Overview

Prader-Willi Syndrome (PWS) is a rare and complex genetic disorder that affects multiple systems in the body. It is primarily characterized by weak muscle tone (hypotonia), poor feeding in infancy, followed by an insatiable appetite and rapid weight gain in early childhood. Other features include short stature, intellectual disability, behavioral issues, and characteristic facial features. PWS affects both males and females equally and occurs in approximately 1 in 10,000 to 30,000 live births. While there is no cure, early diagnosis and comprehensive medical care can significantly improve quality of life for individuals with Prader-Willi Syndrome.

Causes

Prader-Willi Syndrome is caused by a genetic abnormality on chromosome 15, specifically in the region known as 15q11-q13. The condition occurs when certain genes on this chromosome fail to function normally. The main genetic causes include:

• Deletion: About 70% of cases are due to a missing segment of the paternal chromosome 15.
• Maternal uniparental disomy (UPD): Around 25% of cases occur when both copies of chromosome 15 are inherited from the mother and none from the father.
• Imprinting defects: A small percentage of cases are caused by defects in the imprinting center, which affects gene expression.
• Chromosomal translocations or mutations: Rare cases involve structural changes in the chromosomes affecting gene expression.

Symptoms

Symptoms of Prader-Willi Syndrome vary by age and can affect physical, cognitive, and behavioral development:

• Infancy:
  • Severe hypotonia (floppy muscles).
  • Poor sucking reflex and difficulty feeding.
  • Delayed milestones such as sitting and walking.
• Early childhood:
  • Hyperphagia (uncontrollable appetite) leading to obesity if not managed.
  • Rapid weight gain starting between ages 2-6 years.
  • Developmental delays and learning difficulties.
• General features at all ages:
  • Short stature and small hands and feet.
  • Distinctive facial features such as almond-shaped eyes, narrow forehead, and thin upper lip.
  • Behavioral problems including stubbornness, temper tantrums, and obsessive-compulsive tendencies.
  • Delayed or incomplete puberty, infertility.
  • Sleep disturbances, including sleep apnea.
  • Skin picking and reduced pain sensitivity.
  • Risk of type 2 diabetes due to obesity.

Diagnosis

Early diagnosis of Prader-Willi Syndrome is essential to start timely interventions. Diagnostic steps include:

• Clinical evaluation: Observation of characteristic symptoms such as hypotonia, feeding difficulties, and delayed development may raise suspicion.
• Genetic testing:
  • Methylation analysis: A highly sensitive test that detects abnormal gene imprinting on chromosome 15 in over 99% of cases.
  • Fluorescence in situ hybridization (FISH): Identifies deletions in the paternal chromosome 15.
  • DNA microarray: Detects microdeletions or uniparental disomy.
• Other tests: Additional hormonal assessments and developmental evaluations are often conducted to assess complications.

Treatment

Although there is no cure for Prader-Willi Syndrome, a multidisciplinary approach can effectively manage symptoms and improve overall well-being:

• Growth hormone therapy: Helps increase height, improve muscle tone, and decrease body fat, often started in early childhood.
• Strict dietary management: Calorie-controlled diets and close monitoring to prevent obesity due to constant hunger.
• Behavioral therapy: Support for managing compulsive behaviors, emotional issues, and social skills development.
• Physical and occupational therapy: Improves muscle tone, motor skills, and independence in daily activities.
• Speech therapy: Assists in overcoming speech and language delays.
• Hormone replacement therapy: Used during adolescence to address delayed puberty and maintain bone health.
• Regular medical monitoring: Screening and treatment for diabetes, sleep apnea, scoliosis, and other complications.
• Educational support: Individualized education programs (IEP) tailored to the child’s cognitive abilities.

Prognosis

The prognosis for individuals with Prader-Willi Syndrome has improved significantly due to early diagnosis and comprehensive care. With proper dietary management, behavioral interventions, and medical treatment, many individuals with PWS can lead fulfilling lives. However, obesity-related complications remain a major health risk and require lifelong management.

Most individuals have mild to moderate intellectual disabilities and require support throughout life. With advances in growth hormone therapy and better understanding of the syndrome, life expectancy has improved, though it can be reduced by obesity-related diseases. Early intervention, family support, and coordinated medical care greatly enhance the quality of life for individuals with Prader-Willi Syndrome.