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Background: It has been reported that central adrenal insufficiency (CAI) in pediatric patients (pts) with Prader-Willi syndrome (PWS) may be a potential cause of their sudden death. In addition, the risk of CAI may increase during treatment with recombinant human growth hormone (rhGH). Objective: To prevent both over- and undertreatment with hydrocortisone, we evaluated the prevalence of CAI in a large multicenter cohort of pediatric pts with PWS analyzing adrenal response in the low-dose ACTH test (LDAT) and/or the glucagon stimulation test (GST) and reviewing the literature. Methods: A total of 46 pts with PWS were enrolled to the study, including 34 treated with rhGH with a median dose of 0.21 mg/kg/week. LDAT was performed in 46 pts, and GST was carried out in 13 pts. Both tests were conducted in 11 pts. The tests began at 8:00 a.m. Hormones were measured by radioimmunoassays. Serum cortisol response >181.2 ng/mL (500 nmol/L) in LDAT and >199.3 ng/mL (550 nmol/L) in GST was considered a normal response. Additionally, cortisol response delta (the difference between baseline and baseline) >90 ng/mL and doubling/tripling of baseline cortisol were considered indicators of normal adrenal reserve. Results: Three GSTs were not diagnostic (no hypoglycemia obtained). LDAT results suggested CAI in four pts, but in two out of four pts, and CAI was excluded in GST. GST results suggested CAI in only one patient, but it was excluded in LDAT. Therefore, CAI was diagnosed in 2/46 pts (4.3%), 1 treated and 1 untreated with rhGH, with the highest cortisol values of 162 and 175 ng/dL, but only in one test. However, in one of them, the cortisol delta response was >90 ng/mL and peak cortisol was more than tripled from baseline. Finally, CAI was diagnosed in one patient treated with rhGH (2.2%). Conclusion: We present low prevalence of CAI in pediatric pts with PWS according to the latest literature. Therefore, we do not recommend to routinely screen the function of the hypothalamic-pituitary-adrenal axis (HPAA) in all pts with PWS, both treated and untreated with rhGH. According to a review of the literature, signs and symptoms or low morning ACTH levels suggestive of CAI require urgent and appropriate diagnosis of HPAA by stimulation test. Our data indicate that the diagnosis of CAI should be confirmed by at least two tests to prevent overtreatment with hydrocortisone.
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Hidrocortisona , Sistema Hipotálamo-Hipofisario , Sistema Hipófiso-Suprarrenal , Síndrome de Prader-Willi , Humanos , Síndrome de Prader-Willi/tratamiento farmacológico , Síndrome de Prader-Willi/sangre , Síndrome de Prader-Willi/complicaciones , Femenino , Masculino , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Sistema Hipófiso-Suprarrenal/metabolismo , Niño , Preescolar , Hidrocortisona/sangre , Adolescente , Insuficiencia Suprarrenal/diagnóstico , Insuficiencia Suprarrenal/sangre , Insuficiencia Suprarrenal/tratamiento farmacológico , Insuficiencia Suprarrenal/epidemiología , Lactante , Hormona de Crecimiento Humana/sangre , Hormona Adrenocorticotrópica/sangre , Hormona Adrenocorticotrópica/administración & dosificación , Glucagón/sangreRESUMEN
Background: Prader-Willi syndrome (PWS) is a multisystem genetic disorder caused by chromosomal imprinting gene defects, with approximately 70% of cases resulting from paternal deletion of the chromosomal region 15. The main clinical features include severe infantile hypotonia, early-onset childhood obesity, hyperphagia, and underdeveloped external genitalia. As individuals with PWS age, they may exhibit irritability, social dysfunction, impaired gonadal development, and metabolic syndrome. Previous literature places the prevalence of type 2 diabetes mellitus (T2DM) in PWS at approximately 7-24%. Oxytocin is a neuropeptide secreted by the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus and regulates energy metabolism, which is involved in PWS. Due to age limitations, very few patients progress to diabetic nephropathy during childhood, and reports of typical diabetic nephropathy in PWS during childhood are extremely rare. Dulaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist which can be used in the treatment of T2DM. Case Description: This article reports a case of a child with PWS complicated by stage III diabetic nephropathy, providing a retrospective analysis of the diagnosis and treatment process, as well as a review of domestic and international literature, to enhance understanding of this condition. And this article provides a treatment idea for PWS patients with diabetic nephropathy. Conclusions: It is very important to enhance understanding of PWS. And we offer new diagnostic and possible therapeutic approaches for pediatric patients with diabetic nephropathy.
