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9 pages, 545 KiB

Open AccessArticle

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

by Yolanda Couto-Rosende, Diana Garcia-Tirado, Mónica Palacio-Marco, Assumpta Caixàs and Raquel Corripio

J. Clin. Med. 2023, 12(12), 3967; https://doi.org/10.3390/jcm12123967 - 10 Jun 2023

Cited by 1 | Viewed by 1182

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Diseases: Prader-Willi Syndrome)

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18 pages, 3098 KiB

Open AccessArticle

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

by Sara Gámez, Jesus Cobo, Meritxell Fernández-Lafitte, Ramón Coronas, Isabel Parra, Joan Carles Oliva, Aida Àlvarez, Susanna Esteba-Castillo, Olga Giménez-Palop, Raquel Corripio, Diego J. Palao and Assumpta Caixàs

J. Clin. Med. 2023, 12(3), 1155; https://doi.org/10.3390/jcm12031155 - 01 Feb 2023

Viewed by 2647

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Diseases: Prader-Willi Syndrome)

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14 pages, 1185 KiB

Open AccessArticle

Atypical 15q11.2-q13 Deletions and the Prader-Willi Phenotype

by Lionne N. Grootjen, Alicia F. Juriaans, Gerthe F. Kerkhof and Anita C. S. Hokken-Koelega

J. Clin. Med. 2022, 11(15), 4636; https://doi.org/10.3390/jcm11154636 - 08 Aug 2022

Cited by 4 | Viewed by 1827

Abstract

Background: Prader-Willi syndrome (PWS) is a rare genetic disorder resulting from the lack of expression of the PWS region (locus q11-q13) on the paternally derived chromosome 15, as a result of a type I or II paternal deletion (50%), maternal uniparental disomy (43%), [...] Read more.

Background: Prader-Willi syndrome (PWS) is a rare genetic disorder resulting from the lack of expression of the PWS region (locus q11-q13) on the paternally derived chromosome 15, as a result of a type I or II paternal deletion (50%), maternal uniparental disomy (43%), imprinting defect (4%) or translocation (<1%). In very rare cases, atypical deletions, smaller or larger than the typical deletion, are identified. These patients may have distinct phenotypical features and provide further information regarding the genotype–phenotype correlation in PWS. Methods: A prospective study in eight patients (six males and two females) with an atypical deletion in the PWS region accompanies an overview of reported cases. Results: All patients had hypotonia (100%) and many had typical PWS facial characteristics (75%), social and emotional developmental delays (75%), intellectual disabilities (50%), neonatal feeding problems and tube feeding (63%), history of obesity (50%), hyperphagia (50%) and scoliosis (50%). All males had cryptorchidism. Two patients had two separate deletions in the PWS critical region. Conclusions: Our findings provide further insight into PWS genotype–phenotype correlations; our results imply that inclusion of both SNURF-SNPRN and SNORD-116 genes in the deletion leads to a more complete PWS phenotype. A larger deletion, extending further upstream and downstream from these genes, does not cause a more severe phenotype. Conventional PWS methylation testing may miss small deletions, which can be identified using targeted next generation sequencing. PWS’s phenotypic diversity might be caused by differentially methylated regions outside the 15q11.2 locus. Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Diseases: Prader-Willi Syndrome)

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27 pages, 2251 KiB

Open AccessArticle

Health Problems in Adults with Prader–Willi Syndrome of Different Genetic Subtypes: Cohort Study, Meta-Analysis and Review of the Literature

by Anna G. W. Rosenberg, Charlotte M. Wellink, Juan M. Tellez Garcia, Karlijn Pellikaan, Denise H. Van Abswoude, Kirsten Davidse, Laura J. C. M. Van Zutven, Hennie T. Brüggenwirth, James L. Resnick, Aart J. Van der Lely and Laura C. G. De Graaff

J. Clin. Med. 2022, 11(14), 4033; https://doi.org/10.3390/jcm11144033 - 12 Jul 2022

Cited by 8 | Viewed by 4149

Abstract

Prader–Willi syndrome (PWS) is a complex, rare genetic disorder caused by a loss of expression of paternally expressed genes on chromosome 15q11.2-q13. The most common underlying genotypes are paternal deletion (DEL) and maternal uniparental disomy (mUPD). DELs can be subdivided into type 1 [...] Read more.

Prader–Willi syndrome (PWS) is a complex, rare genetic disorder caused by a loss of expression of paternally expressed genes on chromosome 15q11.2-q13. The most common underlying genotypes are paternal deletion (DEL) and maternal uniparental disomy (mUPD). DELs can be subdivided into type 1 (DEL-1) and (smaller) type 2 deletions (DEL-2). Most research has focused on behavioral, cognitive and psychological differences between the different genotypes. However, little is known about physical health problems in relation to genetic subtypes. In this cross-sectional study, we compare physical health problems and other clinical features among adults with PWS caused by DEL (N = 65, 12 DEL-1, 27 DEL-2) and mUPD (N = 65). A meta-analysis, including our own data, showed that BMI was 2.79 kg/m² higher in adults with a DEL (p = 0.001). There were no significant differences between DEL-1 and DEL-2. Scoliosis was more prevalent among adults with a DEL (80% vs. 58%; p = 0.04). Psychotic episodes were more prevalent among adults with an mUPD (44% vs. 9%; p < 0.001). In conclusion, there were no significant differences in physical health outcomes between the genetic subtypes, apart from scoliosis and BMI. The differences in health problems, therefore, mainly apply to the psychological domain. Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Diseases: Prader-Willi Syndrome)

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12 pages, 519 KiB

Open AccessArticle

Long-Term Growth Hormone Treatment of Children with PWS: The Earlier the Start, the Better the Outcomes?

by Lionne N. Grootjen, Demi J. Trueba-Timmermans, Layla Damen, Eva F. Mahabier, Gerthe F. Kerkhof and Anita C. S. Hokken-Koelega

J. Clin. Med. 2022, 11(9), 2496; https://doi.org/10.3390/jcm11092496 - 29 Apr 2022

Cited by 9 | Viewed by 2146

Abstract

Long-term effects of growth hormone (GH) treatment in young children with Prader-Willi syndrome (PWS) have never been compared with untreated age-matched controls with PWS, and it is unclear if starting GH in the first year of life is safe and more effective than [...] Read more.

Long-term effects of growth hormone (GH) treatment in young children with Prader-Willi syndrome (PWS) have never been compared with untreated age-matched controls with PWS, and it is unclear if starting GH in the first year of life is safe and more effective than starting GH in early childhood. We investigated the effects of long-term GH on body composition, anthropometrics and cognition in young children with PWS compared to untreated controls and assessed whether starting GH in the first year of life is optimal and safe. An open-label, prospective study was performed, comparing GH-treated children with untreated controls, and comparing children who started GH in the first year of life (subgroup A) with children who started between 2–5 years (subgroup C). A total of 82 GH-treated children with PWS and 22 age-matched controls with PWS were included. The main outcome measures were body composition, anthropometrics, IQ, and safety parameters. After 8 years, GH-treated children had significantly better body composition and were taller than age-matched controls. Subgroup A had a lower FM% trajectory during treatment than subgroup C and showed a greater and longer-term increase in the LBM index. After 8 years, subgroup A had a lower trunk/peripheral fat ratio (p = 0.043) and higher IQ (p = 0.043). No adverse effects of starting GH in the first year were found. Children with PWS who received long-term GH had a better body composition and growth than untreated age-matched controls and starting GH in the first year of life was optimal and safe. Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Diseases: Prader-Willi Syndrome)

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7 pages, 226 KiB

Open AccessArticle

Serum Asprosin Concentrations in Children with Prader–Willi Syndrome: Correlations with Metabolic Parameters

by Maha Alsaif, Catherine J. Field, Eloisa Colin-Ramirez, Carla M. Prado and Andrea M. Haqq

J. Clin. Med. 2022, 11(8), 2268; https://doi.org/10.3390/jcm11082268 - 18 Apr 2022

Cited by 2 | Viewed by 1736

Abstract

Children with Prader–Willi syndrome (PWS) are characterized by severe obesity. Asprosin is a newly discovered protein hormone produced by the white adipose tissue and is correlated with insulin resistance. The aim of our study was to describe the concentrations of serum asprosin in [...] Read more.

