Prader-Willi Syndrome

(PWS)
Raeanne Jordan, DPD Senior
Medical or Scientific Names
• Prader-Willi
• Prader-Labhart-Willi syndrome
• PWS
• Willi-Prader syndrome
• Prader-Willi-Fanconi syndrome
• PW
Overview – What is PWS
• Genetic disorder that affects many parts of the body and is caused by
complete or partial absence of paternally expressed genes on
chromosome 15
• Affects genetic material responsible for regulation of gene expression (how
genes turn on or off)
• Of the genetic disorders, PWS is the most common cause of life-
threatening pediatric obesity
• Affects many aspects of daily life – eating, behavior and mood,
physical growth, and intellectual development
Cause
• Genetic changes on an “unstable” region of paternally-inherited
chromosome 15 that affects regulation of gene expression
• Referred to as the Prader-Willi Critical Region (PWCR)
• Occurs around the time of conception or during early fetal
development
• Genetic, but not inherited
• Corresponding region on maternal chromosome 15 is always inactive
and cannot make up for the defect inherited from father
• This is known as genomic imprinting
Specific Changes Leading to PWS
1. Deletions - a section of a chromosome is lost or deleted, along with its functions
• Majority of PWS cases; results from deletion in one region (PWCR) of the father’s
chromosome 15
2. Maternal uniparental disomy – child has two copies of chromosome 15 from the
mother and none from the father
• ~25% of cases
3. Imprinting center defect – chromosome 15 inherited from the father is imprinted
in a way that makes the cell unable to “read” the gene
• Small % of cases
• d/t small deletion on father’s gene that controls the imprinting process
4. Translocation – genes in the PWS region move away from the imprinting center
and therefore cannot be read
Prader-Willi Syndrome vs Angelman
Syndrome
• Two distinct diseases both caused by a deletion in some part of
chromosome 15
• Deletion on chromosome 15 from father  Prader-Willi Syndrome
• Deletion on chromosome 15 from mother  Angelman Syndrome
 Symptoms
Physical:
• Slow growth
• Delays in reaching physical activity milestones (standing, walking)
• Short stature
• Poor muscle tone
• Small hands and feet
• Scoliosis
• Difficulty making their eyes work together (strabismus)
• Unique facial features
• Incomplete sexual development
Symptoms
Intellectual:
• Varying levels of intellectual disabilities
• Learning disabilities and delays in starting to talk and develop language are common
Behavioral and Psychiatric:
• Temper tantrums; extreme stubbornness
• Obsessive-compulsive symptoms
• Picking the skin
• General trouble controlling emotions
• Often repeat questions or statements
• Sleep disturbances – excessive daytime sleepiness and disruptions of sleep
• High pain threshold
Nutritional Phases
Phase 0:
• Full-term birth weight and BMI ~ 15-20% less than siblings
• Normal gestational age
• 85% have decreased fetal movements
Phase 1a: 0-9 mos
• “Floppiness” and poor muscle tone
• Weak sucking reflex; uncoordinated sucking inability to breastfeed; slow oral feeds feeding
support or special, widened nipples required
• Weak cry
• Decreased appetite
• Show little or no evidence of being hungry
• Do not cry for food or get excited at feeding time
• FTT would result if feeding only occurred when baby “acted hungry”
Nutritional Phases
Phase 1b: 9-25 mos
• No longer require nutrition support
• Grow steadily along growth curve
• Normal appetite and feeding
Stage 2a: 2-4.5 years
• Infant starts crossing growth curve %tile lines
• No increase in appetite or excessive calories – normal for age
• Will become obese if given RDA for kcal or eating a “typical” toddler
diet
Nutritional Phases
Stage 2b: 4.5-8 years
• Food-seeking behaviors
• Increased appetite
• Inability to control eating
• Easily redirected about food
• Unable to feel satiated by normal food intake, but can feel full
• Will stop eating voluntarily
Nutritional Phases
• Stage 3: age 8 years through adulthood
• Constantly thinking about food
• Will continue eating if portion sizes are not limited
• Rarely (truly) feel full
• Will steal food or money to pay for food; break into neighbors’ houses
• Willing to eat food from garbage or unsavory/inedible items
• Tend to lie about amount and types of food eaten
• If unsupervised, will gain considerable weight over a short period
• Food usually needs to be locked up
• Throw temper tantrums/”meltdowns” related to food
Nutritional Phases
• Stage 4: adulthood (onset as early as 20s or as late as 40s-50s)
• Appetite may be increased, normal, or less than normal
• Noticeable improvement, despite some fluctuations, in appetite control compared to
previous phases
• Can feel full
• Not as preoccupied with food
