Prader-Willi Syndrome - Treatment & Management

Growth hormone is typically deficient in PWS, causing short stature, lack of a pubertal growth spurt, and a high body fat ratio (fat/body weight), even in those with normal weight. (Different centers initiate growth hormone supplementation at different ages.)

Growth hormone (GH) is approved for use in PWS for improvement of body composition, height velocity and linear growth, mobility, behavior and quality of life. Growth hormone therapy may increase muscle mass and function and allow a higher daily calorie intake. Psychosocial development may also be improved. Therapy is initiated at a standard dose of approximately 0.3 mg/kg/wk divided as a daily subcutaneous injection. See the Growth Hormone and PWS Policy Statement (PWSA USA) and the updated guidelines for growth hormones. [Wilson: 2003] Recent reports have noted the occurrence of sudden death during initiation of GH, mainly during sleep and possibly related to severe obesity and sleep disordered breathing (SDB) – more studies are needed to clarify the cause of death in these cases. [Grugni: 2008] [Tauber: 2008]

Because individuals with PWS are at risk for sleep apnea, a sleep study is recommended before beginning GH treatment, with a follow-up study 6-8 weeks later. If there is worsening of obstructive sleep apnea (OSA), then temporarily stopping the GH is recommended until the cause is understood. Frequently the OSA can be corrected by removing the adenoids and tonsils or lowering the dose of GH (if IGF-1 is abnormally high). Thyroid function and cortisol levels (in AM) should also be tested before starting growth hormone treatment. There has been some discussion about adrenal hypofunction in a subset of PWS individuals.

In most individuals with sleep-disordered breathing due to PWS, GH can actually improve (or at least not worsen) the apnea. [Haqq: 2003] [Miller: 2006] [Festen: 2006] Withholding GH from those with sleep apnea may be detrimental, thus monitoring the child with PWS closely when starting GH to make sure that they do not worsen is the recommended approach.

Diabetes mellitus, type II, has been observed in individuals with PWS, particularly in those individuals with obesity. The risk for diabetes is lowered when weight is reduced. Therefore, blood glucose and insulin levels are periodically checked depending upon the level of obesity and use of growth hormone therapy.

Subspecialist Collaborations and Other Resources

Failure to thrive: Food intake during the first 2 years of life requires close management to maintain weight-for-height measures between the 25th and 80th percentile. Published growth standards specifically for use in PWS are available for this purpose - in children PWS Growth Charts ( 431 KB) . [Butler: 1991] and infants [Butler: 2011]. Failure to thrive may necessitate tube feeding. Infants with PWS should be closely monitored for adequate calorie intake and appropriate weight gain. Referral to gastroenterology may be indicated.

Hyperphagia: In older children, hyperphagia due to insatiable appetite may lead to life-threatening weight gain, which can be very rapid and occur even on a low-calorie diet. Excessive uncontrolled over-eating may lead to stomach necrosis and rupture. To control energy intake, a careful food monitoring program is essential for both children and adults with PWS. [Butler: 1991] Restricted caloric intake with vitamin and calcium supplementation, performed under the close supervision of an experienced dietitian, is generally required from age 2-3 years to minimize excessive weight gain and osteoporosis. Successful weight maintenance in children with PWS who have not been treated with growth hormone has been reported with an intake of 8-11 kcal per cm of height per day, whereas children without PWS require 11-14 kcal per cm per day for adequate growth.

Individuals with PWS must be supervised at all times in all settings where food is accessible. Those who have normal weight have only achieved this because of strict external control of their diet and food intake. Involving the patient, family members, and care providers is critical in developing strategies to cope with the hyperphagia and weight and behavior control issues that are characteristic of PWS. [Goldberg: 2002] Tactics include:

• locking away food,
• keeping limited amounts of food in the home,
• continual close supervision of the patient around food or food-related events,
• providing non-food-related rewards,
• reduction of portion sizes using small plates and bowls,
• allowing participation in menu planning and preparation,
• counting calories, and
• having access to food with fewer calories.

