Overview of Health Issues for Children with PWSOverview of Health Issues for Children with PWS

Suzanne B. Cassidy, MDSuzanne B. Cassidy, MDIPWSO PresidentIPWSO PresidentClinical Professor of PediatricsClinical Professor of PediatricsDivision of Medical GeneticsDivision of Medical GeneticsUniversity of California, San FranciscoUniversity of California, San Francisco

Discussion of ProblemsDiscussion of Problems

• Many positive aspects to people with PWS

• This presentation relates to difficulties

• Few well-controlled studies• Different doctors may approach problems differently

• My information based on >30 years directing PWS clinics and conducting clinical research, the medical literature, and discussions with other experts

PWS is Highly Variable

• SyndromeSyndrome = a collection of features that are found together more often than by chance alone• Not every affected individual has every finding

• The severity of each finding in PWS is quite variable

• The severity of one finding does not determine the severity of other findings

• Other family characteristics and life experience can influence appearance, abilities and behavior

• People with PWS can have problems or features unrelated to PWS

The Course in PWS Has ChangedThe Course in PWS Has Changed

• Diagnosis occurs at much younger ages

• Many issues recognized earlier and treatment started

• Growth hormone has made a big difference in some aspects

• Much more knowledge of health issues and how to address them

• Much more educational materials for families and health care providers

• And it will be different in the futureAnd it will be different in the future• Cannot judge the future by the presentCannot judge the future by the present

Age-Focused ApproachAge-Focused Approach

• Newborn (<1 mo)

• Infancy (1 mo. – 1 year)

• Early childhood (1 – 5 years)

• Late childhood (5-13 years)

• Most issues span more than one period

Health Issues in Newborns Health Issues in Newborns (< 1 month)(< 1 month)

• Hypotonia and its consequences

• Lethargy

• Sometimes issues related to delivery problems• Prematurity/postmaturity

Hypotonia of PWSHypotonia of PWS

• Hypotonia = low muscle tone, low resistance to gravity• Manifests as decreased movement and weak suck

• Present in ~100%; Most consistent feature of PWS

• Abnormal brain signals to muscle, not a muscle abnormality

• Evident prenatally• Decreased fetal movement • Abnormal delivery position and timing• Frequent need for assisted delivery (Cesarean common)

• Severe hypotonia lasts weeks to months

• Gradually improves, but doesn’t resolve completely

Consequences of Neonatal HypotoniaConsequences of Neonatal Hypotonia

• Poor suckling• Unable to breast feed, weak suck on bottle• Frequent need for nasogastric tube

(gavage) feeding for weeks to months• Slow feeding thereafter• Failure-to-thrive

• Decreased movement• Increases likelihood of altered head shape• Weak cough, increased pneumonia risk

• Increased congenital hip abnormalities (10-20%)

Other Findings in NewbornsOther Findings in Newborns

• Lethargy; poor arousal

• Weak cry

• Sometimes hypothermia

Management of Hypotonia in the Newborn Management of Hypotonia in the Newborn

• No medication shown to treat hypotonia directly• Compensate for poor suck

• Gavage feeding, special nipples; gastrostomy tube usually not needed

• Assure adequate caloric intake by following growth closely• Frequent feeding of small quantities if taking orally

• Support cheeks• Awaken to feed, if needed• Avoid nipple feeding longer than 20 minutes

• Doctor should check for hip dislocation, treat if present• Refer to services for physical and occupational therapy, if

available• Parents should interact and stimulate baby despite sleepiness

and quietness

Health Issues in Infants Health Issues in Infants (1 month-1 year)(1 month-1 year)

• Hypotonia slowly improving• Feeding issues often still present, may last months

• Motor delays become evident

• Squint is common• Undescended testicles in males (80%-90%)

• Scoliosis is common (40% – 80%)

• Can occur any time throughout childhood

• Gastroesophageal reflux may be present

• Growth deficiency may become apparent

• Sleep apnea in some

• Hypothermia or fever of unknown origin occasionally

Management of Health Issues in InfantsManagement of Health Issues in Infants

• Hypotonia and feeding difficulties• Growth and weight-to-height should be monitored

frequently (monthly) by doctor, nurse or dietician• Calorie intake adjusted accordingly, volume and/or calorie density

• Gavage feeding until nippling well, taking feedings under 20 minutes

• Or move directly to cup and spoon

• Continue physical therapy and developmental stimulation

• Lots of interaction with parents, siblings

• Check thyroid function if hypotonia not improving significantly with time

A Word on SupplementsA Word on Supplements

• Some families have given supplements to their child with PWS• CoQ10, Carnitine, and Fish Oil• Involved in energy metabolism

• Some see improvement in hypotonia, motor development, and/or energy; Others don’t• No evidence of deficiency of these in PWS• No well-controlled studies showing benefit or harm

• Some specialists recommend them, others don’t• Discuss with doctor• Assess benefit

Management in InfantsManagement in Infants

• Ophthalmologist evaluation for squint• Squint treated with patching or surgery

• Regular (annual) ophthalmology visits thereafter

• Doctor to assess testicular position• Refer within the first year for hormonal and/or surgical

treatment if undescended

• Doctor to clinically evaluate for scoliosis • Refer to orthopedist if present

Management in Infants Management in Infants (cont.)(cont.)

