting at the 3rd Asia Pacific PWS conference, 2015
VIDEO: Family Care and Physical Therapy for People with PWS – Georgina Loughnan at the 2014 PWSAI conference.

Excessive Daytime Sleepiness (EDS) is common in PWS and can result in narcoleptic-like symptoms, including falling asleep during the day (hypersomnia), disturbed nocturnal sleep, and sometimes cataplexy. If any apnoea cause has been resolved and narcoleptic-like symptoms persist, treatments for narcolepsy may be successful in improving quality of life.

Narcolepsy is when a person experiences intermittent periods of uncontrollably falling asleep due to their disturbed sleep-wake cycles. In PWS it is suggested that reduced orexin levels could be another possible cause. The prevalence rate of narcolepsy in PWS remains uncertain – multiple sleep latency testing (MSLT) results have been published for patients with PWS and EDS which show a subset of individuals have sleep-onset REM periods of sleep during testing, which is characteristic of narcolepsy, whereas others only have decreased sleep latency consistent with EDS but not true narcolepsy. Prevalence of narcolepsy has been estimated at 35%, and 35.7% in a study examining prevalence of obstructive apnoea.

Narcolepsy can be successfully treated with Modafinil.

For EDS – see E
For cataplexy – see C

The current dietary recommendation for PWS is to follow a reduced carbohydrate diet and to avoid foods which are sweet or have a high glycaemic load. This recommendation is based on the 2013 macronutrient study by Dr Jennifer Miller; the awareness of an increased risk for diabetes in some people with PWS due to an altered glucose metabolism; and the understanding that sweet foods (including artificially sweetened foods) will only exacerbate feelings of hunger. It is also recommended that the dietary intake of infants with PWS is not restricted, that healthy fats necessary for brain development are not avoided, and that all people with PWS are offered a nutritionally balanced diet with sufficient micronutrient intake (vitamins and minerals.)

Dr Jennifer Miller and her team trialed a reduced carbohydrate diet and found that the children who followed the predetermined macronutrient content had lower body fat and weight compared to those who only followed energy intake (calorie) recommendations. They advise that 45% or less carbohydrates, 25-30% proteins and 30% fats with increased exercise improves body composition and reduces the need for dietary restriction. Based on anecdotal data from parent groups, other macronutrient studies are underway which are comparing low carb versus low fat diets for PWS and investigating the modified atkins diet. The hypothesis is that low carb /higher fat diets may decrease hyperphagia and increase satiety. Any long term risks of these diets have not yet been considered.

A low energy diet may be lacking in vitamins A,D,E,K and the minerals iron, calcium and zinc. Common deficiencies in calcium and vitamin D have been observed in PWS which are linked to the development of osteoporosis. Sometimes a multi-vitamin supplement is given to ensure adequate nutrition, but some vitamins can be toxic if given when unnecessary or in high doses and a dietitian should be consulted. See our supplements page for further information.

A reduced-energy intake, well-balanced diet improves weight control in children with Prader-Willi syndrome – J. L. Miller, C. H. Lynn, J. Shuster, & D. J. Driscoll, 2012.

For diabetes – see D

Obesity in PWS is a result of individuals needing a reduced energy intake due to decreased resting energy expenditure from decreased activity and decreased lean body mass (muscle). Hyperphagia (increased appetite /interest in food and lack of satiety) significantly adds to obesity risk if it is not controlled, which is generally not possible for people with PWS to do by themselves. Obesity can occur in young children with PWS before any symptoms of hyperphagia have begun. This is because in nutritional phase 2a (approx 2.1 – 4.5yrs), weight gain starts to occur without any increase in dietary intake. It is from this time that energy intake needs to be reduced to less than what is normally age appropriate in order to prevent obesity. Retrospective studies of growth data from children not diagnosed until later years found that these children were already obese before entering phase 2b when the increased appetite begins, and that this change only worsened their existing obesity. For these reasons, it is very important that excessive weight gain does not occur because it can be extremely difficult to lose, especially once a person has become hyperphagic.

Obesity in PWS tends to affect the central region of the body: abdomen, thighs and buttocks. Abnormal fat composition is seen in PWS, with increased subcutaneous fat (directly under the skin) and decreased visceral fat (around the body organs.)

There are many health problems associated with obesity in PWS, including hypoventilation, oedema, pulmonary embolism and type 2 diabetes, which some people with PWS may be more susceptible to. Respiratory failure and cardiopulmonary factors are the leading causes of death in PWS and are presumed to be largely obesity related. Use of continuous positive air pressure (CPAP) and nasal intermittent positive pressure ventilation (NIPPV) may be beneficial, but oxygen should be used cautiously because of the risk of hypoventilation and Co2 retention.

