Prader-Willi Syndrome 

Updated: Oct 10, 2018
Author: Ann Scheimann, MD, MBA; Chief Editor: Luis O Rohena, MD, MS, FAAP, FACMG 

Overview

Practice Essentials

Prader-Willi syndrome (PWS) is a disorder caused by a deletion or disruption of genes in the proximal arm of chromosome 15 or by maternal disomy in the proximal arm of chromosome 15. Commonly associated characteristics of this disorder include diminished fetal activity, obesity, hypotonia, mental retardation, short stature, hypogonadotropic hypogonadism, strabismus, and small hands and feet.

In 1887, Langdon Down described the first patient with Prader-Willi syndrome as an adolescent girl with mental impairment, short stature, hypogonadism, and obesity and attributed these symptoms to polysarcia.[1] In 1956, Prader et al reported a series of patients with similar phenotypes.[2] In 1981, Ledbetter et al identified deletions located between bands 15q11 and 15q13 and determined it to be the site for Prader-Willi syndrome.[3, 4]

Diagnosis

Genetic testing for Prader-Willi syndrome includes chromosomal or microarray analysis and assessment for methylation patterns in the Prader-Willi syndrome region.

Fasting measurements of serum insulinlike growth factor-1 (IGF-1) and insulinlike growth factor binding protein-3 (IGFBP-3) levels are good screening measurements for underlying growth hormone deficiency. Refer patients with diminished growth velocity and abnormal levels of IGF-1 and IGFBP-3 to a pediatric endocrinologist for provocative growth hormone stimulation testing.

Assess thyroid and adrenal status in patients when clinically warranted.

Measure glycosylated hemoglobin in patients with Prader-Willi syndrome who are obese to assess for the development of type 2 diabetes mellitus as clinically warranted, especially if the patient is taking growth hormone supplementation.

Patients with Prader-Willi syndrome may require the following imaging studies:[5]

  • Magnetic resonance imaging (MRI) of the head (to evaluate for hypopituitarism)
  • Serial dual energy x-ray absorptiometry (DEXA) scanning (for detection and monitoring of osteoporosis) [6]
  • Scoliosis films
  • Chest radiography (if cor pulmonale is suspected)
  • Other imaging modalities as clinically dictated (eg, extremity film for limp evaluation, hip films to screen for hip dysplasia [7] )

Management

Patients with Prader-Willi syndrome frequently require medical care for the following[5] :

  • Initial management of hypotonia or poor feeding
  • Evaluation for hypogonadism or hypopituitarism
  • Management of obesity
  • Monitoring for scoliosis
  • Therapy for behavioral issues

On June 20, 2000, the US Food and Drug Administration (FDA) approved the use of growth hormone in children with genetically confirmed Prader-Willi syndrome and evidence of growth failure.[8, 9, 10]

Patients with Prader-Willi syndrome may require surgical care for treatment of complications of obesity, treatment of cryptorchidism, and scoliosis intervention. They may require urgent surgical attention for abdominal issues. Because of a high pain tolerance and decreased ability to vomit, they may present late with symptoms of cholecystitis, appendicitis, or acute gastric dilation with risk for progression to necrosis.[11, 12]

Tonsillectomy, adenoidectomy, or tracheostomy placement may be required in patients with obstructive sleep apnea.

Pathophysiology

Prader-Willi syndrome is the first human disorder attributed to genomic imprinting. In such disorders, genes are expressed differentially based on the parent of origin. An imprinting center has been identified within 15q11-13; gene expression may be regulated by DNA methylation at cytosine bases.[13] Prader-Willi syndrome results from the loss of imprinted genomic material within the paternal 15q11.2-13 locus.[14] The loss of maternal genomic material at the 15q11.2-13 locus results in Angelman syndrome.[15]

Most cases of Prader-Willi syndrome that involve deletions, unbalanced translocations, and uniparental (maternal) disomy are sporadic. Monozygotic twins are concordantly affected. Approximately 70% of Prader-Willi syndrome cases arise from deletion of band 15q11-13 on chromosome 15. Maternal uniparental disomy caused by chromosomal nondisjunction accounts for 28% of Prader-Willi syndrome cases.[16, 17] Less than 1% of patients have mutations isolated to the imprinting center, which carries a risk of recurrence.[18] Buiting et al have suggested that deletions solely localized to the imprinting center may be due to a failure to erase the maternal imprint during spermatogenesis.[19]