It is also important to keep strict mealtime regimens and to ensure unwavering consistency by both parents and care providers, both inside and outside of the home. See Food and Behavior in PWS (Pittsburgh Partnership) for more information regarding food security and behavior. Individually tailored exercise programs are encouraged - 30 minutes of sustained activity 3-5 times per week are generally recommended. [Butler: 2006] [Holm: 1976] To date, no medication or surgical intervention has been found that would eliminate the need for strict dieting and supervision around food. Bariatric surgery has generally been unsuccessful and not recommended in PWS. [Scheimann: 2008] See also Obesity and diet in Prader-Willi syndrome and Nutrition/Growth/Bone below.

Other: Although they have no known congenital defects involving the gastrointestinal system, children with PWS have decreased sensitivity to gastric fullness and to pain. A decreased pain response may mask the symptoms of gastrointestinal problems such as gastric distention, gastroparesis, and necrosis, which are more common in individuals with PWS. In addition, because vomiting is reduced in children with PWS, they may not respond to eating spoiled or contaminated foods. Children with PWS may present with behavior changes and vague feelings of unwellness that might represent medically urgent gastrointestinal disease. These complaints should be taken seriously by providers. See Emergency alert information for children with PWS.

Gastroesophageal reflux (GER) is common in children with PWS and may be particularly problematic in infants due to their hypotonia. See Gastroesophageal reflux (general).

Vomiting and rumination: Commonly reported features of PWS include a decreased ability to vomit and a high prevalence of rumination. [Alexander: 1987] Dental enamel defects due to rumination should be looked for routinely. Rumination may increase in children with strict behavioral food intake programs. See Rumination (eMedicine) for more information.

Constipation is common in children with PWS (>20%). Rectal ulcers, which may occur due to skin picking, can be exacerbated by large stools and constipation. See Constipation treatment (general) for information about the evaluation and treatment of constipation. Treatment of bowel disorders in individuals with PWS often requires ongoing specialized treatment and monitoring with a multi-disciplinary approach to optimize therapy. See also You can poop too program. The following tools may be helpful: Bowel management algorithm ( 47 KB) ; Bowel management parent information; Bowel management (general) ( 74 KB) ; Constipation evaluation tool ( 84 KB) ; and Home toileting record ( 49 KB) .

Subspecialist Collaborations and Other Resources

A number of nutritional issues arise in children with PWS. These include problems with poor feeding and failure to thrive in early infancy, often requiring the use of special nipples or tube feedings. These generally start to improve by 6 months of age, however insatiable appetite and the resulting risks may begin by 12 months of age. Some of these risks are addressed under Gastro-Intestinal above. For more detail, please see the Nutrition and diet in Prader-Willi syndrome Issue Page.

Subspecialist Collaborations and Other Resources

A common problem that may become a habit in children with PWS is scratching and picking at the skin or mucosal areas of the face, arms, legs, or rectum, sometimes triggered by insect bites or other skin lesions. The skin picking varies in severity and may vary in the same patient over time. Anxiety, stress, or boredom seem to increase the severity of the picking behavior. Over half of adolescents and adults with PWS exhibit this self injurious behavior. Frequent nose bleeds or rectal bleeds should prompt further examination for sores from picking. Rectal ulcers may occur as a result of rectal itching or “digging.”

Treatment includes keeping the fingernails short, behavior modification, limiting the time spent in the bathroom to reduce opportunities for rectal picking, and providing substitute activities for the hands. Skin and mucosal infections can be managed with topical antibiotics, bandaging, and, if necessary, oral antibiotics. Oral topiramate has been shown to reduce skin picking in some cases. [Shapira: 2002]

The very obese individual is also more prone to fungal and bacterial infections, severe ulceration, and cellulitis, due to the inability to cleanse the skin in deep fat folds. Management includes daily cleansing in these folds and air drying with a heat lamp or hair dryer, and the use of medications for infections.

Subspecialist Collaborations and Other Resources

Cardiovascular risk is higher in individuals with PWS for a variety of reasons, including:

• overeating and obesity,
• poor dietary habits,
• diabetes,
• excess work of breathing, and
• unexplained elevations of C-reactive protein in individuals with PWS.

These factors may result in hypertension, left ventricular hypertrophy, and right-sided heart failure, particularly in morbidly obese individuals. Although these are not generally present in young children with PWS, older individuals should be referred to a cardiologist for management as needed.