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Prader-Willi syndrome (PWS) is a complex genetic disorder caused by three different types of molecular genetic abnormalities. The most common defect is a deletion on the paternal 15q11-q13 chromosome, which is seen in about 60% of individuals. The next most common abnormality is maternal disomy 15, found in around 35% of cases, and a defect in the imprinting center that controls the activity of certain genes on chromosome 15, seen in 1-3% of cases. Individuals with PWS typically experience issues with the hypothalamic-pituitary axis, leading to excessive hunger (hyperphagia), severe obesity, various endocrine disorders, and intellectual disability. Differences in physical and behavioral characteristics between patients with PWS due to deletion versus those with maternal disomy are discussed in literature. Patients with maternal disomy tend to have more frequent neurodevelopmental problems, such as autistic traits and behavioral issues, and generally have higher IQ levels compared to those with deletion of the critical PWS region. This has led us to review the pertinent literature to investigate the possibility of establishing connections between the genetic abnormalities and the endocrine disorders experienced by PWS patients, in order to develop more targeted diagnostic and treatment protocols. In this review, we will review the current state of clinical studies focusing on endocrine disorders in individuals with PWS patients, with a specific focus on the various genetic causes. We will look at topics such as neonatal anthropometry, thyroid issues, adrenal problems, hypogonadism, bone metabolism abnormalities, metabolic syndrome resulting from severe obesity caused by hyperphagia, deficiencies in the GH/IGF-1 axis, and the corresponding responses to treatment.
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Estudios de Asociación Genética , Síndrome de Prader-Willi , Síndrome de Prader-Willi/genética , Humanos , Enfermedades del Sistema Endocrino/genética , FenotipoRESUMEN
The autonomic nervous system (ANS) may play a role in the distribution of body fat and the development of obesity and its complications. Features of individuals with Prader-Willi syndrome (PWS) impacted by PWS molecular genetic classes suggest alterations in ANS function; however, these have been rarely studied and presented with conflicting results. The aim of this study was to investigate if the ANS function is altered in PWS. In this case-control study, we assessed ANS function in 20 subjects with PWS (6 males/14 females; median age 10.5 years) and 27 body mass index (BMI) z-score-matched controls (19 males/8 females; median age 12.8 years). Standardized non-invasive measures of cardiac baroreflex function, heart rate, blood pressure, heart rate variability, quantitative sudomotor axon reflex tests, and a symptom questionnaire were completed. The increase in heart rate in response to head-up tilt testing was blunted (p < 0.01) in PWS compared to controls. Besides a lower heart rate ratio with Valsalva in PWS (p < 0.01), no significant differences were observed in other measures of cardiac function or sweat production. Findings suggest possible altered sympathetic function in PWS.