Several genes have been mapped to the 15q11.2-13 region, including the SNRPN gene, P gene (type II oculocutaneous albinism),[20] UBE3A gene (encodes a ubiquitin-protein ligase involved in intracellular protein turnover), and necdin gene (codes for a nuclear protein expressed exclusively in the differentiated mouse brain).[21] Mutations associated with the maternal UBE3A gene result in Angelman syndrome.[19]

A report by Butler et al suggested that individuals with Prader-Willi syndrome have decreased mitochondrial function, with basal respiration, maximal respiratory capacity, and adenosine triphosphate (ATP)–linked respiration in the study differing significantly between Prader-Willi syndrome patients and healthy controls.[22]

The role of ghrelin in the satiety defect found in Prader-Willi syndrome is a subject of active investigation. In 2002, Cummings et al reported significantly elevated ghrelin levels (4.5-fold higher) in individuals with Prader-Willi syndrome.[23] Haqq et al reported improvement in ghrelin levels after octreotide infusion but no significant improvement in postprandial suppression of ghrelin levels.[24] After correction of relative hypoinsulinemia, Goldstone et al reported a residual 1.3-fold to 1.6-fold elevation in fasting ghrelin levels and a 1.2-fold to 1.5-fold elevation in postprandial ghrelin levels in adults with Prader-Willi syndrome.[25]

Epidemiology

Frequency

United States

Most cases of Prader-Willi syndrome are sporadic. Burd et al reported a prevalence rate of 1 per 16,062 population.[26] Butler reported a prevalence rate of 1 per 25,000 population.[27]

International

Prader-Willi syndrome has been reported worldwide. Reported prevalence rates for Prader-Willi syndrome range from 1 per 8000 population in rural Sweden to 1 per 16,000 population in western Japan.[28, 29] Despite findings that suggest a prevalence rate of 1 per 52,000 population in the United Kingdom, Whittington et al estimate that the actual prevalence rate is higher and propose a true prevalence rate of 1 per 45,000 population.[30]

Mortality/Morbidity

Complications due to obesity (eg, slipped capital femoral epiphyses, sleep apnea, cor pulmonale, type 2 diabetes mellitus) and behavioral problems are major contributors to morbidity and mortality in individuals with Prader-Willi syndrome (see Complications). Lamb et al reported premature development of atherosclerosis with severe coronary artery disease in a patient aged 26 years with Prader-Willi syndrome, morbid obesity, and non–insulin-dependent diabetes mellitus.[31]

Wharton et al described a series of 6 patients with Prader-Willi syndrome with dramatic acute gastric distention preceded by symptoms of gastroenteritis.[11] One half of the cases rapidly progressed to massive gastric dilatation and gastric necrosis. One patient died of overwhelming sepsis and disseminated intravascular coagulation. Gastric dilatation spontaneously resolved in 2 children. Gastrectomy was performed in 2 patients; in one patient, gastrectomy was subtotal and distal, whereas in the other patient, gastrectomy was combined with partial duodenectomy and pancreatectomy. An autopsy series by Stevenson et al reported gastric rupture and necrosis as the confirmed cause of death in 3% of the patients with Prader-Willi syndrome, with another 4 suspected cases of gastric necrosis.[12]

In a series of 152 patients with Prader-Willi syndrome, choking episodes were reported as the cause of death in 7.9%.[32]

Another series of patients noted 8 children and 2 adults who had unexpected death, with small adrenal glands noted in 3 of 8 children, raising suspicion for underlying adrenal insufficiency.[33] Subsequent studies have disputed the frequency of central adrenal insufficiency proposed by these authors, believing it to be a rare occurrence.[34]

Assessing a 40-year mortality survey from the Prader-Willi Syndrome Association (USA), Manzardo et al found measurable increases in survival in Prader-Willi syndrome with regard to cardiovascular- and gastrointestinal-related problems. The investigators said the change was probably the result of "earlier diagnosis and proactive interventions to prevent morbid obesity."[35]

Race

Differences in prevalence rates between racial groups have not been consistently reported. However, in a study of 10 black patients with Prader-Willi syndrome, Hudgins et al (1998) suggested that clinical features in black patients differ from those of white patients.[36] In black patients, growth is less affected, hand lengths are usually normal, and the facies are less typical.