Subspecialist Collaborations and Other Resources

Apnea: Up to 90% of children and adults with PWS will have apnea and profound hypoventilation during sleep. [Butler: 2006] This may be due to extrinsic factors such as large tonsils and/or an intrinsic sleep disorder, probably related to hypothalamic dysfunction. Symptoms associated with the sleep disorder may include:

• hypoventilation,
• oxygen desaturation during REM sleep,
• sleep apnea,
• nocturnal enuresis, and
• excessive daytime sleepiness and snoring.

If sleep evaluation finds apnea, consider referral to otolaryngology for evaluation of tonsils and adenoids and/or to a pulmonologist or sleep specialist to consider options such as BIPAP or CPAP.
Nocturnal enuresis may occur secondary to other underlying sleep problems or as an independent problem. If medical treatment is being considered, for example with DDAVP, start with smaller doses than those used in the general population and gradually increase the dose as needed.

Subspecialist Collaborations and Other Resources

Individuals with PWS may be at increased risk for respiratory problems, especially as infants. Problems at birth, due to hypotonia, weak chest muscles, and poor swallowing reflexes, may include asphyxia, apnea, respiratory failure, and hypoventilation.

Subspecialist Collaborations and Other Resources

Individuals with PWS commonly have decreased muscle mass and strength. The few histologic and ultrastructural studies of muscle fibers performed in individuals with PWS have found only minimal abnormalities. A disuse or minimal myopathy may accompany central hypotonia in individuals with PWS. [Sone: 1994] Physical therapy and regular participation in exercise programs are essential in order to improve muscle strength and decrease fat mass. See the Motor development in children with Prader-Willi syndrome Issue Page. Growth hormone therapy and testosterone therapy in adolescent and adult males also improve muscle strength in individuals with PWS.

Individuals with PWS may also present with scoliosis, kyphosis, and/or lordosis. Progression may occur with the increased linear growth during late childhood and adolescence. Treatment with growth hormone or anabolic steroids may exacerbate scoliosis. Scoliosis may compromise lung function and cause discomfort. Children with PWS should be screened regularly for scoliosis and, if scoliosis is present, referred to a pediatric orthopedic surgeon for management. Surgery to correct the scoliosis is sometimes necessary.

Hip dysplasia is observed in approximately 13% of individuals with PWS and should be screened for by the Medical Home provider with referral to an orthopedic surgeon if suspected. Hip ultrasound studies during infancy should be considered.

Osteoporosis is found in up to 50% of adolescents and adults with PWS [Kroonen: 2006] (see the Osteoporosis in children with Prader-Willi syndrome Issue Page) and should be considered in individuals with any fracture that is not consistent with the force of injury. If present, calcium and vitamin D intake should be maximized (see the Calcium and vitamin D (general) Issue Page) and the provider should consider a referral to endocrinology. See also Osteoporosis in individuals with PWS (PWSA USA).

See also Orthopedic concerns in children with PWS from the PWSA (USA).

Subspecialist Collaborations and Other Resources

Common visual problems in PWS include strabismus and myopia. Strabismus includes both esotropia, which is more common, and exotropia. Treatment may involve correction of refractive errors, patching of the better eye, and/or surgical correction of unbalanced eye muscles. Generally, treatment is more successful if started in the first few years of life. Amblyopia, or reduced vision due to disuse of an eye during development (commonly called "lazy eye"), results from inadequately treated strabismus.

Myopia (near-sightedness) and hyperopia (far-sightedness) are also common findings in children with PWS. Periodic screenings with a pediatric ophthalmologist are recommended throughout childhood.

Oculo-cutaneous albinism type 2 has been shown to be linked to the 15q11-q13 region - individuals with PWS due to a deletion in this area may also exhibit signs of depigmentation. Strabismus and impaired visual acuity may also be features of oculo-cutaneous albinism type 2. [Saadeh: 2007]

Subspecialist Collaborations and Other Resources

Individuals with PWS typically have hypogonadotrophic hypogonadism, resulting in decreased estrogen levels in females and decreased testosterone levels in males. In the newborn period, most males have small testes and scrotum. Undescended testes are common in PWS. If the testes are not palpable, referral for a testicular ultrasound and evaluation by a pediatric urologist should be made by about 6 months of age. In newborn females, labial hypoplasia has been reported.

