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European Journal of Pediatrics Jun 2023Genetic syndromes often show facial features that provide clues for the diagnosis. However, memorizing these features is a challenging task for clinicians. In the last...
UNLABELLED
Genetic syndromes often show facial features that provide clues for the diagnosis. However, memorizing these features is a challenging task for clinicians. In the last years, the app Face2Gene proved to be a helpful support for the diagnosis of genetic diseases by analyzing features detected in one or more facial images of affected individuals. Our aim was to evaluate the performance of the app in patients with Silver-Russell syndrome (SRS) and Prader-Willi syndrome (PWS). We enrolled 23 pediatric patients with clinically or genetically diagnosed SRS and 29 pediatric patients with genetically confirmed PWS. One frontal photo of each patient was acquired. Top 1, top 5, and top 10 sensitivities were analyzed. Correlation with the specific genetic diagnosis was investigated. When available, photos of the same patient at different ages were compared. In the SRS group, Face2Gene showed top 1, top 5, and top 10 sensitivities of 39%, 65%, and 91%, respectively. In 41% of patients with genetically confirmed SRS, SRS was the first syndrome suggested, while in clinically diagnosed patients, SRS was suggested as top 1 in 33% of cases (p = 0.74). Face2Gene performed better in younger patients with SRS: in all patients in whom a photo taken at a younger age than the age of enrollment was available, SRS was suggested as top 1, albeit with variable degree of probability. In the PWS group, the top 1, top 5, and top 10 sensitivities were 76%, 97%, and 100%, respectively. PWS was suggested as top 1 in 83% of patients genetically diagnosed with paternal deletion of chromosome 15q11-13 and in 60% of patients presenting with maternal uniparental disomy of chromosome 15 (p = 0.17). The performance was uniform throughout the investigated age range (1-15 years).
CONCLUSION
In addition to a thorough medical history and detailed clinical examination, the Face2Gene app can be a useful tool to support clinicians in identifying children with a potential diagnosis of SRS or PWS.
WHAT IS KNOWN
• Several genetic syndromes present typical facial features that may provide clues for the diagnosis. • Memorizing all syndromic facial characteristics is a challenging task for clinicians.
WHAT IS NEW
• Face2Gene may represent a useful support for pediatricians for the diagnosis of genetic syndromes. • Face2Gene app can be a useful tool to integrate in the diagnostic path of patients with SRS and PWS.
Topics: Humans; Child; Infant; Child, Preschool; Adolescent; Prader-Willi Syndrome; Silver-Russell Syndrome; Family; Computers; Chromosomes, Human, Pair 15
PubMed: 36947243
DOI: 10.1007/s00431-023-04937-x -
American Journal of Medical Genetics.... Feb 2019Prader-Willi syndrome (PWS) is a multi-system disorder resulting from a lack of paternal gene expression in the 15q11.2-q13 region. Using databases compiled through...
Prader-Willi syndrome (PWS) is a multi-system disorder resulting from a lack of paternal gene expression in the 15q11.2-q13 region. Using databases compiled through response questionnaires completed by families known to the Prader-Willi Syndrome Association (USA), this study tested the hypothesis that PWS genetic subtype, BMI, age of diagnosis, clinical symptoms, and growth hormone treatment differ among deceased and living individuals with PWS. Categorical and continuous variables were compared using chi-square and two-group t tests, respectively. Deceased individuals had higher rates of clinical features, including increased weight concerns, heart problems, sleep apnea, other respiratory complications, diabetes, osteoporosis, high pain tolerance, and severe skin picking, when compared to living individuals. Meanwhile, living individuals had higher rates of growth hormone use and early puberty. Obesity and subsequent consequences are the primary contributors to increased mortality in PWS. Additional emphasis on areas to decrease mortality is needed.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Body Mass Index; Child; Child, Preschool; Chromosomes, Human, Pair 15; Female; Growth Hormone; Heart Failure; Humans; Infant; Infant, Newborn; Longitudinal Studies; Male; Middle Aged; Obesity; Paternal Inheritance; Prader-Willi Syndrome; Young Adult
PubMed: 30569567
DOI: 10.1002/ajmg.a.60688 -
PloS One 2019People with Prader-Willi syndrome (PWS) have a distinctive behavioral phenotype that includes intellectual disability, compulsivity, inattention, inflexibility and...
