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Clinical features, diagnosis, and treatment of Prader-Willi syndrome

Author
Ann O Scheimann, MD, MBA
Section Editors
Mitchell E Geffner, MD
Melvin B Heyman, MD, MPH
Deputy Editor
Alison G Hoppin, MD

INTRODUCTION

Prader-Willi syndrome (PWS) is the most common syndromic form of obesity. The syndrome is caused by absence of expression of the paternally active genes on the long arm of chromosome 15. The vast majority of cases occur sporadically.

The clinical features, diagnosis, and approaches to treatment of PWS will be reviewed here. The epidemiology and genetics of this disorder are discussed separately. (See "Epidemiology and genetics of Prader-Willi syndrome".)

CLINICAL MANIFESTATIONS

Prenatal — Affected pregnancies often exhibit reduced fetal activity, polyhydramnios, and breech positioning. Third-trimester ultrasounds may show unusual positioning of the fetal hands and feet, with flexed wrists and dorsi-extended feet with flexed toes [1]. These abnormalities of limb positioning are supported only by case reports, but are probably more specific than other ultrasound findings for Prader-Willi syndrome (PWS). Cytogenetic examination is revealing only if specific molecular diagnosis for PWS is requested. (See 'Genetic testing' below.)

Infancy — Neonatal hypotonia is one of the hallmark features of this disorder and is a valuable clue to initiate diagnostic testing. The profound hypotonia can lead to asphyxia. Affected infants often have feeding difficulties, including a poor suck, which may lead to failure to thrive. Other common features include a weak cry and genital hypoplasia (eg, cryptorchidism, scrotal hypoplasia, or clitoral hypoplasia). Depigmentation of the skin or eyes relative to the familial background is present in 30 to 50 percent of patients [2,3].

Early childhood — Toddlers with PWS demonstrate late acquisition of major motor milestones. Children between one and six years of age commonly manifest symptoms of hyperphagia with progressive development of obesity if access to food is unrestricted. Body composition is abnormal, with reduced lean body mass and increased fat mass as compared with normal and obese controls [4,5]. Perhaps as a result of the reduced lean body mass, resting energy expenditure is also reduced [6]. Short stature is usually present during childhood and most patients fail to have a pubertal growth spurt. Most patients with PWS have growth hormone deficiency. (See 'Growth hormone deficiency' below.)

                                

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Literature review current through: Nov 2016. | This topic last updated: Thu Jun 16 00:00:00 GMT 2016.
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References
Top
  1. Bigi N, Faure JM, Coubes C, et al. Prader-Willi syndrome: is there a recognizable fetal phenotype? Prenat Diagn 2008; 28:796.
  2. Butler MG. Hypopigmentation: a common feature of Prader-Labhart-Willi syndrome. Am J Hum Genet 1989; 45:140.
  3. Cassidy, SB, Schwartz, S. Prader-Willi syndrome. in: GeneReviews. Available at: www.genetests.org. (Accessed on August 11, 2011).
  4. Brambilla P, Bosio L, Manzoni P, et al. Peculiar body composition in patients with Prader-Labhart-Willi syndrome. Am J Clin Nutr 1997; 65:1369.
  5. Eiholzer U, Blum WF, Molinari L. Body fat determined by skinfold measurements is elevated despite underweight in infants with Prader-Labhart-Willi syndrome. J Pediatr 1999; 134:222.
  6. van Mil EA, Westerterp KR, Gerver WJ, et al. Energy expenditure at rest and during sleep in children with Prader-Willi syndrome is explained by body composition. Am J Clin Nutr 2000; 71:752.
  7. Butler, MG, Hanchett, JM, Thompson, T. Clinical Findings and Natural History of Prader-willi Syndrome. In: Management of Prader-willi Syndrome, Butler, MG, Lee, PDK, Whitman, BY (Eds), Springer, New York 2006. p.3.
