Effect of semaglutide on weight loss and glycaemic control in patients with Prader-Willi Syndrome and type 2 diabetes.

Prader-Willi Syndrome (PWS) is the most common genetic cause of obesity, occurring in approximately 1 in 15,000 newborns. It results from the lack of expression of genes on the paternal allele of the chromosomal region 15q-11q13 (65-75% due to type 1 or type 2 deletion). Individuals with PWS experience associated symptoms such as hypotonia, hyperphagia, and early-onset obesity (before 5 years of age). Around 20% of adults with PWS also develop type 2 diabetes. Previous studies have shown the beneficial effects of GLP1-RA medications, such as exenatide and liraglutide, in treating type 2 diabetes in PWS. However, there is limited information available on the use of semaglutide in PWS. This study aimed to evaluate the effects of semaglutide on weight loss and glycaemic control in four patients with PWS and type 2 diabetes associated with obesity. The patients were started on weekly subcutaneous progressive doses of semaglutide.

Corrigendum: Kidney disease in adults with Prader-Willi syndrome: international cohort study and systematic literature review.

[This corrects the article DOI: 10.3389/fendo.2023.1168648.].

Long-term treatment persistence and maintained reduction of LDL-cholesterol levels with evolocumab over 30 months: Results from the Spanish cohort of the European prospective HEYMANS study / Persistencia al tratamiento a largo plazo y reducción mantenida de los niveles de colesterol LDL con evolocumab durante 30 meses: resultados de la cohorte española del estudio prospectivo europeo HEYMANS

Aims: Limited data exist on low-density lipoprotein-cholesterol (LDL-C) level variability or long-term persistence with the monoclonal antibody evolocumab in routine clinical practice. HEYMANS (NCT02770131) is the first multi-country, multicenter, observational study of European patients initiating evolocumab as part of their routine clinical management, based on local reimbursement criteria (overall data recently published). The aim of this analysis is to describe clinical characteristics, baseline and changes in LDL-C levels, treatment patterns and persistence to evolocumab over 30 months in the Spanish cohort using data from the HEYMANS Registry. Methods: HEYMANS was a prospective study of adult patients (≥18 years) who received at least one dose of evolocumab. A total of 1951 patients were enrolled from 12 countries and were followed up for 30 months after evolocumab initiation. Data were collected for 6 months before evolocumab initiation and up to 30 months thereafter. The Spanish cohort included patients who started evolocumab in routine clinical practice from March 2016 to September 2019. Demographic and clinical characteristics, lipid-lowering therapies (LLT), and lipid levels were collected. (AU)

Objetivos: Existen datos limitados sobre la variabilidad del nivel de colesterol de lipoproteínas de baja densidad (cLDL) o la persistencia a largo plazo con el anticuerpo monoclonal evolocumab en la práctica clínica habitual. HEYMANS (NCT02770131) es el primer estudio observacional multicéntrico y multinacional de pacientes europeos que iniciaron tratamiento con evolocumab en la práctica clínica habitual, basado en criterios de reembolso locales. El objetivo fue evaluar las características clínicas, los cambios en los niveles de cLDL, los patrones de tratamiento y la persistencia a este con evolocumab en la cohorte española con un seguimiento de 30 meses, utilizando datos del registro HEYMANS. Métodos: HEYMANS fue un estudio prospectivo de pacientes adultos (≥18 años) que recibieron al menos una dosis de evolocumab prescrita. Se incluyeron 1.951 sujetos de 12 países. Los datos fueron recopilados desde los seis meses previos al inicio del tratamiento hasta los 30 meses posteriores. La cohorte española incluyó pacientes que comenzaron evolocumab en la práctica clínica habitual desde marzo del 2016 hasta septiembre del 2019. Se recogieron las características demográficas y clínicas, los tratamientos hipolipemiantes (LLT) y el perfil lipídico. (AU)

Genetic testing for familial hyperparathyroidism: clinical-genetic profile in a Mediterranean cohort.