Children with Prader–Willi syndrome (PWS) are characterized by severe obesity. Asprosin is a newly discovered protein hormone produced by the white adipose tissue and is correlated with insulin resistance. The aim of our study was to describe the concentrations of serum asprosin in children with PWS compared to those with overweight/obesity and normal weight, and to explore the postprandial change in asprosin concentrations in participants with PWS and BMI-z matched controls. We enrolled 52 children, 23 with PWS, 8 with overweight/obesity, and 21 with normal weight. Fasting levels of asprosin, glucose, and insulin were collected in all children, and postprandial asprosin and fasting levels of acyl ghrelin (AG) and leptin were also determined in a subsample of participants. There were no significant differences among groups in fasting levels of asprosin, glucose, insulin, and HOMA-IR. Fasting serum asprosin and 1-h post-meal serum asprosin did not differ in children with PWS nor in BMI-z matched controls. Fasting asprosin showed an adjusted positive correlation with glucose in children with obesity (r = 0.93, p = 0.007) but not in children with PWS nor children with normal weight. Circulating asprosin might be a predictor of early alterations in glucose metabolism in children with obesity. More research is needed to further explain the association between asprosin, food intake, metabolism, and obesity in PWS. Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Diseases: Prader-Willi Syndrome)

11 pages, 776 KiB

Open AccessArticle

Impact of Deprivation on Obesity in Children with PWS

by Sabrina Grolleau, Marine Delagrange, Melina Souquiere, Catherine Molinas, Gwenaëlle Diene, Marion Valette and Maithé Tauber

J. Clin. Med. 2022, 11(8), 2255; https://doi.org/10.3390/jcm11082255 - 18 Apr 2022

Cited by 1 | Viewed by 1600

Abstract

Our study aimed to evaluate the social deprivation score in families with a child with Prader-Willi syndrome (PWS) and analyze its impact on the occurrence of obesity in the affected child. We included 147 children with PWS followed in our reference center with [...] Read more.

Our study aimed to evaluate the social deprivation score in families with a child with Prader-Willi syndrome (PWS) and analyze its impact on the occurrence of obesity in the affected child. We included 147 children with PWS followed in our reference center with Evaluation of the Deprivation and Inequalities of Health in Healthcare Centres by the EPICES score. Deprivation (EPICES ≥ 30) was found in 25.9% of the population. Compared with the non-obese children, children with obesity had more deprived families, 50.0 vs. 18.0% (p = 0.0001); were older, with a median of 10.1 vs. 6.0 years (p = 0.0006); were less frequently treated with growth hormone (GH), 80.6 vs. 91.9% (p = 0.07). The mothers of obese children were more frequently obese, 46.9 vs. 13.3% (p < 0.0001), and achieved high study levels less frequently (≥Bac+2), 40.9 vs. 70.1% (p = 0.012). The multivariate logistic regression indicated that age, living in a deprived family, and having a mother with overweight/obesity were significantly associated with an increased risk of obesity (respectively, OR = 3.31 (1.26–8.73) and OR = 6.76 (2.36–19.37)). The same risk factors of obesity observed in the general population were found in children with PWS. Families at risk, including social deprivation, will require early identification and a reinforced approach to prevent obesity. Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Diseases: Prader-Willi Syndrome)

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11 pages, 1054 KiB

Open AccessArticle

Thrombosis Risk History and D-dimer Levels in Asymptomatic Individuals with Prader–Willi Syndrome

by Lisa Matesevac, Jennifer L. Miller, Shawn E. McCandless, Jaret L. Malloy, Jessica E. Bohonowych, Caroline Vrana-Diaz and Theresa V. Strong

J. Clin. Med. 2022, 11(7), 2040; https://doi.org/10.3390/jcm11072040 - 05 Apr 2022

Cited by 2 | Viewed by 2224

Abstract

Individuals with Prader–Willi syndrome (PWS) may be at higher risk of developing blood clots as compared to the typical population, but this risk is poorly understood. It is also unclear if laboratory testing of D-dimer concentration might be useful to screen for thrombosis [...] Read more.

Individuals with Prader–Willi syndrome (PWS) may be at higher risk of developing blood clots as compared to the typical population, but this risk is poorly understood. It is also unclear if laboratory testing of D-dimer concentration might be useful to screen for thrombosis in PWS. Here, we surveyed the thrombosis history of 883 individuals with PWS and evaluated the D-dimer concentration in a subset of 214 asymptomatic individuals, ages 5–55. A history of at least one blood clot was reported by 3.6% of respondents. Thrombosis increased with age, but no significant difference was found on the basis of sex or family history. Genetic subtype was a significant factor when considering only those with a known subtype, and individuals with a history of edema had significantly more blood clots. In the D-dimer sub-study, ≈15% of participants had high D-dimer concentrations, and 3.7% had D-dimer values more than twice the normal upper limit. One participant with a high D-dimer result was found to have a blood clot. No significant differences in D-dimer results were found on the basis of age, sex, genetic subtype, family history of blood clots, edema history, or BMI. The D-dimer test does not appear to be a sensitive and specific screening tool for blood clots in asymptomatic individuals with PWS. Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Diseases: Prader-Willi Syndrome)

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14 pages, 1034 KiB

Open AccessArticle

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

by Laia Casamitjana, Laura Blanco-Hinojo, Olga Giménez-Palop, Jesús Pujol, Gerard Martínez-Vilavella, Susanna Esteba-Castillo, Rocío Pareja, Valentín Freijo, Laura Vigil, Joan Deus and Assumpta Caixàs

J. Clin. Med. 2022, 11(7), 1831; https://doi.org/10.3390/jcm11071831 - 25 Mar 2022

Cited by 3 | Viewed by 2052

Abstract

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. [...] Read more.

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. Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Diseases: Prader-Willi Syndrome)

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11 pages, 409 KiB

Open AccessArticle

High Prevalence of Scoliosis in a Large Cohort of Patients with Prader-Willi Syndrome

by Antonino Crinò, Michela Armando, Marco Crostelli, Osvaldo Mazza, Dario Bruzzese, Alessio Convertino, Danilo Fintini, Sarah Bocchini, Sara Ciccone, Alessandro Sartorio and Graziano Grugni

J. Clin. Med. 2022, 11(6), 1574; https://doi.org/10.3390/jcm11061574 - 13 Mar 2022

Cited by 5 | Viewed by 2204

Abstract

The characteristics of scoliosis were investigated in a large cohort of children and adults with Prader–Willi syndrome (PWS), analysing the role of age, gender, puberty, body mass index (BMI), genotype and growth hormone therapy (GHT) on its onset and severity. A retrospective cross-sectional [...] Read more.