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Obesidad Infantil , Síndrome de Prader-Willi , Masculino , Femenino , Humanos , Niño , Síndrome de Prader-Willi/complicaciones , Obesidad Infantil/complicaciones , Estudios de Casos y Controles , Índice de Masa Corporal , Sistema Nervioso AutónomoRESUMEN
The neurohormone oxytocin (OXT) has been implicated in the regulation of social behavior and is intensively investigated as a potential therapeutic treatment in neurodevelopmental disorders characterized by social deficits. In the Magel2-knockout (KO) mouse, a model of Schaaf-Yang Syndrome, an early postnatal administration of OXT rescued autistic-like behavior and cognition at adulthood, making this model relevant for understanding the actions of OXT in (re)programming postnatal brain development. The oxytocin receptor (OXTR), the main brain target of OXT, was dysregulated in the hippocampus of Magel2-KO adult males, and normalized upon OXT treatment at birth. Here we have analyzed male and female Magel2-KO brains at postnatal day 8 (P8) and at postnatal day 90 (P90), investigating age, genotype and OXT treatment effects on OXTR levels in several regions of the brain. We found that, at P8, male and female Magel2-KOs displayed a widespread, substantial, down-regulation of OXTR levels compared to wild type (WT) animals. Most intriguingly, the postnatal OXT treatment did not affect Magel2-KO OXTR levels at P8 and, consistently, did not rescue the ultrasonic vocalization deficits observed at this age. On the contrary, the postnatal OXT treatment reduced OXTR levels at P90 in male Magel2-KO in a region-specific way, restoring normal OXTR levels in regions where the Magel2-KO OXTR was upregulated (central amygdala, hippocampus and piriform cortex). Interestingly, Magel2-KO females, previously shown to lack the social deficits observed in Magel2-KO males, were characterized by a different trend in receptor expression compared to males; as a result, the dimorphic expression of OXTR observed in WT animals, with higher OXTR expression observed in females, was abolished in Magel2-KO mice. In conclusion, our data indicate that in Magel2-KO mice, OXTRs undergo region-specific modifications related to age, sex and postnatal OXT treatment. These results are instrumental to design precisely-timed OXT-based therapeutic strategies that, by acting at specific brain regions, could modify the outcome of social deficits in Schaaf-Yang Syndrome patients.
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Prader-Willi syndrome (PWS) is a complex genetic disorder with three PWS molecular genetic classes and presents as severe hypotonia, failure to thrive, hypogonadism/hypogenitalism and developmental delay during infancy. Hyperphagia, obesity, learning and behavioral problems, short stature with growth and other hormone deficiencies are identified during childhood. Those with the larger 15q11-q13 Type I deletion with the absence of four non-imprinted genes (NIPA1, NIPA2, CYFIP1, TUBGCP5) from the 15q11.2 BP1-BP2 region are more severely affected compared with those with PWS having a smaller Type II deletion. NIPA1 and NIPA2 genes encode magnesium and cation transporters, supporting brain and muscle development and function, glucose and insulin metabolism and neurobehavioral outcomes. Lower magnesium levels are reported in those with Type I deletions. The CYFIP1 gene encodes a protein associated with fragile X syndrome. The TUBGCP5 gene is associated with attention-deficit hyperactivity disorder (ADHD) and compulsions, more commonly seen in PWS with the Type I deletion. When the 15q11.2 BP1-BP2 region alone is deleted, neurodevelopment, motor, learning and behavioral problems including seizures, ADHD, obsessive-compulsive disorder (OCD) and autism may occur with other clinical findings recognized as Burnside-Butler syndrome. The genes in the 15q11.2 BP1-BP2 region may contribute to more clinical involvement and comorbidities in those with PWS and Type I deletions.
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Síndrome de Prader-Willi , Humanos , Proteínas Portadoras/genética , Cromosomas , Cromosomas Humanos Par 15 , Magnesio , Síndrome de Prader-Willi/genéticaRESUMEN
With the increasing worldwide application of the Prechtl general movements assessment (GMA) beyond its original field of the early prediction of cerebral palsy (CP), substantial knowledge has been gained on early neuromotor repertoires across a broad spectrum of diagnostic groups. Here, we aimed to profile the neuromotor functions of infants with Prader-Willi syndrome (PWS) and to compare them with two other matched groups. One group included infants with CP; the other included patients who were treated at the same clinic and turned out to have inconspicuous developmental outcomes (IOs). The detailed GMA, i.e., the motor optimality score-revised (MOS-R), was used to prospectively assess the infants' (N = 54) movements. We underwent cross-condition comparisons to characterise both within-group similarities and variations and between-group distinctions and overlaps in infants' neuromotor functions. Although infants in both the PWS and the CP groups scored similarly low on MOS-R, their motor patterns were different. Frog-leg and mantis-hand postures were frequently seen in the PWS group. However, a PWS-specific general movements pattern was not observed. We highlight that pursuing in-depth knowledge within and beyond the motor domain in different groups has the potential to better understand different conditions, improve accurate diagnosis and individualised therapy, and contribute to deep phenotyping for precision medicine.
