What is Prader-Willi Syndrome?
Prader-Willi syndrome is a rare genetic disorder caused by a defect of genes in the proximal arm of chromosome-15 which leads to life-threatening childhood obesity. It is associated with obesity, hypogonadism, intellectual deficits, small stature along with small hands, and feet.
A child with PraderWilli Syndrome
The first case of Prader-Willi syndrome was first described in a mentally impaired adolescent girl in 1887 by Langdon Down and was later described in medical literature in 1956 by Swiss doctors Andrea Prader, Alexis Labhart, and Heinrich Willi.
Presence of characteristic facial features like almond-shaped eyes, narrow bifrontal diameter, and the nasal bridge thin upper lip and downturned mouth. These features are noticed soon after birth.
Prader-Willi syndrome has been described worldwide and is a genetic disorder occurring in approximately 1 in every 15,000 live birth. It affects males and females equally, all races and ethnicities are equally susceptible.It is highly unlikely for parents to have more than one child with Prader-Willi syndrome.
PWS is caused due to abnormality in the expression of genes on Chromosome 15 specifically on the long arm of chromosome 15. This abnormality can be attributed to the following :
The defects seen in Prader-Willi syndrome is mostly attributed to hypothalamic disorder, which may explain some typical features of the syndrome like delayed growth and hyperphagia as the hypothalamus is the center for hormone production, growth, and hunger regulation.
Various studies have implied the role of Ghrelin in satiety defect and have found Ghrelin to be about 4-5 folds higher in people with PWS. (Ghrelin is a hormone produced by enteroendocrine cells and is also known as the Hunger Hormone)
Three sets of diagnostic criteria have been established for the diagnosis of Prader-Willi Syndrome. These are major, minor, and supportive.
These criteria though they dont have points, aid in the diagnosis of the disease.
Based on the guidelines established by Holmes et.al the diagnosis of Prader-Willi syndrome is highly likely in children younger than 3 years if they score 5 points with 3 of those coming from the major criteria.
In the case of children older than 3 years with Prader Willi syndrome is highly likely if they score 8 points with 4 from major criteria.
Magnetic Resource Imaging (MRI) of the head to assess hypopituitarism. The individuals with Prader-Willi syndrome are at risk of pathological fractures, however high degrees of pain tolerance in these patients make it necessary to diagnose fractures to prevent stiffness and malunion of fractures. DEXA Scan: To detect complications of osteoporosis. Scoliosis Film of the vertebra.
To reach the diagnosis of PWS we need to differentiate it from other diseases which may be causing similar features:
These conditions can be differentiated from PWS with the help of the DNA Methylation technique.
Apart from these, other genetic conditions are causing short stature and obesity which need to be ruled out:
There is no permanent cure for Prader-Willi syndrome currently, and the treatment of the syndrome requires a multidisciplinary approach from geneticists, endocrinologists, nutritionists, pulmonologists, neurologists to prevent complications from PWS.
The treatment is generally directed towards symptomatic relief and problem management.
The treatment plan needs to be continuously reassessed as the child grows older as it needs changes.
Early diagnosis and treatment of PWS can go a long way in improving their quality of life and help them reach their full potential.
Children with PWS require proper care apart from specific symptomatic treatments. Most children can benefit from the following:
Infants with PWS have low muscle tone consequentially they are unable to breastfeed properly. A pediatrician can help by recommending special feeding methods and prescribing high-calorie diets. Use of a Nasogastric tube may be required.
A proper diet low on calories but providing necessary nutrition is key in managing the weight of PWS in children. Supplemental vitamins and minerals are required for balanced growth. Proper diet complemented with increased physical activity help in weight management. The child should exercise for at least 60 minutes. The exercise routine should be broken down into multiple 5- 10 minute sessions in children having decreased energy levels.
As the desire for appetite in children with PWS is high, parents need to keep strict vigilance on their eating habits, there should be proper meal times, food should be kept out of their view and no extra feeding should be done.
Human growth hormone (HGH) treatment. An endocrinologist can help decide if the baby will benefit from HGH injections. In children with Prader-Willi syndrome, it helps in facilitating growth, decreasing body fat content, increasing muscle size, and muscle tone.
Sex hormone treatment. Children with PWS have a very low sex hormone level, requiring hormone replacement therapy (Testosterone for males; estrogen and progesterone for females). HRT begins as the child approaches puberty. Apart from raising hormonal levels, it helps also in preventing bone thinning. Orchidopexy may be required for Cryptorchidism (Undescended testis).
Treating sleep disturbances related to PWS can improve daytime sleepiness and behavioral issues in children.
Strict parenting is required to keep the behavior in check, especially concerning food, to prevent over-eating; a proper diet plan needs to be formulated. Calmness is required while dealing with children showing temper tantrums- the situation should be deflated as soon as possible by engaging the child in another topic. Medication may be required in some cases.
A psychologist or a psychiatric consultation may be required to address obsessive-compulsive disorders, skin picking, or mood disorders in children with PWS. The childs nails should be trimmed so that they do not develop cellulitis or other skin infections as a result of constant skin picking; any cases of skin infection should be treated immediately using antibiotics.
Most people with Prader-Willi syndrome will need specialized care and supervision throughout their lives for continuous consultation with the doctor is required to transition medical care to adulthood.
In cases of severe skin and pinching and psychoses, Anti-depressant or anti-psychotics can be helpful. SSRIs are the antidepressants of choice. These drugs however come with associated risks, so they are generally avoided below the age of 18. Cognitive-behavioral therapy may be required in some cases. It is a talking therapy that helps to change the way the patient thinks and behaves to modify unhealthy behavioral patterns.
Patients with Prader-Willi syndrome are at risk of developing the following complications:
People with PWS, who receive early treatment usually have a normal lifespan and can function in a group home setting, perform vocational work.
People with PWS, having normal IQ can expect to accomplish many of the things their peers do. However, each person requires lifelong support from the people involved to lead an independent life.
Complications due to morbid obesity and psychological issues can affect the quality of life and sometimes shorten life expectancy in patients with PWS.
Scientists worldwide have been working on finding a permanent cure and improving the quality of life by reducing complications for PWS by carrying out various researches worldwide.
Livoletide is being monitored as a drug to reduce ghrelin and consequently hyperphagia and obesity.
A randomized, double-blind placebo-controlled study conducted in 2019 in 47 adults who took 3-4 mg of Livoletide once a day for two weeks, reported a significant decrease in food-related behaviors as compared to people who were given a placebo.