Background: Approximately 10% of primary hyperparathyroidism cases are hereditary, due to germline mutations in certain genes. Although clinically relevant, a systematized genetic diagnosis is missing due to a lack of firm evidence regarding individuals to test and which genes to evaluate. Methods: A customized gene panel (AIP, AP2S1, CASR, CDC73, CDKN1A, CDKN1B, CDKN2B, CDKN2C, GCM2, GNA11, MEN1, PTH, RET, and TRPV6) was performed in 40 patients from the Mediterranean area with suspected familial hyperparathyroidism (≤45 years of age, family history, high-risk histology, associated tumour, multiglandular disease, or recurrent hyperparathyroidism). We aimed to determine the prevalence of germline variants in these patients, to clinically characterize the probands and their relatives, and to compare disease severity in carriers versus those with a negative genetic test. Results: Germline variants were observed in 9/40 patients (22.5%): 2 previously unknown pathogenic/likely pathogenic variants of CDKN1B (related to MEN4), 1 novel variant of uncertain significance of CDKN2C, 4 variants of CASR (3 pathogenic/likely pathogenic variants and 1 variant of uncertain significance), and 2 novel variants of uncertain significance of TRPV6. Familial segregation studies allowed diagnosis and early treatment of PHPT in first-degree relatives of probands. Conclusion: The observed prevalence of germline variants in the Mediterranean cohort under study was remarkable and slightly higher than that seen in other populations. Genetic screening for suspected familial hyperparathyroidism allows the early diagnosis and treatment of PHPT and other related comorbidities. We recommend genetic testing for patients with primary hyperparathyroidism who present with high-risk features.

Psychopathological profile before and after bariatric surgery.

Presurgical psychopathological assessment usually focuses on detecting severe mental disorders. However, mild intensity psychopathology and eating behaviour pattern may also influence postsurgical outcomes. The aim was to identify psychopathology and eating behaviour pattern in candidates prepared for bariatric surgery compared to a normative population before and after surgery. A cohort of 32 patients seeking bariatric surgery in a university hospital between March 2016 and March 2017 were evaluated with Personality Assessment Inventory (PAI), 36-item EDE-Q and BES before and after surgery. Thirty-two patients before and 26 one year after surgery were included. The PAI presurgical psychometric profile suggested a mild mixed adjustment disorder focused on somatic complaints. After surgery, patients improved in somatic complaints (p < 0.001), and depression (p = 0.04). Related eating disorders were more common than those of the normative group and improved significantly after surgery in scores for compulsive intake (BES p < 0.001) and overall key behaviours of eating disorders and related cognitive symptoms (EDE-Q/G p < 0.001). In our cohort ready for bariatric surgery a mild psychopathological profile is still present and becomes closer to that of the normative group after surgery. Further studies are needed to evaluate the effects of mild psychopathology on outcomes after bariatric surgery.

Kidney disease in adults with Prader-Willi syndrome: international cohort study and systematic literature review.