The characteristics of scoliosis were investigated in a large cohort of children and adults with Prader–Willi syndrome (PWS), analysing the role of age, gender, puberty, body mass index (BMI), genotype and growth hormone therapy (GHT) on its onset and severity. A retrospective cross-sectional study was performed in 180 patients with genetically confirmed PWS (96 females), aged 17.6 ± 12 years. Eighty-five subjects (47%) were obese. One hundred and fifty subjects (83.3%) were on GHT, while 30 patients had never been treated. Overall, 150 subjects (83.3%) were affected by scoliosis, 80.2% of children and adolescents and 87.8% of adults. A mild degree of scoliosis was observed in 58 patients (38.7%), moderate in 43 (28.7%) and severe in 49 (32.6%). Median age at diagnosis of scoliosis was 6.3 years, while the severe forms were diagnosed earlier (median age: 3.8 years). The cumulative probability at 5 years of age was equal to 0.403 and almost doubled at 15 years. No significant associations were found between scoliosis and genotype, gender, pubertal stage, GHT and BMI. A corset was prescribed to 75 subjects (50%) at a median age of 7.5 years, while 26 subjects (17.3%) underwent surgery at a median age of 13.1 years. Our data indicate that scoliosis is one of the major concerns for PWS patients that increases with age, and therefore suggest the need for regular systematic monitoring of spinal deformity from paediatric age. Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Diseases: Prader-Willi Syndrome)

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10 pages, 1292 KiB

Open AccessArticle

Free Insulin-like Growth Factor (IGF)-I in Children with PWS

by Layla Damen, Melitza S. M. Elizabeth, Stephany H. Donze, Sjoerd A. A. van den Berg, Laura C. G. de Graaff and Anita C. S. Hokken-Koelega

J. Clin. Med. 2022, 11(5), 1280; https://doi.org/10.3390/jcm11051280 - 26 Feb 2022

Cited by 4 | Viewed by 1670

Abstract

In children with Prader–Willi syndrome (PWS), the standard growth hormone (GH) dose often results in high immunoreactive IGF-I levels. These high immunoreactive IGF-I levels lead to concern because their long-term effects are unknown. As a result, clinicians have to lower the GH dose, [...] Read more.

In children with Prader–Willi syndrome (PWS), the standard growth hormone (GH) dose often results in high immunoreactive IGF-I levels. These high immunoreactive IGF-I levels lead to concern because their long-term effects are unknown. As a result, clinicians have to lower the GH dose, which worsens body composition and quality of life. As clinical features do not seem to correspond to immunoreactive IGF-I values, it is questionable whether immunoreactive IGF-I is a suitable marker for GH dosing, or whether another parameter better reflects IGF-I bioavailability and bioactivity. We, therefore, investigate serum immunoreactive IGF-I, free IGF-I and IGFBP-3 levels in 70 GH-treated children with PWS. Our study showed that, although immunoreactive IGF-I levels were high (>2 SDS) in the vast majority of prepubertal and pubertal children, free IGF-I SDS levels were <0 SDS in most and <1 SDS in all. Free IGF-I correlated with the immunoreactive IGF-I, IGFBP-3 and IGF-I/IGFBP-3 ratio. We conclude that there is a major discrepancy between immunoreactive and free IGF-I levels. While in the majority of GH-treated children with PWS, immunoreactive IGF-I levels were high, free IGF-I levels were <0 SDS in most. Our data appear to be very reassuring and suggest that free IGF-I levels should also be taken into consideration when the immunoreactive IGF-I levels are >2 SDS in GH-treated children with PWS. Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Diseases: Prader-Willi Syndrome)

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13 pages, 506 KiB

Open AccessArticle

Prenatal and Neonatal Characteristics of Children with Prader-Willi Syndrome

by Lionne N. Grootjen, Nathalie E. M. Uyl, Inge A. L. P. van Beijsterveldt, Layla Damen, Gerthe F. Kerkhof and Anita C. S. Hokken-Koelega

J. Clin. Med. 2022, 11(3), 679; https://doi.org/10.3390/jcm11030679 - 28 Jan 2022

Cited by 5 | Viewed by 2113

Abstract

Objective: Prader-Willi syndrome (PWS) is a rare genetic syndrome with a wide spectrum of clinical features in early life. Late diagnoses are still present. We characterized the perinatal and neonatal features of PWS, compared them with those of healthy newborns and assessed the [...] Read more.

Objective: Prader-Willi syndrome (PWS) is a rare genetic syndrome with a wide spectrum of clinical features in early life. Late diagnoses are still present. We characterized the perinatal and neonatal features of PWS, compared them with those of healthy newborns and assessed the prenatal and neonatal differences between the genetic subtypes. Design: A cohort study in children with PWS. The prevalence of variables was compared with healthy infants (PLUTO cohort) and to population statistics from literature. Patients: 244 infants with PWS and 365 healthy infants. Measurements: Data on prenatal and neonatal variables in both cohorts. Population statistics were collected through an extensive literature search. Results: A higher prevalence of maternal age >35 years was found in PWS compared to healthy infants and population statistics, and the highest maternal age was found in the mUPD group. Higher prevalence of polyhydramnios, caesarean section, labour induction and breech presentation, and lower birth weight SDS was found in PWS compared to healthy infants. High prevalences of decreased fetal movements (78.5%), hypotonia (100%), cryptorchism (95.9%) and poor sucking/tube feeding (93.9%) were found in PWS. Conclusions: This study presents an overview of prenatal and neonatal variables in infants with PWS compared to healthy infants. Our findings may increase clinical awareness of the early perinatal signs of PWS by obstetricians, neonatologists and all those involved in infant care, enabling early diagnosis and start of multidisciplinary treatment. Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Diseases: Prader-Willi Syndrome)

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30 pages, 45812 KiB

Open AccessArticle

What Every Internist-Endocrinologist Should Know about Rare Genetic Syndromes in Order to Prevent Needless Diagnostics, Missed Diagnoses and Medical Complications: Five Years of ‘Internal Medicine for Rare Genetic Syndromes’

by Anna G. W. Rosenberg, Minke R. A. Pater, Karlijn Pellikaan, Kirsten Davidse, Anja A. Kattentidt-Mouravieva, Rogier Kersseboom, Anja G. Bos-Roubos, Agnies van Eeghen, José M. C. Veen, Jiske J. van der Meulen, Nina van Aalst-van Wieringen, Franciska M. E. Hoekstra, Aart J. van der Lely and Laura C. G. de Graaff

J. Clin. Med. 2021, 10(22), 5457; https://doi.org/10.3390/jcm10225457 - 22 Nov 2021

Cited by 7 | Viewed by 3202

Abstract

Patients with complex rare genetic syndromes (CRGS) have combined medical problems affecting multiple organ systems. Pediatric multidisciplinary (MD) care has improved life expectancy, however, transfer to internal medicine is hindered by the lack of adequate MD care for adults. We have launched an [...] Read more.