INTRODUCTION
People with Prader-Willi syndrome (PWS) have a distinctive behavioral phenotype that includes intellectual disability, compulsivity, inattention, inflexibility and insistence on sameness. Inflexibility and inattention are at odds with the cognitive flexibility and attention to social cues needed to accurately perceive the social world, and implicate problems in social cognition. This study assessed two social cognition domains in people with PWS; emotion recognition and social perception. We identified changes in social cognition over an approximate two-year time period (M = 2.23 years), relative strengths and weakness in social cognition, and correlates and predictors of social cognition.
METHODS
Emotion recognition and social perception were examined at two time points in 94 individuals with PWS aged 5 to 62 years (M = 13.81, SD = 10.69). Tasks administered included: standardized IQ testing; parent-completed measures of inattention and inflexibility; standard emotion recognition photos (fear, sadness, anger, happy); and videotaped social perception vignettes depicting negative events with either sincere/benign or insincere/hostile interactions between peers.
RESULTS
An atypical trajectory of negative emotion recognition emerged, marked by similar levels of poor performances across age, and confusion between sad and anger that is typically resolved in early childhood. Recognition of sad and fear were positively correlated with IQ. Participants made gains over time detecting social cues, but not in forming correct conclusions about the intentions of others. Accurately judging sincere intentions remained a significant weakness over time. Relative to sincere intentions, participant's performed significantly better in detecting negative social cues, and correctly judging trickery, deceit and lying. Age, IQ, inattention, and recognition of happy and sad accounted for 29% of variance in social perception.
CONCLUSION
Many people with PWS have deficits in recognizing sad, anger and fear, and accurately perceiving the sincere intentions of other people. The impact of these deficits on social behavior and relationships need to be better understood.
Topics: Adolescent; Adult; Child; Child, Preschool; Cognition Disorders; Cognitive Dysfunction; Emotions; Female; Humans; Middle Aged; Prader-Willi Syndrome; Social Behavior; Social Perception; Young Adult
PubMed: 31622356
DOI: 10.1371/journal.pone.0223162 -
Frontiers in Endocrinology 2023Prader-Willi syndrome (PWS) is a rare genetic disorder resulting from lack of expression of the paternally derived chromosome 15q11-13, associated with several... (Review)
Review
A rare occurrence of non-classic congenital adrenal hyperplasia and type 1 diabetes mellitus in a girl with Prader-Willi Syndrome: Case report and review of the literature.
Prader-Willi syndrome (PWS) is a rare genetic disorder resulting from lack of expression of the paternally derived chromosome 15q11-13, associated with several complications, including pubertal disorders, short stature, hyperphagia, obesity, glucose metabolism abnormalities, scoliosis, obstructive sleep apnea syndrome (OSAS) and behavioral problems. We report the case of a girl affected by PWS who presented at the age of 5.9 with premature pubarche, accelerated linear growth and advanced bone age (BA). She was subsequently diagnosed with non-classic congenital adrenal hyperplasia (CAH) confirmed by genetic analysis. Considering the clinical, biochemical, and genetic findings, hydrocortisone therapy was started to prevent rapid BA acceleration and severe compromission of final height. During infancy, short stature and low levels of insulin-like growth factor-1 (IGF-1) for age and gender led to suspicion of growth hormone deficiency (GHD), confirmed by stimulation testing (arginine and clonidine). rhGH therapy was administered and continued until final height was reached. During endocrinological follow up she developed impaired glucose tolerance with positive markers of β-cell autoimmunity (anti-glutamic acid decarboxylase antibodies, GAD Ab), which evolved over time into type 1 diabetes mellitus and insulin therapy with a basal-bolus scheme and an appropriate diet were needed.