Background: Prader-Willi syndrome (PWS) is a rare, complex, genetic disorder characterized by hyperphagia, hypotonia, delayed psychomotor development, low muscle mass and hypothalamic dysfunction. Adults with PWS often have obesity, hypertension and type 2 diabetes mellitus (DM2), known risk factors for cardiovascular disease (CVD) and chronic kidney disease (CKD). Early symptoms of CVD and CKD may be masked by intellectual disability and inability to express physical complaints. Furthermore, kidney diseases are often asymptomatic. Therefore, renal and cardiovascular disease might be missed in patients with PWS. Microalbuminuria is an early sign of microvascular damage in the kidneys and other vascular beds. Therefore, we screened our adult PWS cohort for the presence of elevated urinary albumin and (micro)albuminuria. Methods: We retrospectively collected anthropometric measurements, blood pressure, medical history, medication use, urine dipstick and biochemical measurements form electronic patient files. In addition, we performed a systematic literature review on kidney disease in PWS. Results: We included 162 adults with genetically confirmed PWS (56% male, median age 28 years), of whom 44 (27%) had DM2. None had known CVD. All subjects had normal estimated glomerular filtration rate (eGFR) according to non-PWS reference intervals. Elevated urinary albumin or (micro)albuminuria was present in 28 (18%); 19 out of 75 (25%) had an increased urinary albumin-to-creatinine ratio (UACR) and 10 out of 57 (18%) had an increased urinary protein-to-creatinine ratio. Elevated urinary albumin was present at a young age (median age 26 (IQR 24-32) years) and was associated with an significantly higher BMI and LDL-cholesterol levels and higher prevalence of DM2, hypertension and dyslipidemia than those with normal UACR (p=0.027, p=0.019, p<0.001, p<0.001, p=0.011 and respectively). Conclusion: Upon screening, one in every five adults with PWS had increased urinary albumin or (micro)albuminuria, early signs of microvascular disease. All had normal eGFR, according to non-PWS reference intervals, and none had a formal diagnosis of CVD. As muscle mass is low in PWS, creatinine levels and eGFR may be spuriously normal. Urinalysis in this patient group can be used as a screening tool for microvascular (kidney) disease. We propose an algorithm for the detection and management of microvascular disease in adults with PWS.

Malignancies in Prader-Willi Syndrome: Results From a Large International Cohort and Literature Review.

CONTEXT: Prader-Willi syndrome (PWS) is a complex disorder combining hypothalamic dysfunction, neurodevelopmental delay, hypotonia, and hyperphagia with risk of obesity and its complications. PWS is caused by the loss of expression of the PWS critical region, a cluster of paternally expressed genes on chromosome 15q11.2-q13. As life expectancy of patients with PWS increases, age-related diseases like malignancies might pose a new threat to health. OBJECTIVE: To investigate the prevalence and risk factors of malignancies in patients with PWS and to provide clinical recommendations for cancer screening. METHODS: We included 706 patients with PWS (160 children, 546 adults). We retrospectively collected data from medical records on past or current malignancies, the type of malignancy, and risk factors for malignancy. Additionally, we searched the literature for information about the relationship between genes on chromosome 15q11.2-q13 and malignancies. RESULTS: Seven adults (age range, 18-55 years) had been diagnosed with a malignancy (acute lymphoblastic leukemia, intracranial hemangiopericytoma, melanoma, stomach adenocarcinoma, biliary cancer, parotid adenocarcinoma, and colon cancer). All patients with a malignancy had a paternal 15q11-13 deletion. The literature review showed that several genes on chromosome 15q11.2-q13 are related to malignancies. CONCLUSION: Malignancies are rare in patients with PWS. Therefore, screening for malignancies is only indicated when clinically relevant symptoms are present, such as unexplained weight loss, loss of appetite, symptoms suggestive of paraneoplastic syndrome, or localizing symptoms. Given the increased cancer risk associated with obesity, which is common in PWS, participation in national screening programs should be encouraged.

A Personalized Approach to Determining the Caloric Needs of Children with Prader-Willi Syndrome Treated with Growth Hormone.

Prader-Willi Syndrome (PWS) is the most frequent cause of genetic obesity. Early reports indicate that children with PWS require 20-40% fewer calories than healthy children to maintain adequate growth. Growth hormone treatment for children with PWS, approved in 2000, affects the body composition and probably affects energy requirements. This retrospective cross-sectional study analyzed the caloric intake in children with PWS aged from 6 months to 12 years old who underwent growth hormone treatment, comparing the patients' caloric intake calculated from parent-recorded dietary intake versus the recommended caloric intake for healthy children, taking into account the age, sex, height, weight, and physical activity. We analyzed the data from 25 patients (13 (52%) boys; mean age, 6.72 ± 2.81 y; median age at starting growth hormone treatment, 1.4 y (IQR: 0.78-2.29); 17 (68%) normal weight and 8 (32%) overweight or obese). The mean daily energy intake was 1208 ± 186 kcal/d, representing 96.83% ± 18.66 of the recommended caloric intake for healthy children. The caloric intake in children with PWS treated with growth hormone was very similar to that recommended for healthy children; thus, we should rethink the dietary recommendations for these children.