For hyperphagia – see H
For diabetes – see D
For hypoventilation – see H
For oedema / edema – see O
For venous thromboembolism – see V

Fluid retention is usually first noticed in the lower legs and is a warning sign that obesity is affecting health. Oedema in PWS is usually a symptom of hypoventilation which can lead to respiratory failure if untreated.

Oedema sometimes goes unnoticed in an obese person because it may visually appear no different to body fat. One test for oedema is by feel – the tissue will feel more firm or hard than other areas of body fat. Another sign of oedema may be rapid weight gain that is not explained by increased access to food. Oedema starts in the lower body and spreads higher as health deteriorates.

In addition to hypoventilation, other complications of oedema can occur. Venous stasis and lymphatic damage increase risk for ulcers, thrombosis and cellulitis. Diagnosing a cellulitis infection is made more difficult by the possible absence of fever and pain.

The most essential treatment for oedema is to increase leg movement and physical activity. Diuretics are not recommended and over-use of oxygen therapy should be avoided.

Oedema (Fluid Retention) in Prader-Willi Syndrome – Linda M. Gourash, MD, Pittsburgh Partnership, Clinical Advisory Board, PWSA-USA

For hypoventilation – see H

Pain and sensitivity signalling can impaired in PWS and this can hide the presence of serious injury or infection. Pain may not be felt until severe. Parents and carers should note any subtle changes in condition or behaviour. When pain is felt, people with PWS may describe a general feeling of unwellness as they are often unable to describe the pain well or to localise where the pain is coming from.

(Note: If a person with PWS experiences abdominal pain, it should be considered whether the person has obtained free access to food or has consumed unsavoury food items.)

Post anaesthesia recovery may be complicated by obesity, central and obstructive apnoea, hypotonia, chronic aspiration and adverse reactions to medications. Overnight observation should be considered for typical outpatient procedures.

Prolonged drowsiness after anaesthesia may occur as a result of underlying somnolence (sleepiness) in PWS and may be related to central sleep apnoea (more prevalent in infants.) Patients with PWS should not eat until the effects of anaesthesia have fully worn off as choking is a significant risk in PWS (see choking and swallowing – C). Progressing more slowly than usual from liquids to solid food is recommended. Extra time should be allowed for the recovery of GI function as some degree of gastroparesis (slow or stalled movement of food from the stomach to the intestine) is thought to be common in PWS which means there is an increased risk of a blockage occurring following anaesthesia.

During extubation (when a breathing tube is removed), thick saliva (common in PWS) can complicate airway management and hypotonia may also affect the ability to cough effectively to clear the airways.

An obese individual with PWS is more prone to obstructive apnoea and pulmonary compromise. Significant body edema is also common in obese individuals and treatment with diuretics may be necessary.

Pain sensitivity is often altered in PWS, so any pain that is out of proportion to the procedure (i.e. lack of pain) could signal that something else is wrong. Pain medications should be used with caution and at lower doses as the combination of anaesthetic with pain medication may cause excessive sedation and suppress breathing. This combination of medicines can also further slow digestion so a distended abdomen or abdominal pain should be urgently evaluated. An individual may also have altered blood oxygen or blood carbon dioxide levels that will change their response to medications.

For medicine contraindications – see M

In PWS, there are increased rates of oppositionality, aggression, impulsivity and ‘thought’ problems (seeing things /hearing voices /strange ideas). In some cases, behavioural episodes can become extreme and an evaluation may be needed for psychotic disorders.

Individuals with PWS are more susceptible to mood disorders or depression, particularly during adolescence and early adulthood. The prevalence of mental illness in adults with PWS is high (17 – 28% in PWS by deletion and 64 – 65% in PWS by UPD.) Non-psychotic depressive illness and depressive illness with psychotic symptoms are the major cause of illness in those with PWS by deletion, but in PWS by UPD, almost all individuals diagnosed with mental illness suffered psychotic symptoms, with a frequent diagnosis of bipolar illness. The susceptibility of people with PWS to periods of low mood also makes them susceptible to periods of elevated mood or hypomania. This may manifest as sustained irritability, increased emotional volatility and increased self confidence, but is not as severe as actual mania which usually requires hospitalisation. These fluctuations in mood are referred to as mood disorders and can develop into bipolar disorder when highs and lows repeatedly occur.

