para>Sudden death after initiation of growth hormone therapy due to worsening of obstructive sleep apnea has been reported, so before initiating growth hormone, a sleep study should be done (6)[B].
Contraindications to growth hormone: weight >225% of ideal, uncontrolled diabetes, respiratory compromise, acute respiratory infection, untreated severe sleep apnea, active cancer, psychosis
Hormone replacement during puberty is controversial due to increased risk of stroke with estrogen replacement and worsening of behavioral problems with testosterone replacement.
‚
ISSUES FOR REFERRAL
- All patients should be assessed by an ophthalmologist.
- Early involvement of physical, speech, and occupational therapy
- Endocrine referral for discussion of growth hormone replacement and sex hormone therapy
SURGERY/OTHER PROCEDURES
- Surgical and hormonal correction of cryptorchidism
- Tonsillectomy and adenoidectomy may be necessary in those with sleep apnea and especially considered before growth hormone initiation.
- Results of surgical weight loss procedures are inconsistent, and patients seem to have greater risks than benefits.
ALERT
Patients are at increased risk of respiratory complications during the perioperative period when undergoing adenotonsillectomy, so close monitoring is required.
Unusually high complication rates for scoliosis surgery have been reported.
‚
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
- Screen infants for strabismus.
- Routine monitoring of height, weight, and BMI
- Screen for diabetes mellitus if BMI is >95th percentile.
- Monitor for sleep disturbances and obtain sleep study, especially before growth hormone initiation or if concerned about sleep apnea.
- Evaluate for behavior and psychiatric disturbances at least annually.
- Monitor for recurrence of cryptorchidism after orchidopexy.
- Examine annually for scoliosis: If patient is obese, consider radiographs of the spine.
- Dual energy x-ray absorptiometry (DEXA) scans to monitor bone density starting at age 5 years and every 2 to 3 years thereafter
- Monitor calcium and vitamin D intake.
- Specialized group homes are an option for adults with PWS to provide behavior and diet monitoring.
DIET
- Oromotor evaluation, swallow study, and thickened high caloric feedings may be needed in neonates/infants; significant dysfunction may warrant gastrostomy or fundoplication.
- Fundoplication must be used with caution due to tendency to overeat following infancy.
- When hyperphagia begins, strict supervision of food intake with restricted access to food in home, including locks on refrigerator and cabinets.
- Food seeking behaviors can lead to issues such as eating garbage, frozen/spoiled food, or potentially toxic items.
- Regular consultation with dietician
ALERT
Monitor eating habits because binge eating can lead to acute gastric dilation, choking episodes, or toxic ingestions, which can lead to death.
‚
PATIENT EDUCATION
- Genetic counseling for families of children who have imprinting center deletions, due to the possibility of recurrence in subsequent pregnancies
- Discuss issues of guardianship, wills, and advocacy by adolescence.
- Patients can often work in a structured setting with support.
PROGNOSIS
- Increased morbidity and mortality due to obesity, diabetes, and hypertension, which can be prevented with good programs
- With improved treatments, most children live until adulthood and can work.
- Most experience decline in physical and psychological function with advancing age.
COMPLICATIONS
- Obesity-related problems (diabetes, cardiovascular problems, sleep apnea, right-sided heart failure)
- Thrombophlebitis
- Skin infections from skin picking
REFERENCES
11 Gross ‚ N, Rabinowitz ‚ R, Gross-Tsur ‚ V, et al. Prader-Willi syndrome can be diagnosed prenatally. Am J Med Genet A. 2015;167A(1):80 " “85.22 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(5):E92.33 Angulo ‚ MA, Butler ‚ MG, Cataletto ‚ ME. Prader-Willi syndrome: a review of clinical, genetic, and endocrine findings. J Endocrinol Invest. 2015;38(12):1249 " “1263.44 Cassidy ‚ SB, Schwartz ‚ S, Miller ‚ JL, et al. Prader-Willi syndrome. Genet Med. 2012;14(1):10 " “26.55 Deal ‚ CL, Tony ‚ M, H ƒ ¶ybye ‚ C, et al. Growth Hormone Research Society workshop summary: consensus guidelines for recombinant human growth hormone therapy in Prader-Willi syndrome. J Clin Endocrinol Metab. 2013;98(6):E1072 " “E1087.66 Goldstone ‚ AP, Holland ‚ AJ, Hauffa ‚ BP, et al. Recommendations for the diagnosis and management of Prader-Willi syndrome. J Clin Endocrinol Metab. 2008;93(11):4183 " “4197.
ADDITIONAL READING
- Allen ‚ K. Managing Prader-Willi syndrome in families: an embodied exploration. Soc Sci Med. 2011;72(4):460 " “468.
- Bigi ‚ N, Faure ‚ JM, Coubes ‚ C, et al. Prader-Willi syndrome: is there a recognizable fetal phenotype? Prenat Diagn. 2008;28(9):796 " “799.
- Duker ‚ AL, Ballif ‚ BC, Bawle ‚ EV, et al. Paternally inherited microdeletion at 15q11.2 confirms a significant role for the SNORD116 C/D box snoRNA cluster in Prader " “Willi syndrome. Eur J Hum Genet. 2010;18(11):1196 " “1201.
- Manning ‚ KE, McAllister ‚ CJ, Ring ‚ HA, et al. Novel insights into maladaptive behaviours in Prader-Willi syndrome: serendipitous findings from an open trial of vagus nerve stimulation [published online ahead of print May 27, 2015]. J Intellect Disabil Res.
- Miller ‚ JL. Approach to the child with Prader-Willi syndrome. J Clin Endocrinol Metab. 2012;97(11):3837 " “3844.
- Tauber ‚ M, Mantoulan ‚ C, Copet ‚ P, et al. Oxytocin may be useful to increase trust in others and decrease disruptive behaviours in patients with Prader-Willi syndrome: a randomised placebo-controlled trial in 24 patients. Orphanet J Rare Dis. 2011;6:47.
- Tuysuz ‚ B, Kartal ‚ N, Erener-Ercan ‚ T, et al. Prevalence of Prader-Willi syndrome among infants with hypotonia. J Pediatr. 2014;164(5):1064 " “1067.
CODES
ICD10
Q87.1 Congenital malform syndromes predom assoc w short stature ‚
ICD9
759.81 Prader-Willi syndrome ‚
SNOMED
Prader-Willi syndrome (disorder) ‚
CLINICAL PEARLS
- PWS is a rare genetic disorder caused by a deletion, UPD, or an imprinting center defect resulting in the absence of expression of a region of the paternal chromosome 15.
- Characterized by hypotonia in early infancy followed by hyperphagia and behavior problems beginning in toddlerhood or early childhood
- Although there are clinical diagnostic criteria, genetic testing is the gold standard to confirm the diagnosis.
- A multidisciplinary approach is necessary to maximize the child 's potential.
- Weight control is critical to prevent obesity-related morbidity and mortality.