Long-term treatment persistence and maintained reduction of LDL-cholesterol levels with evolocumab over 30 months: Results from the Spanish cohort of the European prospective HEYMANS study.

AIMS: Limited data exist on low-density lipoprotein-cholesterol (LDL-C) level variability or long-term persistence with the monoclonal antibody evolocumab in routine clinical practice. HEYMANS (NCT02770131) is the first multi-country, multicenter, observational study of European patients initiating evolocumab as part of their routine clinical management, based on local reimbursement criteria (overall data recently published). The aim of this analysis is to describe clinical characteristics, baseline and changes in LDL-C levels, treatment patterns and persistence to evolocumab over 30 months in the Spanish cohort using data from the HEYMANS Registry. METHODS: HEYMANS was a prospective study of adult patients (≥18 years) who received at least one dose of evolocumab. A total of 1951 patients were enrolled from 12 countries and were followed up for 30 months after evolocumab initiation. Data were collected for 6 months before evolocumab initiation and up to 30 months thereafter. The Spanish cohort included patients who started evolocumab in routine clinical practice from March 2016 to September 2019. Demographic and clinical characteristics, lipid-lowering therapies (LLT), and lipid levels were collected. RESULTS: In total, 201 patients were included in the Spanish cohort. Median follow-up (Q1-Q3) was 30.0 (12-30) months. A total of 61.7% of patients were men and the mean (standard deviation) age was 59.5 (10.8) years. Most patients (68.7%) had experienced a prior cardiovascular event, 45.3% had coronary artery disease or stable angina, and 60.2% had a diagnosis of familial hypercholesterolemia. Overall, 57.7% of patients were receiving treatment with statins, most of them with high-intensity statins (85.3%); 45.8% of patients were intolerant to statins, and 26.4% of patients did not receive any LLT. At baseline, median (Q1-Q3) LDL-C levels were 151 (123-197) mg/dL. After 3 months of treatment, baseline LDL-C decreased by 66% to a median of 50 (30-83) mg/dL and these levels were maintained over time, with a median LDL-C of 55 (40-99) mg/dL at 30 months. At months 10-12 of treatment, LDL-C levels<55mg/dL were achieved by 56.3% of patients. LDL-C levels<70mg/dL were achieved by 70.1% of patients, and a lowering of LDL-C levels ≥50% was achieved by 76.8% of patients. The percentage of patients on evolocumab treatment was 95% at 12 months and 93% at 30 months. CONCLUSIONS: In the Spanish cohort in routine clinical practice, evolocumab therapy provided a reduction in LDL-C levels consistent with that reported in previous clinical trials, which was sustained during 30 months of follow-up. Treatment with evolocumab was started at LDL-C levels 50% higher than those recommended by The Spanish Society of Arteriosclerosis and the Therapeutic Positioning Report. The probability of achieving the 2019 ESC/EAS LDL-C goals would improve with combination therapy and also with a lower LDL-C threshold when starting evolocumab. Persistence to evolocumab remained high during follow-up, with a very low percentage of discontinuation (5% at 12 months; 7% at 30 months).

An Exploratory Analysis on the 2D:4D Digit Ratio and Its Relationship with Social Responsiveness in Adults with Prader-Willi Syndrome.