Topics: Female; Humans; Prader-Willi Syndrome; Diabetes Mellitus, Type 1; Adrenal Hyperplasia, Congenital; Human Growth Hormone; Obesity
PubMed: 37124733
DOI: 10.3389/fendo.2023.1148318 -
Journal of Endocrinological... Oct 2022In Prader-Willi syndrome (PWS) adult patients, sleep-breathing disorders, especially obstructive sleep apnoea syndrome (OSAS), are very common, whose missed or delayed...
INTRODUCTION
In Prader-Willi syndrome (PWS) adult patients, sleep-breathing disorders, especially obstructive sleep apnoea syndrome (OSAS), are very common, whose missed or delayed diagnosis can contribute to further increase cardiovascular morbidity and mortality.
PURPOSE
The aim of this cross-sectional study was to evaluate differences in sleep-breathing parameters obtained by overnight cardiorespiratory polygraphy in 13 adult PWS patients and 13 individuals with non-syndromic obesity as controls matched by age, sex, and BMI.
METHODS
In all subjects' anthropometric parameters, body composition using bioimpedance analysis and overnight cardiorespiratory monitoring parameters were obtained.
RESULTS
Ten (76.9%) PWS patients were diagnosed with OSAS, most notably nine (69.2%) and one PWS (7.7%) with mild and severe OSAS, respectively. Compared with the control group, PWS patients had evidence of higher apnoea-hypopnea index (AHI) (p = 0.04) and oxyhaemoglobin desaturation index (ODI) (p = 0.009). However, no differences were found between the two groups regarding OSAS categories or diagnosis of nocturnal respiratory failure. In the PWS group, there were no significant correlations among AHI, ODI and hypoxemia index (T90) and anthropometric measurements, fat mass (FM), and FM percentage (%). Conversely, in the control group, the sleep-related respiratory indices evaluated correlated positively with BMI, waist circumference, FM and FM%.
CONCLUSIONS
This study confirmed that AHI and ODI indices were worse in PWS than in age, sex and BMI-matched controls. The lack of their significant association with the anthropometric parameters and FM supported the existence of PWS-related mechanisms in OSAS pathophysiology that are independent of visceral obesity and FM.
Topics: Adult; Body Composition; Body Mass Index; Case-Control Studies; Cross-Sectional Studies; Humans; Polysomnography; Prader-Willi Syndrome; Sleep Apnea, Obstructive
PubMed: 35723851
DOI: 10.1007/s40618-022-01831-5 -
The Journal of Clinical Endocrinology... Dec 2020Prader-Willi syndrome (PWS) is a complex hypothalamic disorder, combining hyperphagia, hypotonia, intellectual disability, and pituitary hormone deficiencies. Annual...
CONTEXT
Prader-Willi syndrome (PWS) is a complex hypothalamic disorder, combining hyperphagia, hypotonia, intellectual disability, and pituitary hormone deficiencies. Annual mortality of patients with PWS is high (3%). In half of the patients, the cause of death is obesity related and/or of cardiopulmonary origin. Health problems leading to this increased mortality often remain undetected due to the complexity and rareness of the syndrome.
OBJECTIVE
To assess the prevalence of health problems in adults with PWS retrospectively.
PATIENTS, DESIGN, AND SETTING
We systematically screened 115 PWS adults for undiagnosed health problems. All patients visited the multidisciplinary outpatient clinic for rare endocrine syndromes at the Erasmus University Medical Center, Rotterdam, Netherlands. We collected the results of medical questionnaires, interviews, physical examinations, biochemical measurements, polygraphy, polysomnography, and radiology.
MAIN OUTCOME MEASURES
Presence or absence of endocrine and nonendocrine comorbidities in relation to living situation, body mass index, genotype, and demographic factors.