Although psychiatric problems are more prevalent in those who have PWS by UPD, there are other predisposing factors, such as stress sensitivity, cognitive impairments, problem solving deficits, speech/language disorder, impaired social skills and coping strategies, plus family history of psychiatric disorders. Signs and symptoms may be difficult to detect – please read information listed below. Little is known about the early phase of illness and risk factors that predict the emergence of psychosis in PWS, but there is compelling evidence that earlier intervention leads to improved mental health outcomes.

Possible interventions for psychiatric illness in PWS may involve medication and psychological strategies. Response to medications and dose can be both unique to PWS and can vary in individuals, therefore treatments need to be carefully considered and monitored. Possible new future interventions may include oxytocin and vagal nerve stimulation.

The Mental Health of People with Prader-Willi Syndrome – Prof Tony Holland, University of Cambridge, 2017
Prader-Willi Syndrome: A Primer for Psychiatrists – Drs Forster and Gourash, The Pittsburgh Partnership, 2005.
Psychotropic Medication Tip Sheet for Patients with Prader-Willi Syndrome for Health Care Providers – Elisabeth M. Dykens and Elizabeth Roof, Vanderbilt University, for PWSA(USA)
VIDEO: When and Why to Consider Psych Medications in PWS – Elizabeth Roof (FPWR)

For mental health – see M
For medications sometimes used  – see Other Medicines
For anxiety – see A

Due to hypogonadism (see H), pubertal development in PWS is usually delayed, progresses slowly, remains incomplete and is sometimes disordered.

Premature adrenarche (see A) can happen in up to approximately 1/5 of children with PWS and cause changes in the body, such as new hair growth, body odour, skin and mood changes, but this is not related to pubertal onset which is usually delayed in PWS. At the onset of puberty, most girls will experience early pubertal development normally with some breast growth, but menstruation may not start or may be very delayed. Girls may develop oligomenorrhea (infrequent menstrual periods) which is often only periodical spotting, but primary amenorrhea (absent menstruation) is slightly more common. For boys, adrenarche is normal, but the penis and testes may remain small with full development rarely reached.
A very small number of children with PWS are affected by precocious (early) puberty.

Treatment with sex hormone therapies can help advance puberty if it stalls, but they can also be prescribed for different reasons. Oestrogen therapy for girls may trigger menstruation, but can also prevent osteoporosis, particularly if given during the period of bone building (before age 25-30 yrs.) Testosterone therapy is also thought to increase bone density and help prevent osteoporosis, but whilst it may improve sexual function, it is unlikely to affect penile length in sexually mature men unless there has been a significant deficiency of testosterone. Attempts to increase penis size are more effective during infancy. If gonadtropins are given to encourage testes to descend, they can also increase penis size whilst stimulating the testis to produce testosterone. Androgen (testosterone) therapy is also more successful in early childhood because of an increased number of androgen receptors at that time.

For hypogonadism – see H
For premature adrenarche – see A
For fertility – see F

Respiratory failure remains the leading reported cause of death in PWS across all age groups (31%). Respiratory failure associated with respiratory illness or aspiration is more likely in infants and children while obesity-related factors and sleep apnoea are a more likely cause in adults. However, the underlying pathology for respiratory failure continues to puzzle researchers, but it is thought it could also be secondary to undiagnosed aspiration, pulmonary embolism or an unspecified neurological disturbance. (Butler, Merlin G. et al. “Causes of Death in Prader-Willi Syndrome: PWSA(USA) 40-Year Mortality Survey.” 2016)

The increased risk for respiratory difficulties is possibly complicated by hypotonia (weak chest muscles) and central, obstructive or mixed sleep apnoea. Ventilatory control responses to hypoxemia and hypercapnia are known to be altered in PWS and aspiration and stomach reflux problems are also common in infants. Sleep related breathing problems occur more frequently with young age and in cases of severe hypotonia, narrow airway, morbid obesity or where respiratory problems have previously required intervention, such as asthma, chronic respiratory infections, hypoventilation with hypoxia and respiratory failure.
It is recommended that a sleep study is considered for patients with severe obesity, hypotonia, a history of respiratory problems and prior to sedation, surgery or starting growth hormone treatment. A history of excessive daytime sleepiness or snoring are also indicators of sleep apnoea and signify the need for a sleep study. A sudden increase in weight or change in exercise tolerance also suggest the need for a prompt sleep study.

Respiratory Problems in Prader-Willi Syndrome – James Loker, M.D. Pediatric Cardiologist, for The Gathered View (ISSN 1077-9965), PWSA(USA), 2006.
Disorders of Sleep and Ventilatory Control in Prader-Willi Syndrome – Gillett, E. S., & Perez, I. A. , 2016.

