OVERVIEW

What is Prader-Willi Syndrome?

Prader-Willi Syndrome (abbreviated as PWS), also known as hypotonia-intellectual disability-hypogonadism-obesity syndrome or Prader-Willi syndrome, commonly referred to as "Little Fatty Willi Syndrome," is a genetic disorder caused by the deletion (or functional defect) of genes on chromosome 15.

Children with this condition may exhibit reduced fetal movement during pregnancy, hypotonia in the neonatal period, feeding difficulties and malnutrition in infancy, as well as self-inflicted skin damage, short stature, and characteristic facial features (such as dolichocephaly, narrow face, almond-shaped eyes, small mouth, thin upper lip, downturned corners of the mouth, and fairer skin compared to family members). Later, they may develop intellectual disabilities, hypogonadism, and progressive obesity due to excessive food intake, leading to life-threatening complications such as diabetes, hyperlipidemia, hypertension, scoliosis, and cardiopulmonary failure. Lifelong supervised care is required.

Is Prader-Willi Syndrome Common?

Prader-Willi Syndrome is the most common obesity-related syndrome.

The incidence rate varies among different populations worldwide, occurring in approximately 1 in 10,000 to 30,000 individuals. There is currently no prevalence data for this condition in China. It is estimated that there are about 350,000 to 400,000 PWS patients globally, with no significant difference in prevalence between males and females.

SYMPTOMS

What are the common manifestations of Prader-Willi syndrome?

The main clinical symptoms of Prader-Willi syndrome include short stature, fair skin, skin picking, and speech defects. In the neonatal period, severe hypotonia, feeding difficulties, slow growth, and hypogonadism are observed. During early childhood, obesity, a narrow forehead, almond-shaped eyes, and a small mouth are characteristic facial features.

Due to hypothalamic dysfunction, an insatiable appetite and intense food-seeking behavior typically emerge around the age of 2, leading to uncontrolled eating, persistent weight gain, and severe obesity. Additionally, mild to moderate intellectual disability is common, along with tendencies toward irritability, stubbornness, defiance, argumentativeness, stealing (food), and lying.

Lifelong supervision is necessary to prevent life-threatening complications such as diabetes, hyperlipidemia, hypertension, scoliosis, and cardiopulmonary failure caused by severe obesity.

What are the characteristic prenatal features of Prader-Willi syndrome?

Common prenatal manifestations include reduced fetal movement, polyhydramnios, and an abnormally large fetal abdominal circumference. Late-pregnancy ultrasounds may reveal unusual fetal hand and foot postures, such as wrist flexion and dorsiflexion of the feet with toe curling.

What are the characteristic features of Prader-Willi syndrome before the age of 3?

• Physical characteristics at birth may be subtle but become more pronounced with age, including a long head, narrow face, almond-shaped eyes, small mouth, thin upper lip, downturned mouth corners, and fairer skin compared to family members.

• Hypotonia ("floppy infant") may lead to severe complications like apnea. Weak sucking and feeding difficulties often result in slow or stalled growth. Delays in motor and speech development are evident early on.

• Genital hypoplasia is common, such as underdeveloped scrotum, cryptorchidism, and small penis in males, or absent/severe underdevelopment of labia and clitoris in females.

What are the characteristic features of Prader-Willi syndrome between ages 3–10?

• Children exhibit small hands/feet, slender hands with loss of ulnar curvature, swollen hands, tapered fingers, and short stature. Overeating leads to overweight or obesity.

• Hypotonia improves with age but remains below normal. Cognitive, motor, and speech delays are significant, with IQ typically below 70. Speech articulation issues, learning difficulties, and behavioral problems (e.g., stubbornness, skin picking, temper tantrums) are common.

• Some may develop pubic/axillary hair. Severe overeating can cause gastric perforation or obesity-related complications, a leading cause of death.

What are the characteristic features of Prader-Willi syndrome during adolescence?

• Obesity progressively worsens.

• Muscle tone improves but remains weaker than peers.

• Behavioral issues intensify, including food stealing, hoarding, or abnormal eating habits.

• Delayed/incomplete puberty occurs without the typical growth spurt.

What are the characteristic features of Prader-Willi syndrome in adulthood?

• Adults are short (average height: 155 cm for males, 148 cm for females without growth hormone therapy). Mild hypotonia persists.