Prader-Willi syndrome (PWS) is a genetic disorder produced by a lack of expression of paternally derived genes in the 15q11-13 region. Research has generally focused on its genetic and behavioral expression, but only a few studies have examined epigenetic influences. Prenatal testosterone or the maternal testosterone-to-estradiol ratio (MaTtEr) has been suggested to play an important role in the development of the 'social brain' during pregnancy. Some studies propose the 2D:4D digit ratio of the hand as an indirect MaTtEr measure. The relationship between social performance and MaTtEr has been studied in other neurodevelopmental conditions such as Autism Spectrum Disorder (ASD), but to our best knowledge, it has never been studied in PWS. Therefore, our study aims to clarify the possible existence of a relationship between social performance-as measured using the Social Responsiveness Scale (SRS)-and MaTtEr levels using the 2D:4D ratio. We found that, as a group, PWS individuals have shorter index and ring fingers than the control group, but no significant difference in the 2D:4D ratios. The 2D:4D ratio showed a correlation only with Restricted Interests and Repetitive Behavior Subscale, where a positive correlation only for male individuals with PWS was found. Considering only PWS with previous GH treatment during childhood/adolescence (PWS-GH), index and ring fingers did not show differences in length with the control group, but the 2D:4D ratio was significantly higher in the right or dominant hand compared to controls.

Bone Health in Adults With Prader-Willi Syndrome: Clinical Recommendations Based on a Multicenter Cohort Study.

CONTEXT: Prader-Willi syndrome (PWS) is a rare complex genetic syndrome, characterized by delayed psychomotor development, hypotonia, and hyperphagia. Hormone deficiencies such as hypogonadism, hypothyroidism, and growth hormone deficiency are common. The combination of hypotonia, low physical activity, and hypogonadism might lead to a decrease in bone mass and increase in fracture risk. Moreover, one would expect an increased risk of scoliosis due to hypotonia and low physical activity. OBJECTIVE: To study the prevalence and risk factors for skeletal problems (reduced bone mineral density, fractures, and scoliosis) in adults with PWS. METHODS: We retrospectively collected patient characteristics, medical history, medication, biochemical measurements, dual-energy X-ray absorptiometry scans, and spinal X-rays and reviewed the current literature. RESULTS: We included 354 adults with PWS (median age 31 years; 43% males), of whom 51 (14%) had osteoporosis (T-score below -2.5) and 143 (54%) had osteopenia (T-score -1 to -2.5). The most prevalent modifiable risk factors for osteoporosis were hypogonadism, insufficient dairy intake, sedentary lifestyle, and corticosteroid use. Male sex was associated with osteoporosis (P = .005). Growth hormone treatment was not associated with osteoporosis. A history of vertebral fractures was present in 10 (3%) and nonvertebral fractures in 59 (17%). Scoliosis was present in 263 (80%), but no modifiable risk factors were identified. CONCLUSION: Besides scoliosis, osteoporosis is common in adults with PWS. Based on the literature and the risk factors for osteoporosis found in our cohort, we provide practical clinical recommendations to avoid skeletal complications in these vulnerable patients.

An adapted scale to evaluate insight in Prader-Willi Syndrome

ObjectiveTo develop an insight scale for Prader-Willi Syndrome (PWS), a genetically determined neurodevelopmental disorder with different psychopathological and behavioural problems.MethodologyA sample of 36 PWS patients (58.3% women) attended at the Endocrinological Department of the Corporació Sanitària Parc Taulí (Sabadell, Barcelona) was evaluated. Insight was assessed by means of an adapted version of the Scale of Unawareness of Mental Disorder (SUMD), including three general insight dimensions: awareness of having a PWS, awareness of the effects of psychopharmacological medication and awareness of the social consequences, as well as three items that assess awareness of each particular symptom of the disease (obesity/overweight, excessive appetite and excessive food intake).ResultsThe final Scale included six items and demonstrated an adequate internal consistency (Cronbach Alfa of 0.857 for Caregivers and 0.798 for Clinicians) but a high inter-rate variability. External validation using an Analytical-Visual Insight Scale was adequate.ConclusionsThe Adapted version for Prader-Willi patients of the Scale of Unawareness of Mental Disorder (APW-SUD) showed adequate psychometric properties and it is an easy to administer means to assess insight in this population. (AU)