For sleep-disordered breathing / sleep apnoea – see S
For hypoventilation – see H

Scoliosis is a sideways curvature of the spine that mostly occurs in preschoolers and during the growth spurt just before puberty. Prevalence estimates vary for PWS, but scoliosis is thought to occur approximately 70% of individuals, although many of these curves will be mild. Studies revealed that 23% will develop a curve before their 4th birthday. Of those diagnosed with some degree of spinal curve, surveys revealed that 66% were detected by the age of 10, with 85% identified by age 15.  Two types of scoliosis have been identified in PWS: long C-curve type (LCS – only present in infants) and the idiopathic S-shaped curve (IS). The centre of balance is thought to be altered in PWS and individuals may walk with their head forward – kyphosis can develop later on and is an outward curve of the upper spine so that the person bends forward / appears hunched.

Frequent spine examinations are recommended because early detection may reduce the need for surgery. Doctors often examine the spine as a child bends forward (Adam’s Forward Bend Test), but due to differences in presentation in PWS, a curve may remain hidden and is unlikely to seem as severe during a physical examination. Therefore the most reliable, accurate screen for scoliosis is an x-ray of the spine. Dr. Harold van Bosse recommends yearly x-rays from unassisted sitting to approx 4 years old. Following this, monitoring with thorough spine exams should be sufficient, but with close observation from the age of 10. Parents should request an x-ray if they have concerns.

Preventative measures include building core and upper body strength to help combat hypotonia and improve posture. Specific exercises are recommended for kyphosis. Early scoliosis treatment may involve casting and/or bracing – the latter can be problematic in PWS due to obesity or compliance issues. When casting and bracing does not bring about desired results, spinal surgery inserting expandable rods may be considered, with definitive spinal fusions for older children. Generally speaking, a curve that is less than 20-25 degrees will be monitored, a curve greater than 20 degrees may be treated with casting or bracing (depending on age), then surgery will be indicated for curves greater than 40-50 degrees, with expandable growing rods implanted anytime between 5 – 7 yrs and lasting until 10-12 years.

Scoliosis is not considered a contraindication for growth hormone treatment (Table 1. Recommendation VI). Children treated with GH had similar onset and curve progression of scoliosis to those not treated with GH. Indeed, GHT is believed to be helpful because it improves lean muscle mass and bone density. Recent data has confirmed that GHT helps to ward off scoliosis in infants.

Clinical Observations and Treatment Approaches for Scoliosis in Prader–Willi Syndrome – Harold J.P. van Bosse and Merlin G. Butler, 2020.
Guidelines on Scoliosis Monitoring and Treatment for Children with Prader-Willi Syndrome – Author: Harold J. P. van Bosse, MD, Contributors: Janice Agarwal, PT Jamie Bassel, MD Janalee Heinemann, MSW & Jennifer Miller, MD, 2010.
A Primer on Scoliosis Surgery for Prader-Willi Syndrome – Harold J. P. van Bosse, MD
Effects of 8 years of growth hormone treatment on scoliosis in children with Prader–Willi syndrome – Grootjen LN, Rutges JPHJ, Damen L, Donze SH, Juriaans AF, Kerkhof GF, Hokken-Koelega ACS, 2021.
Randomized Controlled Trial to Investigate the Effects of Growth Hormone Treatment on Scoliosis in Children with Prader-Willi Syndrome – Dutch Growth Research Foundation, 2009

Seizures are abnormal electrical disturbances in the brain. It is thought that there is an increased risk for seizure disorder in PWS that is 3-5 times that of the general population. This risk is mainly for those with PWS by deletion because seizure susceptibility is likely to be associated with some of the deleted genes.

A 2014 review of literature found existing data about the clinical characteristics of epilepsy and EEG abnormalities in PWS to be controversial, with prevalence rates for epilepsy ranging from 4-26%. There are various types of seizure which have been recorded in PWS, but the majority are focal epilepsy (partial seizures). These are often characterised by staring spells or absence. It has also been observed that the first episodes of epilepsy usually occur in children before 2yrs.

The occurrence of febrile seizures associated with fever are also up to twice as frequent as in the general paediatric population.

Skin picking is common in PWS, but severity varies and some individuals may bite nails, pull hair, eyelashes or teeth instead. Picking may take the form of scratching at sores and insect bites or may involve creating large, open wounds which easily become infected. It’s usually a repetitive habit behaviour which worsens with boredom and may be a form of self-stimulation. Sometimes it can even be to provoke a reaction or seek attention. It is hard for the individual to stop due to difficulties in thought switching and a lack of impulse control. It is also known that neurological signalling is impaired in PWS, so individuals may not feel pain or disgust as intensely when picking. Less frequently, the skin picking may be as a result of anxiety or emotional distress. Although it can appear to be a compulsive behaviour, medications targeting OCD or anxiety have proven unhelpful.

