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Prader-Willi Syndrome (PWS) is a rare genetic disorder typically characterized by decreased social interaction, hyperphagia, poor behavioral control and temper tantrums, together with a high risk of morbid obesity unless food intake is controlled. The genetic defects that cause PWS include paternal 15q deletion (estimated in 60% of cases), chromosome 15 maternal uniparental disomy (UPD) (estimated in 35% of cases) and imprinting defects and translocations. Several studies indicate an oxytocin deficiency in PWS. Oxytocin is a hypothalamic nonapeptide with receptors located in the brain and in various other tissues in the body. It acts as a neuropeptide in several brain areas of great importance for behavioral and metabolic effects, as well as a neurohypophyseal hormone released into the circulation. Oxytocin in both rats and humans has strong and long-lasting behavioral and metabolic effects. Thus, an oxytocin deficiency might be involved in several of the behavioral and metabolic symptoms characterizing PWS. Treatment with oxytocin has, in some studies, shown improvement in psycho-social behavior and hyperphagia in individuals with PWS. This review focus on the behavioral and metabolic effects of oxytocin, the symptoms of a potential oxytocin deficiency in PWS and the effects of oxytocin treatment.
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Prader-Willi syndrome (PWS) is a rare genetic disorder caused by the loss of paternal genes on chromosome 15. The Aberrant Behavior Checklist (ABC) is a standardized rating scale for assessing problematic behaviors in persons with developmental disabilities. Our study aims to describe ABC scores in youth with PWS and track their change over time. The analysis included 69 patients. Mean ABC scores were compared in four age groups (5-8, 9-12, 13-16, and 17-22 years). A statistically significant difference was found only in the Irritability subscale, with lower scores in the 5-8 age group compared to the 9-12 age group. For change over time, scores for Irritability, Lethargy, Stereotypic Behavior, Hyperactivity subscales, and Total score were likely to decrease after age 12. Irritability subscale scores of males were predicted to increase more than those of females between ages of 5 and 12 . The Lethargy score in the nondeletion group had a greater reduction than the deletion group in the 12-20 year range. This study highlights the need for systematic collection and characterization of behavioral data given the burden of maladaptive behaviors that often persist for a lifetime.
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INTRODUCTION: Prader-Willi syndrome (PWS) represents a difficult challenge for spine surgeons, due to the association of a structural scoliosis, with a prevalence between 15 and 86%. Conservative therapy is a viable option, but surgery is increasingly becoming the treatment of choice. METHODS: The authors reviewed a series of 15 patients affected by PWS treated at their institution between 2008 and 2023. The mean age at index treatment was 9 years and 3 months (range 1-15 years) with a prevalence of female subjects. Primary scoliotic curve ranged from 14 to 102°, and mean thoracic kyphosis was 56° (range 20-75°). Eleven patients underwent conservative treatment, while four were treated surgically. RESULTS: Mean follow-up was 5 years and 3 months (range 2-12 years). Among the 11 patients treated conservatively, only two showed improvements of the coronal curve, while the remaining nine displayed a worsening of the deformity during follow-up. Complication rate after surgery was 75%. One patient developed paraplegia after pedicle screw positioning. One patient displayed rod breakage and PJK that required revision surgery proximally. Hardware deep infection was seen in one case where it was necessary to proceed with instrumentation removal after 10 years. DISCUSSION AND CONCLUSIONS: Spine surgery represents a convincing option in patients affected by PWS, but the risks of complications are high. Correct patient selection must be the main objective, and multilevel pedicle screw fixation should be the procedure of choice. Traditional growing rod should be prudently evaluated in every single case.
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Síndrome de Prader-Willi , Escoliose , Humanos , Escoliose/cirurgia , Feminino , Síndrome de Prader-Willi/complicações , Síndrome de Prader-Willi/cirurgia , Adolescente , Criança , Masculino , Pré-Escolar , Lactente , Doenças Raras/cirurgia , Resultado do Tratamento , Fusão Vertebral/métodos , Estudos RetrospectivosRESUMO
Current published guidelines for routine care of women with Prader-Willi syndrome (PWS) do not include recommendations for gynecologic examinations. We describe our experience with gynecological examinations in women with PWS and offer recommendations for routine health care for these patients. Data were collected on all 41 PWS females ages ≥12 year, followed in our national Israeli multidisciplinary clinic between the years 2011 and 2022. Menstrual data and findings on external gynecological examination, including evaluation of the vulva and hymen were recorded at yearly visits. During the gynecological evaluation the topic of sexual education was discussed. Pelvic ultrasound, specifically for antral follicular count, was performed for those visiting the clinic during 2020-2022. Blood samples for luteinizing hormone (LH), follicular stimulating hormone (FSH), and estradiol were obtained routinely and DEXA scans for bone density were done when indicated. Of the 41 women, (median age at start of follow-up 17 years, range [12.3-39], BMI 30.4 kg/m2 [IQR 23.5-37.1]), 39 women agreed to external gynecological examination. Eleven women (27%) had spontaneous menses, with menarche at the age of 14 to as late as 31 years. The hymen was intact in all except one. Poor hygiene was observed in eight women, three women with vulvovaginitis, and five with irritated vulva related to poor hygiene. Gynecological ultrasound was performed in 27 women. In 22, endometrial thickness was less than 5 mm. The median antral follicular count (AFC) was 6 (<10th percentile for age). No correlation between AFC and menstruation or BMI was found. Mean FSH level was 5.7 ± 3.6 IU, LH was 2.29 ± 2.23, and estradiol was 128 ± 76 pmol/L. Data on DEXA measurements were available in 25 women aged 16-39. Median spine T score was -1.3 (range between 0.5 and -3.7), and hip T score was -1.2 (range between 0.8 and -3.3). A negative correlation was found between endometrial thickness and the presence of osteopenia or osteoporosis (r = -0.5, p = 0.013). Despite our recommendations, only eight of 14 women agreed to hormonal treatment or contraception. One woman who received treatment had a thromboembolic event. Routine health care for women with PWS should include gynecological examinations. The gynecological evaluation should include external genital examination, assessment of hygiene, obtaining a blood sample for hormone levels, and documenting a history of sexual experience or sexual abuse. Hormonal treatment or contraception should be offered when appropriate.
