Scoliosis and rare diseases: our experience with the Prader-Willi syndrome.

INTRODUCTION: Prader-Willi syndrome (PWS) represents a difficult challenge for spine surgeons, due to the association of a structural scoliosis, with a prevalence between 15 and 86%. Conservative therapy is a viable option, but surgery is increasingly becoming the treatment of choice. METHODS: The authors reviewed a series of 15 patients affected by PWS treated at their institution between 2008 and 2023. The mean age at index treatment was 9 years and 3 months (range 1-15 years) with a prevalence of female subjects. Primary scoliotic curve ranged from 14 to 102°, and mean thoracic kyphosis was 56° (range 20-75°). Eleven patients underwent conservative treatment, while four were treated surgically. RESULTS: Mean follow-up was 5 years and 3 months (range 2-12 years). Among the 11 patients treated conservatively, only two showed improvements of the coronal curve, while the remaining nine displayed a worsening of the deformity during follow-up. Complication rate after surgery was 75%. One patient developed paraplegia after pedicle screw positioning. One patient displayed rod breakage and PJK that required revision surgery proximally. Hardware deep infection was seen in one case where it was necessary to proceed with instrumentation removal after 10 years. DISCUSSION AND CONCLUSIONS: Spine surgery represents a convincing option in patients affected by PWS, but the risks of complications are high. Correct patient selection must be the main objective, and multilevel pedicle screw fixation should be the procedure of choice. Traditional growing rod should be prudently evaluated in every single case.

Metabolic and bariatric surgery for obesity in Prader Willi syndrome: systematic review and meta-analysis.

Obesity is the leading cause of morbidity and mortality in patients with Prader-Willi Syndrome (PWS). Our objective was to compare changes in body mass index (BMI) after metabolic and bariatric surgery (MBS) for the treatment of obesity (BMI ≥35 kg/m2) in PWS. A systematic review of MBS in PWS was performed using PubMed, Embase, and Cochrane Central, identifying 254 citations. Sixty-seven patients from 22 articles met criteria for inclusion in the meta-analysis. Patients were organized into 3 groups: laparoscopic sleeve gastrectomy (LSG), gastric bypass (GB), and biliopancreatic diversion (BPD). No mortality within 1 year was reported in any of the 3 groups after a primary MBS operation. All groups experienced a significant decrease in BMI at 1 year with a mean reduction in BMI of 14.7 kg/m2 (P < .001). The LSG groups (n = 26) showed significant change from baseline in years 1, 2, and 3 (P value at year 3 = .002) but did not show significance in years 5, 7, and 10. The GB group (n = 10) showed a significant reduction in BMI of 12.1 kg/m2 in the first 2 years (P = .001). The BPD group (n = 28) had a significant reduction in BMI through 7 years with an average reduction of 10.7 kg/m2 (P = .02) at year 7. Individuals with PWS who underwent MBS had significant BMI reduction sustained in the LSG, GB, and BPD groups for 3, 2, and 7 years, respectively. No deaths within 1 year of these primary MBS operations were reported in this study or any other publication.

Angelman and Prader-Willi Syndromes: Sister Imprinting Disorders With High Complication Rates Following Spinal Deformity Surgery.

We sought to examine the modern surgical treatment of spinal deformity associated with sister imprinting disorders, Prader-Willi syndrome (PWS) and Angelman syndrome (AS), with emphasis on the specific complications encountered in these patient populations. Fifteen patients with PWS and 5 patients with AS who underwent surgical intervention for spinal deformity between 2000 and 2018 were identified. Postoperative complications were classified using the modified Clavien-Dindo-Sink (CDS) system and further categorized into specific subtypes including excessive drainage, dehiscence, implant failure, infection, and delayed wound healing. Perioperative and final follow-up radiographic data were analyzed. Mean age at surgery was 12.9 years (range, 4-21 years) with mean follow-up of 46.1 months (range, 1-145 months). There were postoperative complications in 17 patients (85%). Ten major complications (CDS ≥ 3) occurred in 9 patients (45%). These included 5 infections requiring reoperation, 1 seroma requiring drainage, 2 severe cervical-thoracic deformities requiring reoperation, 1 implant failure requiring reoperation, and 1 death secondary to fungal sepsis and thromboembolic disease. Eight additional patients (40%) had minor complications (CDS 1 or 2). Eight intraoperative complications occurred in 5 patients (25%), including loss of neuromonitoring signals and cerebrospinal fluid leaks. Surgical intervention for scoliosis in PWS and AS continues to have high complication rates secondary to medical and behavioral comorbidities found in these patient populations. The exact etiology of the high complication rates encountered cannot be definitively stated, but both syndromes frequently present with a number of unique features that may predispose patients to develop surgical complications. [Orthopedics. 2023;46(4):e223-e229.].