Sex

Prader-Willi syndrome is caused by the loss of the paternal copy in the proximal arm of chromosome 15 in the region of 15p11-13. Differences in prevalence rates between sexes have not been reported.

Age

Prader-Willi syndrome is a genetic disorder with lifelong implications.

 

Presentation

History

See the list below:

  • Infants with Prader-Willi syndrome (PWS) commonly exhibit hypotonia, poor suck (with requirement of gavage feedings), weak cry, and genital hypoplasia (eg, cryptorchidism, scrotal hypoplasia, clitoral hypoplasia).[37] Neonatal hypotonia is one of the hallmark features of this disorder and is a valuable clue to initiate diagnostic testing.[38]

  • Toddlers with Prader-Willi syndrome demonstrate late acquisition of major motor milestones (eg, sitting at age 12 mo, walking at age 24 mo).

  • Children aged 1-6 years present with symptoms of hyperphagia with progressive development of obesity.

  • Short stature is generally present during childhood; a minority of patients present later with lack of pubertal growth spurt.[39]

  • Sleep disturbances, ranging from central or obstructive sleep apnea to narcolepsy, are common.[40] Exacerbation of obstructive sleep apnea shortly after initiation of growth hormone therapy is a recent concern.

  • Most patients with Prader-Willi syndrome have growth hormone deficiency, as determined with provocative testing.[39]

  • Pubic and axillary hair may grow prematurely in children with Prader-Willi syndrome, but other features of puberty are generally delayed or incomplete.[39]

  • Testicular descent has occurred as late as in adolescence; menarche may occur as late as age 30 years in the presence of significant weight loss.[39]

  • Mild intellectual disability is common.[41]

  • Obesity complications (eg, sleep apnea, cor pulmonale, diabetes mellitus, atherosclerosis), hypogonadism (osteoporosis), and behavioral issues are common problems in adults with Prader-Willi syndrome.[42]

Behavioral problems

Patients with Prader-Willi syndrome often demonstrate behavioral problems.[43]  Young children exhibit temper tantrums, stubbornness, and obsessive-compulsive behaviors.

Behavioral issues often compromise the level of academic performance. Obsessive-compulsive behaviors and perseveration are challenging for children with Prader-Willi syndrome in the classroom setting.[41]  Features of psychosis are present in 5-10% of young adults with Prader-Willi syndrome.[44, 45]

Food-seeking behaviors may include eating garbage, eating frozen food, and stealing resources to obtain food. High thresholds for vomiting and pain tolerance can complicate binging on spoiled foods and delay treatment for GI disease. Death due to choking episodes has been reported.[32] After episodes of binge eating (eg, at holidays), both thin and obese individuals with Prader-Willi syndrome have developed abdominal discomfort, with acute gastric dilation observed using radiography. Some patients have developed gastric necrosis.[12]

A study by Gito et al indicated that among persons with Prader-Willi syndrome, food-related behaviors are more severe in males whose condition is deletion related than in females with gene deletion or in males with maternal uniparental disomy. However, these behaviors were found to be milder in males with maternal uniparental disomy than in females with such disomy.[46]

Physical

Holm et al established the following diagnostic criteria for Prader-Willi syndrome.[47] Based on these guidelines, the diagnosis of Prader-Willi syndrome is highly likely in children younger than 3 years with 5 points (3 from major criteria) or in those older than 3 years with 8 points (4 from major criteria).

  • Major criteria (1 point each)

    • CNS - Infantile central hypotonia

    • GI - Infantile feeding problems and/or failure to thrive

    • Nutrition - Rapid weight gain in children aged 1-6 years

    • Craniofacial - Characteristic facial features such as narrow bifrontal diameter, almond-shaped palpebral fissures, narrow nasal bridge, and down-turned mouth

    • Endocrine - Hypogonadism

    • Developmental - Developmental delay and/or mental retardation

  • Minor criteria (one half point each)

    • Neurologic - Decreased fetal movement and/or infantile lethargy

    • Pulmonary - Sleep disturbance and/or sleep apnea

    • Endocrine - Short stature for predicted height by mid adolescence

    • Dermatologic - Hypopigmentation

    • Orthopedic - Small hands and feet

    • Orthopedic - Narrow hands with straight ulnar border

    • Ophthalmologic – Esotropia and/or myopia

    • Dental - Thick viscous saliva

    • Otolaryngology - Speech articulation defects

    • Psychiatric - Skin picking (Some patients with Prader-Willi syndrome have become anemic from chronic rectal bleeding secondary to skin picking.)