Patients with complex rare genetic syndromes (CRGS) have combined medical problems affecting multiple organ systems. Pediatric multidisciplinary (MD) care has improved life expectancy, however, transfer to internal medicine is hindered by the lack of adequate MD care for adults. We have launched an MD outpatient clinic providing syndrome-specific care for adults with CRGS, which, to our knowledge, is the first one worldwide in the field of internal medicine. Between 2015 and 2020, we have treated 720 adults with over 60 syndromes. Eighty-nine percent of the syndromes were associated with endocrine problems. We describe case series of missed diagnoses and patients who had undergone extensive diagnostic testing for symptoms that could actually be explained by their syndrome. Based on our experiences and review of the literature, we provide an algorithm for the clinical approach of health problems in CRGS adults. We conclude that missed diagnoses and needless invasive tests seem common in CRGS adults. Due to the increased life expectancy, an increasing number of patients with CRGS will transfer to adult endocrinology. Internist-endocrinologists (in training) should be aware of their special needs and medical pitfalls of CRGS will help prevent the burden of unnecessary diagnostics and under- and overtreatment. Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Diseases: Prader-Willi Syndrome)

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14 pages, 1303 KiB

Open AccessArticle

Diabetes Mellitus in Prader-Willi Syndrome: Natural History during the Transition from Childhood to Adulthood in a Cohort of 39 Patients

by Alice Clerc, Muriel Coupaye, Héléna Mosbah, Graziella Pinto, Virginie Laurier, Fabien Mourre, Christine Merrien, Gwenaëlle Diene, Christine Poitou and Maithé Tauber

J. Clin. Med. 2021, 10(22), 5310; https://doi.org/10.3390/jcm10225310 - 15 Nov 2021

Cited by 5 | Viewed by 1737

Abstract

Type 2 diabetes mellitus (T2DM) affects 20% of patients with Prader-Willi syndrome (PWS), with many cases diagnosed during the transition period. Our aim was to describe the natural history of T2DM in patients with PWS before the age of 25 years and to [...] Read more.

Type 2 diabetes mellitus (T2DM) affects 20% of patients with Prader-Willi syndrome (PWS), with many cases diagnosed during the transition period. Our aim was to describe the natural history of T2DM in patients with PWS before the age of 25 years and to develop screening and preventive strategies. Thirty-nine patients followed in the French PWS Reference Center were included (median age 25.6 years [23.7; 31.7]). Twenty-one had been treated with growth hormone (GH), fifteen had not, and three had an unknown status. The median age at T2DM diagnosis was 16.8 years (11–24) and the median BMI was 39 kg/m² [34.6; 45], with 34/35 patients living with obesity. The patients displayed frequent psychiatric (48.3% hospitalization,) and metabolic (56.4% hypertriglyceridemia,) comorbidities and a parental history of T2DM (35.7%) or overweight (53.6%) compared to the PWS general population. There was no difference in BMI and metabolic complications between the GH-treated and non-GH-treated groups at T2DM diagnosis. Patients with PWS who develop early T2DM have severe obesity, a high frequency of psychiatric and metabolic disorders, and a family history of T2DM and overweight. These results underline the need for early identification of patients at risk, prevention of obesity, and repeated blood glucose monitoring during the transition period. Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Diseases: Prader-Willi Syndrome)

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14 pages, 1490 KiB

Open AccessArticle

Hunger and Satiety Peptides: Is There a Pattern to Classify Patients with Prader-Willi Syndrome?

by Marta Bueno, Ester Boixadera-Planas, Laura Blanco-Hinojo, Susanna Esteba-Castillo, Olga Giménez-Palop, David Torrents-Rodas, Jesús Pujol, Raquel Corripio, Joan Deus and Assumpta Caixàs

J. Clin. Med. 2021, 10(21), 5170; https://doi.org/10.3390/jcm10215170 - 04 Nov 2021

Cited by 3 | Viewed by 2055

Abstract

Hyperphagia is one of the main problems of patients with Prader-Willi syndrome (PWS) to cope with everyday life. The underlying mechanisms are not yet well understood. Gut-brain hormones are an interrelated network that may be at least partially involved. We aimed to study [...] Read more.

Hyperphagia is one of the main problems of patients with Prader-Willi syndrome (PWS) to cope with everyday life. The underlying mechanisms are not yet well understood. Gut-brain hormones are an interrelated network that may be at least partially involved. We aimed to study the hormonal profile of PWS patients in comparison with obese and healthy controls. Thirty adult PWS patients (15 men; age 27.5 ± 8.02 years; BMI 32.4 ± 8.14 kg/m²), 30 obese and 30 healthy controls were studied before and after eating a hypercaloric liquid diet. Plasma brain-derived neurotrophic factor (BDNF), leptin, total and active ghrelin, peptide YY (PYY), pancreatic polypeptide (PP), Glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and amylin were determined at times 0′, 30′, 60′ and 120′. Cluster analysis was used. When considering all peptides together, two clusters were established according to fasting hormonal standardized concentrations. Cluster 1 encompassed most of obese (25/30) and healthy controls (28/30). By contrast, the majority of patients with PWS were located in Cluster 2 (23/27) and presented a similar fasting profile with hyperghrelinemia, high levels of leptin, PYY, GIP and GLP-1, compared to Cluster 1; that may reflect a dysfunction of these hunger/satiety hormones. When peptide behavior over the time was considered, PP concentrations were not sustained postprandially from 60 min onwards in Cluster 2. BDNF and amylin did not help to differentiate the two clusters. Thus, cluster analysis could be a good tool to distinguish and characterize the differences in hormone responses between PWS and obese or healthy controls. Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Diseases: Prader-Willi Syndrome)

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13 pages, 1011 KiB

Open AccessArticle

by Ingrid Caroline van Nieuwpoort, Tessa N. A. Slagboom, Sigridur Jakobsdóttir, Jan Berend Deijen, Dick J. Veltman, Leopold M. G. Curfs and Madeleine L. Drent

J. Clin. Med. 2021, 10(21), 5133; https://doi.org/10.3390/jcm10215133 - 31 Oct 2021

Cited by 7 | Viewed by 2050

Abstract

(1) Background: Prader–Willi syndrome (PWS) is characterized by hyperphagia, resulting in morbid obesity if not controlled. The primary aim of this study was to investigate whether PWS patients show altered activation of brain areas involved in hunger. As a secondary objective, we assessed [...] Read more.

(1) Background: Prader–Willi syndrome (PWS) is characterized by hyperphagia, resulting in morbid obesity if not controlled. The primary aim of this study was to investigate whether PWS patients show altered activation of brain areas involved in hunger. As a secondary objective, we assessed whether there is an association between these brain areas and several endocrine and metabolic factors in the fasting state. (2) Methods: 12 PWS adults and 14 healthy controls (siblings) performed a food-related experimental task after an overnight fast while brain activation in regions of interest was measured by functional MRI. (3) Results: In controls, significantly more activation was found in the left insula (p = 0.004) and the bilateral fusiform gyrus (p = 0.003 and 0.013) when the individuals were watching food as compared to non-food pictures, which was absent in PWS patients. Moreover, in PWS adults watching food versus non-food pictures a significant negative correlation for glucose and right amygdala activation (p_fwe = 0.007) as well as a positive correlation for leptin and right anterior hippocampus/amygdala activation (p_fwe = 0.028) was demonstrated. No significant associations for the other hormonal and metabolic factors were found. (4) Conclusions: PWS individuals show aberrant food-related brain activation in the fasting state. Leptin is associated with activation within the neural motivation/reward circuitry, while the opposite is true for glucose. Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Diseases: Prader-Willi Syndrome)

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9 pages, 705 KiB

Open AccessArticle

A Quality Improvement Project to Implement Choking Prevention and First Aid Education in Prader–Willi Syndrome Caregivers

by Kathryn S. Obrynba, Kathryn Anglin, Amy Moffett, Tracie Steinke and Manmohan K. Kamboj

J. Clin. Med. 2021, 10(21), 4993; https://doi.org/10.3390/jcm10214993 - 27 Oct 2021

Viewed by 1687

Abstract

Prader–Willi syndrome (PWS) is a complex neurodevelopmental genetic disorder characterized by hypotonia and hyperphagia. Consequently, individuals with PWS are at high risk of choking, and choking is a leading cause of morbidity and mortality. The aim of this quality improvement (QI) project is [...] Read more.