Critical review of bariatric surgical outcomes in patients with Prader-Willi syndrome and other hyperphagic disorders.

OBJECTIVE: The aim of this study was to review bariatric procedure outcomes among patients with Prader-Willi syndrome (PWS), melanocortin 4 receptor (MC4R) mutations, Bardet-Biedl syndrome, and hypothalamic obesity. METHODS: Systematic published literature review used the following search terms: "Prader-Willi syndrome," "Bardet-Biedl syndrome," "hyperphagia," "bariatric surgery," "MC4R"/"melanocortin 4 receptor", "hypothalamic obesity," and "bariatric procedure." Information collected included demographics, genetics, anthropometry, procedure type, outcomes, and complications, with inclusion of case series and clinical reports given the rarity of the disorders. For PWS, postoperative weight-change percentage and BMI up to 14 years following surgery were analyzed using general linear mixed models, with descriptive outcomes for other conditions. RESULTS: A total of 54 publications were identified, with variable follow-up periods for 202 patients (114 with PWS, 43 with MC4R mutations, 7 with Bardet-Biedl syndrome, and 38 with hypothalamic obesity) among bariatric procedures. Weight loss of patients with PWS was greatest within 1 year of surgery, with weight-change percentage not significantly different from 0 at 5 years. Long-term results in other conditions were variable and featured suboptimal weight loss and increased reoperation risk. CONCLUSIONS: Bariatric procedures among hyperphagic individuals, including those with PWS, report variable results and outcomes. Benefits of bariatric surgery may be less durable in hyperphagic disorders in comparison with other patients with severe obesity.

Patients with Prader-Willi Syndrome (PWS) Underwent Bariatric Surgery Benefit more from High-Intensity Home Care.

BACKGROUND: Long-term weight loss effect of bariatric surgeries for patients with Prader-Willi Syndrome (PWS) remains controversial since factors like postoperative home care intensity may impact the outcome. The aim of this study was to evaluate the role of home care intensity on long-term weight loss effect of bariatric surgery in patients with PWS. METHODS: This was a prospective observational study on patients with PWS undergoing bariatric surgery and patients were enrolled from July 2015 to December 2016. Detailed information of patients' weight and behaviors was recorded by caregivers postoperatively. The intensities of home care applied to patients were classified into four categories (high, moderate, low, and very low) according to the records. RESULTS: Six cases (3 males, 3 females) were enrolled in this study with LSG (n = 2), RYGB (n = 3), and LSG-DJB (n = 1) as their primary operation. The mean BMI of these participants was 46.78 ± 11.63 kg/m2, and the mean age was 17.66 ± 6.59 years. All patients had at least 5 years of follow-ups, and the %EWL were 51.57 ± 23.36%, 64.54 ± 18.97%, 35.34 ± 36.53%, 19.45 ± 41.78%, and - 4.74 ± 71.50% in the half, first, second, third, and fifth year after surgery respectively. Two patients with high-intensity home care achieved a %EWL of 70.57 ± 8.86% in the fifth year after surgery. CONCLUSIONS: Overall long-term weight loss of bariatric surgery for patients with PWS was not found through the follow-ups. Two patients with high-intensity home care maintained weight loss at the fifth-year follow-up, suggesting a pivotal role of high-intensity home care in long-term outcomes of bariatric surgery in patients with PWS.

