Clinical Background
Prader-Willi syndrome (PWS) is characterized by severe hypotonia and feeding difficulties in infancy with gradual development of hyperphagia and morbid obesity in early childhood.
Epidemiology
- Incidence - 1/10,000-1/25,000
- Sex - equal distribution
Inheritance
- 70% have a deletion of chromosome 15q11.12-13
- 25-29% have uniparental disomy of maternal chromosome 15
- <1% have an imprinting center defect only detectable by sequencing
Pathophysiology
- Spectrum of neuroendocrine disturbances suggests developmental abnormalities of the hypothalamus
Recurrence Risk
- For determining the recurrence risk for parents, the specific genetic mechanism causing PWS in the prior affected child must be determined
- The recurrence risk is up to 50% for couples whose previous child has an imprinting center mutation
- The recurrence risk is <1% for parents whose affected child has PWS due to any other mechanism besides an imprinting center mutation
Clinical Presentation
- Severe hypotonia and feeding difficulties in infancy
- Delayed motor and language milestones
- Behavioral problems - temper tantrums, stubbornness, obsessive-compulsive traits
- Hypogonadism
- Short stature
- Facial features - narrow bifrontal diameter, down-turned mouth, almond-shaped palpebral fissures
- Hyperphagia and morbid obesity
- Complications of obesity are the main cause of morbidity and mortality
- Diabetes mellitus
- Obstructive sleep apnea
- Cardiorespiratory insufficiency
Treatment
- Team approach is best - physical, speech, occupational and behavioral therapies
- Consider growth hormone treatment
- Screen for causes of future morbidity
- Weight management programs
See Also