  • Supportive criteria (no points)

    • Neurology - High pain threshold and normal neuromuscular evaluation for hypotonia

    • Gastroenterology - Decreased vomiting

    • Endocrinology - Ineffective thermoregulation, early adrenarche, and/or osteoporosis, adrenal insufficiency[39]

    • Orthopedics – Scoliosis or kyphosis[48]

    • Developmental - Jigsaw puzzle proficiency[47]

Causes

See the list below:

  • Prader-Willi syndrome is due to the loss of the paternal copy of chromosome 15q11.2-13.[4]

  • Most cases of Prader-Willi syndrome are sporadic. More than 70% of patients have a deletion of the paternal copy; approximately 25% of patients with Prader-Willi syndrome have maternal uniparental disomy in chromosome 15. The remainder of patients with this disorder have a translocation or other structural alteration in chromosome 15.

  • Most manifestations of Prader-Willi syndrome are attributable to hypothalamic dysfunction.

 

DDx

Diagnostic Considerations

These include the following:

  • Angelman syndrome

  • Scoliosis

  • Hypotonia

  • Bardet-Biedl syndrome

  • Cohen syndrome

  • Albright hereditary osteodystrophy

  • Maternal uniparental disomy of chromosome 14

Differential Diagnoses

 

Workup

Laboratory Studies

See the list below:

  • Genetic testing[49, 5]

    • Genetic testing for Prader-Willi syndrome (PWS) includes chromosomal or microarray analysis and assessment for methylation patterns in the Prader-Willi syndrome region.

    • Methylation patterns can be determined with Southern blot hybridization or polymerase chain reaction (PCR) using DNA primers that can detect methylated cytosine.

    • Analysis for underlying uniparental disomy requires samples from both parents and the child with Prader-Willi syndrome.

    • Fluorescent in situ hybridization (FISH) can be used to confirm prenatal diagnosis when a deletion in the 15q region is suspected after chorionic villus sampling or amniocentesis.

    • In a patient with an imprinting center mutation, test both biological parents for the presence of asymptomatic mutations in the imprinting center; such mutations indicate a higher risk for recurrence.

  • Hypogonadism[39, 5]

    • Most patients with Prader-Willi syndrome have hypothalamic dysfunction that manifests as short stature, central obesity, hypogonadism, and osteoporosis.

    • Fasting measurements of serum insulinlike growth factor-1 (IGF-1) and insulinlike growth factor binding protein-3 (IGFBP-3) levels are good screening measurements for underlying growth hormone deficiency.

    • Refer patients with diminished growth velocity and abnormal levels of IGF-1 and IGFBP-3 to a pediatric endocrinologist for provocative growth hormone stimulation testing.

    • Assess thyroid and adrenal status in patients when clinically warranted.

    • Hypopituitarism has been reported in some patients with Prader-Willi syndrome.

  • Obesity[39, 50, 51, 5]

    • Measure glycosylated hemoglobin in patients with Prader-Willi syndrome who are obese to assess for the development of type 2 diabetes mellitus as clinically warranted, especially if the patient is taking growth hormone supplementation.

    • Evaluate patients with Prader-Willi syndrome for biochemical evidence of pickwickian syndrome (eg, hypercarbia, polycythemia) as clinically warranted.

    • If symptoms suggest sleep apnea or narcolepsy, perform a sleep study with multiple sleep latency testing.

Imaging Studies

See the list below:

  • Individuals with Prader-Willi syndrome are at risk for pathologic fractures secondary to underlying osteoporosis. A high pain tolerance may allow for minimal symptoms of discomfort with obvious deformity. Patients with Prader-Willi syndrome may require the following imaging studies:[5]

    • MRI of the head (to evaluate for hypopituitarism)

    • Serial dual energy x-ray absorptiometry (DEXA) scanning (for detection and monitoring of osteoporosis)[6]

    • Scoliosis films

      Severe typical scoliosis. Severe typical scoliosis.
    • Chest radiography (if cor pulmonale is suspected)

    • Other imaging modalities as clinically dictated (eg, extremity film for limp evaluation, hip films to screen for hip dysplasia[7] )

  • In patients who suddenly develop abdominal distention, abdominal pain, or a decrease in appetite, imaging including plain abdominal radiography, abdominal ultrasonography, or CT scanning and gastrointestinal series may be warranted to screen for possible conditions such as acute gastric dilation, cholelithiasis, or pancreatitis.