Hospital outcomes in pediatric patients with Prader-Willi syndrome (PWS) undergoing orthopedic surgery: A 12-year analysis of national trends in surgical management and inpatient hospital outcomes.

BACKGROUND: The incidence of orthopedic disorders amongst patients with Prader-Willi Syndrome (PWS) is high when compared to the general pediatric population. The purpose of this retrospective study was to define the most commonly performed orthopedic procedures in pediatric patients with PWS and to characterize the peri-operative outcomes of these patients. METHODS: The Kids Inpatient Database (KID) was queried to collect data and identify all pediatric patients with PWS who underwent orthopedic procedures from 2001 to 2012. A total of 3684 patients with PWS were identified, 334 of who underwent an orthopedic procedure. Population demographics, comorbidities, and specific procedures undergone were defined. The incidences of postoperative complications and length of associated hospital stay were additionally evaluated. RESULTS: Mean age of patients in this sample was 10.33 years (SD 4.5). The most common comorbidities included obesity (18.1%), chronic pulmonary disease (14.1%), hypothyroidism (5.1%), hypertension (5.1%), and uncomplicated diabetes (4%). Common procedures were spinal fusion (165/334, 49%) and lower extremity procedures (50/334, 15%). Complications included acute blood loss anemia, device related complications, pneumonia, sepsis, and urinary tract infections. The overall complication rate was 35.6%. Average hospital lengths of stay for patients undergoing spinal fusion was 6.68 days (SD 4.13), lower extremity orthopedic procedure was 5.65 days (SD 7.4), and all other orthopedic procedures was 7.74 days (SD 16.3). CONCLUSIONS: Orthopedic disorders are common in patients with PWS. Consequently, spinal fusions and lower extremity procedures are commonly performed in this patient population. Associated comorbid conditions may negatively impact surgical outcomes in these patients. This information should prove useful in the peri-operative management of patients with PWS undergoing orthopedic surgery and for shared decision making with families.

Outcomes of Adenotonsillectomy for Obstructive Sleep Apnea in Prader-Willi Syndrome: Systematic Review and Meta-analysis.

OBJECTIVES: Prader-Willi syndrome (PWS) increases the risk of obstructive sleep apnea (OSA) due to obesity, hypotonia, and abnormal ventilatory responses. We evaluated post-adenotonsillectomy complications, polysomnography changes, and quality of life in children with OSA and PWS. STUDY DESIGN: Systematic review and meta-analysis. METHODS: We conducted a systematic review and meta-analysis by searching PubMed, Embase, Cochrane, Web of Science, and Scopus. Two researchers independently reviewed studies about adenotonsillectomy for OSA in patients <21 years with PWS. We extracted study design, patient numbers, age, complications, polysomnography, and quality of life. We pooled postoperative changes in apnea hypopnea index (AHI) for meta-analysis. We applied Methodological Index for Nonrandomized Studies (MINORS) criteria to assess study quality. RESULTS: The initial search yielded 169 studies. We included 68 patients from eight studies with moderate to high risk of bias. Six studies reported on complications and 12 of 51 patients (24%) had at least one. Velopharyngeal insufficiency was the most commonly reported complication (7/51, 14%). We included seven studies in meta-analysis. Mean postoperative improvement in AHI was 7.7 (95% CI: 4.9-10.5). Postoperatively 20% (95% CI: 3%-43%) had resolution of OSA with AHI < 1.5 while 67% (95% CI: 50%-82%) had improvement from severe/moderate OSA to mild/resolved (AHI < 5). Two studies evaluated quality of life and demonstrated improvement. CONCLUSIONS: Children with PWS undergoing adenotonsillectomy for OSA have a substantial risk of postoperative complications that may require additional interventions, especially velopharyngeal insufficiency. Despite improvements in polysomnography and quality of life, many patients had residual OSA. This information can be used to counsel families when considering OSA treatment options. Laryngoscope, 131:898-906, 2021.

Bariatric surgery for Prader-Willi syndrome was ineffective in producing sustainable weight loss: Long term results for up to 10 years.

