Health supervision for children with Prader-Willi syndrome


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Health supervision for children with Prader-Willi syndrome

  1. 1. Clinical Report−−Health Supervision for Children With Prader-Willi Syndrome Shawn E. McCandless and THE COMMITTEE ON GENETICS Pediatrics; originally published online December 27, 2010; DOI: 10.1542/peds.2010-2820 The online version of this article, along with updated information and services, is located on the World Wide Web at: PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2010 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275. Downloaded from by guest on February 4, 2012
  2. 2. FROM THE AMERICAN ACADEMY OF PEDIATRICS Guidance for the Clinician in Rendering Pediatric CareClinical Report—Health Supervision for Children WithPrader-Willi SyndromeShawn E. McCandless, MD, and THE COMMITTEE ONGENETICS abstractKEY WORDS This set of guidelines was designed to assist the pediatrician in caringPrader-Willi syndrome, Prader-Labhart-Willi syndrome,uniparental disomy, genetic testing for children with Prader-Willi syndrome diagnosed by clinical featuresABBREVIATIONS and confirmed by molecular testing. Prader-Willi syndrome providesPWS—Prader-Willi syndrome an excellent example of how early diagnosis and management canUPD—uniparental disomy improve the long-term outcome for some genetic disorders. PediatricsGH—growth hormone 2011;127:195–204IGF—insulin-like growth factorThis document is copyrighted and is property of the AmericanAcademy of Pediatrics and its Board of Directors. All authors INTRODUCTIONhave filed conflict of interest statements with the American Prader-Willi syndrome (PWS) (also Prader-Labhart-Willi syndrome) is aAcademy of Pediatrics. Any conflicts have been resolved through recognizable pattern of physical findings with significant cognitive,a process approved by the Board of Directors. The AmericanAcademy of Pediatrics has neither solicited nor accepted any neurologic, endocrine, and behavioral abnormalities caused by lack ofcommercial involvement in the development of the content of expression of genes from an imprinted region of the paternally inher-this publication. ited chromosome 15q11-q13, near the centromere. Originally de-The guidance in this report does not indicate an exclusive scribed in 1958,1 PWS was the first recognized disorder related tocourse of treatment or serve as a standard of medical care. genomic imprinting in humans2 and provides an excellent example ofVariations, taking into account individual circumstances, may beappropriate. how early diagnosis and meticulous management can markedly im- prove the long-term outcome for people with some genetic disorders. PWS affects both genders equally and occurs in people from all geo- graphic regions; its estimated incidence is 1 in 15 000 to 1 in 25 000 live births.3,4 Affected infants uniformly have significant hypotonia, early feeding problems, and difficulty with weight gain. Later, a second phase of the disorder ensues with hyperphagia (excessive appetite for food), which leads to obesity and characteristic behavior problems. Without adequate weight control and management of eating behaviors, massive obesity and associated complications of diabetes, sleep apnea, and right-sided heart failure occur; death typically occursdoi:10.1542/peds.2010-2820 in the fourth decade of life. With careful weight control, people withAll clinical reports from the American Academy of Pediatrics PWS can remain healthy well into older adult life, and some people areautomatically expire 5 years after publication unless reaffirmed, known to live into their seventh decade.revised, or retired at or before that time. The findings of PWS are listed in Table 1. Clinical diagnostic criteriaPEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). have been developed and validated5 (Table 2), but now that reliableCopyright © 2011 by the American Academy of Pediatrics molecular testing is readily available, these clinical criteria should be considered guidelines to help define people for whom further diagnos- tic testing is indicated.6 In general, PWS should be considered in any infant with significant hypotonia, particularly in the setting of poor feeding, reduced spontaneous arousal for feeding, and hypogonadism (undescended testes, small phallus, or small clitoris). In older chil- dren, the diagnosis should be considered when there is impaired sati- ety for food, especially with rapid weight gain. Likewise, poor linear growth, especially in the presence of excessive caloric intake, should also raise suspicion for PWS. Hypogonadism, hypotonia, developmentalPEDIATRICS Volume 127, Number 1, January 2011 195 Downloaded from by guest on February 4, 2012
  3. 3. TABLE 1 Clinical Findings in PWS TABLE 1 Continued when assisting in the provision of aFetal Sleep comprehensive medical home for chil- Breech position Snoring/obstructive sleep apnea Reduced fetal activity Central apnea during sleep dren and adults with PWS. They are Polyhydramnios Excessive daytime sleepiness based on a thorough review of the per-Growth Early-morning waking tinent medical literature and incorpo- Short stature Night-awakening for food-seeking Failure to thrive in infancy Voice rate experimental data and the experi- Central obesity Hypernasal speech ence of clinicians with expertise inHead and neck Weak or squeaky cry in infancy Dolichocephaly caring for people with PWS. As with all Endocrine Narrow bitemporal diameter Hyperinsulinemia chronic medical conditions, establish- Almond-shaped eyes GH deficiency ing a medical home is essential to the Strabismus Hypogonadotropic hypogonadism