Orthopedic and Surgical Approach in Prader Willi

Syndrome Patients

Popoiu MC1, David VL2, Sima L3, Boia ES1, Badeti R2, Puiu M1

1. University of Medicine and Pharmacy “Victor Babes” Timisoara2. Children Hospital Louis Turcanu Timisoara 3. Municipal Hospital Timisoara

Diagnostic

Holm, Cassidy, Butlerdeveloped consensual diagnostic criteria

In 1993

Major criteria

1. Neonatal and infantile central hypotonia with poor suck2. Feeding problems -poor weight gain/failure to thrive3. Excessive or rapid weight gain on weight-for-length chart 4. Characteristic facial features with dolichocephaly in infancy, narrow face or

bifrontal diameter, almond-shaped eyes, small-appearing mouth with thin upper lip, down-turned corners of the mouth (3 or more required)

5. Hypogonadism— Genital hypoplasia 6. Delayed or incomplete gonadal maturation with delayed pubertal signs in the

absence of intervention after 16 years of age 7. Global developmental delay in a child younger than 6 years of age; mild to

moderate mental retardation or learning problems in older children8. Hyperphagia/food foraging/obsession with food9. Deletion 15q11–q13 on high resolution or othercytogenetic/molecular

abnormality of the Prader-Willi chromosome region, including maternal disomy

Minor Criteria

1. Decreased fetal movement, infantile lethargy or weak cry in infancy2. Characteristic behavior problems —temper tantrums, violent outbursts and

obsessive/compulsive behavior; tendency to be argumentative, oppositional, rigid, and stubborn; perseverating, stealing, and lying

3. Sleep disturbance or sleep apnea4. Short stature for genetic background by age 15 5. Hypopigmentation—fair skin and hair compared to family6. Small hands and/or feet for height age7. Narrow hands with straight ulnar border8. Eye abnormalities 9. Thick, viscous saliva with crusting at the corners of the mouth10. Speech articulation defects11. Skin picking

The first stage FAILURE TO THRIVE Birth to 5 years.

• Low birth weight, decreased activity in mother’s womb/babies arrive past their due date

• Weak muscle tone• Feeding difficulties - poor sucking reflexes /require special feeding

techniques• Poor weight gain and slow physical growth• Small hands and feet• Excessive sleepiness• Developmental delays • Speech and language difficulties and delays• Underdeveloped genitals – undescended testicles

The second stage THRIVING TOO WELL Between 5 years throughout lifetime

• Increased appetite and weight control problems

• Behavior problems

• Learning difficulties with mental retardation

• Speech difficulties

• Motor delays

• Short stature without growth hormone therapy

Obesity

• Imbalance between energy intake and energy expenditure

• Necessary is 40% calories compared with non-obese

• Obesity can become life-threatening if not controlled

Genital hypoplasia and cryptorchidism

• Cryptorchidism is reported in >90% of cases

• Small testes and scrotal hypoplasia

• Micropenis

• Inguinal hernia can occur in >90% of cases

• Hypoplasia of the clitoris and/or labia minor

Cryptorchidism evaluation

• Nonpalpable testicle-inguinal/pelvic ultrasound

• Magnetic resonance imaging (MRI)

• Measurements of testosterone, LH, and FSH

• Bilateral cryptorchidism - Gonadal stimulation testing to document functional testicular tissue

Cryptorchidism treatment

• Gonadotropin 500–1000 U by intramuscular injection twice a week for 5 weeks (10 doses total)

• Post-test testosterone level of >100–200 ng/ dL is indicative of testicular activity

• Spontaneous descent of a cryptorchid testicle may occur

• Timing for surgical exploration and orchidopexy have been controversial

Orchiopexy

• Reduces the risk for cancer

• Reduces the risk for testicular torsion

• Preserve the testicular function and fertility

Musculoskeletal Disorders

• Are universal features of PWS

• Physical therapy is an essential element of treatment

• Growth hormone treatment improve muscle strength and endurance

Scoliosis

• Commonly observed disorder in PWS

• Diagnosed clinically in childhood

• 50-80% of individuals affected

• Pathogenesis - neuromuscular scoliosis

• Abnormal kyphosis or lordosis

Scoliosis

• Need an orthopedist consultation

• Clinical screening and serial spine radiographs

• Spinal orthosis for mild to moderate curves to improve the functional position of the trunk

• Surgical intervention for severe, rapidly-progressing curves (difficult due to poor bone and tissue quality)

Scoliosis

Osteoporosis

• Compromised bone strength predispose to an increased risk of fracture

• Osteoporosis in PSW patients often lead to bone fractures with decreased deep pain sensation

• X-ray absorptiometry (DXA) is the standard diagnostic method for assessment of bone mineral density

• Bisphosphonate

• Estrogen replacement therapy preserve bone mass and reduction of fracture risk

Anesthesia-Obesity

• Obese individuals are prone to obstructive apnea, pulmonary compromise, and diabetes

• Altered blood oxygen or blood carbon dioxide levels change response to medication