BACKGROUND: Obesity control in Prader-Willi syndrome (PWS) is notoriously difficult. The role of bariatric surgery in PWS remains controversial as long-term data are lacking. OBJECTIVES: To evaluate the 10-year outcomes of bariatric surgery in PWS. METHODS: This was a prospective observational study on PWS patients who received bariatric surgery and multidisciplinary follow-up programmes for obesity control. Outcomes on weight reduction and comorbidity resolution were evaluated. RESULTS: Between 2008 and 2013, five PWS patients (two males, mean age 19.2 ± 3.0 years) with body mass index of 47.3 ± 6.9 kg m-2 received sleeve gastrectomy (n = 2), one anastomosis gastric bypass (n = 2), and Roux-en-Y gastric bypass (n = 1) after failing all non-operative weight loss programmes. The median follow-up was 8.4 ± 2.2 years. The best mean percentage of total weight loss (%TWL) was achieved at 2 years (24.7%). %TWL dropped to 23.3% at 3 years, 11.9% at 5 years, 4.1% at 8 years, and 0% at 10 years. Each patient had at least three comorbidities preoperatively, but none of them had resolution of any one of the comorbidities at the last follow-up. CONCLUSIONS: Bariatric surgery could not produce sustainable long-term weight loss or comorbidity resolution in PWS. This study suggests that bariatric surgery cannot be recommended to PWS patients as a standard treatment.

Orchidopexy in children with Prader-Willi syndrome: Results of a long-term follow-up study.

INTRODUCTION: Prader-Willi syndrome (PWS) is a rare (1:20.000) genetic condition affecting both males and females. Among other features, in boys, the syndrome is characterized by cryptorchidism in 86-100% of cases, hypogonadism, delayed puberty and infertility. The aim of the present study is to appraise the results of orchidopexy in this selected population of children. STUDY DESIGN: A follow-up study of children with PWS treated for undescended testes at a single institution over a 20-year period was performed. Patients were identified from a National PWS registry and reviewed at a special follow-up clinic. Data were collected from electronic and hard copies records and reported as median (range). RESULTS: Thirty-three children (1-17 years) were identified. Co-morbidities were present in 22 (66%) and 15 (45%) were on growth-hormone therapy. Six patients (19%) had normal testes palpable in the scrotum; twenty-seven (81%) had undescended testes and required orchidopexy. Thirteen (48%) underwent a bilateral procedure for a total of 40 procedures. A 2-stage Fowler-Stephens orchidopexy was required in 2 (7%) testes. At surgery hypotrophic testes were documented in 6 (22%) patients. Age at orchidopexy was 1.4 years (0.5-5.5). Age at FU was 7.2 years (1.7-17). Length of follow-up is 3.5 years (0.4-14). At follow-up 16 (40%) testes were of normal size and palpable in the scrotum; 7 (17.5%) testes required redo-orchidopexy. All patients (6/33) over 16 years of age that had testosterone levels tested had values below normal limits after successful orchidopexy. CONCLUSIONS: This study evaluates the results of orchidopexy in a large population of children with PWS. At follow-up, only 40% of testes were of normal size and in the scrotum. This information should be taken into consideration for patients' management and pre-operative parents' counseling.

Sleeve gastrectomy leads to weight loss in the Magel2 knockout mouse.