Over 80% of adolescents and adults with PWS will experience incomplete sexual maturation. Some children show early growth of underarm and pubic hair but then don't progress through puberty normally. Both sexes have good responses to treatment for hormone deficiencies, although side effects have been reported. Males with PWS typically don't progress past midpuberty and make no mature sperm. Testosterone levels are usually low and testosterone replacement beginning early in adolescence is often helpful. Normal levels of testosterone are needed to preserve bone mass and prevent osteoporosis. Testosterone replacement also increases muscle mass and strength. In older males with a small penis, a short course of testosterone can be given to improve appearance and size.

Most females with PWS do not have regular menstrual cycles and if they do menstruate, may have early menopause. Hypoplasia of the labia and/or clitoris in teenage females is common. The use of estrogen replacement therapy for women with PWS is not well established but may help preserve bone mass and reduce osteoporosis.

Fertility has only been documented in a few rare cases. Sexually active individuals should be counseled regarding the risk of pregnancy and the risk of having a child with PWS (50%, except when the mutation is due to maternal disomy).

Sexuality needs to be discussed with adolescents with disabilities and their parents in an effort to address common issues that may include:

• the assumption that teens with disabilities do not need this information,
• the lack of sex education specific to people with disabilities,
• motor impairments that may make sexual function difficult, e.g., condom use,
• the presence of intellectual impairment that might complicate the imparting and understanding of sex education material,
• concerns about sexual exploitation in this population, and
• body image concerns on the part of the adolescents.

See Sexuality and People with Disabilities ( 257 KB) .

Subspecialist Collaborations and Other Resources

Referral to and regular follow-up by a dentist should be part of the overall treatment plan. However, providing preventive dental care may be difficult for the following reasons:

• Cognitive and fine motor skills may limit the child's ability to perform brushing and flossing. Early emphasis on brushing and flossing is important.
• Behavioral and health issues (e.g., sleep apnea, congenital heart disease) may increase the difficulty of dental visits and increase the risks of using sedation in the dental setting.

Children with PWS are prone to dental problems due to:

• soft dental enamel making it easier for caries to develop. Special toothbrushes can be used that are less abrasive and help maintain the enamel and improve oral hygiene.
• tendency to grind their teeth and because sugar intake may be large.
• overproduction of saliva that results in thick, crusted deposits in the corners of the mouth and difficulty for the saliva to coat and protect the teeth. Products to increase and somewhat thin the saliva are available.

The primary care provider's role should include:

• Discussing the need for routine dental care with families and ensuring that the child and family have been instructed on dental hygiene and fluoride supplementation. The CDC's page My Water's Fluoride provides information about fluoride levels in local water sources.
• Helping families identify an appropriate dentist and/or funding. Dental check-ups are recommended by age 1 and then every 6 months.
• Offering the family information about dental care specific to PWS. Ensure that families and dental care providers are aware of medical issues that may impact care (e.g., need for bacterial prophylaxis, sedation risks).
• Monitoring general oral hygiene and dental health at well child visits and discussing issues with families as they arise. If signs of periodontal disease are evident, refer to a dental provider as-soon-as possible; periodontal disease can be rapidly progressive.
• Helping the child, teen, and family manage halitosis, which may result in societal exclusion. It may improve with simple interventions such as tongue brushing, mouth washes, breath fresheners, and better dental hygiene or may require evaluation for medical issues, including chronic sinusitis, gastro-esophageal reflux, drooling, and periodontal disease.

Subspecialist Collaborations and Other Resources

Please consult your local dentist for input, recommendations, and follow-up for oral pathology and hygiene.