ObjetivoDesarrollar una escala de insight para el síndrome de Prader-Willi (PWS), un trastorno del desarrollo genéticamente determinado, con diferentes problemas psicopatológicos y conductuales.MetodologíaEvaluamos una muestra de 36 PWS (58,3% mujeres), atendidos en el Departamento de Endocrinología de la Corporació Sanitària Parc Taulí (Sabadell, Barcelona). El insight fue valorado mediante una versión adaptada de la Scale of Unawareness of Mental Disorder, incluyendo tres dimensiones generales: conciencia de tener PWS, conciencia de los efectos de la medicación psicofarmacológica, y conciencia de las consecuencias sociales, así como tres ítems que valoran el insight de cada síntoma particular de la enfermedad (obesidad/sobrepeso, excesivo apetito y exceso de ingesta).ResultadosLa escala final incluye seis ítems y ha demostrado una adecuada consistencia interna (alfa de Cronbach de 0,857 para cuidadores y de 0,798 para clínicos), pero una alta variabilidad interobservador. La validación externa usando una escala analítico-visual de insight fue adecuada.ConclusionesLa versión adaptada para pacientes con PWS de la Scale of Unawareness of Mental Disorder muestra adecuadas propiedades psicométricas y es una vía fácil de administrar para evaluar el insight en esta población. (AU)

New Insights in Cytokines in Childhood Obesity: Changes in TWEAK and CD163 After a 2-Year Intervention Program in Prepubertal Children With Obesity.

Objective: Obesity is characterized by a low-grade inflammatory state in adipose tissue. Tumor Necrosis Factor Weak Inducer of Apoptosis (TWEAK) and Cluster of Differentiation 163 (CD163) are cytokines potentially involved in the pathogenesis of obesity. Little is known about them in children. The aim of this study was to observe serum levels of TWEAK and CD163 in prepubertal children with obesity compared to lean, and to evaluate its changes after a 2-year intervention program in children with obesity. Methods: Case-control study with a prospective follow-up of cases for 2 years in a referral pediatric endocrine outpatient centre. Seventy-three prepubertal children with obesity, and forty-seven age- and gender-matched lean controls were studied. Sixty-two cases finished the program. Anthropometric parameters, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), lipid profile, and concentrations of TWEAK and CD163 were determined. Children with obesity were re-evaluated after a 2-year intervention program consisting of diet and exercise. Weight loss was considered if z-score Body Mass Index (BMI) decreased at least 0.5 Standard Deviations (SD). Results: We observed higher CD163 levels in children with obesity compared to controls. No significant differences were observed in TWEAK and CD163/TWEAK ratio at baseline. After the 2-year intervention program, TWEAK levels were higher and CD163/TWEAK ratio was lower in children with weight loss than those without weight loss. CD163 decreased in both groups. Conclusion: TWEAK and CD163 seem to have a role in the pathogenesis of obesity in prepubertal children.

One Year of Recombinant Human Growth Hormone Treatment in Adults with Prader-Willi Syndrome Improves Body Composition, Motor Skills and Brain Functional Activity in the Cerebellum.

We compared body composition, biochemical parameters, motor function, and brain neural activation in 27 adults with Prader-Willi syndrome and growth-hormone deficiency versus age-and sex-matched controls and baseline versus posttreatment values of these parameters after one year of recombinant human growth hormone (rhGH) treatment. To study body composition, we analyzed percentage of fat mass, percentage of lean mass, and muscle-mass surrogate variables from dual X-ray absorptiometry. Biochemical parameters analyzed included IGF-I, glucose metabolism, and myokines (myostatin, irisin, and IL6). To explore muscle function, we used dynamometer-measured handgrip strength, the Timed Up and Go (TUG) test, and the Berg Balance Scale (BBS). To study brain activation, we acquired functional magnetic resonance images during three motor tasks of varying complexity. After one year of treatment, we observed an increase in lean mass and its surrogates, a decrease in fat mass, improvements in TUG test and BBS scores, and increased neural activation in certain cerebellar areas. The treatment did not significantly worsen glucose metabolism, and no side-effects were reported. Our findings support the benefits of rhGH treatment in adults with Prader-Willi syndrome and growth-hormone deficiency on body composition and suggest that it may also improve balance and brain neural activation.