Prader–Willi syndrome (PWS) is a complex neurodevelopmental genetic disorder characterized by hypotonia and hyperphagia. Consequently, individuals with PWS are at high risk of choking, and choking is a leading cause of morbidity and mortality. The aim of this quality improvement (QI) project is to provide choking prevention and first aid education from 0% to 80% of PWS caregivers seen in a multidisciplinary PWS clinic, and to assess the effectiveness of this education program. A QI initiative was developed to standardize and implement choking prevention and first aid education for PWS caregivers. Using a Likert scale, pre- and post-education assessments were conducted to measure caregiver (1) awareness of the PWS choking risk, (2) self-reported knowledge of choking prevention strategies, and (3) comfort in providing choking first aid. The American Heart Association Family and Friends^® CPR (Dallas, TX, USA) curriculum was utilized. Education was provided during a regularly scheduled PWS clinic appointment. At project conclusion, 45/52 (87%) of PWS caregivers received education. A post-education assessment revealed an improvement in PWS caregivers’ awareness of choking risk, self-reported knowledge of choking prevention strategies, and comfort in providing choking first aid. This QI project supports a practice change to implement choking prevention and first aid education as standard process within our PWS clinic. Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Diseases: Prader-Willi Syndrome)

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14 pages, 578 KiB

Open AccessArticle

Effects of COVID-19 Lockdown on Weight, Body Composition, and Behavior of Children, Adolescents, and Young Adults with Prader–Willi Syndrome

by Andrea Karoline Mohr, Constanze Laemmer, Sandra Schulte and Bettina Gohlke

J. Clin. Med. 2021, 10(20), 4746; https://doi.org/10.3390/jcm10204746 - 16 Oct 2021

Cited by 5 | Viewed by 1838

Abstract

To reduce transmission of the coronavirus disease 2019 (COVID-19), many countries implemented lockdowns, causing the closure of childcare services. This study was designed to evaluate the impact of the COVID-19 lockdown in March–April 2020 on children, adolescents, and young adults with Prader–Willi syndrome [...] Read more.

To reduce transmission of the coronavirus disease 2019 (COVID-19), many countries implemented lockdowns, causing the closure of childcare services. This study was designed to evaluate the impact of the COVID-19 lockdown in March–April 2020 on children, adolescents, and young adults with Prader–Willi syndrome (PWS) living in Germany. We recruited 180 participants with a genetically confirmed PWS. All families completed a questionnaire, and participants underwent a post-lockdown assessment; the last examination before the lockdown was determined as the pre-lockdown assessment. We used bivariate analyses to compare pre- and post-lockdown outcomes. Weight standard deviation scores (SDS_PWS) and body mass index (BMI)-SDS_PWS remained stable or even decreased in some age groups. A statistically significant gain in lean body mass (LBM) was found in all groups <18 years of age. We observed an increase in IGF-I and IGFBP-3 concentrations without a significant change in growth hormone (GH) dosage. Most families (95.4%) reported set mealtimes and implementation of structured activities (72.2%) during the lockdown period. We therefore suggest that the favorable development of weight/BMI and LBM was caused by an interplay of a suspected enhanced GH administration and continuous parental commitment. However, more intense behavioral problems were observed in 45.7%, which persisted post-lockdown in 33.7%. Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Diseases: Prader-Willi Syndrome)

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16 pages, 657 KiB

Open AccessArticle

Anti-Obesity Medication Use in Children and Adolescents with Prader–Willi Syndrome: Case Review and Literature Search

by Victoria E. Goldman, Monica N. Naguib and Alaina P. Vidmar

J. Clin. Med. 2021, 10(19), 4540; https://doi.org/10.3390/jcm10194540 - 30 Sep 2021

Cited by 11 | Viewed by 4422

Abstract

(1) Background: children with Prader-Willi syndrome (PWS) have high obesity rates due to hyperphagia and decreased metabolic rates. Although anti-obesity medications (AOMs) are prescribed to this population, there are no consensus guidelines on acceptability, safety, and efficacy. We present literature review and case [...] Read more.

(1) Background: children with Prader-Willi syndrome (PWS) have high obesity rates due to hyperphagia and decreased metabolic rates. Although anti-obesity medications (AOMs) are prescribed to this population, there are no consensus guidelines on acceptability, safety, and efficacy. We present literature review and case series on AOMs in youth with PWS. (2) Methods: we performed PubMed review from January 2000 to April 2021 utilizing keywords: “Prader-Willi syndrome” or “PWS” and “medication” including: topiramate, metformin, phentermine, liraglutide, orlistat, oxytocin, semaglutide, naltrexone-bupropion. For our case series, patients were identified through retrospective chart reviews from a multi-disciplinary PWS clinic. Eligibility criteria: age ≤ 18 years, genetically confirmed PWS, AOM use for at least 16 weeks, and recent anthropometric data. (3) Results: a literature search yielded 14 articles (3 topiramate, 1 metformin, 4 liraglutide, 5 oxytocin, 1 naltrexone–bupropion). All studies reported improved hyperphagia with variable BMI effects. Ten adolescents met case series eligibility (mean age 13.2 ± 2.6 years, 40% female; AOMs: 6 metformin, 5 topiramate, 2 semaglutide, 3 liraglutide). After AOM course, 60% had decreased or stable BMI z-score. No significant side effects. (4) Conclusions: results suggest AOMs may be useful for weight management in youth with PWS. Additional studies are required to validate findings and support AOM treatment guidelines. Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Diseases: Prader-Willi Syndrome)

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21 pages, 1033 KiB

Open AccessArticle

Thyroid Function in Adults with Prader–Willi Syndrome; a Cohort Study and Literature Review

by Karlijn Pellikaan, Fleur Snijders, Anna G. W. Rosenberg, Kirsten Davidse, Sjoerd A. A. van den Berg, W. Edward Visser, Aart J. van der Lely and Laura C. G. de Graaff

J. Clin. Med. 2021, 10(17), 3804; https://doi.org/10.3390/jcm10173804 - 25 Aug 2021

Cited by 12 | Viewed by 2692

Abstract

Prader–Willi syndrome (PWS) is a complex genetic syndrome combining hypotonia, hyperphagia, a PWS-specific neurocognitive phenotype, and pituitary hormone deficiencies, including hypothyroidism. The low muscle mass associated with PWS causes a low energy expenditure due to a low basal metabolic rate. Combined with increased [...] Read more.