Intervention techniques involve distraction, redirection and keeping hands busy. Creams and lotions can be used to moisturise the wound, making it less tempting, and to minimise infection. It’s a good idea to make picking less convenient by cutting nails and dressing the wound. It is also best to ensure no attention is given to the behaviour – positive or negative. If the individual is seeking sensory stimulation, sometimes providing more socially appropriate forms of stimulation help, such as scheduled, regular massage. Sensory stimulation should not be linked to the behaviour in case it rewards it.

A study by Dr Miller and Dr Angulo (2013) found that PharmaNAC (N-acetylcysteine) improved skin picking behaviours in all 35 trial participants with PWS. N-acetylcysteine is a supplement which replenishes intracellular levels of the natural antioxidant glutathione. Dr Miller recommends the effervescent form, PharmaNAC, because it is absorbed well and the sealed packs mean that it does not degrade through oxidisation with the air, making it less effective. This form is not currently available in New Zealand but can be purchased from overseas. (NAC is also used in the wider population to support immunity and lung function, and in the autistic community where abnormalities in glutathione pathways have been implicated.) In severe cases of skin picking, a prescription medicine called Topiramate is sometimes used.

Skin Picking in Prader-Willi Syndrome – Linda Gourash, MD, Janice Forster, MD, The Pittsburgh Partnership

For PharmaNAC /  N-acetylcysteine – see Supplements page

Sleep disorders in PWS are very common and include central and obstructive sleep apnoea, oxygen desaturation, altered sleep architecture, excessive daytime sleepiness (EDS), narcolepsy and cataplexy. These problems might be associated with cranio-facial features, hypotonia and respiratory weakness (particularly in infancy), weight gain or to dysfunction of the hypothalamus affecting the sleep-wake cycles and reduced hypocretin/ orexin levels. Sleep disorders affect both quantity and quality of sleep, so whilst it may seem that a person sleeps for a sufficient amount of time, the overall amount of sleep may be decreased. Management of sleep disorders is essential to improving health, cognition, behaviour and overall quality of life.

Sleep Problems in Prader-Willi Syndrome – Dr J Forster, The Gathered View (ISSN 1077-9965), PWSA(USA), 2014
Review: Disorders of Sleep and Ventilatory Control in Prader-Willi Syndrome – Emily S. Gillett and Iris A. Perez, 2016
Sleep Review: PWS and Sleep-Disordered Breathing – Jennifer Miller and Mary Wagner, 2013

For sleep disordered breathing / apnoea – see S
For EDS – see E
For narcolepsy – see N
For cataplexy – see C
For respiratory concerns – see R

It is thought that people with PWS are at increased risk for venous thrombosis with new data revealing that pulmonary embolism accounted for 7% of deaths. Most of these are thought to be obesity related.

Pulmonary embolisms (PEs) are caused by a blocked artery in the lungs. The blockage is usually a blood clot that originally formed in a deep vein in the leg (deep vein thrombosis). Prolonged bed rest should be avoided.

Although usually mild, almost all children with PWS are long sighted to some degree which requires monitoring. Regular vision tests are recommended. Long sightedness in children may correct itself or spectacles may be required. A few children with PWS are short sighted. Astigmatism is also common in PWS and is when there are imperfections in the shape of the lens which can affect focusing.

Vision problems and deficiency in stereopsis (reduced depth perception and 3D vision) can also be caused by the very common conditions of strabismus (see S) and amblyopia (lazy eye).

Vision and Care of the Eyes 2—5 years – PWSA(UK)

It was thought that vomiting is unlikely in PWS, but FPWR parent surveys revealed that just over 50% of people with PWS had in fact vomited, although it may occur less frequently. (Reflux / rumination are commonly seen and are controlled by a different mechanism to true vomiting.) Although vomiting is one of the body’s normal self-defence mechanisms, in people with PWS who do not ordinarily vomit, the presence of vomiting may be cause for concern and could signal serious illness, blockage or rupture.
Lack of vomiting is of concern during episodes of gastric illness or food poisoning and a problem in the event of poisonous substances being consumed. Emetics given to induce vomiting may be ineffective.

Vomiting may be perilous for someone with PWS due to potentially not being able to vomit strongly due to their low muscle tone. A safe vomiting position for a person living with PWS is lying flat on their side in the coma or recovery position (as per the general population). Carers should be advised of this risk, including nurses / doctors when attending medical centres or hospitals.