  8. Vendrame M, Maski KP, Chatterjee M, et al. Epilepsy in Prader-Willi syndrome: clinical characteristics and correlation to genotype. Epilepsy Behav 2010; 19:306.
  9. de Lind van Wijngaarden, RF, DeKlerk, LW, Festen, DA, Hokken-Koelega, AC. Scoliosis in Prader-Willi syndrome: Prevalence, effects of age, gender, body mass index, lean body mass and genotype. Arch Dis Child 2008 Feb 8; Epub ahead of print.
  10. Einfeld SL, Kavanagh SJ, Smith A, et al. Mortality in Prader-Willi syndrome. Am J Ment Retard 2006; 111:193.
  11. Sinnema M, Schrander-Stumpel CT, Maaskant MA, et al. Aging in Prader-Willi syndrome: twelve persons over the age of 50 years. Am J Med Genet A 2012; 158A:1326.
  12. Whittington JE, Holland AJ, Webb T. Ageing in people with Prader-Willi syndrome: mortality in the UK population cohort and morbidity in an older sample of adults. Psychol Med 2015; 45:615.
  13. Bennett JA, Germani T, Haqq AM, Zwaigenbaum L. Autism spectrum disorder in Prader-Willi syndrome: A systematic review. Am J Med Genet A 2015; 167A:2936.
  14. Schaaf CP, Gonzalez-Garay ML, Xia F, et al. Truncating mutations of MAGEL2 cause Prader-Willi phenotypes and autism. Nat Genet 2013; 45:1405.
  15. Milner KM, Craig EE, Thompson RJ, et al. Prader-Willi syndrome: intellectual abilities and behavioural features by genetic subtype. J Child Psychol Psychiatry 2005; 46:1089.
  16. Dykens EM, Roof E. Behavior in Prader-Willi syndrome: relationship to genetic subtypes and age. J Child Psychol Psychiatry 2008; 49:1001.
  17. Vogels A, Matthijs G, Legius E, et al. Chromosome 15 maternal uniparental disomy and psychosis in Prader-Willi syndrome. J Med Genet 2003; 40:72.
  18. Martin A, State M, Koenig K, et al. Prader-Willi syndrome. Am J Psychiatry 1998; 155:1265.
  19. Shapira NA, Lessig MC, Murphy TK, et al. Topiramate attenuates self-injurious behaviour in Prader-Willi Syndrome. Int J Neuropsychopharmacol 2002; 5:141.
  20. Bonnot O, Cohen D, Thuilleaux D, et al. Psychotropic treatments in Prader-Willi syndrome: a critical review of published literature. Eur J Pediatr 2016; 175:9.
  21. Miller JL, Angulo M. An open-label pilot study of N-acetylcysteine for skin-picking in Prader-Willi syndrome. Am J Med Genet A 2014; 164A:421.
  22. Whitman, BY, Thompson, T. Neurodevelopmental and Neuropsychological Aspects of Prader-willi Syndrome. In: Management of Prader-Willi Syndrome, Butler, MG, Lee, PDK, Whitman, BY (Eds), Springer, New York 2006. p.264.
  23. Sinnema M, Boer H, Collin P, et al. Psychiatric illness in a cohort of adults with Prader-Willi syndrome. Res Dev Disabil 2011; 32:1729.
  24. Whittington J, Holland A, Webb T, et al. Cognitive abilities and genotype in a population-based sample of people with Prader-Willi syndrome. J Intellect Disabil Res 2004; 48:172.
  25. Curfs LM, Fryns JP. Prader-Willi syndrome: a review with special attention to the cognitive and behavioral profile. Birth Defects Orig Artic Ser 1992; 28:99.
  26. Wharton RH, Wang T, Graeme-Cook F, et al. Acute idiopathic gastric dilation with gastric necrosis in individuals with Prader-Willi syndrome. Am J Med Genet 1997; 73:437.