Procedures

See the list below:

  • Assess the growth hormone axis and adrenal axis under the supervision of an endocrinologist if clinically warranted.[39]

 

Treatment

Medical Care

Patients with Prader-Willi syndrome (PWS) frequently require medical care for the following[5] :

  • Initial management of hypotonia or poor feeding
  • Evaluation for hypogonadism or hypopituitarism
  • Management of obesity
  • Monitoring for scoliosis
  • Therapy for behavioral issues

On June 20, 2000, the US Food and Drug Administration (FDA) approved the use of growth hormone in children with genetically confirmed Prader-Willi syndrome and evidence of growth failure.[8, 9, 10]  A study by Bakker et al indicated that growth hormone therapy improves the health-related quality of life (HRQOL) in children with Prader-Willi syndrome. The study included annual HRQOL assessments over an 11-year period.[52]

A prospective cohort study by Donze et al reported that in infants and toddlers with Prader-Willi syndrome who underwent 3 years of growth hormone therapy, mental and motor development tended to see a greater increase in patients who began treatment at a younger age and who had lower psychomotor development at baseline. Using the Bayley Scales of Infant Development II, the investigators also found that over the 3-year treatment course, mental development increased from a mean (standard error of the mean [SEM]) baseline value of 58.1% to 79.6%, while mean (SEM) motor development rose from 41.9% at baseline to 78.2%.[53]

A study by Scheermeyer et al indicated that in infants (aged 2-12 mo) with Prader-Willi syndrome, the effects of low-dose growth hormone treatment (4.5 mg/m2/wk) on growth and development are comparable to those of higher-dose treatment (7 mg/m2/wk). Moreover, although IGF levels rose in response to the lower-dose therapy, the increase was not excessive, signaling that the lower-dose approach may decrease long-term treatment risks.[54]

A double-blind, placebo-controlled, crossover study by Miller et al suggested that low-dose intranasal oxytocin therapy may reduce appetite drive in patients with Prader-Willi syndrome, as well as improve socialization, anxiety, and repetitive behaviors in these individuals.[55]

Surgical Care

See the list below:

  • Patients with Prader-Willi syndrome may require surgical care for treatment of complications of obesity, treatment of cryptorchidism, and scoliosis intervention. They may require urgent surgical attention for abdominal issues. Because of the high pain tolerance and decreased ability to vomit, they may present late with symptoms of cholecystitis, appendicitis, or acute gastric dilation with risk for progression to necrosis.[11, 12]

  • Tonsillectomy, adenoidectomy, or tracheostomy placement may be required in patients with obstructive sleep apnea.

  • Biliopancreatic diversion and gastric bypass surgery have been ineffective for long-term weight reduction.[56, 57] Significant disruption in the enterohepatic circulation of bile acids may result in deficiencies of fat-soluble vitamins and steatorrhea with anal pruritus due to bile acids. Anal pruritus may exacerbate rectal-picking compulsions. Deficiencies of fat-soluble vitamins may exacerbate the following:

    • Osteoporosis (vitamin D)

    • Hypochromic anemia (vitamin E)

    • Hyporeflexia (vitamin E)

    • Spinocerebellar ataxia (vitamin E)

    • Coagulopathy (vitamin K)

    • Night blindness (vitamin A)

    • Enhanced susceptibility to infections (vitamin A)

Consultations

Patients with Prader-Willi syndrome may require the support of the following specialists:[7]

  • Geneticist for initial diagnosis and counseling

  • Developmental pediatrician for stimulation programs

  • Endocrinologist for management of hypogonadism

  • Nutritionist for dietary counseling

  • Ophthalmologist for management of strabismus

  • Pulmonologist for management of sleep apnea

  • Psychiatrist, psychologist, or both for management of behavioral issues

  • Gastroenterologist for GI issues

Diet

Patients with Prader-Willi syndrome have hyperphagia (onset in children aged 1-6 y) and diminished basal metabolic rate. Various treatment modalities for weight control, ranging from behavioral modification to anorexic agents, have been largely unsuccessful in curbing hyperphagia. However, these modalities may yield some success when used at group home settings.[7, 57]

  • Significant dietary restrictions are not implemented during early childhood to ensure optimal myelination.