BACKGROUND: Prader-Willi syndrome (PWS) is a genetic disorder characterized by hyperphagia, obesity, cardiopulmonary diseases, and increased mortality. Although successful weight loss improves health in PWS, few treatments cause sustained weight loss in obese patients let alone obese individuals with PWS. OBJECTIVES: The present study uses the Magel2 knockout (KO) mouse, an animal model of PWS, to conduct a preclinical study on the efficacy of sleeve gastrectomy (SG) in PWS. SETTING: Academic research laboratory, United States. METHODS: We performed sham or SG surgeries in 24- to 28-week-old male Magel2 KO and wild-type littermate control mice (WT) who had been maintained on a high-fat diet for 10 weeks. We monitored weight, food intake, and fat and lean mass pre- and postoperatively. Fasting glucose, glucose tolerance, and counter-regulation were measured postoperatively. RESULTS: Magel2 KO animals had similar recovery and mortality rates compared with WT. SG resulted in similar weight loss, specifically loss of fat but not lean mass, in both Magel2 KO and WT mice. SG also resulted in significantly lower fasting glucose levels and a reduction in fat intake in both Magel2 KO and WT mice. We also found that Magel2 KO mice failed to increase their food intake in response to the glucoprivic agent 2-deoxy-D-glucose, suggesting impaired glucose counter-regulation, but this occurred regardless of surgical status. All results were considered significant when P< .05. CONCLUSION: We find in this mouse model of PWS, SG is a well-tolerated, effective strategy for weight and fat loss.

Obstructive sleep apnea in Prader-Willi syndrome: risks and advantages of adenotonsillectomy.

Obstructive sleep apnea is a well-known clinical manifestation of Prader-Willi syndrome. The aim of our study is to evaluate the efficacy of adenotonsillectomy for the treatment of the disorder as well as the improvement of their post-operative quality of life. Five patients with moderate to severe obstructive sleep apneas and adenotonsillar hypertrophy of grade III-IV underwent adenotonsillectomy. Pre- and postoperative apneas and Quality of Life were assessed respectively with a polysomnography with multi-sleep latency test and with the pediatric Quality of Life questionnaire, performed before and 6 months after surgery. A decrease of apnea/hypopnea index values has been detected between pre- and post-surgery (t=2.64, P=0.005), as well as oxygen desaturation index values (t=5.51, P=0.005), multi-sleep latency test (t=4.54, P=0.01), and of the values of pediatric Quality of Life questionnaire. No correlation has been detected between body mass index and apnea/hypopnea index, oxygen desaturation index and multi-sleep latency test values pre- and post-adenotonsillectomy. A correlation has been found between multi-sleep latency test and oxygen desaturation index values post-surgery (P=0.04). No post-operative complications were observed. Our data underline the efficacy of surgery in Prader-Willi patients with adenotonsillar hypertrophy in order to improve their quality of life.

[Anesthesia for ten patients with Prader-Willi syndrome].

Previous reports indicate that Prader-Willi syndrome may present various problems during anesthesia and the perioperative period. We retrospectively investigated anesthesia records of 10 patients (2 adults and 8 children) who were diagnosed to have Prader-Willi syndrome, and who had an operation under anesthesia. Three patients had small mouths, small jaws or both. Decreased musle mass was observed in 2 patients. Two patients were morbidly obese (BMI 33, and 51). General anesthesia was used in 9 patients. Spinal anesthesia under fluoroscopy was performed in the remaining one patient who was morbidly obese (BMI 51). Among 9 patients who received general anesthesia, mask ventilation was difficult in one patient, but insertion of an oral airway relieved the problem. Difficult tracheal intubation occurred in one patient. No other major problems occurred. We conclude that the incidence of problems during anesthesia and postoperative period in patients with Prader-Willi syndrome would be less than previously considered.

Velopharyngeal dysfunction in children with Prader-Willi syndrome after adenotonsillectomy.