Prader–Willi syndrome (PWS) is a complex genetic syndrome combining hypotonia, hyperphagia, a PWS-specific neurocognitive phenotype, and pituitary hormone deficiencies, including hypothyroidism. The low muscle mass associated with PWS causes a low energy expenditure due to a low basal metabolic rate. Combined with increased energy intake due to hyperphagia, this results in a high risk of obesity and associated cardiovascular disease. To reduce the high mortality in PWS (3% yearly), exercise is extremely important. As hypothyroidism can impair exercise tolerance, early detection is crucial. We performed a literature search for articles on hypothyroidism in PWS, measured thyroid hormone (TH) levels in 122 adults with PWS, and performed a medical file search for medication use. Hypothyroidism (low free thyroxin) was present in 17%, and often central in origin (80%). Triiodothyronine levels were lower in patients who used psychotropic drugs, while other TH levels were similar. One in six patients in our cohort of adults with PWS had hypothyroidism, which is more than in non-PWS adults (3%). We recommend yearly screening of free thyroxin and thyroid-stimulating hormone levels to avoid the negative effects of untreated hypothyroidism on basal metabolic rate, body mass index, and cardiovascular risk. Additionally, we recommend measuring TH concentrations 3–4 months after the start of growth hormone treatment. Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Diseases: Prader-Willi Syndrome)

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11 pages, 2399 KiB

Open AccessArticle

Hyperprolactinemia in Adults with Prader-Willi Syndrome

by Anna Sjöström, Karlijn Pellikaan, Henrik Sjöström, Anthony P. Goldstone, Graziano Grugni, Antonino Crinò, Laura C. G. De Graaff and Charlotte Höybye

J. Clin. Med. 2021, 10(16), 3613; https://doi.org/10.3390/jcm10163613 - 16 Aug 2021

Cited by 4 | Viewed by 2001

Abstract

Prader-Willi syndrome (PWS) is a rare neurodevelopmental genetic disorder typically characterized by body composition abnormalities, hyperphagia, behavioural challenges, cognitive dysfunction, and hypogonadism. Psychotic illness is common, particularly in patients with maternal uniparental disomy (mUPD), and antipsychotic medications can result in hyperprolactinemia. Information about [...] Read more.

Prader-Willi syndrome (PWS) is a rare neurodevelopmental genetic disorder typically characterized by body composition abnormalities, hyperphagia, behavioural challenges, cognitive dysfunction, and hypogonadism. Psychotic illness is common, particularly in patients with maternal uniparental disomy (mUPD), and antipsychotic medications can result in hyperprolactinemia. Information about hyperprolactinemia and its potential clinical consequences in PWS is sparse. Here, we present data from an international, observational study of 45 adults with PWS and hyperprolactinemia. Estimated prevalence of hyperprolactinemia in a subset of centres with available data was 22%, with 66% of those related to medication and 55% due to antipsychotics. Thirty-three patients were men, 12 women. Median age was 29 years, median BMI 29.8 kg/m², 13 had mUPD. Median prolactin was 680 mIU/L (range 329–5702). Prolactin levels were higher in women and patients with mUPD, with only 3 patients having severe hyperprolactinemia. Thyroid function tests were normal, 24 were treated with growth hormone, 29 with sex steroids, and 20 with antipsychotic medications. One patient had kidney insufficiency, and one a microprolactinoma. In conclusion, severe hyperprolactinemia was rare, and the most common aetiology of hyperprolactinemia was treatment with antipsychotic medications. Although significant clinical consequences could not be determined, potential negative long-term effects of moderate or severe hyperprolactinemia cannot be excluded. Our results suggest including measurements of prolactin in the follow-up of adults with PWS, especially in those on treatment with antipsychotics. Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Diseases: Prader-Willi Syndrome)

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14 pages, 293 KiB

Open AccessArticle

Effects of Childhood Multidisciplinary Care and Growth Hormone Treatment on Health Problems in Adults with Prader-Willi Syndrome

by Karlijn Pellikaan, Anna G. W. Rosenberg, Kirsten Davidse, Anja A. Kattentidt-Mouravieva, Rogier Kersseboom, Anja G. Bos-Roubos, Lionne N. Grootjen, Layla Damen, Sjoerd A. A. van den Berg, Aart J. van der Lely, Anita C. S. Hokken-Koelega and Laura C. G. de Graaff

J. Clin. Med. 2021, 10(15), 3250; https://doi.org/10.3390/jcm10153250 - 23 Jul 2021

Cited by 9 | Viewed by 1841

Abstract

Prader-Willi syndrome (PWS) is a complex hypothalamic disorder. Features of PWS include hyperphagia, hypotonia, intellectual disability, and pituitary hormone deficiencies. The combination of growth hormone treatment and multidisciplinary care (GHMDc) has greatly improved the health of children with PWS. Little is known about [...] Read more.

Prader-Willi syndrome (PWS) is a complex hypothalamic disorder. Features of PWS include hyperphagia, hypotonia, intellectual disability, and pituitary hormone deficiencies. The combination of growth hormone treatment and multidisciplinary care (GHMDc) has greatly improved the health of children with PWS. Little is known about the effects of childhood GHMDc on health outcomes in adulthood. We retrospectively collected clinical data of 109 adults with PWS. Thirty-nine had received GHMDc during childhood and adolescence (GHMDc+ group) and sixty-three had never received growth hormone treatment (GHt) nor multidisciplinary care (GHMDc− group). Our systematic screening revealed fewer undetected health problems in the GHMDc+ group (10%) than in the GHMDc− group (84%). All health problems revealed in the GHMDc+ group had developed between the last visit to the paediatric and the first visit to the adult clinic and/or did not require treatment. Mean BMI and the prevalence of diabetes mellitus type 2 were significantly lower in the GHMDc+ group compared to the GHMDc− group. As all patients who received GHt were treated in a multidisciplinary setting, it is unknown which effects are the result of GHt and which are the result of multidisciplinary care. However, our data clearly show that the combination of both has beneficial effects. Therefore, we recommend continuing GHMDc after patients with PWS have reached adult age. Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Diseases: Prader-Willi Syndrome)

19 pages, 1745 KiB

Open AccessArticle

Effects of Recombinant Human Growth Hormone Treatment, Depending on the Therapy Start in Different Nutritional Phases in Paediatric Patients with Prader–Willi Syndrome: A Polish Multicentre Study

by Agnieszka Lecka-Ambroziak, Marta Wysocka-Mincewicz, Katarzyna Doleżal-Ołtarzewska, Agata Zygmunt-Górska, Anna Wędrychowicz, Teresa Żak, Anna Noczyńska, Dorota Birkholz-Walerzak, Renata Stawerska, Maciej Hilczer, Monika Obara-Moszyńska, Barbara Rabska-Pietrzak, Elżbieta Gołębiowska, Adam Dudek, Elżbieta Petriczko, Mieczysław Szalecki and on behalf of the Polish Coordination Group for rhGH Treatment

J. Clin. Med. 2021, 10(14), 3176; https://doi.org/10.3390/jcm10143176 - 19 Jul 2021

Cited by 11 | Viewed by 2563

Abstract

Recombinant human growth hormone (rhGH) treatment is an established management in patients with Prader–Willi syndrome (PWS), with growth promotion and improvement in body composition and possibly the metabolic state. We compared anthropometric characteristics, insulin-like growth factor 1 (IGF1) levels, metabolic parameters and the [...] Read more.