  27. Stevenson DA, Heinemann J, Angulo M, et al. Deaths due to choking in Prader-Willi syndrome. Am J Med Genet A 2007; 143A:484.
  28. Zipf WB, O'Dorisio TM, Cataland S, Sotos J. Blunted pancreatic polypeptide responses in children with obesity of Prader-Willi syndrome. J Clin Endocrinol Metab 1981; 52:1264.
  29. Butler MG, Carlson MG, Schmidt DE, et al. Plasma cholecystokinin levels in Prader-Willi syndrome and obese subjects. Am J Med Genet 2000; 95:67.
  30. Cummings DE, Clement K, Purnell JQ, et al. Elevated plasma ghrelin levels in Prader Willi syndrome. Nat Med 2002; 8:643.
  31. Haqq AM, Farooqi IS, O'Rahilly S, et al. Serum ghrelin levels are inversely correlated with body mass index, age, and insulin concentrations in normal children and are markedly increased in Prader-Willi syndrome. J Clin Endocrinol Metab 2003; 88:174.
  32. Erdie-Lalena CR, Holm VA, Kelly PC, et al. Ghrelin levels in young children with Prader-Willi syndrome. J Pediatr 2006; 149:199.
  33. Han JC, Muehlbauer MJ, Cui HN, et al. Lower brain-derived neurotrophic factor in patients with prader-willi syndrome compared to obese and lean control subjects. J Clin Endocrinol Metab 2010; 95:3532.
  34. Holm VA, Cassidy SB, Butler MG, et al. Prader-Willi syndrome: consensus diagnostic criteria. Pediatrics 1993; 91:398.
  35. Gunay-Aygun M, Schwartz S, Heeger S, et al. The changing purpose of Prader-Willi syndrome clinical diagnostic criteria and proposed revised criteria. Pediatrics 2001; 108:E92.
  36. Monaghan KG, Van Dyke DL. Laboratory testing for Prader-Willi syndrome. In: Management of Prader-willi Syndrome, Butler MG, Lee PDK, Whitman BY (Eds), Springer, New York 2006. p.79.
  37. Burman P, Ritzén EM, Lindgren AC. Endocrine dysfunction in Prader-Willi syndrome: a review with special reference to GH. Endocr Rev 2001; 22:787.
  38. Grugni G, Guzzaloni G, Moro D, et al. Reduced growth hormone (GH) responsiveness to combined GH-releasing hormone and pyridostigmine administration in the Prader-Willi syndrome. Clin Endocrinol (Oxf) 1998; 48:769.
  39. Eiholzer U, Stutz K, Weinmann C, et al. Low insulin, IGF-I and IGFBP-3 levels in children with Prader-Labhart-Willi syndrome. Eur J Pediatr 1998; 157:890.
  40. Thacker MJ, Hainline B, St Dennis-Feezle L, et al. Growth failure in Prader-Willi syndrome is secondary to growth hormone deficiency. Horm Res 1998; 49:216.
  41. Grugni G, Marostica E, Crinò A, et al. Deconvolution-based assessment of pituitary GH secretion stimulated with GHRH+arginine in Prader-Willi adults and obese controls. Clin Endocrinol (Oxf) 2013; 79:224.
  42. Eiholzer U, l'Allemand D, Rousson V, et al. Hypothalamic and gonadal components of hypogonadism in boys with Prader-Labhart- Willi syndrome. J Clin Endocrinol Metab 2006; 91:892.
  43. McCandless SE, Committee on Genetics. Clinical report—health supervision for children with Prader-Willi syndrome. Pediatrics 2011; 127:195.
  44. Bakker NE, Wolffenbuttel KP, Looijenga LH, Hokken-Koelega AC. Testes in infants with Prader-Willi syndrome: human chorionic gonadotropin treatment, surgery and histology. J Urol 2015; 193:291.