Cognitive and Adaptive Effects of Early Growth Hormone Treatment in Prader-Willi Syndrome Patients: A Cohort Study.

BACKGROUND: Prader-Willi Syndrome (PWS) is a genetically based neurodevelopmental disease characterized by obesity, hyperphagia, and mild to moderate intellectual disability. Treatment with growth hormone (GH) could provide cognitive benefits. The objective of the present study was to compare the cognitive and adaptive performance of 31 patients with genetically confirmed PWS grouped in two cohorts, one treated with GH before 2 years old (Group 1) and the other receiving the treatment later (Group 2). METHOD: We compared two variables necessary to diagnose intellectual disability: intellectual performance, using the Weschler scales, and adaptive behavior, using the DABS scale. The scores were analyzed by means of non-parametric statistical tests. RESULTS: Group 1 (n = 10) obtained higher and statistically significant scores in Total Intelligence Quotient (TIQ), General Ability Index (GAI), and General Adaptive Behavior (GAB), implying better cognitive and adaptive performance compared to Group 2. CONCLUSIONS: Treatment with GH should be administered in the early stage of development (before 2 years old) to obtain greater benefits at the cognitive and adaptive levels.

Social Responsiveness and Psychosocial Functioning in Adults with Prader-Willi Syndrome.

Although various studies have investigated symptoms of autism spectrum disorder (ASD) in Prader−Willi syndrome (PWS), little is known about the consequences of these symptoms, especially in psychosocial function. We aimed to explore ASD symptoms in adults with PWS with special attention to psychosocial functionality. This cross-sectional study included 26 adults (15 women) with PWS who attended a reference unit for rare diseases. Participants' primary caregivers completed the Social Responsiveness Scale (SRS), and clinicians assessed multidimensional functioning with the Personal and Social Performance Scale (PSP). Impaired social responsiveness was identified in 20 (76.9%) participants, and manifest to marked difficulties in social functioning were identified in 13 (50%). Participants with impaired social responsiveness (SRS ≥ 60) had significantly worse scores in functionality measured with the PSP (U = 12.5; p = 0.009) and with three of the four PSP main areas. Moreover, scores for the Social Cognition domain of the SRS correlated positively with the Socially useful activities (p < 0.05) and Personal and social relationships (p < 0.01) main areas of the PSP. These results suggest that difficulties in social skills should be assessed in all psychosocial evaluations of patients with PWS.

An adapted scale to evaluate insight in Prader-Willi Syndrome.

OBJECTIVE: To develop an insight scale for Prader-Willi Syndrome (PWS), a genetically determined neurodevelopmental disorder with different psychopathological and behavioural problems. METHODOLOGY: A sample of 36 PWS patients (58.3% women) attended at the Endocrinological Department of the Corporació Sanitària Parc Taulí (Sabadell, Barcelona) was evaluated. Insight was assessed by means of an adapted version of the Scale of Unawareness of Mental Disorder (SUMD), including three general insight dimensions: awareness of having a PWS, awareness of the effects of psychopharmacological medication and awareness of the social consequences, as well as three items that assess awareness of each particular symptom of the disease (obesity/overweight, excessive appetite and excessive food intake). RESULTS: The final Scale included six items and demonstrated an adequate internal consistency (Cronbach Alfa of 0.857 for Caregivers and 0.798 for Clinicians) but a high inter-rate variability. External validation using an Analytical-Visual Insight Scale was adequate. CONCLUSIONS: The Adapted version for Prader-Willi patients of the Scale of Unawareness of Mental Disorder (APW-SUD) showed adequate psychometric properties and it is an easy to administer means to assess insight in this population.