• Absence of temper tantrums/”meltdowns” r/t food
• Most adults have not gone into this phase – unclear if many ever will
Diagnosis
• In most cases, diagnosis is prompted by physical symptoms in the newborn
• Formal diagnostic criteria depends on age:
• Children younger than 3 years must have at least four major criteria and at least one
minor criterion
• Children 3 years and older must have at 5 major criteria and at least 3 minor criteria
• Genetic testing is used to confirm diagnosis and determine specific cause
• Early diagnosis is best in order to begin interventions and treatment of
symptoms
• Prenatal genetic testing is available for at-risk pregnancies
Diagnostic Testing – Genetic Confirmation
Medical Treatment &
Management
Medical Management & Treatment
• Requires multidisciplinary approach – genetics, endocrinology,
nutrition, pulmonology and sleep, behavior, intervention services with
care coordination
• No cure
• Goal: early diagnosis and treatment to help prevent or reduce the
number of challenges experienced by affected individuals
• Types of treatment depend on the individual’s age/stage and
symptoms
Medical Management and Treatment
• Growth hormone (GH) therapy
• Increases height, LBM, and mobility
• Decreases fat mass
• Improves movement and flexibility from infancy through adulthood
• May prevent or reduce behavioral difficulties when given early in life
• Can help improve speech, abstract reasoning, information processing
• Improves sleep quality and REE
Medical Management and Treatment
• Treatment of eye problems by a pediatric ophthalmologist
• Treatment of spine curvature by an orthopedist
• Sleep studies and treatment
• Physical therapy
• Behavioral therapy (structure and routine; firm limit-setting)
• Medication
• Special needs programs
• Sex hormone treatments and/or corrective surgery
• Placement in group homes during adulthood
MNT
Nutrition Assessment
• Review medical history and clinical data
• Nutritional phase; comorbidities; other diagnoses; DNI
• Anthropometrics – height, weight, HC; arm circumference and triceps
skinfold
• Plot on appropriate CDC growth chart
• BMI may be distorted, but plotting over time is useful in determining unusual
changes
• Biochemical data – same labs as non-PWS pt + FBG or GTT
• NFPE – fat mass and LBM
Nutrition Assessment
• Dietary intake – information varies depending on their age
• Infants: careful dietary history and analyze energy and nutrient intake
• Ask about feeding skill development and GI issues (GERD d/t hypotonia)
• Toddler: carefully assess portion sizes, frequency of feeding, and types of food served
• Childhood & teens: same as toddler + information on environmental control techniques
• Establish eating patterns and food preferences, appetite level, and quantity needed to feel satiated (if
at all)
• Feeding skills
• Weak oral skills and poor sucking skills in first year
• Delayed feeding skills as child matures
• Chewing and swallowing problems (may be associated with low muscle tone)
• Behavioral feeding issues associated with insatiable appetite and not being provided food  tantrums
• Additional concerns – activity level; cognitive skills; economic resources
Lifelong Nutrition Considerations
• Hyperphagia
• Lack of food selectivity
• High pain tolerance
• Propensity for acute gastric dilation and necrosis
• Increased threshold for vomiting
• Aspiration and choking risk
• Constipation
• Infancy: feeding and swallowing difficulty
 Common nutrition-related diagnoses and etiologies
Diagnoses Etiology and/or signs and symptoms
Breastfeeding difficulty Feeding difficult with weak and/or uncoordinated suck
Inadequate oral intake Poor weight gain
Low appetite
Excessive Energy Intake Increased body adiposity
Overweight/obesity BMI >85th %tile at age 2-20 years
Reduced energy needs (hypotonia)
Self-monitoring deficit
Limited adherence to nutrition-related recommendations Inability to limit or refuse foods offered
Lack of family or social support for implementing changes

Undesirable food choices Intake is inconsistent with diet quality guidelines

Unable to independently select foods consist with food
quality and energy needs
Intake of unsafe food Food obsession
Hyperphagia
Eating serves a purpose other than nourishment
Pica
MNT
• The best diet for each child should be based on their weight-for-
length, rate or weight gain, growth velocity, and energy level during
the day
• Close oversight of diet throughout life ensures adequate provision of
macronutrients and micronutrients
MNT
• Best practice = early intervention
• Parental counseling and caloric restriction have NOT been shown to
change the timing or progression of phases
• HAVE been successful in keeping weight-for-height normal in many
infants and young children before phase 2b.