• Some young adults show psychotic symptoms, while behavioral issues decline in older patients.

• Incomplete sexual development leads to infertility, amenorrhea, or irregular menstruation.

What severe complications can Prader-Willi syndrome cause?

Binge eating may result in gastric rupture, choking due to rapid/unchewed food intake, or life-threatening obesity-related conditions like diabetes, hyperlipidemia, hypertension, scoliosis, and cardiopulmonary failure.

These complications pose fatal risks to patients.

CAUSES

How is Prader-Willi syndrome acquired?

Prader-Willi syndrome is a genetic disorder caused by genetic issues. 65%-75% of cases result from paternal chromosomal deletions, 20%-30% from maternal uniparental disomy, and 1%-3% from imprinting defects.

Is Prader-Willi syndrome contagious?

Prader-Willi syndrome is not contagious; it is a genetic disorder.

Is Prader-Willi syndrome hereditary?

Prader-Willi syndrome is hereditary as it is a genetic disorder.

DIAGNOSIS

How is Prader-Willi Syndrome Diagnosed?

When diagnosing Prader-Willi syndrome, doctors primarily refer to the clinical diagnostic criteria proposed in 1993, with confirmation through genetic testing.

• For children aged 3 or younger, if the diagnostic score reaches 5 points (with 4 points from major criteria), the likelihood of Prader-Willi syndrome is very high.

• For children over 3 years old and adults, a score of 8 points is required (with 5 or more points from major criteria).

Specific criteria are as follows:

• Major Criteria (1 point each):

  • Neonatal and infantile hypotonia, poor sucking ability; feeding difficulties and failure to thrive in infancy;
  • Excessive weight gain, obesity, and hyperphagia between ages 1–6;
  • Characteristic facial features, such as dolichocephaly in infancy, narrow face, almond-shaped eyes, small mouth, thin upper lip, and downturned corners of the mouth (three or more features required);
  • Hypogonadism, delayed or incomplete puberty, delayed sexual maturation;
  • Global developmental delay or mild to moderate intellectual disability.
    
    

• Minor Criteria (0.5 points each):

  • Decreased fetal movement, infantile lethargy, or weak cry;
  • Characteristic behavioral issues, such as temper tantrums, emotional outbursts, and compulsive behaviors;
  • Sleep disturbances or sleep apnea;
  • Short stature by age 15 (unrelated to family genetics), hypopigmentation (compared to family members);
  • Small hands and/or feet for height;
  • Narrow hands with straight ulnar borders;
  • Eye abnormalities (esotropia, myopia);
  • Thick, viscous saliva with crusting at the corners of the mouth;
  • Speech articulation defects;
  • Skin picking.

Individuals suspected of having Prader-Willi syndrome should undergo genetic testing for definitive diagnosis.

What Tests Are Needed for Prader-Willi Syndrome?

Common tests include genetic testing, endocrine function assessments, fasting blood glucose or oral glucose tolerance tests, and polysomnography.

• Genetic Testing: Primarily used to confirm the diagnosis.
• Endocrine Function Tests: Mainly for evaluating and managing comorbid conditions, including growth hormone, insulin-like growth factor-1, gonadal hormones, cortisol, adrenocorticotropic hormone, and thyroid function.
• Fasting Blood Glucose or Oral Glucose Tolerance Test: Screens for diabetes.
• Polysomnography: Assesses sleep apnea.

TREATMENT

Which department should I visit for Prader-Willi syndrome?

Pediatrics, Endocrinology, Psychiatry/Psychology, Neonatology, Pediatric Internal Medicine.

Can Prader-Willi syndrome resolve on its own?

Prader-Willi syndrome is a genetic disorder and cannot resolve on its own.

How is Prader-Willi syndrome treated?

Treatment for Prader-Willi syndrome includes: dietary behavior and nutritional management, management of gonadal dysgenesis and puberty-related issues, growth hormone therapy, and addressing other associated endocrine problems.

• Dietary behavior and nutritional management: Early dietary intervention and long-term nutritional monitoring can improve the condition.

  • For infants with hypotonia and feeding difficulties, ensure adequate caloric intake. For those with weak sucking ability, nasogastric tube feeding or specialized nipples may be used.

