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Prader-Willi Syndrome (PWS)

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Treatment

Prader-Willi syndrome (PWS) is a multisystemic neurobehavioral condition characterized by severe hypotonia, feeding difficulties, poor growth, and developmental delays in the first few years of life. During early childhood, hyperphagia, uncontrolled hunger, and weight gain develop and may lead to morbid obesity if left unmanaged.1 Early diagnosis is key to initiating the interventions necessary for optimal outcomes; however, treatments are beneficial at whatever age the disease is diagnosed.2

Patients with PWS must be treated by a multidisciplinary team given the effects of the disorder on multiple body systems, including the endocrine, reproductive, musculoskeletal, pulmonary, and nervous systems.3

Diet and Nutrition for PWS

One of the critical aspects of PWS care is the careful supervision of diet and nutrition. Dietary interventions differ depending on the phase of PWS.

During infancy, poor suck reflex makes feeding difficult and, without adequate intervention, may lead to failure to thrive. Special nipples or tube feeding may be required to ensure proper nutrition and growth during this phase of PWS. Height, weight, and body mass index are routinely assessed to monitor growth during infancy.2

After the onset of hyperphagia in early childhood, strict supervision of the patient’s daily food intake is essential. Access to food must be limited to prevent rapid weight gain and obesity, and the patient must be kept from stealing and hoarding food. In the home, cabinets and refrigerators containing food need to be locked and trash bins must be inaccessible. In other environments where food is available, including schools, the patient’s access must also be monitored.2

Individuals with PWS and their caregivers should routinely attend consultations with dietitians or nutritionists. These health care professionals can develop and recommend well-balanced, low-calorie diets, monitor anthropometric measurements to ensure that a healthy weight is maintained, and assess vitamin and mineral intake, particularly to determine if vitamin D or calcium supplementation is needed.2

Read more about PWS diet and nutrition

Hormone Therapy for PWS

Many of the signs and symptoms of PWS are caused by dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, including hypogonadism, growth hormone deficiency, dysfunctional temperature regulation, hypothyroidism, excessive appetite, and related obesity.4 

Read more about PWS etiology

Depending on their symptoms, individuals with PWS may require hormone replacement therapies:

  • Growth hormone (GH) therapy is started in infancy or at diagnosis to increase height, lean body mass, and mobility and to decrease fat mass. It is often continued during adulthood at 20% to 25% of the recommended dose for children.2
  • Thyroid hormone replacement therapy is given for hypothyroidism, which is frequently central in origin. Levels of thyroid-stimulating hormone are often normal, so free T4 measurement is required for diagnosis.5
  • Sex hormone replacement therapy (testosterone for males, estrogen for females) is used to treat hypogonadism or delayed onset of puberty.2,5 

Read more about PWS therapies

Other Pharmacological Treatments for PWS

Diabetes Therapies

Metformin (sold as Glucophage® and Fortamet®, among others) is the first-line treatment for type II diabetes mellitus in individuals with PWS. When monotherapy is inadequate, sulfonylureas, dipeptidyl peptidase-4 (DPP-4) inhibitors, or glucagon-like peptide-1 (GLP-1) agonists may be combined. GLP-1 agonists include the following6: 

  • Semaglutide (sold as Ozempic®, Wegovy®, and Rybelsus®)
  • Byetta® (exenatide)
  • Trulicity® (dulaglutide)
  • Liraglutide (sold as Victoza® and Saxenda®)

Sodium glucose cotransporter-2 (SGLT-2) inhibitors may be added to combination therapies in uncontrolled cases.6-8 If neither monotherapy nor combination therapy is sufficient to control type II diabetes mellitus, insulin treatment is initiated.6

Psychotropic Therapies for Behavioral Symptoms

Serotonin reuptake inhibitors are used to manage obsessive-compulsive symptoms and psychosis.2 Psychotropic treatments for the management of behavioral symptoms include the following9:

  • Risperdal® (risperidone) 
  • Prozac® (fluoxetine) 
  • Naltrexone (sold as Revia® and Vivitrol®)
  • Topiramate (sold as Topamax® and Topiragen®)
  • Luvox® (fluvoxamine)
  • N-acetyl cysteine (NAC)
  • Fintepla® (fenfluramine)

Corticosteroids

Corticosteroids may be prescribed if a patient with PWS has a concurrent diagnosis of central adrenal insufficiency (CAI),10 although this is rare.10,11 Corticosteroids have also been routinely prescribed for individuals with PWS during periods of psychological stress; however, they should be used with caution because they increase the risk of osteoporosis. Corticosteroid administration is advised only for patients with a confirmed diagnosis of CAI.10

Rehabilitative Therapies and Educational Support

Physical therapy may benefit children with PWS. It is used to increase muscle strength, treat hypotonia, and help patients attain developmental milestones. Routine exercise should be encouraged to increase lean body mass and prevent weight gain.2 

Physical therapy may also be beneficial for managing musculoskeletal conditions commonly associated with PWS, including osteopenia/osteoporosis and scoliosis. 2,10,12 Muscle strengthening, weight-bearing exercises, and physical activity can decrease the risk for osteoporosis/osteopenia.10 Core strengthening and sensory integration starting in infancy may prevent the onset of kyphosis or scoliosis due to hypotonia.12

Speech therapy addresses articulation difficulties and language delays. Speech therapy may be included in an early intervention program, which should begin as soon as possible and continue during childhood.2 

Educational support benefits school-age children with PWS who have learning disabilities and cognitive impairments, providing necessary assistance with schoolwork.2 