MNT – Infancy
• Discuss use of feeding tubes (NG or gastrostomy tubes) with
increased caloric-density formula to minimize volume
• Use of special nipples/feeders
• Avoid prolonged oral feeding time (keep <20 minutes per feeding)
• Discuss the importance of stimulating the infant
• As infant reaches ~9 mos (stage 1b), begin transitioning from TF
• Refer to early-intervention services
MNT - Infancy
• Caloric needs may be, but are not always, somewhat reduced
• Adjust diet to maintain appropriate weight gain as determined by frequent
weight checks
• Plot growth by using standard pediatric growth charts, paying special
attention to weight-for-length measurements
• Monitor time/work of feeding and caloric density of formula/breast
milk
• Provide overview of long-term nutrition management
MNT - Infancy
• 0-6 mos: consume solely breastmilk or formula
• May require concentration to increase calories & nutrition in less volume
• 6 mos: purees may be start slowly at a tbsp and be increased over a
few months
• Introduce a new food on a weekly basis
• Concentrated breastmilk or formula no longer needed
• 10 mos: formula may decrease to <8 oz, 3-4x/d
• Recommend families begin to modify the diet for all family members to
ensure balanced nutrition
MNT – Toddler/Early Childhood
• Encourage families to establish optimal dietary and physical exercise
patterns to prevent obesity
• Structured dietary protocol allows child to learn that meals are provided at
specified times so that pattern of grazing doesn’t develop.
• Review caloric intake and suggest ways to provide less calorically-
dense foods
• Discuss need for family members, child care providers, and school
staff to understand strict food management and routine
MNT- Toddler/Early Childhood
• When increasing weight gain without a change in calories is noted:
• Caloric restriction – 50-80% RDA for age
• Ensure the diet remains well-balanced – 30% fat, 45% CHO, 25% pro; meeting
essential nutrient needs
• If children with PWS remain on “typical” American toddle diet (60-70% CHO), their
obesity worsen.
• Provide small portions of meats, vegetables, grains, and fruits and limited
amounts of sweets
• Continue to follow growth parameters closely – at lease 1x/mo
MNT – Late Childhood
• Continue to stress the need for dietary management and daily
exercise to avoid obesity
• Maintain caloric restriction and balanced diet:
• 50-80% RDA for age
• Ensure the diet remains well-balanced – 30% fat, 45% CHO, 25% pro
• Continue to follow growth parameters closely – at lease 1x/mo
• Due to high pain tolerance, special attention should be given to risk of
gastric/intestinal necrosis after binge-eating
• Collaboration with school food service is important!
MNT – Adolescence to Early Adulthood
• Evaluate diet, caloric intake, and exercise program
• Stress obesity prevention; initiate weight-loss strategy if needed
• Maintain caloric restriction and balanced diet:
• 50-80% RDA for age
• Ensure the diet remains well-balanced – 30% fat, 45% CHO, 25% pro
MNT – General Recommendations
• Calorie restriction should be considered d/t decreased energy expenditure
• Provide nourishing CHO, such as grains and vegetables
• Recommend avoiding sugars and artificial sweeteners because of added calories
• Drink adequate fluids
• Provide protein at every meal
• Multivitamin w/ minerals
• Avoid gummy vitamins due to overall deficient minerals, risk of abuse, and calorie
content
• Recommend using powders or unpalatable chewable vitamins
• Ketogenic diet???
