Prader-Willi Syndrome (PWS)

Prader-Willi syndrome (PWS) is a rare genetic disease caused by the loss of expression of paternally inherited genes in the chromosome 15q11-13 region.1 PWS affects several systems, including the endocrine system, causing hypotonia, short stature, and hypogonadism. Eating disorders ranging from anorexia to hyperphagia are also typically reported in PWS, as well as a deficit of satiety and a high risk of severe obesity. Patients present with intellectual and learning disabilities, obsessive-compulsive symptoms, and compromised motor and language development.1

Obesity and its complications are important causes of comorbidity and mortality in PWS.1,2 Several of the comorbidities of PWS include diabetes, breathing disorders (which may or may not be associated with obstructive sleep apnea, pulmonary embolism, and respiratory failure), and gastrointestinal problems.2,3 Both screening for and treating these conditions are an important part of patient care.1

Endocrine and Metabolic Disturbances

Hypothyroidism and central adrenal insufficiency are observed in approximately 10% of cases.4 Patients may also present with insulin resistance and diabetes; type 2 diabetes mellitus affects approximately 20% of patients.4,5

Hypertension and hypertriglyceridemia are metabolic comorbidities that are more prevalent in individuals with PWS than in the general population.5

Read more about PWS clinical features

Breathing Disorders

Breathing-related sleep disorders are common in PWS, including central apnea and obstructive sleep apnea syndrome.6 Periodic breathing and central apnea may be more common in infants.4 Central apnea may eventually resolve, and patients can benefit from oxygen therapy; however, central apnea can also cause death.6

Obesity and obesity-related narrowing of the upper airways are major risk factors for obstructive sleep apnea syndrome (OSAS).6,7 Upper airway narrowing may develop when fat deposited around the upper airway compresses it. Other risk factors for OSAS include facial dysmorphism, viscous respiratory secretions, scoliosis, hypotonia, and obstruction due to adenotonsillar hypertrophy.6,7 Treatment with growth hormone may worsen OSAS.6

Obstructive hypoventilation and sleep apnea are more common during rapid eye movement (REM) sleep.7 

Other breathing disorders observed in PWS include abnormal ventilatory control and restrictive ventilatory impairment due to thoracic muscle hypotonia.7 Narcolepsy-like symptoms and desaturation may also develop, which are worse during REM sleep.4

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Osteoporosis and fractures may develop in patients with PWS. Scoliosis may also be present. These conditions are caused by deficiencies of growth and sex steroid hormones associated with PWS, and monitoring is required.4

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Behavioral Disturbances

Comorbid behavioral disturbances are common in PWS. These include aggression, obsessive-compulsive behaviors, skin picking, and temper tantrums. It has been suggested that cycloid psychosis and bipolar disorder are comorbidities of PWS.8

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Other Comorbidities

Thrombotic events, such as deep vein thrombosis and pulmonary embolism, as well as other forms of venous or arterial thrombosis, may occur in patients with PWS, although infrequently.9

Constipation and symptoms of constipation, such as a sensation of anorectal obstruction and straining during defecation, are frequent in patients with PWS. Adequate intake of dietary fiber, particularly in children, can alleviate these problems.10

Read more about PWS diet and nutrition


  1. Höybye C, Tauber M. Approach to the patient With Prader-Willi syndrome. J Clin Endocrinol Metab. 2022;107(6):1698-1705. doi:10.1210/clinem/dgac082
  2. Crinò A, Grugni G. Update on diabetes mellitus and glucose metabolism alterations in Prader-Willi syndrome. Curr Diab Rep. 2020;20(2):7. doi:10.1007/s11892-020-1284-5
  3. Prader-Willi syndrome. Orphanet. Accessed July 19, 2023.
  4. Butler MG, Manzardo AM, Forster JL. Prader-Willi syndrome: clinical genetics and diagnostic aspects with treatment approaches. Curr Pediatr Rev. 2016;12(2):136-166. doi:10.2174/1573396312666151123115250
  5. Clerc A, Coupaye M, Mosbah H, et al. Diabetes mellitus in Prader-Willi syndrome: natural history during the transition from childhood to adulthood in a cohort of 39 patients. J Clin Med. 2021;10(22):5310. doi:10.3390/jcm10225310
  6. Wong SB, Yang MC, Tzeng IS, Tsai WH, Lan CC, Tsai LP. Progression of obstructive sleep apnea syndrome in pediatric patients with Prader-Willi syndrome. Children (Basel). 2022;9(6):912. doi:10.3390/children9060912
  7. Festen DA, Hokken-Koelega AC. Breathing disorders in Prader-Willi syndrome: the role of obesity, growth hormone treatment and upper respiratory tract infections. Expert Rev Endocrinol Metab. 2007;2(4):529-537. doi:10.1586/17446651.2.4.52
  8. Singh D, Sasson A, Rusciano V, Wakimoto Y, Pinkhasov A, Angulo M. Cycloid psychosis comorbid with Prader-Willi syndrome: a case series. Am J Med Genet A. 2019;179(7):1241-1245. doi:10.1002/ajmg.a.61181
  9. Butler MG, Oyetunji A, Manzardo AM. Age distribution, comorbidities and risk factors for thrombosis in Prader-Willi syndrome. Genes (Basel). 2020;11(1):67. doi:10.3390/genes11010067
  10. Alyousif Z, Miller JL, Sandoval MY, MacPherson CW, Nagulesapillai V, Dahl WJ. The effects of Bifidobacterium animalis ssp. lactis B94 on gastrointestinal wellness in adults with Prader-Willi syndrome: study protocol for a randomized controlled trial. Trials. 2018;19(1):256. doi:10.1186/s13063-018-2648-x

Reviewed by Harshi Dhingra, MD, on 7/20/2023.