Up-slanting palpebral fissures Diabetes mellitus (type 2) smooth and effective provision of care Myopia Behavior/mental health to the individual person and support to Hyperopia Skin picking Thin upper lip his or her family, which is best Rectal picking Small-appearing mouth Food related behavioral problems achieved when the primary care pro- Down-turned corners of mouth Thick, viscous (reduced) saliva Temper tantrums vider and consultants communicate ef- Difficulty with transitions Enamel hypoplasia Stubbornness fectively and clearly delineate their re- Early dental caries spective roles in the care of the Obsessive behaviors Dental crowding and malocclusion Perseverant speech person.Ocular Obsessive-compulsive disorder Strabismus Psychosis Nystagmus Elopement GENETICS AND GENOMICS OF PWS Cataracts (rare) Miscellaneous Retinal hypopigmentation Temperature instability PWS is associated with lack of expres- Foveal hypoplasia sion of several genes on the paternally High pain threshold Hyperopia Unusual skill with jigsaw puzzles inherited chromosome 15. This region MyopiaRespiratory contains genes that are normally “im- Hypoventilation Obstructive sleep apnea printed,” which means that they are Central sleep apnea delays, speech-articulation defects, differentially expressed (used to makeGastrointestinal and characteristic physical appear- RNA and proteins) depending on Feeding problems in infancy ance should all raise the index of sus- Gastroesophageal reflux whether the chromosome was inher- Decreased vomiting picion. Significant neonatal hypotonia ited from the father or the mother. OnGenitourinary is present in essentially all children for the maternally inherited chromosome Small penis Scrotal hypoplasia whom molecular testing eventually 15, these genes are transcriptionally Cryptorchidism confirms the diagnosis of PWS7; there- silenced by hypermethylation of their Hypoplastic labia minora fore, this history should be actively Hypoplastic clitoris promoter regions. Therefore, only theSkeletal sought during evaluation of older paternally inherited chromosome pro- Osteoporosis children. duces the gene products. These Osteopenia Scoliosis These guidelines are intended to be changes are referred to as “epige- Kyphosis suggestions for health care providers netic,” because they do not involve a Small hands and feet Narrow hands with straight ulnar border ClinodactylySkin, nails, hair TABLE 2 Suggested Criteria for Prompting Molecular Testing for PWS Hypopigmentation Age at Assessment Features Sufficient to Prompt DNA Testing Blonde to light-brown hair Birth to 2 y Significant hypotonia with poor suck and difficulty with weight gain Frontal hair upsweepNeurologic 2–6 y Congenital hypotonia with history of poor suck; global developmental Severe neonatal hypotonia that improves with delay age 6–12 y History of congenital hypotonia with poor suck (hypotonia often persists), Poor neonatal suck and swallow reflexes global developmental delay, and excessive eating (hyperphagia; Poor gross motor coordination obsession with food) with central obesity if uncontrolled Poor fine motor coordination 13 y through adulthood Cognitive impairment, usually mild mental retardation, excessive eating Mild-to-moderate mental retardation (hyperphagia; obsession with food) with central obesity if Learning disabilities uncontrolled, and hypothalamic hypogonadism and/or typical behavior Increased risk of seizures problems (including temper tantrums and obsessive-compulsive Global developmental delay features) Speech-articulation problems Adapted from Gunay-Aygun M, Schwartz S, Heeger S, O’Riordan MA, Cassidy SB. Pediatrics. 2001;108(5). Available at: Hyperphagia FROM THE AMERICAN ACADEMY OF PEDIATRICS Downloaded from by guest on February 4, 2012
  4. 4. FROM THE AMERICAN ACADEMY OF PEDIATRICSchange in the sequence of the DNA but, of chromosome 15 from the mother chromosome 15, both of which origi-instead, involve a change to the and no copy from the father. nate from the mother. Alternatively,genomic structure that affects regula- 3. Imprinting errors, which occur in the sperm could have no copy of chro-tion of expression. 5% or fewer cases, involve a defect mosome 15 as a result of a paternalThe part of chromosome 15 involved in of the process of switching the im- meiotic error, and the resulting con-PWS contains several segments of du- print when the father passes on a ceptus would have only 1 chromosomeplicated DNA that predispose to rear- copy of the chromosome 15 that he 15. Such an embryo would also berangements, either deletion or dupli- inherited from his mother. spontaneously aborted unless a sec-cation, of the PWS region. Absence of ond, mitotic error occurred after fer- 4. Finally, PWS has been described asthe paternally inherited contribution tilization that duplicates the mater- a result of a balanced translocationof the PWS region of chromosome 15 nally contributed chromosome 15. In involving chromosome 15 thatleads to lack of the gene products and either case, an infant born from such a moves the genes in the region awaycauses the findings of PWS. In contrast, pregnancy would be missing the pater- from the imprinting center.several other genes in the region are nally contributed chromosome 15 and, Several recent reports suggested that therefore, would only have inactive,silenced by methylation on the pater- the essential PWS phenotype may be maternally imprinted copies of thenally inherited allele. Absence of the caused by loss of the imprinted HBII-85 genes in the PWS region.maternally inherited contribution of cluster of small nucleolar RNAsthis region causes Angelman syn- The third mechanism, an “imprinting (snoRNAs), which, if confirmed, will bedrome, a completely different disorder error,” leads to a situation in which the one of the first developmental disor-caused by lack of expression of a sin- imprinted (silenced) genes that the fa- ders shown to be caused by loss ofgle gene in the region (UBE3A). ther inherited from his mother cannot microRNA.8,9A short sequence of DNA in the region be reactivated. The infant inherits 1 The PWS region of chromosome 15 is copy of chromosome 15 from each par-called the “imprinting center” seems flanked by segments of duplicated ent, but the PWS region is fully methyl-to control switching and maintenance DNA, which predisposes to deletion, or ated on both copies of chromosome 15of the imprinting pattern, which is crit- duplication, during recombination in and, thus, is silenced in both copies.ical, because half of a male’s copies of meiosis. This seems to be the reason This mechanism, although rare, is im-chromosome 15 carry the silenced for the high frequency of the typical portant to identify, because the inabil-genes inherited from his mother. When deletion in PWS and in some other re- ity to switch the imprint can be an in-he, in turn, passes copies of his moth- current microdeletions. It is important herited trait, which means that a maner’s chromosome 15 to his own off- to recognize that the normal chromo- with an inherited imprinting defectspring, those genes must be reacti- some structure in the region plays a has up to a 50% recurrence risk withvated, which “switches” the imprint. significant role in the development of each pregnancy to sire another childIt becomes clear, then, that there are the genetic defect; thus, PWS has been with PWS. The rare case of PWS attrib-multiple mechanisms by which a per- described as a “genomic disorder” to utable to a balanced translocation alsoson may end up with no functional distinguish it from other genetic disor- may have an increased recurrence(transcriptionally active) copies of the ders that are specifically caused by an risk if the father carries the samegenes in this critically important re- alteration in the sequence of the DNA.10 translocation on the chromosome 15gion of chromosome 15 and, thus, have he inherited from his mother. Neither UPD is thought to result most oftenPWS. deletion nor UPD is known to be asso- from meiotic nondisjunction that leads1. The most common situation ( 70% to trisomy for chromosome 15 and, ciated with increased recurrence risk. of cases) is that the paternally in- thus, is associated with increased ma- Although subtle differences have been herited chromosome 15 contains a ternal age. Trisomy 15 is the most com- shown between groups of people with microdeletion of 3 to 4 megabases mon trisomy at the time of conception deletions compared with UPD,11–16 for of genetic material spanning the but can only survive if there is a second the most part, there are no major dif- PWS region. mitotic division error after fertilization ferences in phenotype among the var-2. In approximately 20% of cases, the that eliminates 1 of the 3 chromo- ious causes. The exception is the find- affected infant has maternal unipa- somes 15. If the paternally contributed ing of hypopigmentation, which is rental disomy (UPD), which means chromosome is lost, the embryo will most notable in people with PWS who that the child inherited both copies revert to having the normal 2 copies of have a deletion of the OCA2 gene (aPEDIATRICS Volume 127, Number 1, January 2011 197 Downloaded from by guest on February 4, 2012
  5. 5. often helpful. Later, after hyperphagia Methylation begins, the diet must be quite calori- analysis FISH cally restricted, often to as little as Yes Yes PWS due to 60% of the calories that similarly sized Abnormal? Abnormal? deletion 15q11-13 children without PWS might require for adequate growth. This diet re- No No quires careful attention to the balance of essential nutrients, which is oftenConsider other disorders Molecular analysis for UPD best achieved by referral and regular Infant hypotonia: Yes PWS due to follow-up with a dietitian who is knowl- •chromosome rearrangement Abnormal? •spinal muscular atrophy type I maternal UPD edgeable about PWS. •myotonic dystrophy •other myopathy/neuropathy No Feeding Tubes (Nasogastric or Older children (obesity): •fragile X syndrome Gastrostomy Tubes) •Bardet Biedl syndrome •microscopic chromosome PWS due to imprinting defect; Infants with PWS have poor feeding be- rearrangement family studies needed cause of weak suck, easy fatigability,FIGURE 1 and low muscle tone. The need for as-Flowchart of recommended molecular testing strategy for PWS. sisted feeding is nearly universal in the first 4 to 6 months; use of nursing sys-nonimprinted gene in the PWS region (FISH) reveal no evidence of deletion or tems with 1-way valves and manual as-of chromosome 15 associated with au- balanced rearrangement, the next sistance of sucking, originally de-tosomal recessive oculocutaneous al- step is to obtain blood from the par- signed for infants with cleft palate (eg,binism type II).17,18 Recently, some au- ents and the child to evaluate for UPD. Haberman nipple, Pigeon feeder), canthors suggested that there may be If biparental inheritance is discovered greatly reduce reliance on feedingsubtle differences in neurocognitive in the face of abnormal methylation tubes. Nasogastric tubes, whendevelopment in children with deletions and normal FISH results, then, by pro- needed, are generally well tolerateddepending on the location of the prox- cess of elimination, the cause is as- and rarely required for more than 3 toimal break point.19 Others have not ob- sumed