Prader-Willi Syndrome Prader-Willi Syndrome Association (USA) 8588 Potter Park Drive, Suite 500 Sarasota, FL 34238 (800) 926-4797 pwsausa@pwsausa.org http://www.pwsausa.org "Strengthening Awareness Through Knowledge and Communication"

Prader-Willi Syndrome Increased Awareness of PWS Means… More Diagnoses and Earlier Identification which leads to… Early Intervention Services and Appropriate Treatment and Management Strategies which leads to… Improved Quality of Life for Individuals Born with the Syndrome and their Families William, 2 yrs Aspyn, 6 mo

Prader-Willi Syndrome Documented cases of PWS go back to the 17th Century Portrait of 6 year old Dona Eugenia Martinez Vallejo (c. 1680) who displays classic characteristics of PWS. This painting is often regarded as the earliest illustration of PWS.

Prader-Willi Syndrome In 1956, PWS was identified as a constellation of symptoms by Swiss physicians A. Prader, H. Willi and A. Labhart PWS is a lifelong, life-threatening, non-inherited genetic disorder that results from a defect on Chromosome 15 PWS occurs in 1 in 12,000-15,000 births, or approximately 25,000 people in U.S. Of these, 75-80% are either undiagnosed or unknown to PWSA(USA). In NV, there are only 39 known cases of PWS; 13 of which are in the greater Las Vegas area. There are an additional 70-75% either undiagnosed or unknown to PWSA(USA). PWS equally affects all races and both sexes.

Prader-Willi Syndrome Two major types of PWS – Deletion (70%); Uniparental Disomy (UPD) (25%); Other (5%) PWS is now easily diagnosed with a blood test PWS is one of the 10 most common conditions seen in genetics clinics, and is the most common genetic cause of obesity Without intervention, PWS leads to obesity-related medical problems and eventual premature death

Clinical Features PWS can be thought of as a Two-stage Disorder Stage 1 – Infancy Stage Low birth weight and subsequent failure to thrive Severe muscle weakness (hypotonia), excessive sleepiness Suck/swallow problems, reflux, respiratory problems Subtle dysmorphic facial features such as “triangle” shaped mouth, narrow forehead, almond-shaped eyes Underdeveloped sexual organs (small labia majora in girls, small penis & undescended testes in boys) Delayed motor/physical milestones Sitting – 12-13 months Walking – 24-36 months Trike riding – 4 years if ever First words – 21 months Sentences – 3 ½ years

Clinical Features Stage 2 – Hunger Stage Between ages 2-6, hyperphagia symptoms begin with a preoccupation with food and/or compulsion to eat Voracious appetite begins as brain does not receive/process signals of feeling “full” Slow metabolic rate causes rapid weight gain Low energy level makes it difficult to exercise Emotional labiality and behavioral manifestations Sitting – 12-13 months Walking – 24-36 months Trike riding – 4 years if ever First words – 21 months Sentences – 3 ½ years PWS is a spectrum disorder. All symptoms vary in degree from person to person.