  45. Goldstone AP, Holland AJ, Hauffa BP, et al. Recommendations for the diagnosis and management of Prader-Willi syndrome. J Clin Endocrinol Metab 2008; 93:4183.
  46. de Lind van Wijngaarden RF, Otten BJ, Festen DA, et al. High prevalence of central adrenal insufficiency in patients with Prader-Willi syndrome. J Clin Endocrinol Metab 2008; 93:1649.
  47. Stevenson DA, Anaya TM, Clayton-Smith J, et al. Unexpected death and critical illness in Prader-Willi syndrome: report of ten individuals. Am J Med Genet A 2004; 124A:158.
  48. Farholt S, Sode-Carlsen R, Christiansen JS, et al. Normal cortisol response to high-dose synacthen and insulin tolerance test in children and adults with Prader-Willi syndrome. J Clin Endocrinol Metab 2011; 96:E173.
  49. O'Donoghue FJ, Camfferman D, Kennedy JD, et al. Sleep-disordered breathing in Prader-Willi syndrome and its association with neurobehavioral abnormalities. J Pediatr 2005; 147:823.
  50. Sedky K, Bennett DS, Pumariega A. Prader Willi syndrome and obstructive sleep apnea: co-occurrence in the pediatric population. J Clin Sleep Med 2014; 10:403.
  51. Meyer SL, Splaingard M, Repaske DR, et al. Outcomes of adenotonsillectomy in patients with Prader-Willi syndrome. Arch Otolaryngol Head Neck Surg 2012; 138:1047.
  52. Pavone M, Paglietti MG, Petrone A, et al. Adenotonsillectomy for obstructive sleep apnea in children with Prader-Willi syndrome. Pediatr Pulmonol 2006; 41:74.
  53. Clarke DJ, Waters J, CORBETT JA. Adults with Prader-Willi syndrome: abnormalities of sleep and behaviour. J R Soc Med 1989; 82:21.
  54. Maas AP, Didden R, Bouts L, et al. Scatter plot analysis of excessive daytime sleepiness and severe disruptive behavior in adults with Prader-Willi syndrome: a pilot study. Res Dev Disabil 2009; 30:529.
  55. Bruni O, Verrillo E, Novelli L, Ferri R. Prader-Willi syndrome: sorting out the relationships between obesity, hypersomnia, and sleep apnea. Curr Opin Pulm Med 2010; 16:568.
  56. Camfferman D, McEvoy RD, O'Donoghue F, Lushington K. Prader Willi Syndrome and excessive daytime sleepiness. Sleep Med Rev 2008; 12:65.
  57. Stevenson DA, Heinemann J, Angulo M, et al. Gastric rupture and necrosis in Prader-Willi syndrome. J Pediatr Gastroenterol Nutr 2007; 45:272.
  58. Holm VA, Laurnen EL. Prader-Willi syndrome and scoliosis. Dev Med Child Neurol 1981; 23:192.
  59. de Lind van Wijngaarden RF, de Klerk LW, Festen DA, Hokken-Koelega AC. Scoliosis in Prader-Willi syndrome: prevalence, effects of age, gender, body mass index, lean body mass and genotype. Arch Dis Child 2008; 93:1012.
  60. Cowell CT, Dietsch S. Adverse events during growth hormone therapy. J Pediatr Endocrinol Metab 1995; 8:243.
  61. Carrel AL, Myers SE, Whitman BY, Allen DB. Benefits of long-term GH therapy in Prader-Willi syndrome: a 4-year study. J Clin Endocrinol Metab 2002; 87:1581.
  62. Nagai T, Obata K, Ogata T, et al. Growth hormone therapy and scoliosis in patients with Prader-Willi syndrome. Am J Med Genet A 2006; 140:1623.
  63. de Lind van Wijngaarden RF, de Klerk LW, Festen DA, et al. Randomized controlled trial to investigate the effects of growth hormone treatment on scoliosis in children with Prader-Willi syndrome. J Clin Endocrinol Metab 2009; 94:1274.