to be an imprinting defect. The 6 months. The use of a gastrostomyserved such a difference13; therefore, possible role of testing for defects of tube (generally with placement of athe clinical utility of defining the break the HBII-85 small nucleolar RNA cluster button-style device) can be avoided inpoints is not clear at this time. remains to be elucidated. most cases, but if, after consideringDIAGNOSTIC TESTING the risks and benefits of both ap- SPECIAL CONSIDERATIONS FOR THE proaches, a decision to use a gastros-Diagnostic testing for PWS, as outlined INFANT AND CHILD IN WHOM PWS tomy tube is made, the device shouldin Fig 1, should begin with methylation IS DIAGNOSED be promptly removed when no longeranalysis to confirm the absence of pa- Nutrition needed. Poor feeding is a transientternally imprinted genes in the PWS re- Maintenance of adequate and appro- problem in PWS, and the increased ab-gion of chromosome 15. When only a priate nutrition is central to the care of dominal fat mass with reduced musclematernal methylation pattern is seen,PWS is confirmed, but additional test- people with PWS at every age. Infants that characterizes this disorder en-ing is needed to identify the specific may require support of feeding for sev- sures a cosmetically disfiguring scarcause, which allows for appropriate eral months. Caloric needs may be, but at the site of the gastrostomy tubecounseling regarding recurrence risk. are not always, somewhat reduced in (families sometimes refer to this asThe recurrence risk for spontaneous infants with PWS, and infants with PWS the “second belly-button”). These 2 fac-deletions or UPD is low ( 1%), typically do not spontaneously demand tors, relatively specific to PWS, maywhereas the recurrence risk of im- feedings. Therefore, the infant’s diet significantly alter the risk/benefit anal-printing mutations can be as high as must be adjusted as needed to main- ysis regarding the approach to tube50%. If the methylation analysis is con- tain appropriate weight gain as deter- feedings compared with the decision-sistent with PWS and the karyotype mined by frequent weight checks. In- making process for children with dis-and fluorescence in situ hybridization creased caloric density of feedings is abilities attributable to other causes.198 FROM THE AMERICAN ACADEMY OF PEDIATRICS Downloaded from by guest on February 4, 2012
  6. 6. FROM THE AMERICAN ACADEMY OF PEDIATRICSEndocrine Considerations and perience has suggested that treat- bone density27,29 and possible stabiliza-Recombinant Human Growth ment can begin at as early as 2 to 3 tion of behavior decline.30 Studies areHormone months of age. It is important that par- in progress to evaluate the use of GH inGeneralized hypothalamic insuffi- ents be thoroughly informed about the adults with PWS.31 However, there isciency is characteristic of PWS and potential benefits and the potential for nothing to suggest that endogenousmanifests as dysregulation of the undesired effects. Specifically, there GH insufficiency improves in later life;hypothalamic-pituitary axis (including have been several deaths in children therefore, it is reasonable to considergrowth hormone [GH], thyroid func- as young as 3 years with PWS within 6 continuing therapy into adulthood.tion, and possibly regulation of the ad- months of initiating GH therapy. The Pretreatment laboratory evaluation torenal cortex), appetite, thermoregula- role of GH in those deaths, if any, is not document sequelae of GH insufficiency,tion, and respiratory control. Recent known. Adenotonsillar hypertrophy to exclude other causes of slow linearwork demonstrated the possibility that and obstructive apnea may occur dur- growth in people with PWS, and to de-centrally mediated adrenal insuffi- ing GH therapy; therefore, current rec- fine baseline parameters related tociency may be an underrecognized ommendations for management in- potential complications of therapy of-contributor to premature deaths clude polysomnography (sleep study) ten includes:among people with PWS.20,21 It is rec- before and 6 to 10 weeks after begin- ● polysomnography;ommended that early-morning serum ning GH treatment, regardless of age. ● measurement of plasma insulin-likeadrenocorticotropic hormone and cor- Polysomnography results are fre- growth factor 1 (IGF1), IGF-bindingtisol concentrations be evaluated quently abnormal in people with PWS, protein 3 (IGFBP3), thyroxine, andwhen the child is well and repeated and both central and obstructive hy- thyrotropin levels, a complete bloodduring any severe illness. Consider- popnea are common.24 Evidence of ob- count, and a basic metabolic profileation should be given to prophylactic structive sleep apnea should be man- (with calcium); andtherapy with hydrocortisone during aged according to accepted standards ● left hand and wrist radiography forrare episodes of critical illness in chil- of care25 (this American Academy of bone age (in older children).dren with PWS, pending measurement Pediatrics clinical practice guideline was published in 2002 and has not Follow-up should include:of adrenocorticotropic hormone andserum cortisol. Discussion with a pedi- been updated) and, specifically, should ● repeat polysomnography 6 to 10atric endocrinologist is helpful in de- lead to referral to an otolaryngologist weeks after initiation of therapytermining whether provocative testing for evaluation of airway, increased ef- (consider repeating in 1 year andis indicated in early childhood. fort to reduce weight, and consider- any time at which there are new or ation of delaying (or stopping) GH worsening symptoms);GH insufficiency is considered to be treatment until