INTRODUCTION: Prader-Willi syndrome (PWS) is a rare genetic disorder with an incidence rate of 1 in 10,000-30,000. Patients with PWS typically have symptoms related to hypotonia, obesity, and hypothalamic dysfunction. A high rate of obstructive sleep apnea (OSA) is found among this population of patients. Adenotonsillectomy has been advocated as a first line approach for treatment of OSA in patients with PWS. Velopharyngeal dysfunction (VPD) is a known complication of adenotonsillectomy. VPD can also be present in patients with global hypotonia, such as those with PWS. The objective of this study is to review the occurrence of VPD in patients with PWS after adenotonsillectomy for OSA. METHODS: A retrospective review was performed of all patients with PWS and OSA from a tertiary pediatric hospital between the years of 2002 and 2012. Pre- and post-operative sleep studies and sleep disordered breathing symptoms, post-operative VPD assessment by the speech-language pathologist (SLP), and VPD treatments were evaluated. RESULTS: Eleven patients (five males and six females), fitting the inclusion criteria, were identified. The age of the patient at the initial otolaryngologic evaluation ranged from 2 to 9 years. All patients underwent adenotonsillectomy for sleep disordered breathing. Four patients were diagnosed with post-operative hypernasality after assessment by a speech-language pathologist. The hypernasality ranged from mild to moderately severe. Of the four patients with hypernasality, two were found to have structural issues requiring surgery (pharyngeal flap). Both of the surgical patients experienced significant improvement in their VPD after surgery. The remaining two patients were found to have articulation error patterns that were considered more developmental in nature and both responded to speech therapy. All patients, except one, had improvement in their polysomnogram or sleep symptoms after adenotonsillectomy. However, three patients continue to require continuous positive airway pressure at night. CONCLUSION: Velopharyngeal dysfunction may occur after adenotonsillectomy in patients with Prader-Willi Syndrome. Families should be counseled of this risk and the potential need for operative intervention to correct it.

The mini-gastric bypass in the management of morbid obesity in Prader-Willi syndrome: a viable option?

AIMS: To test the efficacy of the mini-gastric bypass (MGB) in the treatment of morbid obesity related to the Prader-Willi Syndrome (PWS). PATIENTS AND METHODS: Three young male patients (mean age 15.6 years) complaining with PWS were treated by MGB with the aim to improve morbid obesity associated with the syndrome. Preoperative body mass index was 51 ± 4.13 kg/m(2). Two patients suffered from both hypertension and frequent sleep apnea crises. The mean preoperative level of fasting plasma acyl ghrelin was 1417.26 ± 289.37 pg/ml. All patients underwent a laparoscopic MGB. RESULTS: The postoperative period was uneventful and all patients were discharged on the fifth postoperative day. The patients suffering from both hypertension and respiratory crises are now free from receiving any therapeutic support. When measured, the postoperative level of fasting plasma acyl ghrelin decreased to 675.5, 524.6, and 353.1 pg/ml, respectively. An excess weight loss of 79% has been recorded at two years so far. To date, no nutritional impairment, weight regain, or need for revision surgery has been recorded. CONCLUSION: MGB appears to provide an effective weight reduction in patients suffering from PWS without determining significant nutritional impairment or weight regain. Larger studies are however required.

Outcomes of adenotonsillectomy in patients with Prader-Willi syndrome.

OBJECTIVE: To assess the efficacy of upper airway surgical intervention in patients with Prader-Willi syndrome (PWS). Due to reports of sudden death in children undergoing treatment with growth hormone for PWS, detection of sleep-disordered breathing by polysomnography (PSG) has been recommended. DESIGN: Retrospective study. SETTING: Multidisciplinary PWS Center at a tertiary care children's hospital. PATIENTS: Thirteen pediatric patients with PWS who underwent adenotonsillectomy (T&A) with pre-PSG and post-PSG. MAIN OUTCOME MEASURES: Comparison of PSG results before and after T&A. RESULTS: Six of our patients were girls (46%); 8 had genetic characteristics consistent with deletion (61%), and the remaining 5 had genetic characteristics consistent with uniparental disomy (39%). The median age at T&A was 3 years (age range, 6 months to 11 years), and the median age at start of growth hormone treatment was 8.5 months (range, 2 months to 6 years). Nine of the 13 patients had mild to moderate obstructive sleep apnea (OSA) or obstructive hypoventilation (69%); in 8 of these 9, breathing normalized after T&A. Four children had severe OSA prior to surgery (31%). Breathing normalized in 2 of these after surgery, but 2 had PSG findings of residual combined obstructive and central apneas postoperatively. CONCLUSIONS: Adenotonsillectomy, while effective in most children with PWS who demonstrate mild to moderate OSA, may not be curative in children with severe OSA. An increase in central apneas can occur in some children with PWS postoperatively, and it is important to repeat PSG after surgery. Further studies are necessary to determine optimal treatment for some children with PWS and sleep-disordered breathing.