  64. Accadbled F, Odent T, Moine A, et al. Complications of scoliosis surgery in Prader-Willi syndrome. Spine (Phila Pa 1976) 2008; 33:394.
  65. Rees D, Jones MW, Owen R, Dorgan JC. Scoliosis surgery in the Prader-Willi syndrome. J Bone Joint Surg Br 1989; 71:685.
  66. Tokutomi T, Chida A, Asano Y, et al. A non-obese boy with Prader-Willi syndrome shows cardiopulmonary impairment due to severe kyphoscoliosis. Am J Med Genet A 2006; 140:1978.
  67. Kroonen LT, Herman M, Pizzutillo PD, Macewen GD. Prader-Willi Syndrome: clinical concerns for the orthopaedic surgeon. J Pediatr Orthop 2006; 26:673.
  68. Davies PS, Evans S, Broomhead S, et al. Effect of growth hormone on height, weight, and body composition in Prader-Willi syndrome. Arch Dis Child 1998; 78:474.
  69. Angulo MA, Castro-Magana M, Lamerson M, et al. Final adult height in children with Prader-Willi syndrome with and without human growth hormone treatment. Am J Med Genet A 2007; 143A:1456.
  70. Sipilä I, Sintonen H, Hietanen H, et al. Long-term effects of growth hormone therapy on patients with Prader-Willi syndrome. Acta Paediatr 2010; 99:1712.
  71. Humatrope® Somatropin (rDNA origin) for injection vials and cartridges for use with the HumatroPen™ injection device. Eli Lilly and Company, Indianapolis, March 2004.
  72. Nutropin Depot® [somatropin (rDNA origin) for injectable suspension]. Genentech, Inc. San Francisco, October 2004.
  73. Wilson TA, Rose SR, Cohen P, et al. Update of guidelines for the use of growth hormone in children: the Lawson Wilkins Pediatric Endocrinology Society Drug and Therapeutics Committee. J Pediatr 2003; 143:415.
  74. Carrel AL, Myers SE, Whitman BY, Allen DB. Growth hormone improves body composition, fat utilization, physical strength and agility, and growth in Prader-Willi syndrome: A controlled study. J Pediatr 1999; 134:215.
  75. Eiholzer U, Gisin R, Weinmann C, et al. Treatment with human growth hormone in patients with Prader-Labhart-Willi syndrome reduces body fat and increases muscle mass and physical performance. Eur J Pediatr 1998; 157:368.
  76. Lindgren AC, Hagenäs L, Müller J, et al. Growth hormone treatment of children with Prader-Willi syndrome affects linear growth and body composition favourably. Acta Paediatr 1998; 87:28.
  77. Eiholzer U, Weber R, Stutz K, Steinert H. Effect of 6 months of growth hormone treatment in young children with Prader-Willi syndrome. Acta Paediatr Suppl 1997; 423:66.
  78. Obata K, Sakazume S, Yoshino A, et al. Effects of 5 years growth hormone treatment in patients with Prader-Willi syndrome. J Pediatr Endocrinol Metab 2003; 16:155.
  79. Eiholzer U, L'allemand D, Schlumpf M, et al. Growth hormone and body composition in children younger than 2 years with Prader-Willi syndrome. J Pediatr 2004; 144:753.
  80. Carrel AL, Moerchen V, Myers SE, et al. Growth hormone improves mobility and body composition in infants and toddlers with Prader-Willi syndrome. J Pediatr 2004; 145:744.
  81. Galassetti P, Saetrum Opgaard O, Cassidy SB, Pontello A. Nutrient intake and body composition variables in Prader-Willi syndrome--effect of growth hormone supplementation and genetic subtype. J Pediatr Endocrinol Metab 2007; 20:491.
  82. Bakker NE, Kuppens RJ, Siemensma EP, et al. Eight years of growth hormone treatment in children with Prader-Willi syndrome: maintaining the positive effects. J Clin Endocrinol Metab 2013; 98:4013.