polysomnography re- ● monitoring of IGF1 at least twiceuniversal in PWS, so provocative diag-nostic testing is not required in the sults improve. It has also been sug- yearly, dosing GH to keep IGF1 inface of reduced growth velocity. In the gested that GH could be associated physiologic range; andfirst year of life, reduced growth veloc- with unexpected death by increasing ● monitoring of head circumferenceity may not be readily identified, but resting energy expenditure (through at each visit, because GH treatmentboth controlled clinical trials22,23 and increased muscle bulk) in children can cause abnormal growth of theclinical experience have demonstrated with underlying abnormalities of cen- head, especially if the fontanellesthat there is often significant response tral respiratory drive attributable to are open when GH is treatment with GH, primarily in im- PWS, although there is a suggestion inproved lean mass, improved motor de- the literature that treatment with GH Behavioral Food Controlsvelopment, and normalization of body may be associated with modest im- After the onset of hyperphagia, chil-habitus. Decisions about use of GH provement in the central respiratory dren with PWS may develop a widetherapy and management are best drive.26 range of food-related behaviors, in-made in consultation with a pediatric There is mounting evidence from con- cluding actively seeking food, eatingendocrinologist. Although GH treat- trolled clinical trials that GH therapy in nonfood items (eg, animal chow,ment has been approved by the US children improves linear growth, lean spoiled food, decorative items thatFood and Drug Administration for chil- mass and lean-to-fat ratio,27 and respi- look like food, searching in garbagedren with PWS older than 2 years with ratory drive,26,28 and there has been cans, etc), stealing money to buy food,documented growth failure, clinical ex- suggestion of beneficial effects on and even running away from home toPEDIATRICS Volume 127, Number 1, January 2011 199 Downloaded from by guest on February 4, 2012
  7. 7. search for food in a wider area. Con- behaviors, particularly skin-picking, adults with PWS develop depression,trol of these behaviors is complex but become prominent. In later childhood anxiety, and, in some cases, true psy-centers on strategies to limit access to and the early adolescent years, food- chosis. Parents should be counseled tofood (eg, locks on cabinets and refrig- seeking behaviors may increase and identify early indicators of these pro-erators), limit exposures that make are often associated with lying, and oc- cesses to facilitate appropriate medi-the child think about food (eg, birthday casionally stealing, to obtain food. cal intervention.treats sitting on the teacher’s desk Some teenagers with PWS have a dis-during the school day), and instill con- turbing tendency to sneak off to HEALTH SUPERVISION FROM BIRTHfidence that the next meal will be search for food, which is potentially TO 1 MONTH: NEWBORN INFANTSserved on time by scrupulously main- quite dangerous and difficult to man- Evaluationtaining mealtime routines. Relatives age. Typical of the adolescent years, theand social contacts must be educated teenager with PWS is often overly confi- ● Confirm the diagnosis of PWS (Fig 1)to realize that “sneaking” food to the dent of his or her ability to handle risks and review the implications of thechild with PWS is not an appropriate and dangerous situations. It is important molecular testing results with themethod of demonstrating affection, to recognize that teenagers with PWS parents.and, in fact, undermines the child’s deal with many of the same neurodevel- ● Review history for:nutritional regimen and sense of opmental and hormonal issues that all ● growth and development;well-being. adolescents encounter, and, similar to ● feeding problems; and their typically developing peers, many ofHypogonadism ● symptoms of obstructive apnea. their behavioral issues seem to stabilize,Both males and females are affected, although not disappear entirely, as they ● Physical examination should in-although the primary external mani- reach adulthood. clude evaluation of:festations in females (clitoral and la- ● hypotonia, and Management of the many complex be-bia minora hypoplasia) may not be ob- havioral issues is best accomplished ● hypogonadism.vious with cursory evaluation. A through an active partnership of thetherapeutic trial of human chorionic parents, the primary care provider, Anticipatory Guidancegonadotropin (hCG) is indicated for and a developmental/behavioral spe- ● Review the phenotype, discuss thetreatment of undescended testes be- cialist (pediatrician or psychologist). specific findings with both parentsfore surgery, because avoidance of Behavioral management that focuses whenever possible, and talk aboutgeneral anesthesia is desirable for in- on rewarding desired behaviors and potential clinical manifestations as-fants with low muscle tone and poten-tial for underlying respiratory compro- ignoring, when possible, undesirable sociated with the syndrome; thesemise. Added benefits of a course of hCG behaviors seems to be most effective. issues may have to be reviewedmay include increased scrotal size and Early recognition of developing behav- again at a subsequent meeting.partial normalization of phallus length, ior problems is critical for maximizing ● Point out both early and late feedingthereby improving surgical outcomes the effectiveness of such an approach. Parents should be counseled that of- issues and the dichotomous naturefor undescended testes and facilitat- of feeding problems (ie, too little asing later standing micturition. fering