Language: Speech and language skills of individuals with PWS vary greatly, ranging from being nonverbal to having normal skills in adulthood. For children with PWS, the development of speech and language is often delayed, sometimes not combining words until they are six years of age. Problems are seen with speech rate, voice quality, and coordinating movements of the tongue, lips, jaws, and palate, leading to slow, slurred, and/or nasal speech. Most will have greater delays in expressive language, compared to receptive language. Difficulties with auditory short-term memory, order processing, and auditory verbal processing skills may affect vocabulary, grammar, and conversational abilities. Despite oral difficulties, children with PWS may show strengths in written language skills and reading, although reading comprehension may be poor. Speech and language difficulties continue into adolescence and adulthood. In these stages, emphasis should be placed on functional language skills and life-skills training. See Services below and the Normal pattern of speech development (general) Issue Page for normal language milestones.

Sign language, picture communication boards, and augmentative communication devices should be considered for individuals with verbal communication problems. Referrals should be made as early as possible to speech and language pathologists. Aiding communication may help with behavior problems. See also the Augmentative Communication (general) Issue Page.

Subspecialist Collaborations and Other Resources

Behavioral issues often impact the child with PWS and their family more than any other aspect of the condition, though they are often due to other primary manifestations of the disorder. To avoid secondary behavioral issues, hyperphagia needs to be managed consistently by family, teachers, health care providers and anyone who interacts with the child. Controlling both the quantity and types of food that are available is essential. Attempts to suppress appetite with medication have been unsuccessful, but continue to be an active area of research. Conflicts related to food may lead to other behavioral problems. Aggressive behaviors or acting out can also be problematic.

Family support and anticipatory guidance for developmental delays and medical problems should be provided. Transitions and life changes are easier if the person with PWS is prepared for them, for example by allowing the child with PWS to visit a new school and meet his/her prospective teachers. Children with PWS should have a clear idea of expectations and the limits set for them, including those related to participation in social activities and interactions with other children.

Co-management with psychology and/or psychiatry may be important if simple measures are ineffective. The choice of psychotropic medication is the same as in typical patients with psychiatric diagnoses. Because many individuals with PWS may respond differently, dosing should start low and be titrated upward based on response.

Mood stabilizers have been used successfully for treating mood disorders and severe impulse control. Valproate and lithium are well tolerated at typical doses. Carbamazepine and oxcarbazepine should be used with care because of the increased risk for hyponatremia. Individuals with PWS will sometimes ingest large quantities of flavored beverages or water making them more susceptible to hyponatremia than non-PWS subjects.

Serotonin reuptake inhibitors have induced mood activation in some individuals with PWS causing worsening of behavioral problems or resulting in psychosis. The worsening behavior after an initial favorable response to medication may cause some physicians to increase the dose which further complicates treatment. However, when monitored closely, this class of medications can effectively treat OCD and depression in PWS individuals.

It is important to monitor all medications that may affect eating behavior and weight gain. In well-controlled environments, neuroleptics, atypical neuroleptics, valproic acid, and lithium have been used effectively without discernable change in food seeking behavior. [Forster: 2008] In severe cases, the child may need to be admitted to a facility that has experience in dealing with behavioral issues secondary to underlying medical problems.

Subspecialist Collaborations and Other Resources

Individuals with PWS typically have decreased cognitive functioning. IQ scores are generally in the range of mild to moderate intellectual disability (see the Intellectual disability/mental retardation module and Psychometric testing (general)), although scores may range from normal to profound disability. The type of gene alteration causing the PWS plays a role in IQ score results - individuals with PWS due to uniparental disomy (UPD) have higher verbal than performance scores, while children with PWS due to deletions have higher performance scores. Children with UPD generally perform better than children with deletions and the size of the deletion correlates inversely with performance. Areas primarily affected include reading, spelling, and math. Short-term visual memory is often a weak area, whereas visual perception, organization, and puzzle solving are relative strengths. Children with PWS should have full psychological evaluations, including IQ and achievement, so that school and future planning can be optimized. An Individual Education Plan (IEP) should be initiated as early as possible. See Education & Schools. See also the Cognitive and psychiatric issues in Prader-Willi syndrome Issue Page.

Attention deficit hyperactivity disorder (ADHD) should be treated if present. Co-management with a child psychiatrist may be indicated if medication is required.