RESULTS
Seventy patients (61%) had undiagnosed health problems, while 1 in every 4 patients had multiple undiagnosed health problems simultaneously. All males and 93% of females had hypogonadism, 74% had scoliosis, 18% had hypertension, 19% had hypercholesterolemia, 17% had type 2 diabetes mellitus, and 17% had hypothyroidism. Unfavorable lifestyles were common: 22% exercised too little (according to PWS criteria) and 37% did not see a dietitian.
CONCLUSIONS
Systematic screening revealed many undiagnosed health problems in PWS adults. Based on patient characteristics, we provide an algorithm for diagnostics and treatment, with the aim to prevent early complications and reduce mortality in this vulnerable patient group.
Topics: Adult; Comorbidity; Diagnostic Techniques, Endocrine; Female; Humans; Male; Mass Screening; Missed Diagnosis; Netherlands; Practice Guidelines as Topic; Prader-Willi Syndrome; Prevalence; Retrospective Studies; Surveys and Questionnaires; Young Adult
PubMed: 32877518
DOI: 10.1210/clinem/dgaa621 -
Journal of Intellectual Disability... Jul 2021Prader-Willi syndrome (PWS) is a rare genetic disorder that in many cases is associated with mental health disorders, in addition to characteristic symptoms such as...
BACKGROUND
Prader-Willi syndrome (PWS) is a rare genetic disorder that in many cases is associated with mental health disorders, in addition to characteristic symptoms such as hyperphagia. The current Sars-CoV-2 coronavirus pandemic has led to massive restrictions in health care and social life worldwide. People with PWS represent a particularly vulnerable population group to these restrictions, with unknown impact on their mental health.
METHODS
We conducted an online questionnaire to assess the impact of the restrictions associated with the COVID-19 pandemic on the mental health of people with PWS.
RESULTS
One hundred and eight caregivers completed the survey about individuals with PWS. Individuals with PWS > 6 years (n = 89) were included for evaluation with regard to psychopathological change. Respondents frequently reported an increase in psychopathological symptoms associated with PWS during the lockdown, with 51.7% reporting increased temper outbursts, 43.8% showing signs of sadness, 38.2% being anxious, 55.0% more irritable, and 39.3% showing more food seeking behaviour. Adjusted for the type of accommodation food seeking behaviour and irritability is increased to a significantly lesser extent in people with PWS accommodated in specialised care facilities compared with those living in their family home. No significant difference could be found between the sexes.
CONCLUSION
The COVID-19 pandemic has had a significant effect on the mental health of individuals with PWS, evidenced by an increase in behaviours associated with PWS, including temper outbursts, food-seeking, and irritability, which again underlines their need for specialised care. Individuals living with their families were particularly vulnerable, indicating that they and their families are in special need of support.
Topics: Adolescent; Adult; Behavioral Symptoms; COVID-19; Child; Communicable Disease Control; Female; Humans; Male; Middle Aged; Prader-Willi Syndrome; Young Adult
PubMed: 33754414
DOI: 10.1111/jir.12831 -
Journal of Neurodevelopmental Disorders Jun 2021Prader-Willi syndrome (PWS) is a rare neurodevelopmental genetic disorder associated with a characteristic behavioral phenotype that includes severe hyperphagia and a... (Review)
Review
Prader-Willi syndrome (PWS) is a rare neurodevelopmental genetic disorder associated with a characteristic behavioral phenotype that includes severe hyperphagia and a variety of other behavioral challenges such as temper outbursts and anxiety. These behaviors have a significant and dramatic impact on the daily functioning and quality of life for the person with PWS and their families. To date, effective therapies addressing these behavioral challenges have proven elusive, but several potential treatments are on the horizon. However, a limiting factor for treatment studies in PWS is the lack of consensus in the field regarding how to best define and measure the complex and interrelated behavioral features of this syndrome. The International PWS Clinical Trials Consortium (PWS-CTC, www.pwsctc.org ) includes expert PWS scientists, clinicians, and patient advocacy organization representatives focused on facilitating clinical trials in this rare disease. To address the above gap in the field, members of the PWS-CTC "Behavior Outcomes Working Group" sought to develop a unified understanding of the key behavioral features in PWS and build a consensus regarding their definition and description. The primary focus of this paper is to present consensus definitions and descriptions of key phenotypic PWS behaviors including hyperphagia, temper outbursts, anxiety, obsessive-compulsive behaviors, rigidity, and social cognition deficits. Patient vignettes are provided to illustrate the interrelatedness and impact of these behaviors. We also review some available assessment tools as well as new instruments in development which may be useful in measuring these behavioral features in PWS.