Recombinant human growth hormone (rhGH) treatment is an established management in patients with Prader–Willi syndrome (PWS), with growth promotion and improvement in body composition and possibly the metabolic state. We compared anthropometric characteristics, insulin-like growth factor 1 (IGF1) levels, metabolic parameters and the bone age/chronological age index (BA/CA) in 147 children with PWS, divided according to age of rhGH start into four groups, corresponding to nutritional phases in PWS. We analysed four time points: baseline, rhGH1 (1.21 ± 0.81 years), rhGH2 (3.77 ± 2.17 years) and rhGH3 (6.50 ± 2.92 years). There were no major differences regarding height SDS between the groups, with a higher growth velocity (GV) (p = 0.00) and lower body mass index (BMI) SDS (p < 0.05) between the first and older groups during almost the whole follow-up. IGF1 SDS values were lower in group 1 vs. other groups at rhGH1 and vs. groups 2 and 3 at rhGH2 (p < 0.05). Glucose metabolism parameters were favourable in groups 1 and 2, and the lipid profile was comparable in all groups. BA/CA was similar between the older groups. rhGH therapy was most effective in the youngest patients, before the nutritional phase of increased appetite. We did not observe worsening of metabolic parameters or BA/CA advancement in older patients during a comparable time of rhGH therapy. Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Diseases: Prader-Willi Syndrome)

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11 pages, 842 KiB

Open AccessArticle

Growth Hormone (GH) Treatment Decreases Plasma Kisspeptin Levels in GH-Deficient Adults with Prader–Willi Syndrome

by Olga Giménez-Palop, Laia Casamitjana, Raquel Corripio, Susanna Esteba-Castillo, Rocío Pareja, Néstor Albiñana, Mercedes Rigla and Assumpta Caixàs

J. Clin. Med. 2021, 10(14), 3054; https://doi.org/10.3390/jcm10143054 - 09 Jul 2021

Cited by 1 | Viewed by 4118

Abstract

Obesity and growth hormone (GH)-deficiency are consistent features of Prader–Willi syndrome (PWS). Centrally, kisspeptin is involved in regulating reproductive function and can stimulate hypothalamic hormones such as GH. Peripherally, kisspeptin signaling influences energy and metabolic status. We evaluated the effect of 12-month GH [...] Read more.

Obesity and growth hormone (GH)-deficiency are consistent features of Prader–Willi syndrome (PWS). Centrally, kisspeptin is involved in regulating reproductive function and can stimulate hypothalamic hormones such as GH. Peripherally, kisspeptin signaling influences energy and metabolic status. We evaluated the effect of 12-month GH treatment on plasma kisspeptin levels in 27 GH-deficient adult PWS patients and analyzed its relationship with metabolic and anthropometric changes. Twenty-seven matched obese subjects and 22 healthy subjects were also studied. Before treatment, plasma kisspeptin concentrations in PWS and obese subjects were similar (140.20 (23.5–156.8) pg/mL vs. 141.96 (113.9–165.6) pg/mL, respectively, p = 0.979)) and higher (p = 0.019) than in healthy subjects (124.58 (107.3–139.0) pg/mL); plasma leptin concentrations were similar in PWS and obese subjects (48.15 (28.80–67.10) ng/mL vs. 33.10 (20.50–67.30) ng/mL, respectively, p = 0.152) and higher (p < 0.001) than in healthy subjects (14.80 (11.37–67.30) ng/mL). After GH therapy, lean body mass increased 2.1% (p = 0.03), total fat mass decreased 1.6% (p = 0.005), and plasma kisspeptin decreased to levels observed in normal-weight subjects (125.1(106.2–153.4) pg/mL, p = 0.027). BMI and leptin levels remained unchanged. In conclusion, 12-month GH therapy improved body composition and decreased plasma kisspeptin in GH deficient adults with PWS. All data are expressed in median (interquartile range). Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Diseases: Prader-Willi Syndrome)

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9 pages, 411 KiB

Open AccessArticle

Twenty Years of GH Treatment in Adults with Prader-Willi Syndrome

by Anna Sjöström and Charlotte Höybye

J. Clin. Med. 2021, 10(12), 2667; https://doi.org/10.3390/jcm10122667 - 17 Jun 2021

Cited by 7 | Viewed by 1824

Abstract

Prader-Willi syndrome (PWS) is a rare neurodevelopmental genetic disorder. In adults, the syndrome is characterised by muscular hypotonia, a different body composition with more body fat than muscle mass, hyperphagia, behavioural problems, and cognitive dysfunction. Endocrine deficiencies are common, including growth hormone (GH) [...] Read more.

Prader-Willi syndrome (PWS) is a rare neurodevelopmental genetic disorder. In adults, the syndrome is characterised by muscular hypotonia, a different body composition with more body fat than muscle mass, hyperphagia, behavioural problems, and cognitive dysfunction. Endocrine deficiencies are common, including growth hormone (GH) deficiency. Here, we present data from a cross-sectional study in adults with PWS with a focus on the long-term safety of GH treatment. A total of 22 patients (14 men) were treated with GH for a median of 20 years. Data on body composition, hormones, and metabolic parameters were retrieved from the patients’ medical records. The median age was 27 years. The median GH dose was 0.5 mg/day. Insulin-like growth factor 1 (IGF-I) and blood lipids were normal, while fasting glucose and HbA1c were slightly elevated in three men with diabetes. Fat mass was less than fat free mass in all, though this was less pronounced in women. GH treatment did not negatively affect the metabolic profile, and none developed cardiovascular diseases or cancer. All adults on long-term GH treatment had a normal body composition and our results indicate that treatment was safe. However, PWS is a complex, multisystemic disease and continuous, individual considerations are required during GH treatment, especially in patients with risk factors for adverse effects. Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Diseases: Prader-Willi Syndrome)

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15 pages, 311 KiB

Open AccessArticle

Multidimensional Evaluation of Awareness in Prader-Willi Syndrome

by Jesús Cobo, Ramón Coronas, Esther Pousa, Joan-Carles Oliva, Olga Giménez-Palop, Susanna Esteba-Castillo, Ramon Novell, Diego J. Palao and Assumpta Caixàs

J. Clin. Med. 2021, 10(9), 2007; https://doi.org/10.3390/jcm10092007 - 07 May 2021

Cited by 5 | Viewed by 1799

Abstract

There are no studies about insight or awareness of illness in patients with Prader-Willi Syndrome (PWS). The objective of this study was to explore the level of awareness of the disorder, of the need for medication, and of the social consequences of the [...] Read more.

There are no studies about insight or awareness of illness in patients with Prader-Willi Syndrome (PWS). The objective of this study was to explore the level of awareness of the disorder, of the need for medication, and of the social consequences of the disease, as well as of its main symptoms in PWS. We also aimed to explore relationships between awareness and sociodemographic and clinical characteristics, and to compare all data with a matched sample of patients with psychosis. Insight was assessed by an Adapted version of the Scale of Unawareness of Mental Disorder in a cross-sectional pilot study at a University Hospital. Thirty-six individuals with PWS (58.3% women) were included. Results showed that PWS patients had a good awareness of the illness and of the effects of medication, in contrast to a lack of awareness of illness’ social consequences. Awareness of obesity/overweight was excellent, as was the awareness of excessive appetite. Awareness of excessive food intake was only mild. Insight correlated with age and functionality, but not with BMI. PWS patients showed a better insight into the illness but a similar awareness of the effects of the medication and of the social consequences of the disease as compared to schizophrenia-spectrum patients. This profile of insight may have relevant clinical implications. Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Diseases: Prader-Willi Syndrome)

7 pages, 214 KiB

Open AccessArticle

An Adapted Model for Transition to Adult Care in Young Adults with Prader–Willi Syndrome

by Maria Pedersen and Charlotte Höybye

J. Clin. Med. 2021, 10(9), 1991; https://doi.org/10.3390/jcm10091991 - 06 May 2021

Cited by 3 | Viewed by 1785

Abstract

Background: Prader–Willi syndrome (PWS) is a rare, neurodevelopmental, genetic disease caused by the lack of expression of paternal genes in chromosome 15. The typical characteristics, including hyperphagia, muscular hypotonia, abnormal body composition, hormonal deficiencies, cognitive disabilities, and behavioral problems, appear or worsen in [...] Read more.