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A high-resolution chromosome microarray analysis was performed on 154 consecutive individuals enrolled in the DESTINY PWS clinical trial for Prader-Willi syndrome (PWS). Of these 154 PWS individuals, 87 (56.5%) showed the typical 15q11-q13 deletion subtypes, 62 (40.3%) showed non-deletion maternal disomy 15 and five individuals (3.2%) had separate unexpected microarray findings. For example, one PWS male had Klinefelter syndrome with segmental isodisomy identified in both chromosomes 15 and X. Thirty-five (40.2%) of 87 individuals showed typical larger 15q11-q13 Type I deletion and 52 individuals (59.8%) showed typical smaller Type II deletion. Twenty-four (38.7%) of 62 PWS individuals showed microarray patterns indicating either maternal heterodisomy 15 subclass or a rare non-deletion (epimutation) imprinting center defect. Segmental isodisomy 15 was seen in 34 PWS subjects (54.8%) with 15q26.3, 15q14 and 15q26.1 bands most commonly involved and total isodisomy 15 seen in four individuals (6.5%). In summary, we report on PWS participants consecutively enrolled internationally in a single clinical trial with high-resolution chromosome microarray analysis to determine and describe an unbiased estimate of the frequencies and types of genetic defects and address potential at-risk genetic disorders in those with maternal disomy 15 subclasses in the largest PWS cohort studied to date.
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Síndrome de Prader-Willi , Humanos , Masculino , Síndrome de Prader-Willi/genética , Análisis por Micromatrices , Familia , Cromosomas , Cromosomas Humanos Par 15/genéticaRESUMEN
Background: Prader-Willi syndrome (PWS) is a potentially life threatening, genetic developmental disorder that requires lifelong medical treatment and behavioral management. PWS has a major impact on the patient's social environment. In this study, we have explored traumatic life events and symptoms of posttraumatic stress disorder (PTSD) in family members of individuals with PWS. We have also assessed quality of life in relation to trauma manifestations. In addition, we have evaluated demographic characteristics such as living setting of PWS patients as well as PWS symptom severity. Methods: Data of this observational study were obtained by means of the Life Events Checklist DMS-5, the Posttraumatic Stress Disorder Checklist DSM-5, the abbreviated World Health Organization Quality of Life questionnaire, the Lancashire Quality of Life Profile questionnaire, and a short demographic inventory. The study sample includes 98 adults aged 19 to 80 years (M = 49, SD = 15), who are relatives of 69 individuals with PWS aged 0 to 58 years (M = 19, SD = 13). Participants were recruited via the two Dutch patient associations PWS and the Dutch Digital Center of Expertise PWS. Results: Life time prevalence of traumatic events (93%) was higher in family members of PWS patients ("PWS relatives") than in the general Dutch population (81%). Of those who reported any traumatic event, almost half reported PWS-related events. The prevalence of probable PTSD was higher in PWS relatives (12.1%) than the general lifetime prevalence of PTSD (worldwide, and in the Netherlands 7.4%). Predominant trauma symptoms in PWS relatives were "negative changes in arousal and reactivity" and "negative changes in cognition and mood;" both significantly negatively related to quality of life. Symptom severity of PWS individuals, as well as the associated trauma symptom severity of their relatives increased with age of the PWS individual. The presence of trauma symptoms was less frequent among relatives of PWS individuals living in a care facility. Conclusions: Having a relative with PWS is associated with higher prevalence of traumatic experiences and greater vulnerability to PTSD. Raising awareness in health care professionals of trauma symptoms in PWS relatives may contribute to effective treatment of their psychosocial stress. In addition, timely interventions might prevent family members from developing psychopathology like PTSD.