• Pulmonary hypertension, right ventricular hypertrophy and right-heart failure

Anesthesia-High Pain Threshold

• Individuals with PWS may not respond to pain in the same manner as others

• Helpful in post-operative management, but it may mask underlying problems

• Pain is the body's way of alerting us for problems

Anesthesia- Temperature Instability

• The hypothalamus regulates the body's temperature

• Depolarizing muscle relaxants (succinylcholine) should be avoided unless absolutely necessary

risk for malignant hyperthermia

Thick Saliva

• Thick saliva can complicate airway management during extubation

• Thick saliva predisposes to dental cavities and loose teeth

Food-Seeking Behaviors

• It is important to have an empty stomach to reduce the risk of aspiration

• Individuals with PWS generally have an excessive appetite and may not tell you the truth if they have eaten just prior surgery

• A naso-gastric probe should be placed prior to any oral intubation

Skin Picking

• Skin picking can complicate healing of IV sites and wounds

• Usually if these remain well covered, they will be left alone

• Restraints or thick gloves may be used to protect surgical wounds during healing

Difficult IV Access

• Due to obesity and lack of muscle mass, individuals with PWS may pose difficulties with insertion of an intravenous line

• Ultrasound evaluation for the position of the vessels

Recovery Post Anesthesia

• Drowsiness may be due to the underlying somnolence and a component of central apnea

• For typical outpatient procedures, consideration should be given to an overnight observation

Gastrointestinal

• In the neonate - extremely weak suck reflex

• Nasogastric tube-feeding is often used to meet nutritional needs

• Many infants require gastrostomy tube placement to facilitate feeding

• a 30-degree incline post feeds decrease ability to vomit

Gastrointestinal

• Abdominal and rectal pain, rectal fissures, hemorrhoids, and rectal bleeding

• Diarrhea is more frequently than constipation in PWS

• Rectal ulcers - as a result of a regional skin picking

Treatment options for obesity

• Behavioral Modification• Diet• Exercise• Medical therapy• Surgery

Surgery

• Bariatric surgery causes weight loss through either a diminished capacity for food intake and/or via reduced digestion and absorption of food

• Experience with bariatric surgery in PWS is limited

Indications for SurgeryNIH Consensus Panel 1991

• BMI > 40

• BMI > 35 with co-morbidities

• Children and adolescents have not been sufficiently studied to allow a recommendation for surgery

Surgical options for obesity

• Roux-en-Y Gastric Bypass• Bilio-pancreatic diversion• Gastric banding• Vagotomy• Gastroplasty• Jejuno-ileal bypass• Intragastric balloon

Roux-en-Y Gastric Bypass

Bilio Pancreatic DiversionMarceau Procedure

Gastric banding

Intragastric Balloon

Vertical banded gastroplasty

Results

• Gastric restrictive operations and gastric banding failed to maintain long-term weight because of the poor patient compliance

• Jejunoileal bypass caused spectacular weight loss, but patients were unable to run a normal life due to excessive diarrhea

• Vagotomy is not adequate for long-term control of PWS related obesity

• Long-term results after Roux-en-Y Gastric Bypass were better, but high revision rate of the gastric pouch was reported

Conclusions• A multidisciplinary approach is needed to treat individuals with

PWS.

• Pediatricians, family physicians, or internists should be able to treat most patients with PWS in consultation with a clinical geneticist, endocrinologist, dietitian, surgeon and other experts as needed.

• Given the high rate of potential associated morbidities, all individuals with PWS should be regularly screened for abnormal bone structure and back curvature.

• The decreased muscle tone and muscle mass contribute to the lower metabolic rate, leading to physical inactivity and obesity.

• Surgery need to be evaluated.

Literature

• Butler MG, MGLee PD, Whitman BY. Management of Prader−Willi Syndrome. Springer Science Business Media, Inc: New York; 2006

• Marinari MG, Camerini G, Novelli GB. Outcome of biliopancreatic diversion in subjects with prader-willi syndrome. Obesity Surgery, 11, 491-495

• • Papavramidis ST, Kotidis EV, Gamvros O. Prader-Willi syndrome–

associated obesity treated by biliopancreatic diversion with duodenal switch. Case report and literature review. J Pediatr Surg 2006 Jun;41(6):1153-8

• Inge TH, Nancy F. Krebs NF et a. Bariatric Surgery for Severely Overweight Adolescents: Concerns and Recommendations. PEDIATRICS Vol. 114 No. 1 July 2004

• Touquet VLR, Ward WN, Clark CG. Obesity surgery in a patient with the Prader-Wili syndrome. Br. J. Surg. Vol. 70 (1983) 18Ck186

Thank’s to

• Romanian Prader Willi Association• Mrs. Dan Dorica• Prof Dr Puiu Maria• Colleagues from our project: Correlation

of clinic, genetic and epigenetic aspects implicated in the etiology of Prader-Willi/Angelman syndromes: model of multidisciplinary abordation for rare diseases in Romania

Thank You