Type 2 diabetes mellitus can occur in PWS patients and is usually associated with severe obesity and accompanying insulin resistance. The prevalence rate of T2 diabetes in the PWS population exceeds that of the general population and may be up to 25%, with an average age of onset being 20yrs. However, researchers believe that the relationship between obesity and the development of T2 diabetes in PWS is complex and appears to differ to non-PWS patients.
It is thought that some people with PWS have an increased risk for diabetes due to an altered glucose metabolism (impaired fasting glucose, impaired glucose tolerance), particularly after pubertal age and if obese.
Prevention measures include weight control and avoiding sweet foods and those with a high glycaemic load (i.e. potatoes, white rice and bread.) These foods cause spikes in blood sugar and insulin and these continual spikes can elevate risk. It is recommended that PWS patients are monitored for risk of developing diabetes with regular measures of BMI and insulin resistance, particularly during adulthood.
The management of T2 diabetes in PWS is much the same as with the general population with the encouragement of weight loss, increased exercise and the use of drugs, such as metformin, and insulin being introduced if required. New treatments are in the pipeline for PWS, i.e. GLP-1 receptor agonists.
EDS (Excessive Daytime Sleepiness)
Sleep abnormalities are very common in PWS. Many people with PWS need an increased amount of sleep time, but for many individuals this manifests as EDS (Excessive Daytime Sleepiness.) EDS can be associated with central sleep apnoea in younger children and OSA (obstructive sleep apnoea) in older patients, but there are often other contributing factors in PWS, such as hypothalamic dysfunction. The quantity and quality of sleep can appear to be sufficient but excessive sleepiness persists. EDS can result in narcoleptic-like symptoms and treatments for narcolepsy may be successful in improving quality of life.
For narcolepsy – see N
For sleep disorders – see S
For sleep disordered breathing and apnoea – see S
Hypotonia (low muscle tone) is a variable, major characteristic of PWS. Babies are born ‘floppy’ with a weak suck and cry and the reduced muscle tone continues to delay the development of sitting, crawling and walking. Hypotonia also negatively affects body posture and can therefore contribute toward the development of scoliosis. Exercise programmes that target the core and upper body are helpful in trying to prevent this.
In conjunction with physical therapy, growth hormone therapy increases muscle mass and muscle strength. It is best to start treatment as soon as possible because the early years provide the best window of opportunity for skill acquisition and motor development, which in turn, have positive effects on cognitive and social development.
Although hypotonia improves with age, it still persists into adulthood, so motor programmes and exercise need to be a regular part of daily life.
For motor development – see M
Hypoventilation is a consequence of obesity that can lead to respiratory failure and right heart failure. Hypoventilation is when shallow breathing causes sustained hypoxia (decreased oxygen / increased Co2 levels in the blood), usually during the night. This seems to be typical in obese patients with PWS but is relatively uncommon in non-PWS obese patients. Onset may be rapid or gradual with symptoms including decreased stamina and oedema / fluid retention. Treatment to reverse hypoventilation involves increasing activity and restricting calorie intake, whilst avoiding over-use of oxygen therapy. Diuretics are not recommended for oedema.
Management and Rehabilitation of Obesity Hypoventilation and Right Heart Failure in Prader-Willi Syndrome – Drs Linda Gourash and James Hanchett
For oedema / edema – see O
Illness, Flu and Vaccination
Whilst it is thought that those with PWS are not necessarily immune compromised, there may be complications of illness as respiratory weakness is common. Illness can also be difficult to detect, monitor and treat in PWS with body temperature irregularities, an altered pain threshold, a possible lack of vomiting and the unlikelihood of being ‘off food’.
Influenza has the potential to be life-threatening and vaccination for people with PWS is recommended. Annual flu vaccinations are free for people who have PWS in New Zealand. Respiratory tract infections can significantly affect people with PWS, particularly if they are obese or have apnoea /sleep disordered breathing, and hypotonia can affect the ability to cough effectively and clear airways.
Breathing problems have been observed in young children with PWS who have upper respiratory infections during the initiation phase of GH therapy, and whilst there is still some uncertainty about whether GH was responsible for worsening respiratory symptoms, doctors advocate monitoring with several nights of pulse oximetry during upper respiratory infections or briefly pausing treatment.
For body temperature instability – see T
For respiratory concerns – see R
For GI issues – see G
For CAI (central adrenal insufficiency) – see A
A degree of scoliosis (spinal curve) is very common in PWS – see separate section under S. Other orthopaedic concerns in PWS include hip dysplasia, osteoporosis, flat feet and joint laxity.
Hip dysplasia in PWS is fairly common (approx 10 – 30%), but usually mild. This is when the ball and socket of the joint do not develop correctly and instead of sliding smoothly, the joint rubs and grinds. Early diagnosis and treatment with bracing or casts improves outcomes. In some cases, surgery will be recommended, but it is thought that adults with PWS rarely seem to develop hip arthritis requiring hip replacements, so surgery in childhood for hip dysplasia may be less necessary than in the general population – research is ongoing.