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CONTEXT: Acylated ghrelin (AG) stimulates appetite and is elevated compared to its unacylated (UAG) counterpart in Prader-Willi syndrome (PWS). GLWL-01 is a selective, reversible inhibitor of ghrelin O-acyltransferase (GOAT), the enzyme that converts UAG into AG. OBJECTIVE: This work aimed to assess the efficacy, pharmacokinetics, pharmacodynamics, and safety of GLWL-01 in the treatment of PWS patients. METHODS: A double-blind, placebo-controlled, phase 2 crossover study was conducted with 2 active treatment periods of 28 days in 19 patients (aged 16-65 years; body mass index (BMI)â ≥â 28) with genetically confirmed PWS. The study took place in 7 hospital-based study centers in the United States and Canada. Patients received placebo or GLWL-01 (450 mg twice daily) orally after lead-in placebo and washout periods. The Hyperphagia Questionnaire for Clinical Trials and Caregiver Global Impression of Change were used to measure reductions in hyperphagia. Plasma concentrations of AG and UAG were evaluated as correlates. RESULTS: Treatment resulted in statistically significant differences compared to placebo in plasma AG (Pâ =â .0002), UAG (Pâ =â .0488), and AG/UAG (Pâ =â .0003). GLWL-01 did not statistically significantly reduce hyperphagia-related behavior or bring about changes in global clinical end points, as assessed by caregivers. Anthropometric and clinical parameters correlated with obesity did not statistically significantly change in response to treatment. Less than half of patients reported a treatment-emergent adverse event (TEAE). No deaths, serious adverse events, or severe TEAEs were reported. CONCLUSION: GLWL-01 is safe and well tolerated. Pharmacological parameters confirmed the inhibition of GOAT following administration of GLWL-01. Patients' eating behaviors, BMI, blood glucose, and total cholesterol, among other similar measures, were not modified.
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Síndrome de Prader-Willi , Aciltransferasas , Estudios Cruzados , Método Doble Ciego , Ghrelina/uso terapéutico , Humanos , Hiperfagia , Síndrome de Prader-Willi/tratamiento farmacológicoRESUMEN
Prader-Willi syndrome (PWS) is a rare and complex genomic imprinting disorder caused by an absence of expression of paternal genes from chromosome 15q11.2-q13. Clinical manifestations of PWS depends on age. In early infancy, PWS patients is characterized by hypotonia and failure to thrive. Later in life, they can also exhibit hyperphagia, obesity, short stature, hypogonadism, behavioral issues and cognitive disability. Multiple sleep abnormalities including obstructive and/or central sleep apnea, daytime hypersomnolence, and impaired responses to hypercapnia and hypoxia have been described in patients with PWS. Recent studies also demonstrated an increased risk of seizures in PWS patients. Electrical status epilepticus in sleep (ESES) is an age-limited epilepsy with various seizure types, neurophysiological and motor impairment. The classic electroencephalogram (EEG) pattern of ESES involves continuous epileptic activity at 2-3 Hz occupying greater than 85% of non-rapid eye movement (REM) sleep. Treatment of the ESES syndrome consists of anti-epileptic drugs in routine cases, and corticosteroids, gamma globulins, the ketogenic diet, and surgery in refractory cases. In this project, we describe ESES during polysomnography in a 5-year-old female with PWS and no history of seizure disorder. To the best of our knowledge, this is the first case report on ESES in a PWS patient.