  • For older children, strict food management is necessary, including controlled meal schedules and even locking food storage areas. Establish a three-meal plan and avoid giving additional food outside scheduled meal times.

• Management of gonadal dysgenesis and puberty-related issues:

  • Treatment of cryptorchidism and genital hypoplasia, and use of human chorionic gonadotropin (hCG): Male infants treated with testosterone or hCG within the first six months of life may show improved penile size, scrotal development, and potential testicular descent. If medication fails, surgical intervention (preferably before age 2) may be considered.

  • Puberty-related hormone replacement therapy: Sex hormone therapy can induce, promote, or maintain puberty development, support normal bone growth, increase muscle mass, and improve sexual physiology. However, potential issues exist, such as behavioral problems in males with androgen replacement or menstrual hygiene challenges in females with estrogen therapy. The risks and benefits should be thoroughly discussed with guardians before treatment. Precocious puberty is typically monitored without medication.

• Growth hormone therapy:

  • If no major contraindications exist, growth hormone therapy should begin before age 2 to aid muscle development, improve strength, enhance feeding ability, and correct metabolic abnormalities early.

  • Growth hormone therapy can continue into adulthood, as it helps improve body composition, lipid metabolism, and cognitive function even after epiphyseal fusion. Treatment should be paused during infections or respiratory obstruction.

  • Management of other endocrine issues: If hypothyroidism is present, levothyroxine sodium should be administered, with dosage adjustments based on free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels.

What should be noted when using growth hormone for Prader-Willi syndrome treatment?

• Growth hormone is contraindicated in cases of severe obesity, uncontrolled diabetes, uncontrolled severe obstructive sleep apnea, active tumors, or active psychosis.

• Key considerations during growth hormone therapy:

  • Cardiac function: Growth hormone affects myocardial mass and function. Baseline echocardiography is required before treatment, with periodic reassessment during long-term therapy.

  • Insulin resistance and diabetes: Insulin levels rise significantly during treatment, necessitating regular monitoring of glucose and lipid metabolism.

  • Scoliosis: Growth hormone may increase scoliosis risk. Full-spine X-rays should be taken before treatment and every 6–12 months afterward to assess progression and need for corrective measures.

  • Sleep apnea: Growth hormone may enlarge tongue and lymphoid tissues, narrowing airways and worsening apnea, potentially leading to sudden death during respiratory infections. For mild-to-moderate apnea, tonsillectomy often resolves or alleviates symptoms. For severe apnea, tonsillectomy may be less effective, and growth hormone use should be cautious. Regular sleep monitoring is essential. If moderate-to-severe apnea occurs, growth hormone therapy should be paused until apnea is managed.

Can Prader-Willi syndrome be cured?

Prader-Willi syndrome currently has no cure and requires lifelong management.

DIET & LIFESTYLE

What should patients with Prader-Willi syndrome pay attention to in daily life?

Maintaining adequate and appropriate nutritional intake is the core care requirement for children of all ages:

• Due to weak sucking ability and lack of spontaneous feeding behavior, infants with Prader-Willi syndrome often require nasogastric tube feeding or spoon-feeding to maintain adequate weight gain, which may last for several months.

• From ages 2–4, excessive eating, frequent food-seeking behaviors, and obesity may gradually develop. During this stage, the following should be noted:

  • Caloric intake must be strictly restricted, generally limited to only 60% of the amount required for normal growth and development in healthy children of the same weight.

  • Controlling access to food is crucial. Keep minimal food at home, store it securely, and avoid triggering the child's desire to eat. Prioritize low-calorie foods.

  • Establish regular eating schedules and encourage the child to participate in physical activities lasting at least 30 minutes, 3–5 times per week.

Does Prader-Willi syndrome affect fertility?

Prader-Willi syndrome causes incomplete development of reproductive organs, leading to infertility.

PREVENTION

Can Prader-Willi Syndrome Be Prevented?

Genetic counseling may play a role in preventing the birth of children with Prader-Willi syndrome.

How Can Prader-Willi Syndrome Patients Prevent Complications?

• Early diagnosis, intervention, and treatment help control symptoms promptly, prolong survival, and improve quality of life.

• Control obesity and overeating through dietary management and appropriate physical exercise to maintain a healthy weight range.

• Parental support and understanding, encouraging emotional communication, managing mood swings, and participating in group activities help patients integrate into society and prevent complications.