Most children have or develop flat feet as a result of their hypotonia. Feet may ‘turn out’ and some individuals may walk on the outer edges. Treatment is with braces or foot orthotics to stabilise the ankle (AFOs – Ankle-foot orthoses.) Ankle supports are usually needed for young children learning to walk. Feet may also roll inwards due to lax ankle joints so orthotic footwear or insoles are often permanently required. Foot misalignments are more prevalent than in the general population and the congenital defect of club feet is occasionally seen.
For scoliosis and kyphosis – see S
For osteoporsis – see O
For joint laxity / hypermobility – see J
Osteoporosis (low bone mineral density) is very common in adults with PWS, particularly after age 30, and is thought to be related to growth hormone and sex hormone deficiencies, with hypotonia and lack of exercise also likely to be contributing factors. Some medications can also increase osteoporosis risk.
Osteoporosis is diagnosed by DEXA scan and is mostly observed in adolescence or adulthood. Treatment involves maximising or supplementing vitamin D and calcium in the diet (deficiencies of these nutrients are involved in the development of osteoposis.) Hormone replacement therapies are another treatment option, including sex and thyroid hormones, in addition to growth hormone.
Osteoporosis Evaluation and Therapy in Prader-Willi Syndrome – Consensus Statement of the PWSA (USA) Clinical Advisory Board, 2008.
Sleep Disordered Breathing / Sleep Apnoea
Sleep disordered breathing in PWS patients tends to evolve from predominantly central sleep apnoea in infants to obstructive sleep apnoea (OSA) in older children. Other factors that may affect breathing during sleep are cranio-facial features, obesity, hypoventilation and the ventilatory control responses to hypoxemia and hypercapnia, which are known to be altered in PWS. Treatment options include adenotonsillectomy, increased exercise, weight loss and the use of continuous positive airway pressure (CPAP).
Prevalence rates for OSA are very high, just under 80%, with about 1/2 of those being mild cases and about 1/4 being severe. Increased risk for OSA is related to BMI, but OSA can also be present in those who are not obese. Adenotonsillectomy is often recommended for OSA and is successful in the majority of cases, but sometimes mild symptoms persist and occasionally worsen. Velopharyngeal dysfunction causing mild to moderately severe hypernasal speech sometimes occurs in PWS following adenotonsillectomy and this may require further surgery to correct.
Guidelines: Recommendations for Evaluation of Breathing Abnormalities Associated with Sleep in PWS – PWSA (USA) Clinical Advisory Board Consensus Statement, 2007.
Prader-Willi Syndrome and Obstructive Sleep Apnea: Co-occurrence in the Pediatric Population – Sedky K., Bennett D., Pumariega A., 2014
Review: Disorders of Sleep and Ventilatory Control in Prader-Willi Syndrome – Emily S. Gillett and Iris A. Perez, 2016.
For respiratory concerns – see R
For hypoventilation – see H
Strabismus is when the eyes do not align correctly and is sometimes known as ‘crossed eyes’ or squint. It is very common in PWS (approx 54%) and is mostly due to low muscle tone around the eyes causing poor eye coordination. Strabismus may be constant or intermittent, i.e. more apparent with fatigue, and usually improves as muscle tone improves. However, it is important that children with strabismus are monitored by an ophthalmologist because strabismus alters the developing pathways between the eye and brain over time, ultimately affecting visual development.
Vision and Care of the Eyes 2—5 years – PWSA(UK)
For vision problems – see V
Temperature regulation is affected by the disorder of the hypothalamus in PWS and this instability can make illness hard to detect or evaluate. Normal body temperature may be lower than average, causing a slight temperature to raise concern, and some people with PWS may not present with a fever at all when ill. Others may have a higher than usual normal body temperature. This lack of temperature control can mean that some people with PWS may experience fever that is higher than it would be in others. It’s a good idea to know the normal body temperature range of the person with PWS and understand typical variations.
Temperature instability also means that people with PWS often feel too hot or too cold and may wear different layers of clothing for the weather than is usual. Carers learn to recognise whether layers worn are needed in order to feel comfortable or are inappropriate.
For hypothermia – see H
There have been a few cases of water intoxication occurring in relation to some medications with antidiuretic effects, including some neurotropic drugs. Antidiarrhoeal medications should also be avoided as they may cause severe colonic distension.
It is not known, but it is possible that people with PWS may be at higher risk because hormones affecting electrolytes are produced in the hypothalamus and water intake may be excessive if compulsive water drinking becomes a problem. Drinking very large volumes of water may result in body electrolytes becoming unbalanced which can cause hyponatremia (lack of sodium.) Symptoms of hyponatremia – nausea, vomiting, muscle weakness or spasms, confusion, drowsiness, seizure, loss of consciousness.
Medical Alert on Antidiuretic Hormone – Linda Keder, The Gathered View, 1997