  83. Carrel AL, Myers SE, Whitman BY, et al. Long-term growth hormone therapy changes the natural history of body composition and motor function in children with prader-willi syndrome. J Clin Endocrinol Metab 2010; 95:1131.
  84. Takeda A, Cooper K, Bird A, et al. Recombinant human growth hormone for the treatment of growth disorders in children: a systematic review and economic evaluation. Health Technol Assess 2010; 14:1.
  85. van der Klaauw AA, Romijn JA, Biermasz NR, et al. Sustained effects of recombinant GH replacement after 7 years of treatment in adults with GH deficiency. Eur J Endocrinol 2006; 155:701.
  86. Reus L, Pillen S, Pelzer BJ, et al. Growth hormone therapy, muscle thickness, and motor development in Prader-Willi syndrome: an RCT. Pediatrics 2014; 134:e1619.
  87. Festen DA, Wevers M, Lindgren AC, et al. Mental and motor development before and during growth hormone treatment in infants and toddlers with Prader-Willi syndrome. Clin Endocrinol (Oxf) 2008; 68:919.
  88. Siemensma EP, Tummers-de Lind van Wijngaarden RF, Festen DA, et al. Beneficial effects of growth hormone treatment on cognition in children with Prader-Willi syndrome: a randomized controlled trial and longitudinal study. J Clin Endocrinol Metab 2012; 97:2307.
  89. Wolfgram PM, Carrel AL, Allen DB. Long-term effects of recombinant human growth hormone therapy in children with Prader-Willi syndrome. Curr Opin Pediatr 2013; 25:509.
  90. Genotropin prescribing information (Pfizer pharmaceuticals, Inc). Available at: http://labeling.pfizer.com/ShowLabeling.aspx?id=577 (Accessed on June 16, 2013).
  91. Carrel AL, Lee PDK, Mogul HR. Growth hormone and Prader-Willi syndrome. In: Management of Prader-Willi syndrome, 3rd Ed, Butler MG, Lee PDK, Whitman BY. (Eds), Springer Science, New York, NY 2006. p.201.
  92. Deal CL, Tony M, Höybye C, et al. GrowthHormone Research Society workshop summary: consensus guidelines for recombinant human growth hormone therapy in Prader-Willi syndrome. J Clin Endocrinol Metab 2013; 98:E1072.
  93. Mogul HR, Lee PD, Whitman BY, et al. Growth hormone treatment of adults with Prader-Willi syndrome and growth hormone deficiency improves lean body mass, fractional body fat, and serum triiodothyronine without glucose impairment: results from the United States multicenter trial. J Clin Endocrinol Metab 2008; 93:1238.
  94. Gondoni LA, Vismara L, Marzullo P, et al. Growth hormone therapy improves exercise capacity in adult patients with Prader-Willi syndrome. J Endocrinol Invest 2008; 31:765.
  95. Lafortuna CL, Minocci A, Capodaglio P, et al. Skeletal muscle characteristics and motor performance after 2-year growth hormone treatment in adults with prader-willi syndrome. J Clin Endocrinol Metab 2014; 99:1816.
  96. U.S Food and Drug Administration. 2003 Safety Alert: Genotropin (somatropin [rDNA origin]) for injection). Available at www.fda.gov/medwatch/SAFETY/2003/genotropin.htm (Accessed on August 5, 2006).
  97. Lee PDK. Growth hormone and mortality in Prader-Willi syndrome. Growth, Genetics and Hormones journal. Available at: http://www.gghjournal.com/volume22/2/featureArticle.cfm (Accessed on March 27, 2013).
  98. Al-Saleh S, Al-Naimi A, Hamilton J, et al. Longitudinal evaluation of sleep-disordered breathing in children with Prader-Willi Syndrome during 2 years of growth hormone therapy. J Pediatr 2013; 162:263.
