What Are the Primary Signs of Prader-Willi Syndrome
Learn about the main symptoms of Prader-Willi syndrome

Prader-Willi syndrome (PWS) can cause a wide range of symptoms that affect a child’s physical, psychological, and behavioral development.

Symptoms in younger children

  • Almond-shaped eyes
  • Triangular mouth or turned-down mouth
  • Narrow forehead
  • Small hands and feet
  • Thin upper lip
  • Underdeveloped genitalia
  • Poor muscle tone, which may cause a weak sucking reflex
  • Sleepiness and difficulty waking up
  • Poor response to stimulation and weak crying

Symptoms in older children

  • Food cravings and weight gain
  • Short height stature and poor muscular mass
  • Undeveloped sex organs (both gender)
  • Incomplete or delayed puberty
  • Mild to moderate cognitive and intellectual impairment
  • Learning disabilities
  • Behavioral problems, such as temper outbursts and stubbornness
  • Compulsive behavior, such as picking at the skin
  • Speech problems
  • Hypothyroidism (underactive thyroid)
  • Adrenal insufficiency
  • High risk of osteoporosis

What is Prader-Willi syndrome?

Prader-Willi syndrome is a complex genetic disorder characterized by poor muscular tone (severe hypotonia), feeding difficulties, and delayed growth in infants.

The condition typically begins in childhood. The affected child begins to eat excessively (extreme hunger), which leads to chronic overeating (hyperphagia) and develops obesity in later infancy or early childhood. Some people with PWS develop type II diabetes.

PWS affects an estimated 1 in 10,000 to 30,000 people worldwide. It is also called:

  • Prader-Labhart-Willi syndrome
  • PWS
  • Willi-Prader syndrome

What causes Prader-Willi syndrome?

PWS is caused by genetic abnormalities in an unstable region on chromosome 15, disrupting gene expression regulation. Prader-Willi syndrome has autosomal dominant inheritance (inherited from one affected parent) and affects both sexes equally.

During early fetal development, genetic changes responsible for PWS occur in a section of the chromosome called the Prader-Willi critical region (PWCR). Three specific chromosomal changes are:

  • Deletions: Deletion in one area of the paternal chromosome 15 causes the loss of function of multiple genes in the majority (75%) of PWS cases.
  • Maternal uniparental disomy: Typically, a child inherits two copies of chromosome 15, one from each parent. In 20% of cases, a child with PWS has two copies of chromosome 15 from the mother and none from the father.
  • Imprinting center defect: Genes in PWCR on the chromosome that originated from the mother are inactivated due to a process called “imprinting,” which impacts whether the cell can “read” a gene in 5% of cases.

Most cases of PWS are not inherited, particularly those caused by a deletion in the paternal chromosome 15 or maternal uniparental disomy.

Affected people typically have no history of the disorder in their family. Rarely, a genetic change responsible for PWS can be inherited.

How is Prader-Willi syndrome diagnosed?

Prader-Willi syndrome is typically diagnosed based on clinical symptoms, and a blood test is ordered to confirm the diagnosis.

The diagnostic criteria used to diagnose PWS include the following:

  • Major criteria (each criterion scores a point)
    • Characteristic facial features (almond-shaped eyes, down-turned mouth, a narrow distance between the temples, and a thin upper lip)
    • Delayed developmental milestones
    • Feeding problems or failure to thrive in infancy
    • Hypogonadism (underactive sex hormones)
    • Floppy at birth
    • Rapid weight gain between 1-6 years
  • Minor criteria (each criterion scores a point)
    • Decreased fetal movements and infantile lethargy
    • Eyes and vision problems, including squint and short-sightedness
    • Pale skin, hair, and eyes
    • Narrow hands with a straight ulnar border
    • Short height
    • Skin picking
    • Sleep disturbance or sleep apnea
  • Investigations
    • Methylation analysis (encompasses all the major genetic subtypes of PWS)
    • Fluorescence in situ hybridization (used to identify PWS caused by deletion)

How is Prader-Willi syndrome treated?

Although treatment varies depending on symptoms, most cases of Prader-Willi syndrome (PWS) are managed in the following ways:

  • A pediatrician may recommend a high-calorie formula or specific feeding techniques and monitor the child's progress to help them gain weight.
  • Human growth hormone therapy promotes proper development, improves muscle tone, and reduces body fat.
  • Hormone replacement treatment is initiated when the child reaches puberty to help lower the risk of osteoporosis.
  • Undescended testicles may require surgery.
  • Sleep disorder treatment may help with daytime sleepiness and behavioral issues.
  • A dietitian can help develop a nutritious, low-calorie diet to help with weight management while maintaining sufficient nutrition.
  • Supplemental vitamins or minerals may be required to ensure balanced nutrition.
  • Increasing physical activity and exercise helps with weight management and physical development.
  • Because behavioral problems associated with PWS can affect school performance, social relationships, and family life, it is important for children with the condition to have support from their family and friends.
  • Counseling can help patients and their families cope with the emotional aspects of the disease.

What are potential complications of Prader-Willi syndrome?

Children with Prader-Willi syndrome may develop the following complications:

Health Solutions From Our Sponsors

Medically Reviewed on 10/20/2022
References
Image Source: iStock image

Prader-Willi syndrome. https://medlineplus.gov/genetics/condition/prader-willi-syndrome/#inheritance

Prader-Willi syndrome. https://www.mayoclinic.org/diseases-conditions/prader-willi-syndrome/symptoms-causes/syc-20355997

Prader-Willi syndrome. https://dermnetnz.org/topics/prader-willi-syndrome

Prader-Willi Syndrome. https://emedicine.medscape.com/article/947954-overview