prader-willi syndrome 101

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

Birth to age 2Hypotonia with poor suck

https://www.pwsausa.org

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.]