  • Institution of a balanced hypocaloric diet (1000 calories with supplementation of vitamins and calcium) is generally implemented at early school age with careful monitoring by a dietitian.

  • As children with Prader-Willi syndrome become ambulatory, limitation of access to foods is essential for modulation of weight. Placement of locks on cupboards and refrigerators, use of smaller dishes, and restriction of access to food in the school environment help deter excessive weight gain.

  • In patients with morbid obesity, a protein-sparing modified fast with careful medical and nutritional supervision over several weeks may facilitate short-term weight loss.[58]

  • Based on the feeding behaviors of patients with Prader-Willi syndrome, one study assessed laboratory changes, metabolic changes, and growth changes and identified a total of 7 different nutritional phases, with 5 main phases and subphases in phases 1 (poor feeding and failure to thrive in infancy) and 2 (hyperphagia leading to obesity in later childhood). The study shows that progression of the nutritional phases is much more complex than the previously recognized 2 nutritional stages; awareness of these phases may help develop therapies and prevent or delay the early onset of obesity.[59]

Activity

See the list below:

  • Patients with Prader-Willi syndrome have hypotonia and require supplemental occupational and physical therapy to promote acquisition of gross and fine motor skills and to strengthen spinal musculature in order to minimize scoliosis.[48]

  • Encouragement of physical activity at home, at school (eg, increased physical education periods), and in the community (eg, Special Olympics) is essential for modulation of weight.

  • Care providers should be instructed in the Heimlich maneuver.[32]

 

Medication

Medication Summary

Currently, no medications have been found to effectively modify hyperphagia. Growth hormone therapy in patients with growth hormone deficiency improves lean body mass, corrects osteopenia, does not appear to enhance the development of scoliosis, and anecdotally modulates behavior in some patients.[39, 8, 9, 10] Supplementation of sex steroids does improve secondary sex characteristics but may aggravate behavioral disorders.[39]

Growth hormone agents

Class Summary

These agents improve symptoms of growth hormone deficiency.

Human growth hormone (Saizen, Genotropin, Humatrope, Nutropin, Serostim)

Stimulates growth of linear bone, skeletal muscle, and organs. Stimulates erythropoietin, increasing RBC mass.

 

Follow-up

Further Outpatient Care

See the list below:

  • Further outpatient care is targeted toward management of hypogonadism, obesity, and behavioral issues.

Further Inpatient Care

See the list below:

  • Patients with Prader-Willi syndrome (PWS) may require inpatient evaluation and treatment for hypotonia and poor feeding during infancy.

  • Individuals with Prader-Willi syndrome and other medical issues, including scoliosis and complications of obesity or pickwickian syndrome, may require inpatient therapy.

  • Patients with severe behavioral problems may merit admission to a facility staffed with individuals with long-term experience with Prader-Willi syndrome.

Transfer

See the list below:

  • Patients with Prader-Willi syndrome and significant behavioral issues recalcitrant to traditional therapies may benefit from transfer to a center, such as the Children's Institute in Pittsburgh, staffed with individuals with experience in treatment of people with Prader-Willi syndrome.

Deterrence/Prevention

See the list below:

  • Patients with Prader-Willi syndrome have hyperphagia and require restricted access to foods to minimize weight gain. Binge-eating episodes may predispose patients to development of food poisoning and acute gastric dilation. Caregivers of patients with Prader-Willi syndrome should be instructed in the Heimlich maneuver.[32]

  • Evaluate males with Prader-Willi syndrome and cryptorchidism for gonadotropin-releasing hormone (GnRH) and orchiopexy.[39]

  • Routinely monitor for symptoms of sleep apnea. Obtain a sleep study within the few months after initiation of growth hormone therapy at the first sign of symptoms.[8]

  • Routinely screen children for scoliosis.[48, 7]

  • Regularly screen patients with obesity for evidence of type 2 diabetes mellitus.[39]

  • Screen for thyroid and adrenal function when indicated.[7]

Complications

See the list below:

  • Patients with Prader-Willi syndrome can develop complications from the following:

    • Hypogonadism (osteoporosis/pathologic fractures)

    • Obesity due to hyperphagia and hypometabolism (secondary to hypopituitarism): This predisposes patients to premature death from cardiorespiratory failure.

