Alternative names for Prader-Willi syndrome

Prader-Willi-Labhart syndrome

What is Prader-Willi syndrome?

Prader-Willi syndrome is associated with extreme hunger, overeating and development of severe obesity.

Prader-Willi syndrome is a rare complex genetic disorder involving many different systems in the body, including the hypothalamus and pituitary gland, which are parts of the brain controlling hormones and other important functions such as appetite.

The syndrome has characteristic features including severe floppiness as a baby, early onset of exceptional hunger in childhood with overeating and development of severe obesity, short stature, low levels of sex hormones, learning disabilities, behavioural and psychiatric problems with serious consequences and difficult management issues for patients, families and carers.

What causes Prader-Willi syndrome?

Prader-Willi syndrome is an inherited genetic disorder that occurs when genes (or part of genetic material) in a part of chromosome 15, inherited from the person’s father, are missing. This can happen in several different ways.

The genes that are missing in Prader-Willi syndrome are normally involved in the way the brain develops and functions. When they are missing, this leads to problems with how the brain, including the hypothalamus, works.

What are the signs and symptoms of Prader-Willi syndrome?

The following signs and symptoms are seen in Prader-Willi syndrome, though there is a great variation in the number of symptoms that develop and their severity in individuals with Prader-Willi syndrome.

Physical features:

• tendency to be slightly small at birth
• short stature due to growth hormone deficiency and low sex hormones
• characteristic features found in the face with a narrow forehead, almond-shaped eyes and down-turned mouth
• small hands and feet.

Medical:

• reduced movement of the baby during pregnancy
• floppiness as a baby with poor ability to suck and poor weight gain, which improves with age
• excessive daytime sleepiness
• snoring and/or breathing problems at night when asleep, leading to periods when breathing stops for a few seconds (apnoea)
• short-sightedness and/or squints
• thick gluey saliva
• a reduced ability to feel pain
• small genitals at birth in boys and girls
• undescended testes in boys
• childhood development of obesity because of excess fat and poor muscle development (usually starting between the ages of one and three years)
• a feeling of excess hunger and rarely feeling full developing in childhood, usually starting between the ages of three and five years. This can become progressive, leading (if not controlled) to worsening obesity (usually between the ages of 5 to 13 years)
• incomplete delayed puberty, infertility and lack of, or very light, periods in girls
• possibly an increased risk of having an underactive thyroid gland
• speech, language and motor developmental delay with mild to moderate learning difficulties
• reduced vomiting
• curvature of the spine
• type 2 diabetes, heart failure and respiratory problems are more common secondary to obesity

Behavioural:

• behavioural problems with temper tantrums, obsessive behaviours, skin picking, stubbornness and resistance to change.
• increased risk of depression and psychosis in some individuals, which may appear as fluctuating changes in mood, suicidal thoughts, loss of interest, deterioration in the ability to concentrate, change in sleep pattern, under or over-activity, hallucinations, abnormal mental beliefs or experiences.

How common is Prader-Willi syndrome?

The number of children who are affected by Prader-Willi syndrome is about 1 in 30,000 of the population. It affects boys and girls and all ethnic groups equally. Older mothers have a slightly increased risk of having a child with Prader-Willi syndrome but no other risk factors have been found.

Is Prader-Willi syndrome inherited?

Although this is a genetic disease that results from loss of part of the chromosome 15 inherited from the father, this is nearly always something that has arisen spontaneously in a single sperm or fertilised egg. Therefore, there is not usually any increased risk of having a second child with Prader-Willi syndrome. In very rare cases, less than 1 in every 100, when there is a translocation or an inherited imprinting defect present in the father, there may be an increased risk of having a second child with Prader-Willi syndrome.

How is Prader-Willi syndrome diagnosed?  

Prader-Willi syndrome is diagnosed through specialised genetic tests that are performed on DNA from a blood sample from the patient. It is usually suspected and diagnosed within the first weeks and months of life.

• Sometimes DNA samples are needed from the parents to determine exactly which genetic sub-type is present (known as polymorphism analysis).

How is Prader-Willi syndrome treated?  

Treatment and management of Prader-Willi syndrome involves many different medical and social care professionals. As Prader-Willi syndrome is so complex and causes problems from the beginning of life, families and carers need education about the syndrome as well as support from the start. Patient support groups can be particularly helpful.

There are many different aspects to the treatment of Prader-Willi syndrome:

  1. Management of feeding, obesity and mouth care:

• Tube feeding may be needed in newborns and infants for a few weeks or months.
• Management of obesity is essential because drugs and surgery have so far not been of benefit in treating the excess hunger. Bariatric surgery for obesity is also associated with unacceptable risks and is therefore not advised.
• People with Prader-Willi syndrome will need to be supervised to avoid them overeating or being able to buy too much food. Families and carers need to learn, early on, how to control the way food is presented and how easily it is available at home. A low-calorie, well-balanced diet with regular exercise is vital. This type of management affects the patient’s and family’s rights and privacy, so it is important that they have appropriate psychological and behavioural counselling.
• Poor production of saliva may be helped by products designed to increase saliva flow such as special toothpaste, mouthwash and sugarless gum.

