prader-willi syndrome 101
TRANSCRIPT
Prader-Willi Syndrome 101Liz Mizerik, MS, CGC June 24, 2020
OverviewClinical features
Behavioral features
Genetics
Treatment and management
Support
PWSPrevalence: 1:10,000 to 1:30,000
Absence of expressed genes in PWS/AS region, 15q11.2-q13; specifically SNRPN
Complete penetrance
Average age of death is 33 years
Clinical Features
FeaturesHypotonia
Developmental delay
Hypogonadism
Appetite and obesity
Endocrinology
Sleep abnormalities
Behavior
Growth
Strabismus
Scoliosis
Hip dysplasia
Decreased saliva flow
Skin picking
Seizures (10-20%)
Recurrent respiratory infections (<50%)
Nutritional Stages
Ages 2 to 6Hypotonia with history of poor suck
Global developmental delay
https://www.pwsausa.org
Ages 6 to 12History and/or presence of hypotonia with poor suck
Global developmental delay
Excessive eating with obesity (if uncontrolled)
https://www.pwsausa.org
Ages 13+Cognitive impairment (i.e. mild ID)
Excessive eating with obesity (if uncontrolled)
Hypothalamic hypogonadism and/or typical behavior problems
http://www.bioquicknews.com/node/2126
Behavioral Features
Common BehaviorsHyperphagia (overeating) Compulsive behaviors (i.e. skin picking) Tantrums Stubbornness High pain tolerance Lethargic Impulsive Theft
Behavioral ResourcesNational and Texas PWS Associations
Behavioral plan tips
Behavior Tool Kit
Parenting “hacks”
http://www.txpwa.org/resources-prader-willi/behaviours.html
https://www.pwsausa.org/what-we-do/family-medical-support/
Genetics
DiagnosisHigh-resolution chromosome studies and FISH
Microarray
DNA methylation studies: only way to dx PWS caused by all three mechanisms and to differentiate from Angelman syndrome
Greater than 99% detection rate
Mechanisms
Chromosomal rearrangement with deletion of critical region: 1%
“Balanced” chromosome rearrangement breaking within critical region: <1%
Recurrence Risks
Treatment
Feeding IssuesSpecial nipples
Feeding tube
G-button?
Growth HormoneNormalize height
Increase lean body mass
Decrease fat mass
Increases mobility
Possible increases in language and cognition
TherapiesPhysical therapy
Speech therapy
Special education
Behavioral management programs
ObesityDiet (Dietician)
Exercise
Supervision
Hormone treatment
Surveillance
ManagementEndocrinology
Hypothyroidism
Growth hormones
Nutrition
Assess sucking problems and failure to thrive
Routinely measure height, weight, head circumference, and BMI on PWS growth charts
Sleep studies
Respiration/apnea
Development and speech evaluation
Cryptorchidism
Strabismus
Scoliosis (x-rays may be necessary)
Behavior problems and/or obsessive-compulsive features
Assess NutritionMonitor height, weight, and BMI
Every month in infancy
Every six months until age 10
Annually
Annual EvaluationDiabetes mellitus
Hypothyroidism
Sleep study if there is a history of sleep disturbance
Scoliosis (may require an x-ray in the presence of obesity)
DEXA scan for osteoporosis (every two years in adulthood)
Behavioral and psychiatric disturbances
New Therapies?Many drugs under investigation for treatment of hyperphagia, obesity, and behavioral problems
Oxytocin trials completed
ClinicalTrials.gov
Multidisciplinary Clinic
The TeamGastroenterology
Endocrinology
Dietician
Genetics
Psychiatry
Social work
LocationsTexas Children’s Hospital
https://www.texaschildrens.org/departments/prader-willi-clinic
The Children’s Hospital of San Antonio
https://www.christushealth.org/childrens/services-treatments/womens-services/genetics/genetic-counseling-services
Support Resources
Prader-Willi Syndrome AssociationThe basics
Up to date news and research
Parents, family, and friends resources
Resources for providers
Texas PWS AssociationFinancial
Medical
Support groups
Legal
Behaviors
Nutrition and diet http://www.txpwa.org/
Provider ResourcesGeneReviews
Last updated December 2017
https://www.ncbi.nlm.nih.gov/books/NBK1330/
ReferencesCataletto, M., Angulo, M., Hertz, G., & Whitman, B. (2011). Prader-Willi syndrome: A primer for clinicians. International Journal of Pediatric Endocrinology, 2011(1), 12. http://doi.org/10.1186/1687-9856-2011-12. [A quick go-to guide for clinical information about PWS including features, diagnosis, treatment, and management.] Driscoll DJ, Miller JL, Schwartz S, et al. Prader-Willi Syndrome. 1998 Oct 6 [Updated 2016 Feb 4]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1330/. [Comprehensive information about PWS including very detailed descriptions of features and management recommendations.] Ho-Ming, L. (January 01, 2016). Adult Prader-Willi Syndrome: An Update on Management. Case Reports in Genetics, 2016. [Case study of someone diagnosed with PWS in adulthood and the challenges they face.] Margje Sinnema, Stewart L. Einfeld, Constance T.R.M. Schrander-Stumpel, Marian A. Maaskant, Harm Boer, Leopold M.G. Curfs, Behavioral phenotype in adults with Prader–Willi syndrome, Research in Developmental Disabilities, Volume 32, Issue 2, March–April 2011, Pages 604-612, ISSN 0891-4222, http://dx.doi.org/10.1016/j.ridd.2010.12.014. [Descriptions of typical behaviors seen in PWS. This study also notes the behavioral differences in people with PWS syndrome depending on the type of inheritance (maternal UPD or paternal deletion).] Prader-Willi Syndrome (PWS): Condition Information. Retrieved from https://www.nichd.nih.gov/health/topics/prader-willi/conditioninfo/Pages/default.aspx. [General information related to PWS including a frequently asked questions section for common questions patients/families may have.] Prader-Willi syndrome - Genetics Home Reference. Retrieved from https://ghr.nlm.nih.gov/condition/prader-willi-syndrome. [General information about PWS in patient-friendly language.] Prader-Willi Syndrome Association - Prader-Willi Syndrome Association. Retrieved from http://www.pwsausa.org/. [Comprehensive information for patients, families, and friends as well as providers and researchers. Many resources are given for a variety of topics related to PWS (i.e. behavioral issues, new diagnosis, legal issues, etc.]