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Background: Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by hormonal dysregulation, obesity, intellectual disability, and behavioral problems. Most PWS cases are caused by paternal interstitial deletions of 15q11.2-q13.1, while a smaller number of cases are caused by chromosome 15 maternal uniparental disomy (PW-UPD). Children with PW-UPD are at higher risk for developing autism spectrum disorder (ASD) than the neurotypical population. In this study, we used expression analysis of PW-UPD neurons to try to identify the molecular cause for increased autism risk. Methods: Dental pulp stem cells (DPSC) from neurotypical control and PWS subjects were differentiated to neurons for mRNA sequencing. Significantly differentially expressed transcripts among all groups were identified. Downstream protein analysis including immunocytochemistry and immunoblots were performed to confirm the transcript level data and pathway enrichment findings. Results: We identified 9 transcripts outside of the PWS critical region (15q11.2-q13.1) that may contribute to core PWS phenotypes. Moreover, we discovered a global reduction in mitochondrial transcripts in the PW-UPD + ASD group. We also found decreased mitochondrial abundance along with mitochondrial aggregates in the cell body and neural projections of +ASD neurons. Conclusion: The 9 transcripts we identified common to all PWS subtypes may reveal PWS specific defects during neurodevelopment. Importantly, we found a global reduction in mitochondrial transcripts in PW-UPD + ASD neurons versus control and other PWS subtypes. We then confirmed mitochondrial defects in neurons from individuals with PWS at the cellular level. Quantification of this phenotype supports our hypothesis that the increased incidence of ASD in PW-UPD subjects may arise from mitochondrial defects in developing neurons.
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Prader-Willi syndrome (PWS) is a neurogenetic multifactorial disorder caused by the deletion or inactivation of paternally imprinted genes on human chromosome 15q11-q13. The affected homologous locus is on mouse chromosome 7C. The positional conservation and organization of genes including the imprinting pattern between mice and men implies similar physiological functions of this locus. Therefore, considerable efforts to recreate the pathogenesis of PWS have been accomplished in mouse models. We provide a summary of different mouse models that were generated for the analysis of PWS and discuss their impact on our current understanding of corresponding genes, their putative functions and the pathogenesis of PWS. Murine models of PWS unveiled the contribution of each affected gene to this multi-facetted disease, and also enabled the establishment of the minimal critical genomic region (PWScr) responsible for core symptoms, highlighting the importance of non-protein coding genes in the PWS locus. Although the underlying disease-causing mechanisms of PWS remain widely unresolved and existing mouse models do not fully capture the entire spectrum of the human PWS disorder, continuous improvements of genetically engineered mouse models have proven to be very powerful and valuable tools in PWS research.
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Modelos Animales de Enfermedad , Síndrome de Prader-Willi/genética , Síndrome de Prader-Willi/metabolismo , Animales , Mapeo Cromosómico/métodos , Metilación de ADN , Ingeniería Genética/métodos , Genoma , Impresión Genómica , Humanos , Masculino , Ratones , ARN Nucleolar Pequeño/genéticaRESUMEN
Prader-Willi syndrome (PWS) is a neurodevelopmental genetic disorder characterized by multiple system involvement with hypotonia, poor suck with feeding difficulties, growth and other hormone deficiencies, intellectual disability, and behavioral problems with childhood onset of hyperphagia resulting in obesity, if not externally controlled. Transcranial direct current stimulation (tDCS) has been increasingly shown to modulate cognitive and behavioral processes in children and adults, including food-intake behaviors in patients with PWS. This study further reports the positive effects of brief tDCS sessions on Go/NoGo task performance involving food and non-food stimuli images, alterations in N2 brain amplitude, and genetic subgroup differences (maternal disomy 15, UPD; 15q11-q13 deletion, DEL) before and after tDCS as assessed by event-related potentials (ERPs) in 10 adults with PWS. The results indicate a group effect on baseline NoGo N2 amplitude in PWS patients with DEL vs UPD (p =0.046) and a decrease in NoGo N2 amplitude following tDCS (p = 0.031). Our tDCS approach also demonstrated a trend towards decreased response time. Collectively, these results replicate and expand prior work highlighting neurophysiological differences in patients with PWS according to genetic subtype and demonstrate the feasibility in examining neuromodulatory effects of tDCS on information processing in this patient population to stimulate additional research and treatment.