  2. Therapy:

• Physiotherapy programmes are often used in childhood.
• Speech and language therapy during childhood will help with impaired speech and delay in developing language.

  3. Drugs:

• Diabetes mellitus, which is common in Prader-Willi syndrome, may need medication such as metformin, pioglitazone and sometimes insulin.
• Medication to lower cholesterol and blood pressure may be needed.
• Growth hormone therapy should be considered in childhood (certainly as early as one to two years, if not between 6 to 12 months) to improve growth during childhood, adult height, reduce body fat, increase muscle and bone strength and quality of life, and possibly help brain development and function. This may also be effective even after completion of growth in adulthood.
• Occasionally thyroid hormone and rarely, steroid hormones (hydrocortisone) may be needed.
• At some stage, almost all patients will require sex hormonal treatment (testosterone in boys, oestrogen and progesterone in girls) to help start or maintain puberty.
• As adults, treatment with sex hormones is often needed for bone and metabolic health and possible benefits to mental, emotional and physical wellbeing in both boys and girls, and muscle mass in boys.
• Infections from any skin lesion may need treatment with antibiotics.

  4. Surgery:

• If the testes have not descended in boys they may need fixing in the scrotum through surgery during the first or second year of life.
• In cases of disturbed breathing at night (obstructive sleep apnea), surgery to remove tonsils and adenoids may be necessary (especially in children), and sometimes the use of oxygen and machines to help with breathing while asleep (called ‘CPAP’ or ‘NIPPV’).
• Bracing or back surgery are sometimes needed for curvature of the spine.
• Bariatric surgery for obesity is associated with unacceptable risks and is not advised for patients with Prader-Willi syndrome.

  5. Behaviour management:

• It is important to manage temper outbursts, skin picking and repetitive behaviours in a consistent way by trying to reduce the number of times they occur and to manage them when they do occur.
• Severe changes in mood, e.g. depression, or psychosis usually require the expertise of a psychiatrist with experience in people with learning difficulties. People with Prader-Willi syndrome may react strongly to life events, e.g. bereavement or a change in living arrangements.
• Severe mood changes may also be brought on by changes in routine, sleep disturbance or some medications. Doctors may consider the use of antidepressant or anti-psychotic drugs, starting on lower-than-normal doses with careful monitoring for side-effects.
• It is vital that everyone involved in the care of people with Prader-Willi syndrome recognises the difference between the underlying behavioural problems seen in Prader-Willi syndrome and acute psychiatric illness.

Are there any side-effects to the treatment?

During growth hormone replacement there is an increased risk of Diabetes which should be well controlled before starting this treatment and sugar levels should be monitored. Other side-effects of growth hormone treatment such as joint pains and ankle swelling are usually avoided by slow increases in the dose and ensuring that the doses of growth hormone used are not excessive (by measuring insulin-like growth factor-1 levels in the blood).

Unexpected deaths have been reported in infants and children with Prader-Willi syndrome, which are thought to be caused by complications from respiratory infection, sleep apnoea, enlargement of the tonsils and adenoids, and severe obesity. This has been seen in patients who are both receiving and not receiving growth hormone treatment. It does, however, appear that there may be a high-risk period for such problems during the first nine months of growth hormone treatment, particularly in children.

For this reason, it has been advised that growth hormone treatment should be started at a low dose and, before starting this treatment, obesity must be at least controlled. In addition, any breathing problems, particularly relating to during sleep, should be identified and treated. Sleep studies can be carried out before and shortly after beginning treatment. The removal of tonsils and adenoids may be advised.

There is currently no evidence that testosterone treatment causes aggressive behaviour in boys. However, it seems sensible to try and use testosterone gels and patches if possible, and, if using testosterone injections, to start with a lower dose than normal and increase the dose slowly.

What are the longer-term implications of Prader-Willi syndrome?

Complications from obesity may include high blood pressure, diabetes mellitus, heart failure, chest infections and breathing difficulties, even in childhood or early adulthood. If the obesity can be limited through vigorous control of the food environment and exercise, the life span may be normal. Deaths in adults with Prader-Willi syndrome are most often obesity-related due to heart and lung failure, skin infections and pneumonia, and are seen from the teenage years into the 20s, 30s and beyond. Rare reports of life-threatening choking on food and tearing of the stomach have also been described during very large bouts of overeating.

Skin picking can lead to recurrent skin infections.

Are there patient support groups for people with Prader-Willi syndrome?

Prader-Willi Syndrome Association UK may be able to provide advice and support to patients and their families.