Topics: Anxiety; Consensus; Humans; Prader-Willi Syndrome; Quality of Life
PubMed: 34148559
DOI: 10.1186/s11689-021-09373-2 -
RNA Biology Jan 2023The genetic disorder Prader-Willi syndrome (PWS) is mainly caused by the loss of multiple paternally expressed genes in chromosome 15q11-q13 (the PWS region). Early...
The genetic disorder Prader-Willi syndrome (PWS) is mainly caused by the loss of multiple paternally expressed genes in chromosome 15q11-q13 (the PWS region). Early diagnosis of PWS is essential for timely treatment, leading to effectively easing some clinical symptoms. Molecular approaches for PWS diagnosis at the DNA level are available, but the diagnosis of PWS at the RNA level has been limited. Here, we show that a cluster of paternally transcribed snoRNA-ended long noncoding RNAs (, ) derived from the locus in the PWS region can serve as diagnostic markers. In particular, quantification analysis has revealed that 6,000 copies of are present in 1 μL whole blood samples from non-PWS individuals. 3 is absent in all examined whole blood samples of 8 PWS individuals compared to 42 non-PWS individuals and dried blood samples of 35 PWS individuals compared to 24 non-PWS individuals. Further developing a new CRISPR-MhdCas13c system for RNA detection with a sensitivity of 10 molecules per μL has ensured detection in non-PWS, but not PWS individuals. Together, we suggest that the absence of represents a potential marker for PWS diagnosis that can be detected by both RT-qPCR and CRISPR-MhdCas13c systems with only microlitre amount of blood samples. Such an RNA-based sensitive and convenient approach may facilitate the early detection of PWS.
Topics: Humans; Prader-Willi Syndrome; RNA, Long Noncoding; RNA, Small Nucleolar
PubMed: 37405372
DOI: 10.1080/15476286.2023.2230406 -
Biochemical and Biophysical Research... Aug 2024Prader-Willi syndrome (PWS) is a complex epigenetic disorder caused by the deficiency of paternally expressed genes in chromosome 15q11-q13. This syndrome also includes...
Prader-Willi syndrome (PWS) is a complex epigenetic disorder caused by the deficiency of paternally expressed genes in chromosome 15q11-q13. This syndrome also includes endocrine dysfunction, leading to short stature, hypogonadism, and obscure hyperphagia. Although recent progress has been made toward understanding the genetic basis for PWS, the molecular mechanisms underlying its pathology in obesity remain unclear. In this study, we examined the adipocytic characteristics of two PWS-induced pluripotent stem cell (iPSC) lines: those with the 15q11-q13 gene deletion (iPWS cells) and those with 15q11-q13 abnormal methylation (M-iPWS cells). The transcript levels of the lipid-binding protein aP2 were decreased in iPWS and M-iPWS adipocytes. Flow-cytometry analysis showed that PWS adipocytes accumulated more lipid droplets than did normal individual adipocytes. Furthermore, glucose uptake upon insulin stimulation was attenuated compared to that in normal adipocytes. Overall, our results suggest a significantly increased lipid content and defective in glucose metabolism in PWS adipocytes.
Topics: Prader-Willi Syndrome; Adipocytes; Humans; Induced Pluripotent Stem Cells; Glucose; Chromosomes, Human, Pair 15; Fatty Acid-Binding Proteins; Cell Line; DNA Methylation; Gene Deletion; Lipid Metabolism; Insulin
PubMed: 38776833
DOI: 10.1016/j.bbrc.2024.150124