Prader-Willi Syndrome (PWS) is an unusual genetic condition with several physical, cognitive, and behavioural challenges. It typically occurs due to the loss of function of specific genes on chromosome 15.
PWS can arise from genetic mechanisms like deletions, imprinting defects, or uniparental disomy (where the individual inherits both copies from the parents).
This article will examine the Prader-Willi syndrome, its signs and symptoms, types, diagnosis, treatment, management, and the future outlook for affected people.
Why The Name?
Prader-Willi syndrome is named after the Swiss doctors who first described it in 1956. These doctors were Andrea Prader (endocrinologist), Heinrich Willi (pediatrician), and Alexis Labhart (geneticist).
Together, they set the foundation for understanding the genetic and clinical aspects of the disorder.
Studies & Statistics
Since its first description, studies have revealed that the missing genes produce the protein that helps regulate appetite and growth. Without this protein, people with PWS often have problems with their appetite, growth, and development, leading to low muscle tone, delayed development, and impaired cognitive function.
Studies show that every year, about 1 in 20,000 children are born with Prader-Willi syndrome. In a 2015 study, researchers identified three Nigerian children with PWS, and all three had a deletion of part of chromosome 15, which is the most common genetic cause of PWS.
The study also noted that PWS may be underdiagnosed in Nigeria due to a lack of awareness and access to diagnostic testing. However, with better diagnostic procedures like newborn screening and genetic testing, the true incidence of the disorder in Nigeria may become better understood.
How Can We Tell Someone Has PWS?
Generally, a person who has Preader Willi syndrome has a small stature, small hands and feet, and is usually hypopigmented.
Other symptoms differ in intensity from one person to another. These symptoms significantly impact a person’s life, affecting their physical, emotional, and mental health.
They include
1. Insatiable hunger, which leads to uncontrolled eating and extreme weight gain and can be life-threatening.
2. Restricted growth, leading to shorter stature compared to the average height of children of the same age.
3. Weak muscles (hypotonia) cause floppiness and difficulty in physical activities.
4. Learning difficulties affecting academic performance and daily life skills.
5. Behavioral challenges, including emotional outbursts and physical aggression, which can be challenging for caregivers and family members.
6. Low muscle tone and distinctive facial features include a narrow forehead, almond-shaped eyes, and a thin upper lip.
7. Sleep abnormalities like excessive daytime sleepiness and sleep apnea can affect daily activities and health.
8. Delayed or incomplete puberty, which can lead to sexual development issues and fertility problems.
9. Increased risk for health conditions, including high cholesterol, type 2 diabetes, high blood pressure, and scoliosis.
10. Difficulty regulating body temperature, causing sudden episodes of excessive sweating.
Does The Prader Willi Syndrome Have Types?
There are four different types of Prader-Willi syndrome, which are:
1. Classic Prader-Willi Syndrome:
This is the most common type, which occurs when a child has a deletion of the paternal copy of chromosome 15. This deletion usually occurs by chance during the formation of the egg or sperm before the child’s conception.
Children with classic PWS often have low birth weight, and they may experience feeding difficulties and delayed development. Most of them either have an intellectual disability or Autism Spectrum Disorder.
Other symptoms of classic PWS include low muscle tone, sleep disturbances, behavioural issues, and trouble regulating temperature.
2. Maternal Uniparental Disomy (UPD):
This type of PWS occurs when copies of chromosome 15 come from the mother instead of one copy from each parent. It is much less common than classic PWS, and it may have slightly different symptoms.
Children with maternal UPD may not have as much intellectual disability as those with classic PWS. Still, they may have more significant behavioural and emotional problems.
3. Imprinting Center Defect (ICD):
This type of PWS is even rarer than maternal UPD, and it occurs when there is a problem with a gene called Small Nuclear Ribonucleoprotein N (SNRPN).
This gene controls the activity of other genes on chromosome 15, so when it doesn’t work correctly, it can cause PWS symptoms.
Children with ICD may have mild to severe intellectual disability, autism, and behavioural issues. They may also have low muscle tone, trouble sleeping, and difficulty regulating temperature.
4. Chromosome Translocation:
This type occurs when part of chromosome 15 breaks off and attaches to another chromosome.
As a result, the child may be missing some genes from chromosome 15 or have extra copies of other genes. This type of PWS is rare, and the symptoms can vary considerably from person to person.
A Gender Difference
Prader-Willi syndrome can affect individuals of any gender. There is no unique link to sex chromosomes (X and Y).
Research estimates that about 55% of individuals with Prader-Willi syndrome are male, while 45% are female. This statistic shows no substantial difference in the gender distinction.
However, there are some subtle differences in symptoms between males and females. For instance, girls with PWS tend to struggle more with motor skills when compared to boys.
Both genders are prone to experience minimal secondary sexual development, which typically leads to fertility issues.
Test and Diagnosis
Prader-Willi Syndrome (PWS) diagnosis involves a physical examination, observation of behaviors and developmental delays, and genetic testing. The most common genetic test is the DNA methylation test.
Doctors can also use an electroencephalogram (EEG) to look for specific brain activity patterns. Blood tests and brain imaging studies may also be necessary to rule out other conditions.
Doctors may also recommend testing for a deficiency of growth hormone, which is common in people with PWS.
If a diagnosis of PWS is confirmed, the next step is to develop a treatment plan that addresses the individual’s specific needs.
How Can We Treat/Manage This Condition?
It’s important to understand that Prader-Willi syndrome is a lifelong condition with no current cure. Although various treatments can help alleviate symptoms, each individual’s needs are unique, so there is no one-size-fits-all solution.
Some common treatments include
- Behavioural therapy like Applied Behavior Analysis (ABA)
- Occupational and physical therapy to improve motor skills
- Speech therapy to enhance communication skills
- Feeding therapy to manage food intake and behaviours surrounding food
- Medication such as growth hormone therapy, antidepressants, and antipsychotics (in severe cases).
Additionally, a carbohydrate-low-protein-high diet may be recommended, along with a feeding schedule that may include a feeding pump or tube feeding to ensure that the person receives sufficient calories and nutrients.
How Do We Go Forward?
The long-term prognosis for individuals with Prader-Willi syndrome is highly variable, taking into account multiple factors such as symptom severity and quality of treatment.
In general, individuals with PWS can lead fulfilling and joyful lives with adequate treatment and support. While some may require lifelong care, others can live independently with minimal support.
Establishing practical expectations and objectives while prioritizing improving the individual’s quality of life is crucial.
References
- Prader-Willi Syndrome by Mayo Clinic. Retrieved from https://www.mayoclinic.org/diseases-conditions/prader-willi-syndrome/diagnosis-treatment/drc-20356002
- Prader-Willi by Ann Scheimann. Retrieved from https://emedicine.medscape.com/article/947954-overview#a1
- Prvvvader-Willi Syndrome (PWS) by the National Institute Of Child Health And Human Development. Retrieved from https://www.nichd.nih.gov/health/topics/prader-willi
- Human Genome Epidemiology by Centers for Disease Control And Prevention. Retrieved from hvttps://www.cdc.gov/genomics/hugenet/publications/translate.htm