Physiological Characteristics Hypotonia - Weak Muscle Tone Abnormal Growth (short stature, small hands & feet) Problems with Strength, Balance, Coordination, Motor Planning Hyperphagia - Dysfunctional Appetite Regulating System Respiratory Issues Gastrointerological Issues–Gastroparesis, Slow Bowel Motility, Inability to Vomit Hyper- & Hypothermia - Irregularities in Body Temperature Regulating Systems Incomplete Sexual Development Hypopigmentation High Pain Threshold, Bruise Easily Disordered Sleep Cognitive Limitations Speech and Language Issues (Dyspraxia & Apraxia) Dental Problems (decreased saliva production can cause severe problems) Skin Scratching and Picking Temperament and Behavior Issues with Older Children Through Adulthood Social / Psychological / Psychiatric Problems Other common characteristics may include: scoliosis, eye abnormalities (strabismus), medication sensitivity, orthopedic problems The hypothalamus and pituitary gland regulate the production and release of hormones in the body. We can think of ourselves as being a system of hormonal function. Everything we do, think, and feel is a function of hormones. The hypothalamus and pituitary gland do not function properly in the body of someone with PWS. Therefore, symptoms such as these occur: Abnormal growth – Insufficient HGH results in short stature, small hands & feet, narrow forehead, subtle dysmorphic facial features, decreased muscle tone resulting in decreased strength, decreased respiratory function, decreased bone density Hyperphagia – Results from flawed part of brain (hypothalamus) that regulates hunger, satiety, and manages body’s metabolic rate. People with PWS always feel hungry and/or brain obsesses on food at the same time their body’s metabolic system is slowed. Weight gain on considerably small calories. Cognitive limitations – IQs range from 40 to above 100. 95% function in mildly mentally retarded range, independent of IQ testing. Most LD. Speech – Low muscle tone causes dysarthria in some, but most have dyspraxic speech. Dental – Decreased saliva production causes dry mouth, thick, sticky saliva, cavities, decayed teeth, teeth grinding, bad breath, etc. OTC dry mouth products help. High Pain Threshold & Irregular Body Temp Reg – Blunted sensory integration systems and temp relate to defect in hypothalamus. Skin Picking – Factor of blunted sensory system and obsessive features typical of syndrome Incomplete sex development – Babies typically born with small genitalia; male babies undescended testes. Most do not progress thru puberty w/o sex hormone therapy (testosterone or estrogen). Respiratory Issues – Related to lung muscle strength and CNS. Common, including sleep apnea, hypopnea, central sleep apnea. Cause excessive daytime sleepiness which can increase irritability and exacerbate behavior problems. Temperament and behavior – Young children typically loving, happy, compliant. Subtle changes occur making child more easily frustrated, prone to mood swings, temper tantrums, stubbornness, rigidity, argumentativeness, repetitive thoughts and behaviors (OCD). Increase in rate of psychiatric problems. Social / Psychological Problems – Difficulties with social skills acquisition may lead to social isolation. Individuals with higher level cognitive functioning more prone to depression as more aware of differences and limitations. Counseling and meds helpful to reduce depression.

Cognitive Characteristics Most individuals with PWS have decreased intellectual functioning. Average IQ typically 55-70. Distribution generally 5% IQ 85+; 25% Borderline MR; 35% Mild MR; 25% Moderate MR; 25% Moderate MR; 5% Severe MR. Decreased abilities in: Picture recognition Mathematics Short-term memory Daily living skills despite IQ Areas of Strength: Friendliness, affectionate, desire to please, desire to nurture Long-term memory Recognize and evaluate shapes and figures Integrate stimuli in spatial relationship Puzzle solving

Treatment & Management Strategies There is no known cure for PWS. But there are various medications, treatments and therapies that can help manage, reduce or even eliminate some of the symptoms. Treatment consists of a multidisciplinary treatment approach. A typical family will see a multitude of professionals including: Geneticist Endocrinologist Pulmonologist Feeding Specialist Ophthalmologist Dentist RC Case Workers Behaviorist, Psychologist, Psychiatrist Neurologist Urologist (boys) Gastroenterologist Nutritionist Orthopedist Attorney PT, OT, ST, Social Skills Therapists Residential Staff Early Dx – DNA Methylation testing is now widely used to identify all possible genetic defects on chromosome 15 that are believed to cause the syndrome. Early dx gives parents the opportunity to begin appropriate interventions and therapies as early as possible including proper nutritional intake to avoid obesity from the start, growth hormone tx, occupational, physical, speech, social skills, sensory integration therapy, and sex hormone therapy, and establish good, consistent parenting routines. GH Therapy- Probably the single most important advancement in the tx of PWS in the last 50 years, synthetic HGH is recognized worldwide by the leading PWS researchers as tx protocol for PWS. Improves linear growth in children, increased muscle development, decreased body fat, improved body composition, increased bone mineral density, improved physical performance, improved respiratory function, and newer studies suggest improvements in cognitive function. Weight Control & Exercise – The hallmark symptom of PWS is hyperphagia. No medication helpful with this symptom – yet. Important to provide necessary nutrients while restricting calories. Access to food must be limited. Exercise programs made fun must begin early. Weight management vital. Locks on cupboards and frig necessary often. Behavior Management – Behavior management crucial for both weight and behavior problems. Behavior Mod should be prevention oriented. Provide daily routines, structure, firm limits, anticipate problems, avoid arguments. Address underlying anxiety issues which contribute to behavior problems. Provide medications for psychiatric issues if appropriate, esp. SSRIs. Special Education – Most individuals will require special education services. Federal law provides for these services to include special instruction, speech therapy, OT, PT, psychological testing, counseling, and social skills therapy.