Supplements
• Currently no randomized, placebo-controlled clinical trials of
supplements in PWS
• Evidence for possible use is anecdotal
• Decisions to try supplements should be made on an individual basis
with critical thinking
• Global PWS Registry – method of tracking success with supplements
and medications
• Evidence-based guidelines needed for supplement use in individuals
with PWS to standardize therapy and determine if benefits exist
Supplements
• B12 (oral or injection)
• Indications: low serum levels, macrocytic anemia, and individuals following a vegan diet
• DHA
• Indications: individuals on a low-fat diet or those with hyperlipidemia
• DHA or EFA deficiency can arise in individuals on a vegetarian restricted diet
• Sometimes taken to decrease risk of psychiatric disorders, but evidence is conflicting on effectiveness
• Carnitine
• Few children with PWS have low serum levels or deficiency indicated by muscle biopsy
• Trial of L-carnitine has not been shown to have benefit in randomized trials
• Coenzyme Q10
• Studies indicate low plasma levels in PWS are comparable to those in obesity
• May improve the duration of suckling in infants and stamina in up to 20% of patients
• No placebo-controlled large studies are available to assess the benefit of supplementation
Supplements - MCT Oil
• A diet high in MCT may affect the transformation of ghrelin from its inactive
form to its active form
• In PWS, ghrelin is elevated throughout the nutritional phases
• In overweight individuals, MCT oil supplementation has shown to decrease
appetite and food intake
• No formal clinical trials have been conducted in patients with PWS
• Suggested dosing:
• Start at 0.5 mL every other feeding
• Advance to every feeding
• Increase in increments of 0.25-0.5 mL/feeding every 2-3 days as tolerated
• Goal: 1 tsp dosed throughout the day
Nutrition-Related Side Effects
• Serotonin Reuptake Inhibitors (SSRIs)
• N/V/D – taking medicine with food or at bedtime may reduce risk of nausea
• Headache
• Drowsiness
• Dry Mouth
• Dizziness
• Impact on appetite, leading to weight loss or weight gain
Nutrition-Related Side Effects
• Human Growth Hormone Therapy
• Joint pain
• Headache
• Temporary increase in blood sugar levels (stops when GH treatment stops)
Nutrition Education
Nutrition Education
• Nutrition education should be individualized based on patient’s age;
cognitive, functional, and communication abilities; literacy; and level
of understanding
• Use person-centered language to place emphasis on the individual,
not the disability
• Ex: “person with a disability” not “disabled person”
• Inform family about the availability of support groups and discuss
individual resources of support (family, clergy, friends, etc.)
• Provide information about Early-Intervention programs and WIC
Nutrition Education
• Review importance of a meal and exercise regimen
• Counsel on calorie needs, balanced macro- and micronutrient intake, and
administering tube feeds (infancy)
• After onset of hyperphagia: strategies to control food-related behaviors
• Limit access to food (ex: locking cabinets and refrigerators)
• Limit exposures that make the child think about food (ex: birthday treats sitting on
the teacher’s desk during the school day)
• Instill confidence that the next meal will be served on time
• Maintain strict mealtime routines
• Make sure relatives and friends realize that “sneaking” food to the child is not an
appropriate demonstration of affection
Nutrition Education
• Constipation prevention
• Provide adequate fluid and fiber
• Methods for prompting water intake and importance of hydration
• Add fruits or vegetables to provide flavor (ex: strawberries, lemon, cucumber)
• Involve school teachers and food service in food-behavior strategies
and hypocaloric, well-balanced eating
Reference List
1.Academy of Nutrition and Dietetics. Position of the Academy of Nutrition and Dietetics: Nutrition Services for Individuals with Intellectual and Developmental
Disabilities and Special Health Care Needs. Journal of the Academy of Nutrition and Dietetics. Published 2015. Accessed March 2020.
2.Duis J, van Wattum PJ, Scheimann A, et al. A multidisciplinary approach to the clinical management of Prader-Willi syndrome. Mol Genet Genomic Med.
2019;7:e514. doi: 10.1002/mgg3.514.
3.Mahan LK, Raymond JL. Krause’s Food & The Nutrition Care Process. 14th ed. St. Louis, Missouri: Elsevier Inc; 2017.
4.Mayo Clinic Staff. Selective serotonin reuptake inhibitors (SSRIs). Mayo Clinic Website.
https://www.chp.edu/our-services/endocrinology/resources/endocrinology-patient-procedures/growth-hormone-treatment. Published Sept, 17, 2019. Accessed
April 2020.
5.Miller JL, Lynn CH, Driscoll DC, et al. Nutritional phases of Prader-Willi syndrome. Am J Med Genet A. 2011 May; 155A(5): 1040-1049. doi: 10.1002/ajmg.a.33951.
6.National Institute of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development. Prader-Willi Sydrome (PWS): Condition
Information. https://www.nichd.nih.gov/health/topics/prader-willi/conditioninfo/default. Reviewed Dec 1, 2016. Accessed March & April 2020.
7.National Institute of Health, National Human Genome Research Institute. Fluorescence In Situ Hybridization Fact Sheet. Updated July 9, 2015. Accessed March &
April 2020.
8.National Institute of Health, National Human Genome Research Institute. Genetic Imprinting. https://www.genome.gov/genetics-glossary/Genetic-Imprinting.
Accessed March & April 2020.
9.Shawn E. McCandless and The Committee on Genetics. Health supervision for children with Prader-Willi syndrome. Pediatrics. 2011 Jan; 127(1): 195-204. doi:
10.1542/peds.2018-2820.
10.
UPMC Children’s Hospital of Pittsburgh. Growth Hormone Treatment.
https://www.chp.edu/our-services/endocrinology/resources/endocrinology-patient-procedures/growth-hormone-treatment. Published 2010. Accessed April
2020.