• Assessment for GE reflux• Spitting up/vomiting with discomfort or crying, breathing

problems of any kind (gagging, choking, coughing, wheezing, or pneumonia due to aspiration)

• If present, doctor to evaluate and treat• Treated with adjustments to feedings, medication and/or surgery

• Discussion of growth hormone in PWS with doctor or specialist• Appropriate to start treatment in the first few months of life

• Sleep study before starting

Sleep and PWS Sleep and PWS (all ages)(all ages)• Increase in sleep apnea (pauses in breathing) and other

sleep alterations • Central sleep apnea vs. obstructive sleep apnea

• Risk for sleep apnea increased by• Young age• Severe hypotonia• Prior respiratory problems• Severe obesity

• Recommend formal sleep study in all• Strongly recommended before GH treatment

• GH treatment may increase tonsil & adenoid size before throat size• Can be treated, as in general population

• Tonsillectomy, Continous Positive Airway Pressure (CPAP), or other

Health Issues in Early Childhood Health Issues in Early Childhood (1-5 years)(1-5 years)

• Weight and onset of hyperphagia (excess eating)

• Growth

• Visual acuity (eyesight)

• Scoliosis

• Sleep problems

• Decreased saliva and dental problems

• Constipation

• Hypothyroidism

Weight Problems in PWSWeight Problems in PWS

• 3 major causes of tendancy toward excess weight in people with PWS:1. Altered brain perception of having eaten enough (satiety) 2. Decreased requirement for calories

• Probably related to hypotonia, decreased activity and short stature

3. High threshold for vomiting and decreased pain perception, leading to eating large quantities without discomfort

HyperphagiaHyperphagia

• Onset of excessive appetite (hyperphagia) between 1 and 6 years of age, often later• Nearly constant food seeking, variable intensity

• Present regardless of weight

• Physiological mechanism causing hyperphagia still unclear• Currently no proven effective direct treatment • Subject of much research and drug development efforts

Obesity in PWSObesity in PWS

• If uncontrolled externally, drive to eat excessively leads to obesity

• Obesity is the major cause of medical problems and death in people with PWS

• Impact of obesity in early childhood:• Slows motor development

• Respiratory problems, if severe

• Sleep apnea

• Choking due to eating too fast (esp. hot dogs/sausages!) • Is a cause of death in PWS at any age

• Social problems

Treatment of Obesity in PWSTreatment of Obesity in PWS• No currently available safe drug known to decrease urge to eat

• Surgery• High rate of complications and low rate of long term weight loss

• No long-term studies on newer techniques• Prevention and Management of obesity

• Low calorie diet (work with dietician, adjust to level of activity)• Lots of physical activity• Food security (environmental control)

• Lock kitchen; constant supervision, no high calorie foods in the home, compensate for “indiscretion”

• Consistent limits, consistently enforced• Important role for growth hormone

Management of Other Issues in InfaManagement of Other Issues in Infancyncy• Decreased saliva may increase risk for dental problems,

predispose to choking on food, and contribute to speech problems• Encourage liquids

• Arrange visit to dentist no later than age 3 years, preferably earlier• At least twice yearly thereafter

• In later years, special toothpaste, gel, or mouthwash to increase saliva flow

• Constipation• Very common problem, probably related to intestinal hypotonia

• Should be treated aggressively throughout life• Dietary changes, softening agents, increased fiber intake, liquids

• Medications in later years

Management of Other Issues in InfancyManagement of Other Issues in Infancy

• Hypothyroidism (low thyroid hormone production)• Present in 10%-20% of people with PWS

• Can occur at any age

• Can lead to prolonged hypotonia

• Screen annually

• If present, treat with standard dose (a small thyroid hormone pill)

Management of Other Issues in InfancyManagement of Other Issues in Infancy

• Growth

• Care provider to follow closely• Continue growth hormone treatment, if possible

Management of Other Issues in InfancyManagement of Other Issues in Infancy

• Vision• Continue annual ophthalmology evaluation, if possible

• Scoliosis• Doctor to continue annual clinical assessment, consider X-ray

and/or referral if uncertain

• Sleep• Concern about sleep apnea continues• Snoring, spells of not breathing, restless sleep should lead to sleep

study

Health Issues in Later Childhood Health Issues in Later Childhood (5-13 years)(5-13 years)