Treatment & Management Strategies Early Diagnosis – Genetic Testing Growth Hormone Therapy - FDA approved for use in children with PWS. Ongoing studies support FDA approval for use in infants and adults, with many of the following improvements seen: Increased height and growth rate Increased hand & foot size to normal proportions; more “normalized” facial characteristics Decrease in body fat and body mass index (BMI) Increase in muscle development Improved respiratory function Improved physical performance Increase in resting energy expenditure Improved cholesterol levels Increase in bone mineral density Improved cognitive functioning Increased self-esteem Early Dx – DNA Methylation testing is now widely used to identify all possible genetic defects on chromosome 15 that are believed to cause the syndrome. Early dx gives parents the opportunity to begin appropriate interventions and therapies as early as possible including proper nutritional intake to avoid obesity from the start, growth hormone tx, occupational, physical, speech, social skills, sensory integration therapy, and sex hormone therapy, and establish good, consistent parenting routines. GH Therapy- Probably the single most important advancement in the tx of PWS in the last 50 years, synthetic HGH is recognized worldwide by the leading PWS researchers as tx protocol for PWS. Improves linear growth in children, increased muscle development, decreased body fat, improved body composition, increased bone mineral density, improved physical performance, improved respiratory function, and newer studies suggest improvements in cognitive function. Weight Control & Exercise – The hallmark symptom of PWS is hyperphagia. No medication helpful with this symptom – yet. Important to provide necessary nutrients while restricting calories. Access to food must be limited. Exercise programs made fun must begin early. Weight management vital. Locks on cupboards and frig necessary often. Behavior Management – Behavior management crucial for both weight and behavior problems. Behavior Mod should be prevention oriented. Provide daily routines, structure, firm limits, anticipate problems, avoid arguments. Address underlying anxiety issues which contribute to behavior problems. Provide medications for psychiatric issues if appropriate, esp. SSRIs. Special Education – Most individuals will require special education services. Federal law provides for these services to include special instruction, speech therapy, OT, PT, psychological testing, counseling, and social skills therapy.

Treatment & Management Strategies Ongoing family education on the syndrome, along with treatment and management strategies via national PWSA (USA) and PWS NV S.H.A.R.E. Physical, Occupational, Sensory Integration Therapy, Oral Motor/Speech & Language Therapy, Social Skills Therapy Marriage and Family Therapy to help family members manage high and chronic levels of stress, chronic grief, sibling issues, extended family support (or lack thereof) Oral Hygiene products designed to relieve dry mouth symptoms Weight Management Strategies, including restricted calorie diet, 24/7 environmental controls Exercise regimen

Treatment & Management Strategies Behavior Management vs. Behavior Modification Strategies Collaborative Problem Solving Approach as outlined in The Explosive Child, Ross Greene, Ph.D. “No Hope for Food” principles Positive, supportive, routinized, calm environment Praise! Praise! Praise! Special Education Estate Planning, Special Needs Trust & Will, Conservatorship Sex Hormone Replacement Therapy in Adolescence Meaningful Work and Hobbies Residential Living Arrangements Family, Group Home, Supported Living

Outlook today is more hopeful than ever before Normal life expectancy with weight management and 24/7 environmental control of food Media attention increases the public and medical community’s awareness of the syndrome National obesity epidemic has influenced research to better understand the body’s appetite regulating systems. We hope this will lead to the development of medications that will treat PWS-specific hyperphagia, as well as benefit general public.

Early Diagnosis Appropriate Early Intervention Therapies & Management Strategies Improves the quality of life for our children and their families Aspyn, 14 mo William, 3 yrs Aspyn, 17 mo