【Doctor's Explanation】What is Prader-Willi Syndrome?

Introduction

To all expectant mothers considering prenatal testing.
We understand that you are concerned about your baby's health.

In this article, we will explain Prader-Willi Syndrome (PWS), one of the genetic disorders you should know about during pregnancy, in an easy-to-understand manner.

Basic Knowledge

PWS is a congenital genetic disorder first reported in 1956 as a syndrome presenting with endocrine abnormalities such as obesity, diabetes, short stature, and hypogonadism, as well as neurological abnormalities such as developmental delay, hypotonia, unique personality disorders, and behavioral abnormalities.
It is now known to occur with a frequency of approximately 1 in 15,000 births.^*1
The onset mechanisms are as follows:^*1

Recent studies suggest that the loss of function of the "SNORD116" gene in the imprinting region of chromosome 15 (where only the father-derived gene is active) is highly likely to be an extremely important factor in the onset of PWS.^*4

The vast majority of cases are not hereditary, and are thought to occur randomly after fertilization.^*1

Symptoms and Features

◇ Changes in Symptoms by Age

A characteristic feature of PWS symptoms is that they change with age, and there are significant individual differences.^*4

• [Neonatal Period (0-2 years old)] Feeding difficulties due to hypotonia are observed in almost all cases, and tube feeding is often required.^*5
  In addition, hypopigmentation may cause the hair to appear light/blonde-like, and undescended testes or male genital hypoplasia are observed in more than 90% of boys.^*3
• [Early Childhood (2-6 years old)] Although feeding difficulties improve, overall developmental delay is observed. In motor development, delays occur, such as sitting up at 12 months and starting to walk at 24 months.^*2
• [School Age (6-12 years old)] Interest in food increases from around 3 to 4 years old, and it is reported that transition to hyperphagia without a feeling of fullness often occurs around an average age of 8. In addition, mild intellectual disability with an average IQ of 60-70 and characteristic behavioral symptoms emerge.^*1,2
  Furthermore, children with PWS have multiple severe learning disabilities, and their academic performance tends to be poor relative to their intelligence quotient (IQ).^*2
• [Adolescence and Beyond (13 years old to Adult)] Hypogonadism leads to delayed or absent development of secondary sexual characteristics. In addition, behavioral disorders such as irritability, obsessive-compulsive symptoms, and stubbornness become more prominent with age.^*2
  Furthermore, nearly 25% of adults with PWS (especially those with significant obesity) have type 2 diabetes, with an average age of onset reported to be 20 years old.^*2

◇ Physical Characteristics

Facial features include a narrow bifrontal diameter, almond-shaped palpebral fissures, a narrow nasal bridge, and a thin upper lip.
These features may or may not be clearly visible at birth, but generally become gradually more prominent over time.^*2

Other physical features such as scoliosis (40-80%) and strabismus (40-60%) may also be present.^*2

Prognosis and Quality of Life

With proper management, the prognosis of PWS patients improves, with a cohort study reporting an annual mortality rate of approximately 1% to 1.3%.^*6
The primary causes of death in childhood are sudden death associated with respiratory failure or infections, while in adulthood, heart disease/heart failure, pulmonary thromboembolism, obesity-related complications, and gastric issues (gastric rupture, gastric necrosis) have been reported.^*2

Although many patients exhibit mild intellectual disability, approximately 40% show borderline to low-normal intelligence.^*2
After school age, welfare employment becomes the goal, but compared to their intellectual abilities, adaptational issues in the workplace are said to be common.^*1
As they age, their personality may escalate from affectionate to persistent, stubborn, panicky, or violent, and behavioral abnormalities such as shoplifting and lying may stand out, making social adaptation difficult.^*3

Treatment and Care

• • Dietary Therapy:
  Positioned as the most crucial basic treatment.
  Caloric restriction aiming at approximately 10 kcal per centimeter of height and balanced nutritional management are required.^*3,4
• • Exercise Therapy:
  Plays an important role in weight maintenance, with swimming particularly recommended, and is effective for improving muscle strength and body composition.^*3
• • Growth Hormone Replacement Therapy:
  Highly effective for improving height and body composition, increasing muscle mass, and reducing body fat. Early initiation starting in infancy is recommended.^*4
• • Sex Hormone Replacement Therapy:
  Conducted as a treatment for hypogonadism, with expected benefits in improving bone density and providing mental health support.^*3
• • Psychotropic Medications:
  For managing behavioral and psychiatric symptoms, SSRIs (Selective Serotonin Reuptake Inhibitors) and behavioral therapy are utilized.^*2,3
• • Insulin Treatment:
  For type 2 diabetes, dietary and exercise therapies are the foundation, with medications such as metformin, GLP-1 receptor agonists, or SGLT2 inhibitors used as needed.
  Depending on the case, pharmacological therapy including insulin may be considered.⁴

Summary

PWS is a genetic disorder caused by abnormalities in chromosome 15.
In the neonatal period, muscle tone is weak, and a lack of strength is noticeable, but as they grow, overeating, obesity, and characteristic behavioral features begin to appear.
Thus, symptoms changing according to age is a major characteristic.

Today, early detection and proper management can significantly improve patients' quality of life.
At the core of treatment and support are medical interventions such as dietary therapy, exercise therapy, and hormone therapy. Even more crucial is a continuous support system that includes the family.

Thanks to these medical advances and comprehensive support, many patients are now able to lead stable lives.

\ Understand the Risk of Prader-Willi Syndrome /

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