Presentation given by Suzanne Cassidy at the Prader-Willi Association Ireland Annual Conference 2014. For more details, see http://pwsai.ie/annual-conference-2014/
2. DDiissccuussssiioonn ooff PPrroobblleemmss
• 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
3. PWS is Highly Variable
• SSyynnddrroommee = 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
4. The CCoouurrssee iinn PPWWSS HHaass CChhaannggeedd
• 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
• AAnndd iitt wwiillll bbee ddiiffffeerreenntt iinn tthhee ffuuttuurree
• CCaannnnoott jjuuddggee tthhee ffuuttuurree bbyy tthhee pprreesseenntt
5. AAggee--FFooccuusseedd AApppprrooaacchh
• 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
6. HHeeaalltthh IIssssuueess iinn NNeewwbboorrnnss ((<< 11 mmoonntthh))
• Hypotonia and its
consequences
• Lethargy
• Sometimes issues related to
delivery problems
• Prematurity/postmaturity
7. HHyyppoottoonniiaa ooff PPWWSS
• 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
8. CCoonnsseeqquueenncceess ooff NNeeoonnaattaall HHyyppoottoonniiaa
• 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%)
10. MMaannaaggeemmeenntt ooff HHyyppoottoonniiaa iinn tthhee NNeewwbboorrnn
• 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
11. HHeeaalltthh IIssssuueess iinn IInnffaannttss ((11 mmoonntthh--11 yyeeaarr))
• 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
12. MMaannaaggeemmeenntt ooff HHeeaalltthh IIssssuueess iinn IInnffaannttss
• 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
13. AA WWoorrdd oonn SSuupppplleemmeennttss
• 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
14. MMaannaaggeemmeenntt iinn IInnffaannttss
• 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
15. MMaannaaggeemmeenntt iinn IInnffaannttss ((ccoonntt..))
• 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
16. SSlleeeepp aanndd PPWWSS ((aallll aaggeess))
• 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
18. WWeeiigghhtt PPrroobblleemmss iinn PPWWSS
• 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
1. High threshold for vomiting and decreased pain
perception, leading to eating large quantities without
discomfort
19. HHyyppeerrpphhaaggiiaa
• 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
20. OObbeessiittyy iinn PPWWSS
• 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
21. TTrreeaattmmeenntt ooff OObbeessiittyy iinn PPWWSS
• 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
22. MMaannaaggeemmeenntt ooff OOtthheerr IIssssuueess iinn IInnffaannccyy
• 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
23. MMaannaaggeemmeenntt ooff OOtthheerr IIssssuueess iinn IInnffaannccyy
• 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)
24. MMaannaaggeemmeenntt ooff OOtthheerr IIssssuueess iinn IInnffaannccyy
• Growth
• Care provider to follow closely
• Continue growth hormone treatment, if possible
25. MMaannaaggeemmeenntt ooff OOtthheerr IIssssuueess iinn IInnffaannccyy
• 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
26. HHeeaalltthh IIssssuueess iinn LLaatteerr CChhiillddhhoooodd ((55--1133 yyeeaarrss))
• 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
27. Management of HHeeaalltthh IIssssuueess iinn CChhiillddhhoooodd
IIssssuueess aass aatt eeaarrlliieerr aaggeess
• 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
28. Management of HHeeaalltthh IIssssuueess iinn CChhiillddhhoooodd
IIssssuueess aass aatt eeaarrlliieerr aaggeess ((ccoonntt..))
• Sleep apnea
• Sleep study if symptoms occur
• Visual acuity problems
• Routine checks
• Scoliosis
• Monitor clinically, X-ray and/or referral if suspicious
29. Management of HHeeaalltthh IIssssuueess iinn CChhiillddhhoooodd
• 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
30. Stomach DDiillaattiioonn aanndd RRuuppttuurree
• 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
31. A Cortical Addrreennaall IInnssuuffffiicciieennccyy
• 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
32. TThhee FFuuttuurree iiss BBrriigghhtt ffoorr PPWWSS
• 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
33. HHooww YYoouu CCaann HHeellpp
• 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
34. RReessoouurrcceess ffoorr PPWWSS
• 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