food as a reward or withholding food as a punishment is almost always a neonate, too much as an olderBehavior Management counterproductive and should be child), and, as appropriate, discuss avoided. Positive reinforcers are gen- use of nasogastric feedings with in-As the child with PWS ages, there is a creased caloric-density formula toprogression of behavioral issues, erally not difficult to identify, and re- ward systems that use small, short- minimize volume and use of specialmany of which can be anticipated, nipples/feeders (eg, Pigeon feeder,identified early, and managed pro- term goals that progress to larger goals are quite effective. Haberman nipple, other nursers de-spectively. Early childhood is often signed to reduce work of sucking).characterized by rigidity, particularly Finally, young adults with PWS seem to Special attention should be paid to:related to daily routines and long-term be prone to a variety of compulsive be-persistence of temper tantrums and haviors including smoking cigarettes, ● avoidance of prolonged oral feed-oppositional behaviors typical of the and some of them develop frank ing time (usually not 20 min-normally developing 2-year-old. Later, obsessive-compulsive disorder. Like- utes per feeding);perseverant speech and compulsive wise, a significant minority of young ● transition from tube feeding;200 FROM THE AMERICAN ACADEMY OF PEDIATRICS Downloaded from by guest on February 4, 2012
  8. 8. FROM THE AMERICAN ACADEMY OF PEDIATRICS ● maintenance of adequate caloric ● Monitor time/work of feeding and ● benefits of early behavioral mon- intake; and caloric density of foods to maintain itoring and establishment of rou- ● development of appropriate eat- appropriate growth. tines; and ing habits; discuss the impor- ● Perform developmental evaluation, ● importance of limit-setting and tance of normal fat and calorie and refer to early-intervention ser- enforcement. intake for brain development vices (if not already done). ● At 6 to 12 months of age, review the (some parents may start restrict- ● Evaluate boys for undescended tes- psychological support and in- ing too early). tes (or cryptorchidism) and ingui- trafamily relationships, including● Refer infants to early-intervention nal hernia; consider trial of human long-term planning, financial plan- services in the community. chorionic gonadotropin injections ning, and guardianship; reinforce (may be performed in conjunction need for parents to work in partner-● Discuss the importance of stimulat- with pediatric endocrinologist); re- ship, and discuss early relationship- ing the infant, because he or she is counseling for parents if problems fer to pediatric urologist or a urolo- likely to be undemanding. arise. gist who has special expertise and● Inform the family of the availability experience with infants with disabil- ● Review early-intervention services of support and advice from the par- ities if the infant’s testes are relative to the strengths and needs ents of other children with PWS. abnormal. of the infant and family.● Supply contact information for PWS ● Check the infant’s vision at each ● Review the family’s understanding support groups (see “Resources for visit by using developmentally ap- of the risk of recurrence of PWS Parents”). propriate subjective and objective and the availability of prenatal● Point out the strengths of the child criteria; if evidence of strabismus diagnosis. and positive family experiences. or other concern arises, refer the ● Discuss increased risk of seizures● Discuss individual resources for sup- infant to a pediatric ophthalmolo- during childhood (5%–10% of those port, such as family, clergy, and gist or an ophthalmologist who has with PWS), which may be associated friends. special expertise and experience with fever and are generally respon- with infants with disabilities. sive to monotherapy.● Talk about how and what to tell ● Administer vaccines recommended other family members and friends; HEALTH SUPERVISION FROM 1 TO 5 for all children unless there are spe- review methods of coping with long- YEARS: EARLY CHILDHOOD cific contraindications. term disabilities. ● Assess the emotional status of par- Evaluation● Review the recurrence risk in sub- ents and intrafamily relationships; ● Obtain a history and perform a sequent pregnancies and the avail- physical examination with attention educate and support siblings and ability of prenatal diagnosis and ge- to growth and developmental sta- discuss sibling adjustments. netic counseling. tus. PWS-specific growth curves● Give overview of the long-term Anticipatory Guidance should only be used for children management plan. ● Review feeding issues (see above) who are not treated with GH; regular and the infant’s growth and devel- curves should be used for childrenHEALTH SUPERVISION FROM 1 who are treated with GH. opment relative to other childrenMONTH TO 1 YEAR: INFANCY with PWS. ● Feeding issues: monitor food intake and behaviors, and consider refer-Evaluation ● Review GH deficiency and review ral to dietitian who has experience● Review and note clinical features benefits and potential risks of GH with PWS; calorie needs must be and confirm diagnosis, if not done therapy; consider referral to pediat- based on growth rate and are usu- previously. ric endocrinology specialist. ally less than those for similarly● Review routine health maintenance. ● Discuss: sized children without PWS.● Plot growth by using standard ● need for careful dietary manage- ● Annual hearing and vision screen- pediatric growth charts, and pay ment later in childhood; ing evaluation before 3 years of age; special attention to weight-for- ● probability of mild-to-moderate refer the child to a pediatric oph- length measurements. cognitive impairment; thalmologist or ophthalmologistPEDIATRICS Volume 127, Number 1, January 2011 201 Downloaded from by guest on February 4, 2012