  99. Nagai T, Obata K, Tonoki H, et al. Cause of sudden, unexpected death of Prader-Willi syndrome patients with or without growth hormone treatment. Am J Med Genet A 2005; 136:45.
  100. Schrander-Stumpel CT, Curfs LM, Sastrowijoto P, et al. Prader-Willi syndrome: causes of death in an international series of 27 cases. Am J Med Genet A 2004; 124A:333.
  101. Miller J, Silverstein J, Shuster J, et al. Short-term effects of growth hormone on sleep abnormalities in Prader-Willi syndrome. J Clin Endocrinol Metab 2006; 91:413.
  102. Haqq AM, Stadler DD, Jackson RH, et al. Effects of growth hormone on pulmonary function, sleep quality, behavior, cognition, growth velocity, body composition, and resting energy expenditure in Prader-Willi syndrome. J Clin Endocrinol Metab 2003; 88:2206.
  103. Festen DA, de Weerd AW, van den Bossche RA, et al. Sleep-related breathing disorders in prepubertal children with Prader-Willi syndrome and effects of growth hormone treatment. J Clin Endocrinol Metab 2006; 91:4911.
  104. Miller JL, Shuster J, Theriaque D, et al. Sleep disordered breathing in infants with Prader-Willi syndrome during the first 6 weeks of growth hormone therapy: a pilot study. J Clin Sleep Med 2009; 5:448.
  105. Detailed view: Safety labeling changes approved by FDA Center for Drug Evaluation and Research (CDER) -- September 2004. Available at www.fda.gov/medwatch/SAFETY/2004/sep04.htm (Accessed on January 18, 2006).
  106. Craig ME, Cowell CT, Larsson P, et al. Growth hormone treatment and adverse events in Prader-Willi syndrome: data from KIGS (the Pfizer International Growth Database). Clin Endocrinol (Oxf) 2006; 65:178.
  107. Lindgren AC. Somatropin therapy for children with prader-willi syndrome : guidelines for use. Treat Endocrinol 2006; 5:223.
  108. Butler MG, Sturich J, Lee J, et al. Growth standards of infants with Prader-Willi syndrome. Pediatrics 2011; 127:687.
  109. Butler MG, Lee J, Manzardo AM, et al. Growth charts for non-growth hormone treated Prader-Willi syndrome. Pediatrics 2015; 135:e126.
  110. Shapira NA, Lessig MC, Lewis MH, et al. Effects of topiramate in adults with Prader-Willi syndrome. Am J Ment Retard 2004; 109:301.
  111. Haqq AM, Stadler DD, Rosenfeld RG, et al. Circulating ghrelin levels are suppressed by meals and octreotide therapy in children with Prader-Willi syndrome. J Clin Endocrinol Metab 2003; 88:3573.
  112. Tan TM, Vanderpump M, Khoo B, et al. Somatostatin infusion lowers plasma ghrelin without reducing appetite in adults with Prader-Willi syndrome. J Clin Endocrinol Metab 2004; 89:4162.
  113. De Waele K, Ishkanian SL, Bogarin R, et al. Long-acting octreotide treatment causes a sustained decrease in ghrelin concentrations but does not affect weight, behaviour and appetite in subjects with Prader-Willi syndrome. Eur J Endocrinol 2008; 159:381.
  114. Marinari GM, Camerini G, Novelli GB, et al. Outcome of biliopancreatic diversion in subjects with Prader-Willi Syndrome. Obes Surg 2001; 11:491.
  115. Grugni G, Guzzaloni G, Morabito F. Failure of biliopancreatic diversion in Prader-Willi syndrome. Obes Surg 2000; 10:179.
  116. Scheimann AO, Butler MG, Gourash L, et al. Critical analysis of bariatric procedures in Prader-Willi syndrome. J Pediatr Gastroenterol Nutr 2008; 46:80.