Name of disease:

ICD-10 diagnosis code:

Causes:

• Prader-Willi syndrome is caused by a genetic change in a particular region of chromosome number 15.
• Most often, part of the chromosome 15 that was inherited from the person’s father is missing or deleted in this critical region. This small deletion occurs in approximately 60% of cases and usually is not detectable with routine genetic analysis such as amniocentesis.
• Another 35-40% of cases occur when an individual inherits two chromosome 15s from their mother and none from their father. This scenario is termed maternal uniparental disomy (UPD).
• In a very small percentage of cases (1-3%), a small mutation in the Prader-Willi region causes the paternal chromosome 15 genetic material (although present) to be inactive.

Mode of inheritance:

• Deletion and UPD are random occurrences and generally are not associated with an increased risk of recurrence in future pregnancies.
• In the case of an imprinting mutation, Prader-Willi syndrome can reoccur within a family.

Prevalence:

Diagnosis:

• A suspected diagnosis of PWS is usually made by a physician based on clinical symptoms.
• The diagnosis is confirmed by a blood test. A “methylation analysis” can detect >99% of cases, including all of the major genetic subtypes of PWS (deletion, uniparental disomy, or imprinting mutation).
• A “FISH” (fluorescent in-situ hybridisation) test will identify those patients with PWS due to a deletion, but it will not identify those who have Prader-Willi syndrome by “UPD” (uniparental disomy) or an imprinting error.

Age of onset:

Common signs and symptoms:

• An excessive appetite and overeating which can easily lead to dangerous weight gain
• Restricted growth (children are much shorter than average)
• Floppiness caused by weak muscles (hypotonia)
• Learning difficulties
• Lack of sexual development
• Behavioural challenges such as emotional outbursts and physical aggression

Available treatment (medicinal and non-medicinal):

• Use of special nipples or tubes for feeding difficulties
• Strict supervision of daily food intake to prevent rapid weight gain
• Growth Hormone (GH) therapy to increase height, lean body mass, and enhance mobility; decrease fat mass; and improve movement and flexibility
• Treatment of eye problems by a paediatric ophthalmologist
• Treatment of curvature of the spine by an orthopaedist
• Sleep studies and treatment to help improve the quality of sleep
• Physical therapy to increase muscular strength, achieve developmental milestones, and build lean body mass
• Behavioural therapy to control emotions
• Medications, especially serotonin reuptake inhibitors (SRIs), may reduce obsessive-compulsive symptoms. SRIs also may help manage psychosis.
• Early interventions / Special needs programmes
• Sex hormone treatments and/or corrective surgery to treat small genitals (penis, scrotum, clitoris)
• Replacement of sex hormones during puberty may result in the development of adequate secondary sex characteristics (e.g., breasts, pubic hair, a deeper voice)
• Placement in group homes during adulthood

Disease management tips:

• Maintain a daily personal care routine with reminders from caretakers
• Shower or wash daily, avoid baths
• Encourage and praise patient’s good manners by caretakers

References:

• https://www.fpwr.org/blog/pws-receives-specific-disease-code-to-track-medical-care-and-outcomes
• https://www.fpwr.org/what-is-prader-willi-syndrome#causes
• https://www.fpwr.org/what-is-prader-willi-syndrome#hereditary
• https://www.hkjpaed.org/details.asp?id=1126&show=1234
• https://www.fpwr.org/prader-willi-syndrome-diagnosis-treatments
• https://ipwso.org/information-for-families/physical-health-and-exercise/personal-care-for-people-with-pws/#:~:text=Managing%20the%20Necessary%20Routine%20ofhands%2C%20for%20example%2C%20gardening

Other useful websites:

• Prader-Willi Syndrome Association UK
• Foundation for Prader-Willi Research