  9. 9. who has special expertise and expe- ● Discuss need for all family mem- ● Discuss socialization, family status, rience with children with disabili- bers, child care providers, and and relationships, including finan- ties for a thorough evaluation for school staff members to learn cial arrangements and guardian- ocular findings during the second about the disorder, the need for ship; begin discussion of adult living or third year of life or earlier if there strict food management, and devel- arrangements; advise parents to is evidence of cataracts, nystagmus, opment of routines. consider joining waiting list for or strabismus. ● Discuss future pregnancy planning, placement in a group home specifi-● Evaluate annually for scoliosis, and risk of recurrence of PWS, and pre- cally organized for people with PWS regularly assess muscle tone; refer natal diagnosis; remind parents of and recognize that placement may to pediatric orthopedist for man- positive aspects for typically func- take several years (or more). agement of scoliosis as indicated. tioning children of having a sibling ● Discuss the development of age-● Discuss reduced salivation and in- with special needs. appropriate social and self-help creased caries risk by 1 year of age; skills and the development of a HEALTH SUPERVISION FROM 5 TO sense of responsibility. refer to a pediatric dentist or a gen- 13 YEARS: LATE CHILDHOOD eral dentist who has special train- ● Discuss psychosexual development, ing to manage children with special Evaluation physical and sexual development, needs; consider need for more- ● Obtain a history, and perform a menstrual hygiene and manage- frequent dental cleanings (every physical examination with attention ment, fertility, and contraception; 3– 4 vs every 6 months) because of to growth and developmental sta- explain that people with PWS often the increased caries risk. tus; evaluate for scoliosis. have strong feelings of desire for an infant.● Ask about symptoms related to ob- ● Specifically evaluate for behavior is- structive sleep apnea, including sues that may arise in this age ● Discuss symptoms related to ob- snoring, restless sleep, and exces- group, including binge-eating, run- structive sleep apnea, including sive daytime sleepiness; refer to a ning away, and worsening of snoring and restless sleep, and sleep or pulmonary specialist as skin-picking. evaluate for signs of excessive day- indicated. time sleepiness; refer to a sleep or ● Perform vision screening annually pulmonary specialist as indicated. with attention to recurrence ofAnticipatory Guidance strabismus. ● Discuss increased pain tolerance● Review early intervention, including common in people with PWS, particu- ● Perform thyroid-screening tests ev- physical therapy, occupational ther- larly with regard to evaluating for ill- ery 2 to 3 years or if symptomatic. apy, and speech therapy, in the pre- ness or injury; special attention ● Look for signs of premature adren- should be given to risk of intestinal school program and discuss future arche (which often occurs without necrosis after binge-eating, because school placement and performance. progression of other aspects of pre- the high pain tolerance can mask● Assess the child’s behavior, discuss cocious puberty; thus, reassurance symptoms and delay treatment, behavioral management, and ask is often the only intervention which can lead to death; people with specifically about common behav- needed). PWS rarely vomit, so parents should iors seen in those with PWS (eg, ● Discuss management of skin- be aware that vomiting after binge- skin-picking, temper tantrums, picking (primarily behavioral; medi- eating can be an ominous sign. food-seeking, etc), which may begin cations, including topiramate, are during this period. used only in the most severe cases). HEALTH SUPERVISION FROM 13 TO● Discuss sibling adjustments, social- 21 YEARS OR OLDER: ization, and recreational skills. Anticipatory Guidance ADOLESCENCE TO EARLY● Encourage families to establish op- ● Review the child’s development ADULTHOOD timal dietary and physical exercise and appropriateness of school Evaluation patterns to prevent obesity; sched- placement and developmental intervention. ● Perform physical examination with ule annual (or more often) meetings particular emphasis on evidence of: with dietitian to review caloric in- ● Continue to stress the need for di- take and suggest ways to provide etary management and daily exer- ● heart failure; less calorically dense foods. cise to avoid obesity. ● peripheral edema;202 FROM THE AMERICAN ACADEMY OF PEDIATRICS Downloaded from by guest on February 4, 2012