Background: Prader–Willi syndrome (PWS) is a rare, neurodevelopmental, genetic disease caused by the lack of expression of paternal genes in chromosome 15. The typical characteristics, including hyperphagia, muscular hypotonia, abnormal body composition, hormonal deficiencies, cognitive disabilities, and behavioral problems, appear or worsen in young adults, and the development of comorbidities increases. The transition of care of young adults with PWS is a challenge due to the complexity of the disease and the vulnerability of the patients. Multidisciplinary transition clinics are optimal but difficult to implement in clinics with few transitions. Methods: The description of transition care meetings was limited to the pediatric and adult endocrinologists and nurses. The presentation of our checklist was developed to optimize the organization of the transition of young adults with PWS. Results: Two to four patients with PWS are transferred to adult care every year in our hospital. Transition with the adapted program was more comfortable for patients and identification of the individual patient’s comorbidities and special needs could clearly be addressed. Conclusions: In smaller settings, an adapted model including a proper introduction and presentation of the adult team and clinic, careful information about comorbidities and special needs, together with a checklist can optimize the transition of care to adult care. Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Diseases: Prader-Willi Syndrome)

Review

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11 pages, 561 KiB

Open AccessReview

Sleep Disorders in Adults with Prader–Willi Syndrome: Review of the Literature and Clinical Recommendations Based on the Experience of the French Reference Centre

by Pauline Dodet, Federica Sanapo, Smaranda Leu-Semenescu, Muriel Coupaye, Alice Bellicha, Isabelle Arnulf, Christine Poitou and Stefania Redolfi

J. Clin. Med. 2022, 11(7), 1986; https://doi.org/10.3390/jcm11071986 - 02 Apr 2022

Cited by 3 | Viewed by 2034

Abstract

Prader–Willi syndrome (PWS) is a rare, genetic, multisymptomatic, neurodevelopmental disease commonly associated with sleep alterations, including sleep-disordered breathing and central disorders of hypersomnolence. Excessive daytime sleepiness represents the main manifestation that should be addressed by eliciting the detrimental effects on quality of life [...] Read more.

Prader–Willi syndrome (PWS) is a rare, genetic, multisymptomatic, neurodevelopmental disease commonly associated with sleep alterations, including sleep-disordered breathing and central disorders of hypersomnolence. Excessive daytime sleepiness represents the main manifestation that should be addressed by eliciting the detrimental effects on quality of life and neurocognitive function from the patients’ caregivers. Patients with PWS have impaired ventilatory control and altered pulmonary mechanics caused by hypotonia, respiratory muscle weakness, scoliosis and obesity. Consequently, respiratory abnormalities are frequent and, in most cases, severe, particularly during sleep. Adults with PWS frequently suffer from sleep apnoea syndrome, sleep hypoxemia and sleep hypoventilation. When excessive daytime sleepiness persists after adequate control of sleep-disordered breathing, a sleep study on ventilatory treatment, followed by an objective measurement of excessive daytime sleepiness, is recommended. These tests frequently identify central disorders of hypersomnolence, including narcolepsy, central hypersomnia or a borderline hypersomnolent phenotype. The use of wake-enhancing drugs (modafinil, pitolisant) is discussed in multidisciplinary expert centres for these kinds of cases to ensure the right balance between the benefits on quality of life and the risk of psychological and cardiovascular side effects. Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Diseases: Prader-Willi Syndrome)

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9 pages, 893 KiB

Open AccessReview

Targeting the Gut Microbiome in Prader-Willi Syndrome

by Marta Ramon-Krauel, Montse Amat-Bou, Mercedes Serrano, Antonio F. Martinez-Monseny and Carles Lerin

J. Clin. Med. 2021, 10(22), 5328; https://doi.org/10.3390/jcm10225328 - 16 Nov 2021

Cited by 1 | Viewed by 2239

Abstract

Overwhelming evidence demonstrates an important role of the gut microbiome in the development of a wide range of diseases, including obesity, metabolic disorders, and mental health symptoms. Indeed, interventions targeting the gut microbiome are being actively investigated as a therapeutic strategy to tackle [...] Read more.

Overwhelming evidence demonstrates an important role of the gut microbiome in the development of a wide range of diseases, including obesity, metabolic disorders, and mental health symptoms. Indeed, interventions targeting the gut microbiome are being actively investigated as a therapeutic strategy to tackle these diseases. Given that obesity and mental health symptoms are both hallmarks of Prader-Willi syndrome, targeting the gut microbiome may be a promising therapeutical strategy. Only a few studies have investigated the gut microbiome in the context of Prader-Willi syndrome and assessed the efficacy of probiotic supplementation as a therapeutic strategy for this disease. Here, we review the knowledge obtained to this date regarding the gut microbiome in individuals with Prader-Willi syndrome. The limited evidence available indicate that probiotic supplementation improves some metabolic and mental health aspects, however further studies are warranted to determine whether targeting the gut microbiome may constitute a safe and efficient strategy to treat individuals with Prader-Willi syndrome. Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Diseases: Prader-Willi Syndrome)

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Open AccessReview

Physical Activity in Patients with Prader-Willi Syndrome—A Systematic Review of Observational and Interventional Studies

by Alice Bellicha, Muriel Coupaye, Héléna Mosbah, Maithé Tauber, Jean-Michel Oppert and Christine Poitou

J. Clin. Med. 2021, 10(11), 2528; https://doi.org/10.3390/jcm10112528 - 07 Jun 2021

Cited by 9 | Viewed by 2904

Abstract

Physical activity (PA) is an important aspect of the management of patients with Prader-Willi syndrome (PWS). However, the day-to-day implementation of PA programs is particularly challenging in these patients. This systematic review aimed (1) to describe habitual PA and sedentary behavior and (2) [...] Read more.

Physical activity (PA) is an important aspect of the management of patients with Prader-Willi syndrome (PWS). However, the day-to-day implementation of PA programs is particularly challenging in these patients. This systematic review aimed (1) to describe habitual PA and sedentary behavior and (2) to assess the effects of PA interventions and to describe their implementation process, in children and adults with PWS. A systematic search of controlled trials, single-group interventions, observational, and qualitative studies published up to December 2020 was performed. Twenty-five studies were included. Habitual PA was found to be lower in patients with PWS compared to controls without obesity or with non-syndromic obesity. Habitual PA was positively associated with lean body mass and bone parameters in children with PWS, and these finding were strengthened by intervention studies reporting an increase in both outcomes after a PA program. PA programs also improved physical function (muscle strength, walking distance, and coordination), without significant effect on weight and fat mass. Attendance to exercise sessions was usually high and no serious adverse effect was reported. In conclusion, supervised PA programs are beneficial for children and adults with PWS. Support should be provided to families to facilitate their implementation in real-life settings. Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Diseases: Prader-Willi Syndrome)

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