Subspecialist Collaborations and Other Resources

Demands on families of children and adults with PWS are many. The Medical Home, in addition to providing support for the child, can work to ensure that needs are being met as well as possible. Emotional and financial support as well as information about and access to resources are important. Referral to the Prader-Willi Syndrome Association (USA) for information and support by other families, including meetings and Yahoo groups may be invaluable. State/local chapters of the Prader-Willi Syndrome Association may also be available, and be accessed through Prader-Willi Syndrome Association (USA). See Family support (PWSA USA) and SSI guide for children with PWS (PWSA USA) as well as Services, below.

Transition from pediatric to adult life and health care systems can be challenging for individuals with PWS, their families, and their care providers. An important goal in transition planning is to find an acceptable Medical Home where the care provider recognizes the special needs of individuals with PWS and where a support team can be established that can communicate with the pediatric team. Other important goals of transition planning are to identify where the person will live and to identify educational and vocational training needs. Transition should include the following:

• Planning should begin well before the patient will be transitioned.
• Planning should take medical problems and learning disabilities into account.
• Transition planning should be person- and family-centered and take into account cultural, ethnic, and spiritual values. Economic resources of the family need to be considered.
• The overall goals of the youth should be considered. Goals for the future should include measurable outcomes. Transitions should be presented as positive changes in the person's life.
• All members of the health care team, current and future, should agree on the overall plan and how to achieve the outcomes desired.
• Medical management should be planned so there is no interruption in care and so that the patient and family are aware of potential changes in available resources. Medicaid support typically ends at age 19 and social security financial support after age 18.
• Two key members of the transition team are a nutritionist who is familiar with the unique problems of the condition and past management plans and a social worker who can provide information about appropriate medical care and financial resources for adults.
  
  

See Services below.

Excellent resources, including those listed below, are available from the Prader-Willi Syndrome Association USA. Medical Home providers and families of children with PWS are encouraged to visit their web site and see the numerous resources available.

For Professionals

New Medical Alert Info (PWSA USA) ( 1.5 MB)

SSI guide for children with PWS (PWSA USA)

Orthopedic concerns in children with PWS from the PWSA (USA)

Osteoporosis in individuals with PWS (PWSA USA)

Central Adrenal Insufficiency (PWSA USA)

Postoperative Guidelines (PWSA USA)

Growth Hormone Consensus Statement (PWSA USA) ( 64 KB)

Recommendations for Evaluation of Breathing Abnormalities (PWSA USA)

For Parents and Patients

Adaptive Recreation

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Assistive Technology

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Behavioral Programs

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Camps

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Child Psychiatry

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Child Psychology

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Disability Employment

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Early Intervention Programs

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Family Therapy

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General Dentistry for CSHCN

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Group Homes

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Gynecology (Ped/Adol, Special Needs)

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Health Insurance/Funding, Transition

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Learning Evaluations

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Mental Health Clinics, Public

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Neuropsychology

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Nutrition/Dietary

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Occupational Therapy

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Pediatric Cardiology

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Pediatric Dentistry

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Pediatric Dermatology

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Pediatric Endocrinology

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Pediatric Gastroenterology

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Pediatric Genetics

Medical Genetics, more info...
100 N Mario Capecchi Dr
Salt Lake City, UT 84113
Phone: 801-231-3599
Fax: 801-585-7252
http://healthcare.utah.edu/pediatrics/Genetics/index.php

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Pediatric Ophthalmology

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Pediatric Orthopedics

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Pediatric Otolaryngology

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Pediatric Pulmonology

Pediatric Pulmonology, more info...
100 N Mario Capecchi Dr
Salt Lake City, UT 84133
Phone: 801-213-3599
http://healthcare.utah.edu/pediatrics/Pulmonary/index.php

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Pediatric Urology

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Physical Therapy

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Prader-Willi Clinics

Prader-Willi Syndrome Clinic , more info...
44 Mario Capecchi Drive
Salt Lake City, UT 84114
Phone: 801-712-0501
Toll Free Phone: 800-829-8200
http://www.health.utah.gov/cshcn/index.html

Recreation Therapy

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SSI, Supplemental Security Income

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Sleep Studies/Polysomnography

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Social & Recreational Opportunities

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Social Work

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Speech/Language Therapy

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Vocational Education

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