  10. 10. FROM THE AMERICAN ACADEMY OF PEDIATRICS ● skin-picking (perianal areas and sumed to be infertile, although the through adult life (eg, the medical intertriginous folds should be possibility of fertility should always geneticist); when new providers are examined); and be considered. needed, the transferring physician ● scoliosis. ● Discuss sexuality and socializa- should clearly communicate the tion, the need for and degree of person’s needs, and care should● Evaluate diet, caloric intake, and ex- supervision and/or the need for overlap until all providers, as well ercise program, and stress obesity contraception. as patients and their family, are prevention; initiate weight-loss comfortable with the care needed. strategy if needed. ● Explain to the patient and her family● Vision screening should be per- the risk of genetic abnormalities if RESOURCES FOR PARENTS formed annually. she were to become pregnant. Prader-Willi Syndrome Association,● Look for early signs of developing ● Discuss group homes and 8588 Potter Park Dr, Suite 500, Sara- psychosis or increasing obsessive- independent-living opportunities sota, FL 34238; telephone: 800-926-4797 compulsive behaviors seen in a mi- specifically for people with PWS, or 941-312-0400; fax: 941-312-0142; nority of patients (risk is apparently workshop settings, and other Web: higher in cases attributable to UPD community-supported employment Foundation for Prader-Willi Research than deletion, but may occur with (group homes specifically designed Canada (formerly Canadian Prader- either of them). for people with PWS are desirable, Willi Syndrome Organization), 19- but they often have long waiting 13085 Yonge St, Suite 370, Richmond● Evaluate pubertal status and con- lists, so applying during the adoles- Hill, Ontario, Canada L4E 0K2; tele- sider referral to pediatric endocri- cent years is helpful in securing a phone: 866-99-FPWRC (866-993-7972); nology for discussion about pros spot for the future). Web: and cons of sex hormone therapy. ● Discuss intrafamily relationships, fi- Foundation for Prader-Willi Research,Anticipatory Guidance nancial planning, and guardianship. 104 Hume Ave, Alexandria, VA 22301;● Discuss skin care, especially in the ● Facilitate transfer to adult medical telephone: 703-683-7500; fax: 703-836- presence of truncal obesity. care. 0959; Web:● Discuss issues related to transition International Prader-Willi Syndrome into adulthood. TRANSITION TO ADULT CARE Organisation, Web: ● Identify health care providers in the● Discuss possible compulsive behav- LEAD AUTHOR community who are willing to learn iors, including use of tobacco. Shawn E. McCandless, MD – Section on about the special situations of peo- Genetics and Birth Defects Member● Discuss appropriateness of school ple with PWS; ideally, use providers placement, and emphasize ade- with training or experience in the COMMITTEE ON GENETICS, 2010 –2011 quate vocational training within the care of people with special needs. Howard M. Saal, MD, Chairperson Stephen R. Braddock, MD school curriculum while keeping in ● Regular evaluation is needed for: Gregory Enns, MB, ChB mind the special issues related to Jeffrey R. Gruen, MD the need to scrupulously avoid expo- ● weight control (maintenance or James M. Perrin, MD sure to opportunities to obtain food. loss); Robert A. Saul, MD Beth A. Tarini, MD● Provide information on how to rec- ● diabetes; LIAISONS ognize the signs of psychosis. ● hypertension; W. Allen Hogge, MD● Discuss the need for gynecologic ● sleep apnea; American College of Obstetricians and care for pubescent girls. Talk about Gynecologists ● heart failure; James W. Hanson, MD – American College of the risk of Angelman syndrome (at- Medical Genetics – Eunice Kennedy Shriver ● peripheral edema; and tributable to deletion of maternally National Institute of Child Health and Human inherited chromosome 15q11-13) ● behavior management, including Development the use of medications such Michele A. Lloyd-Puryear, MD, PhD – Health with the patient and her family if she Resources and Services Administration were to become pregnant; review as selective serotonin-reuptake Sonja A. Rasmussen, MD, MS – Centers for the fact that there have been 2 case inhibitors. Disease Control and Prevention reports in which a woman has re- ● Some providers may continue to STAFF produced. Men with PWS are as- care for the person with PWS Paul SpirePEDIATRICS Volume 127, Number 1, January 2011 203 Downloaded from by guest on February 4, 2012
  11. 11. REFERENCES 1. Prader A, Labhart A, Willi A. Ein syndrom von lation in a series of 167 deletion and non- mone and Prader-Willi syndrome. In: Butler adipositas, kleinwuchs, kryptorchismus deletion patients with Prader-Willi syn- MG, Lee PDK, Whitman BY, eds. Management und oligophrenie nach myotonieartigem drome. Hum Genet. 1995;96(6):638 – 643 of Prader-Willi Syndrome. 3rd ed. New York, zustand im neugeborenenalter [in Ger- 12. Gunay-Aygun M, Heeger S, Schwartz S, NY: Springer; 2006:201–244 man]. Schweiz Med Wochen. 1956;86:1260 Cassidy SB. Delayed diagnosis in patients 23. Eiholzer U, Schlumpf M, Nordmann Y, 2. Driscoll DJ, Waters MF, Williams CA, et al. with Prader-Willi syndrome due to maternal l’Allemand D. Early manifestations of A DNA methylation imprint, determined by uniparental disomy 15. Am J Med Genet. Prader-Willi syndrome: influence of growth the sex of the parent, distinguishes the An- 1997;71(1):106 –110 hormone. 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Am J Med Genet A. 2004;124A(2): 31. Höybye C, Thorén M. Somatropin therapy in ann D, Kaya-Westerloh S, Passarge E, 158 –164 adults with Prader-Willi syndrome. Treat Horsthemke B. Genotype-phenotype corre- 22. Carrel AL, Lee PDK, Mogul HR. Growth hor- Endocrinol. 2004;3(3):153–160204 FROM THE AMERICAN ACADEMY OF PEDIATRICS Downloaded from by guest on February 4, 2012
  12. 12. Clinical Report−−Health Supervision for Children With Prader-Willi Syndrome Shawn E. McCandless and THE COMMITTEE ON GENETICS Pediatrics; originally published online December 27, 2010; DOI: 10.1542/peds.2010-2820 Updated Information & including high resolution figures, can be found at: Services /peds.2010-2820 Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: ml Reprints Information about ordering reprints can be found online: PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2010 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275. Downloaded from by guest on February 4, 2012