• Issues same as at earlier ages• Growth• Weight, dietary management and exercise• Sleep apnea• Visual acuity problems• Scoliosis

• Skin picking• Increased pain tolerance• Altered temperature control/perception• Early signs of puberty (premature adrenarche)• Risk for gastric dilatation• Cortical adrenal insufficiency

Management of Health Issues in ChildhoodManagement of Health Issues in ChildhoodIssues as at earlier agesIssues as at earlier ages

• Growth• Continue to monitor• Continue growth hormone

• Weight, dietary management and exercise• Consequences of obesity

• Cardiopulmonary compromise • Increased risk for type II diabetes • Obstructive sleep apnea• Tissue swelling; skin breakdown; hygiene problems

• Prevention and management of obesity• Continue low calorie diet, exercise, and access restriction• Continue with consistent, firmly-enforced limit setting• Distraction helps• Dietician if possible

Management of Health Issues in ChildhoodManagement of Health Issues in ChildhoodIssues as at earlier ages Issues as at earlier ages (cont.)(cont.)

• Sleep apnea• Sleep study if symptoms occur

• Visual acuity problems• Routine checks

• Scoliosis • Monitor clinically, X-ray and/or referral if suspicious

Management of Health Issues in ChildhoodManagement of Health Issues in Childhood• Skin and other picking

• Can lead to chronic sores, infection• No commonly used treatment

• Keep hands busy, nails short, use distraction• Preliminary study suggests benefit from N-aceyl cysteine (NAC)

• Increased pain tolerance• Evaluate complaints of internal pain quickly and thoroughly• X-rays after trauma if movements suggestive

• Altered temperature control/perception• Occasional hypothermia or fever of unknown origin • May need guidance on appropriate clothing for the weather

• Early signs of puberty (premature adrenarche) in 15%-20%• Pubic and armpit hair, acne, adult odor• Rest of puberty usually delayed and incomplete

Stomach Dilation and RuptureStomach Dilation and Rupture• An occasional but very serious problem

• Mostly occurs in adolescents or adults, occasionally in older childhood

• Contribution from gastroparesis (weak stomach muscle function causing slow stomach emptying) and constipation

• Mostly follows an overeating binge• Especially in those who are thin after being obese

• Symptoms: • Vomiting • Decreased appetite• Abdominal pain• Bloating, enlarged stomach

• A medical emergency—requires immediate surgery

Cortical Adrenal InsufficiencyCortical Adrenal Insufficiency• Inability of the body to respond to physical stress by producing

adequate cortisol• Adrenal glands are located above the kidneys, produce cortisol• Helps the body respond to physical stress (surgery, trauma, severe

illness) and recover from infections. • Cortisol also helps maintain blood pressure and other

cardiovascular functions• Frequency in PWS varies with study: few % to 60% had

cortical adrenal insufficiency

• Current recommendation:• Screen cortisol and ACTH levels while the child is sick, or • Keep in mind at times of surgery, severe illness or trauma

The Future is Bright for PWSThe Future is Bright for PWS• Anticipate a better, healthier future for PWS• Improvements will occur through the individual and

collaborative efforts of researchers and doctors and through the education and advocacy of national PWS Associations and the International Prader-Willi Syndrome Organisation (IPWSO):• International community of families, care providers and

researchers working to improve care and quality of life• Improved health care and education through collaborative research

efforts and education• Improved public understanding of the issues faced by individuals

with PWS and their families and caregivers

• Improved understanding of the cause and biological development of PWS, leading to improved treatments

How You Can HelpHow You Can Help

• Keep updated through your country organization (PWSAI) and through IPWSO

• Participate in research when asked, to move knowledge forward

• Please, do not forget those less fortunate who live in countries where knowledge, services, even diagnosis is not available • Support IPWSO, whose mission is to improve the quality of life for

people with PWS throughout the world

Resources for PWSResources for PWS• National support organizations and International PWS

Organisation websites

• Recent medical review articles:• Cassidy SB & Driscoll DJ, Prader-Willi syndrome, Eur J Hum Genet,

2009;17(1):3–13

• Cassidy SB et al., Prader-Willi syndrome, Genet Med, 2012; 14(1):10-26

• www.genetests.org: GeneReview on PWS

• American Academy of Pediatrics management guidelines: • McCandless SE. Clinical report—health supervision for children with

Prader-Willi syndrome. Pediatrics. 2011 Jan;127(1):195-204• Growth hormone consensus statement:

• Deal CL et al., J Clin Endocrinol Metab. 2013 Jun;98(6); E1072-87