    • Slipped capital femoral epiphyses/hip dysplasia

    • Sleep apnea: Patients with Prader-Willi syndrome have a primary disturbance in central control of the respiratory drive with diminished responsiveness to hypercapnia during quiet sleep.

    • Cor pulmonale

    • Type 2 diabetes mellitus

    • Neoplasias (eg, Wilms tumors,[60] testicular neoplasias,[61] multiple endocrine neoplasia [MEN1],[62] neoplasias, hematologic neoplasias [leukemia][63] ): Various neoplasias have been rarely reported in patients with Prader-Willi syndrome.

    • Binge-eating episodes: These episodes may predispose patients to choking episodes (which require the Heimlich maneuver), acute gastric dilation with risk of gastric necrosis, and food poisoning from consumption of contaminated food.[11, 32]

Prognosis

See the list below:

  • Patients with Prader-Willi syndrome frequently reach adulthood and are able to function in a group home setting, performing vocational work or attending community college classes.

  • Diminished sensitivity to pain and diminished capacity to vomit may delay the diagnosis of underlying disease (eg, appendicitis).

  • Complications from hypogonadism (eg, osteoporosis/pathologic fracture), behavioral issues (eg, temper tantrums, stubbornness, psychoses), and morbid obesity (eg, type 2 diabetes mellitus, cor pulmonale) may shorten life expectancy and may affect the quality of life.

  • Patients with Prader-Willi syndrome can be mainstreamed into the classroom environment. They require additional speech therapy to enhance verbal skills and should have additional physical activity periods in place of rest periods. These individuals require a structured environment and may need a smaller classroom size for individual attention.

  • Older children with Prader-Willi syndrome may enter vocational programs (with avoidance of food preparation). Some adults have attended community colleges.

 

Questions & Answers

Overview

What is Prader-Willi syndrome (PWS)?

How is Prader-Willi syndrome (PWS) diagnosed?

What are the components of treatment for Prader-Willi syndrome (PWS)?

What is the pathophysiology of Prader-Willi syndrome (PWS)?

What is the prevalence of Prader-Willi syndrome (PWS) in the US?

What is the global prevalence of Prader-Willi syndrome (PWS)?

What is the mortality and morbidity associated with Prader-Willi syndrome (PWS)?

What are the racial predilections of Prader-Willi syndrome (PWS)?

What are the sexual predilections of Prader-Willi syndrome (PWS)?

Which age groups have the highest prevalence of Prader-Willi syndrome (PWS)?

Presentation

Which clinical history findings are characteristic of Prader-Willi syndrome (PWS)?

What are the behavioral signs and symptoms of Prader-Willi syndrome (PWS)?

Which physical findings are characteristic of Prader-Willi syndrome (PWS)?

What causes Prader-Willi syndrome (PWS)?

DDX

Which conditions are included in the differential diagnoses of Prader-Willi syndrome (PWS)?

What are the differential diagnoses for Prader-Willi Syndrome?

Workup

What is the role of lab tests in the workup of Prader-Willi syndrome (PWS)?

What is the role of imaging studies in the workup of Prader-Willi syndrome (PWS)?

What is the role of an endocrinologist in the workup of Prader-Willi syndrome (PWS)?

Treatment

How is Prader-Willi syndrome (PWS) treated?

What is the role of surgery in the treatment of Prader-Willi syndrome (PWS)?

Which specialist consultations are beneficial to patients with Prader-Willi syndrome (PWS)?

Which dietary modifications are used in the treatment of Prader-Willi syndrome (PWS)?

Which activity modifications are used in the treatment of Prader-Willi syndrome (PWS)?

Medications

What is the role of medications in the treatment of Prader-Willi syndrome (PWS)?

Which medications in the drug class Growth hormone agents are used in the treatment of Prader-Willi Syndrome?

Follow-up

What is included in the long-term monitoring of Prader-Willi syndrome (PWS)?

When is inpatient care indicated in the treatment of Prader-Willi syndrome (PWS)?

When is patient transfer indicated in the treatment of Prader-Willi syndrome (PWS)?

How are the complications of Prader-Willi syndrome (PWS) prevented?

What are the possible complications of Prader-Willi syndrome (PWS)?

What is the prognosis of Prader-Willi syndrome (PWS)?