Read more about the PWS care team

Behavioral Therapy for PWS

Social skills training groups are often necessary to manage challenging aspects of PWS, including hyperphagia, inability to regulate emotions, cognitive impairment, and motor planning difficulties.2,13 Social skills training is especially important for individuals with PWS who also have autism spectrum disorder (ASD), which is associated with similar social issues.13,14 Patients with PWS are at increased risk for ASD.14

Behavioral therapy can address obsessive-compulsive behaviors, stubbornness, anger, and inability to regulate emotions. Firm limit-setting strategies and a structured daily routine are recommended for individuals with PWS.2 

Orthopedic Treatment for PWS

Orthopedists assess and treat scoliosis, hip dysplasia, and osteoporosis/osteopenia, which are musculoskeletal conditions frequently seen in individuals with PWS.2,10,12,15

Potential treatments for scoliosis include spinal bracing and casting, ongoing physical therapy, and spinal fusion surgery, depending on the severity of the curve and the skeletal maturity/age of the patient.12 Patients with PWS and their caregivers must be informed of all risks involved in the surgical treatment of scoliosis because the risk for surgical complications is increased in this patient population.12,16

Read more about PWS surgical management

Treatment options for hip dysplasia include a Pavlik harness, closed reduction, a Pavlik harness combined with closed reduction, open reduction, and other surgical interventions.15 

Patients with PWS may undergo total hip or knee arthroplasties at younger ages than the general population; however, research conducted between 2004 and 2014 based on data from the National Inpatient Sample of the Healthcare Cost and Utilization Project has revealed that the rates of these surgical interventions are lower in the PWS population than in the general population. This finding suggests that the aggressive treatment of hip dysplasia in infants with PWS may not be necessary to prevent the need for lower-extremity joint replacement surgery later in life.17 

References

  1. Prader-Willi syndrome. MedlinePlus. Accessed July 26, 2023.
  2. What are the treatments for Prader-Willi syndrome (PWS)? NIH – Eunice Kennedy Shriver National Institute of Child Health and Human Development. Accessed July 26, 2023.
  3. Duis J, van Wattum PJ, Scheimann A, et al. A multidisciplinary approach to the clinical management of Prader-Willi syndrome. Mol Genet Genomic Med. 2019;7(3):e514. doi:10.1002/mgg3.514
  4. Kusz MJ, Gawlik AM. Adrenal insufficiency in patients with Prader-Willi syndrome. Front Endocrinol (Lausanne). 2022;13:1021704. doi:10.3389/fendo.2022.1021704
  5. Pellikaan K, Snijders F, Rosenberg AGW, et al. Thyroid function in adults with Prader–Willi syndrome: a cohort study and literature review. J Clin Med. 2021;10(17):3804. doi:10.3390/jcm10173804
  6. 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
  7. Sano H, Kudo E, Yamazaki T, Ito T, Hatakeyama K, Kawamura N. Efficacy of sodium-glucose cotransporter 2 inhibitor with glucagon-like peptide-1 receptor agonist for the glycemic control of a patient with Prader-Willi syndrome: a case report. Clin Pediatr Endocrinol. 2020;29(2):81-84. doi:10.1297/cpe.29.81
  8. Horikawa Y, Enya M, Komagata M, et al. Effectiveness of sodium-glucose cotransporter-2 inhibitor as an add-on drug to GLP-1 receptor agonists for glycemic control of a patient with Prader–Willi syndrome: a case report. Diabetes Ther. 2018;9(1):421-426. doi:10.1007/s13300-018-0369-5
  9. Bonnot O, Cohen D, Thuilleaux D, Consoli A, Cabal S, Tauber M. Psychotropic treatments in Prader-Willi syndrome: a critical review of published literature. Eur J Pediatr. 2016;175(1):9-18. doi:10.1007/s00431-015-2670-x
  10. van Abswoude DH, Pellikaan K, Rosenberg AGW, et al. Bone health in adults with Prader–Willi syndrome: clinical recommendations based on a multicenter cohort study. J Clin Endocrinol Metab. 2022;108(1):59-84. doi:10.1210/clinem/dgac556
  11. Rosenberg AGW, Pellikaan K, Poitou C, et al. Central adrenal insufficiency is rare in adults with Prader–Willi syndrome. J Clin Endocrinol Metab. 2020;105(7):e2563-e2571. doi:10.1210/clinem/dgaa168
  12. van Bosse HJP, Butler MG. Clinical observations and treatment approaches for scoliosis in Prader–Willi syndrome. Genes (Basel). 2020;11(3):260. doi:10.3390/genes11030260
  13. Social skills and Prader-Willi syndrome. Foundation for Prader-Willi Research. Accessed July 26, 2023.
  14. Kong X, Zhu J, Tian R, et al. Early screening and risk factors of autism spectrum disorder in a large cohort of Chinese patients with Prader-Willi syndrome. Front Psychiatry. 2020;11. doi:10.3389/fpsyt.2020.594934
  15. Trizno AA, Jones AS, Carry PM, Georgopoulos G.  The prevalence and treatment of hip dysplasia in Prader-Willi syndrome (PWS). J Pediatr Orthop. 2018;38(3):e151. doi:10.1097/BPO.0000000000001118
  16. Winsauer AG, Thornberg DC, Rodriguez SM, Poppino KF, Ramo BA. Angelman and Prader-Willi syndromes: sister imprinting disorders with high complication rates following spinal deformity surgery. Orthopedics. 2023;46(4):e223-e229. doi:10.3928/01477447-20230207-07
  17. Hip dysplasia in babies with PWS may not need aggressive treatment. Foundation for Prader-Willi Research. Accessed July 26, 2023.

Reviewed by Harshi Dhingra, MD, on 7/27/2023.

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