Transcript Prader-Willi Syndrome: An Update

Overview of Health Issues for Children with PWS
Suzanne B. Cassidy, MD
IPWSO President
Clinical Professor of Pediatrics
Division of Medical Genetics
University of California, San Francisco
Discussion of Problems
• Many positive aspects to people with PWS
• This presentation relates to difficulties
• Few well-controlled studies
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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
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Syndrome = a collection of features that are found
together more often than by chance alone
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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 Changed
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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 future
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Cannot judge the future by the present
Age-Focused Approach
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Newborn (<1 mo)
Infancy (1 mo. – 1 year)
Early childhood (1 – 5 years)
Late childhood (5-13 years)
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Most issues span more than one period
Health Issues in Newborns (< 1 month)
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Hypotonia and its consequences
Lethargy
Sometimes issues related to
delivery problems
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Prematurity/postmaturity
Hypotonia of PWS
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Hypotonia = low muscle tone, low resistance to gravity
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Present in ~100%; Most consistent feature of PWS
Abnormal brain signals to muscle, not a muscle abnormality
Evident prenatally
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Manifests as decreased movement and weak suck
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 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 Newborns
• Lethargy; poor arousal
• Weak cry
• Sometimes hypothermia
Management of Hypotonia in the Newborn
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No medication shown to treat hypotonia directly
Compensate for poor suck
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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
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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 (1 month-1 year)
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Hypotonia slowly improving
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Squint is common
Undescended testicles in males (80%-90%)
Scoliosis is common (40% – 80%)
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Feeding issues often still present, may last months
Motor delays become evident
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 Infants
• Hypotonia and feeding difficulties
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Growth and weight-to-height should be monitored
frequently (monthly) by doctor, nurse or dietician
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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 Supplements
• Some families have given supplements to their
child with PWS
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CoQ10, Carnitine, and Fish Oil
Involved in energy metabolism
• Some see improvement in hypotonia, motor
development, and/or energy; Others don’t
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No evidence of deficiency of these in PWS
No well-controlled studies showing benefit or harm
• Some specialists recommend them, others don’t
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Discuss with doctor
Assess benefit
Management in Infants
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Ophthalmologist evaluation for squint
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Doctor to assess testicular position
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Squint treated with patching or surgery
Regular (annual) ophthalmology visits thereafter
Refer within the first year for hormonal and/or surgical
treatment if undescended
Doctor to clinically evaluate for scoliosis
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Refer to orthopedist if present
Management in Infants (cont.)
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Assessment for GE reflux
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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
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Treated with adjustments to feedings, medication and/or surgery
Discussion of growth hormone in PWS with doctor or
specialist
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Appropriate to start treatment in the first few months of life
Sleep study before starting
Sleep and PWS (all ages)
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Increase in sleep apnea (pauses in breathing) and other
sleep alterations
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Risk for sleep apnea increased by
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Central sleep apnea vs. obstructive sleep apnea
Young age
Severe hypotonia
Prior respiratory problems
Severe obesity
Recommend formal sleep study in all
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Strongly recommended before GH treatment
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GH treatment may increase tonsil & adenoid size before throat size
Can be treated, as in general population
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Tonsillectomy, Continous Positive Airway Pressure (CPAP), or other
Health Issues in Early Childhood (1-5 years)
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Weight and onset of hyperphagia (excess eating)
Growth
Visual acuity (eyesight)
Scoliosis
Sleep problems
Decreased saliva and dental problems
Constipation
Hypothyroidism
Weight Problems in PWS
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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
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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
Hyperphagia
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Onset of excessive appetite (hyperphagia) between 1 and 6
years of age, often later
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Nearly constant food seeking, variable intensity
Present regardless of weight
Physiological mechanism causing hyperphagia still unclear
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Currently no proven effective direct treatment
Subject of much research and drug development efforts
Obesity in PWS
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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:
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Slows motor development
Respiratory problems, if severe
Sleep apnea
Choking due to eating too fast (esp. hot dogs/sausages!)
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Is a cause of death in PWS at any age
Social problems
Treatment of Obesity in PWS
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No currently available safe drug known to decrease urge to eat
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Surgery
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High rate of complications and low rate of long term weight loss
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No long-term studies on newer techniques
Prevention and Management of obesity
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Low calorie diet (work with dietician, adjust to level of activity)
Lots of physical activity
Food security (environmental control)
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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 Infancy
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Decreased saliva may increase risk for dental problems,
predispose to choking on food, and contribute to speech
problems
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Encourage liquids
Arrange visit to dentist no later than age 3 years, preferably earlier
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At least twice yearly thereafter
In later years, special toothpaste, gel, or mouthwash to increase saliva flow
Constipation
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Very common problem, probably related to intestinal hypotonia
Should be treated aggressively throughout life
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Dietary changes, softening agents, increased fiber intake, liquids
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Medications in later years
Management of Other Issues in Infancy
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Hypothyroidism (low thyroid hormone production)
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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 Infancy
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Growth
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Care provider to follow closely
Continue growth hormone treatment, if possible
Management of Other Issues in Infancy
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Vision
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Scoliosis
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Continue annual ophthalmology evaluation, if possible
Doctor to continue annual clinical assessment, consider X-ray
and/or referral if uncertain
Sleep
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Concern about sleep apnea continues
Snoring, spells of not breathing, restless sleep should lead to sleep
study
Health Issues in Later Childhood (5-13 years)
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Issues same as at earlier ages
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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 Childhood
Issues as at earlier ages
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Growth
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Continue to monitor
Continue growth hormone
Weight, dietary management and exercise
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Consequences of obesity
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Cardiopulmonary compromise
Increased risk for type II diabetes
Obstructive sleep apnea
Tissue swelling; skin breakdown; hygiene problems
Prevention and management of obesity
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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 Childhood
Issues as at earlier ages (cont.)
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Sleep apnea
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Visual acuity problems
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Sleep study if symptoms occur
Routine checks
Scoliosis
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Monitor clinically, X-ray and/or referral if suspicious
Management of Health Issues in Childhood
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Skin and other picking
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Keep hands busy, nails short, use distraction
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Preliminary study suggests benefit from N-aceyl cysteine (NAC)
Evaluate complaints of internal pain quickly and thoroughly
X-rays after trauma if movements suggestive
Altered temperature control/perception
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Increased pain tolerance
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Can lead to chronic sores, infection
No commonly used treatment
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 Rupture
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An occasional but very serious problem
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Contribution from gastroparesis (weak stomach muscle
function causing slow stomach emptying) and constipation
Mostly follows an overeating binge
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Especially in those who are thin after being obese
Symptoms:
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Mostly occurs in adolescents or adults, occasionally in older
childhood
Vomiting
Decreased appetite
Abdominal pain
Bloating, enlarged stomach
A medical emergency—requires immediate surgery
Cortical Adrenal Insufficiency
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Inability of the body to respond to physical stress by producing
adequate cortisol
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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
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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 PWS
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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):
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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 Help
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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
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Support IPWSO, whose mission is to improve the quality of life for
people with PWS throughout the world
Resources for PWS
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National support organizations and International PWS
Organisation websites
Recent medical review articles:
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American Academy of Pediatrics management guidelines:
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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
McCandless SE. Clinical report—health supervision for children with
Prader-Willi syndrome. Pediatrics. 2011 Jan;127(1):195-204
Growth hormone consensus statement:
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Deal CL et al., J Clin Endocrinol Metab. 2013 Jun;98(6); E1072-87