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PURPOSE: The benefits of growth hormone (GH) therapy in Prader-Willi syndrome (PWS) children are well established, but there is still considerable controversy regarding whether GH treatment can improve cognitive, motor, and behavioral development in PWS children. The objectives of this meta-analysis were to quantitatively evaluate the effects of GH on cognitive, motor function, and behavioral development in PWS children. METHODS: Randomized controlled trials (RCTs) examining the effects of GH on cognitive, motor, and behavioral development in PWS children were identified by searching the MEDLINE, EMBASE, and Cochrane Library databases. Intervention effects were represented by Hedges'g and pooled to calculate effect sizes using a random-effects model. RESULTS: Ten relevant studies comprising data from 302 participants were finally included. We observed no significant difference in cognitive performance between the GH treatment group and the control group (p = 0.197). GH treatment was shown to remarkably improve motor development in PWS children compared with the control treatment (p < 0.001), with moderate positive treatment effects (Hedges'g [95% CI] = 0.71 [0.38, 1.03]). There were no significant differences between the GH group and the control group based on objective assessments of behavioral development (p = 0.53). CONCLUSIONS: The meta-analysis suggested that GH treatment had a significantly positive effect on motor development, with moderate treatment effects in PWS children; however, there was no evidence of effects on cognitive or behavioral development.
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Hormona de Crecimiento Humana , Síndrome de Prader-Willi , Niño , Cognición , Hormona del Crecimiento , Humanos , Síndrome de Prader-Willi/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Previous studies regarding the prevalence of Autism Spectrum Disorder (ASD) in patients with Prader-Willi Syndrome (PWS) have implicated heterogenous findings. Additionally, the early screening of ASD high-risk population for ASD and identifying ASD risk factors in PWS patients have not been explored. This study included 218 Chinese PWS patients aged 3 months to 18 years old. 78% of subjects were identified as high risk for ASD by ASQ-3 Communication domain score for those younger than 3 years of age and 84% of subjects were classified as high risk for ASD by the GARS-3 for those aged 3 years and older. Among PWS clinical measurements, under-height (P = 0.0186), overweight (P = 0.0248), and obstructive sleep apnea (P = 0.0259) were each significantly correlated with ASD risk. These risk factors and their internal relationship with ASD or ASD traits warrant further studies.
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Prader-Willi syndrome (PWS) is a complex multisystemic condition caused by a lack of paternal expression of imprinted genes from the 15q11.2-q13 region. Limited literature exists on the association between molecular classes, growth hormone use, and the prevalence of psychiatric phenotypes in PWS. In this study, we analyzed nine psychiatric phenotypes (depressed mood, anxiety, skin picking, nail picking, compulsive counting, compulsive ordering, plays with strings, visual hallucinations, and delusions) recognized in PWS and investigated associations with growth hormone treatment (GHT), deletions (DEL) and uniparental disomy (UPD) in a cohort of 172 individuals with PWS who met the criteria for analysis. Associations were explored using Pearson chi-square tests and univariable and multivariable logistic regression analyses to control for confounding exposures. This observational study of the largest dataset of patients with PWS to date suggested the following genetic subtype and phenotype correlations in psychiatric behaviors: (1) skin picking was more frequent in those with DEL vs. UPD; (2) anxiety was more common in those with UPD vs. DEL; and (3) an increased frequency of anxiety was noted in the UPD group treated with GHT compared to the DEL group. No other significant associations were found between the genetic subtype or GHT including for depressed mood, nail picking, compulsive counting, compulsive ordering, playing with strings, and visual hallucinations. Further studies will be required before any conclusions can be reached.