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Exame Ginecológico , Síndrome de Prader-Willi , Humanos , Adulto , Feminino , Adolescente , Criança , Adulto Jovem , Síndrome de Prader-Willi/diagnóstico , Hormônio Luteinizante , Hormônio Foliculoestimulante , EstradiolRESUMO
BACKGROUND AND OBJECTIVES: Port wine birthmark, also known as port wine stain (PWS) is a skin discoloration characterized by red/purple patches caused by vascular malformation. PWS is typically treated by using lasers to destroy abnormal blood vessels. The laser heating facilitates selective photothermolysis of the vessels and attenuates quickly in the tissue due to high optical scattering. Therefore, residual abnormal capillaries deep in the tissue survive and often lead to the resurgence of PWS. Ultrasound (US) has also been proposed to treat PWS, however, it is nonselective with respect to the vasculature but penetrates deeper into the tissue. We aim to study the feasibility of a hybrid PWS treatment modality combining the advantages of both modalities. MATERIALS AND METHODS: In this manuscript, we propose a photoacoustic (PA) guided US focusing methodology for PWS treatment which combines the optical contrast-based selectivity with US penetration to focus the US energy onto the vasculature. The PA signals collected by the transducers, when time-reversed, amplified, and transmitted, converge onto the PWS, thus minimally affecting the neighboring tissue. We performed two- and three-dimensional simulations that mimic realistic transducers and medium properties in this proof of concept study. RESULTS: The time-reversed PA signals when transmitted from the transducers converged onto the vasculature, as expected, thus reducing the heating of the neighboring tissue. We observed that while the US focus is indeed affected due to experimental factors such as limited-view, large detector separation and finite detection bandwidth, and so forth, the US did focus completely or partially onto the vasculature demonstrating the feasibility of the proposed methodology. CONCLUSION: The results demonstrate the potential of the proposed methodology for PWS treatment. This treatment method can destroy the deeper capillaries while minimally heating the neighboring tissue, thus reducing the chances of the resurgence of PWS and as well as cosmetic scarring.
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Mancha Vinho do Porto , Humanos , Mancha Vinho do Porto/diagnóstico por imagem , Mancha Vinho do Porto/terapia , Estudos de Viabilidade , Lasers , Cicatriz , Análise EspectralRESUMO
Port-wine stains (PWS) are frequently refractory to laser treatments. The aim of this study is to evaluate the role of treatment interval time. From 1990, 216 patients underwent Pulsed Dye Laser sessions. The laser sessions were scheduled at a minimum interval of 4 weeks to a maximum of 48 weeks. Clinical outcomes were assessed 8 weeks after the last laser session. Better results were obtained with 8 weeks interval time between therapy session, and high efficacies were also found for intervals of 4, 6 and 10 weeks. For greater interval instead, the effectiveness is significantly lower.
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Terapia a Laser , Lasers de Corante , Mancha Vinho do Porto , Humanos , Lasers de Corante/uso terapêutico , Resultado do Tratamento , Mancha Vinho do Porto/radioterapia , Mancha Vinho do Porto/cirurgia , Terapia a Laser/métodosRESUMO
Fourier-based imaging has been widely adopted for microwave imaging thanks to its efficiency in terms of computational complexity without compromising image resolution. Together with other backpropagation imaging algorithms like delay-and-sum (DAS), they are based on a far-field approach to the electromagnetic expression relating to fields and sources. To improve the accuracy of these techniques, this contribution presents a modified version of the well-known Fourier-based algorithm by taking into account the field radiated by the Tx/Rx antennas of the microwave imaging system. The impact on the imaged targets is discussed, providing a quantitative and qualitative analysis. The performance of the proposed method for subsampled microwave imaging scenarios is compared against other well-known aliasing mitigation methods.
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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 , Análise em Microsséries , Família , Cromossomos , Cromossomos Humanos Par 15/genéticaRESUMO
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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Obesidade Infantil , Síndrome de Prader-Willi , Masculino , Feminino , Humanos , Criança , Síndrome de Prader-Willi/complicações , Obesidade Infantil/complicações , Estudos de Casos e Controles , Índice de Massa Corporal , Sistema Nervoso AutônomoRESUMO
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 de Transporte/genética , Cromossomos , Cromossomos Humanos Par 15 , Magnésio , Síndrome de Prader-Willi/genéticaRESUMO
The hypothalamus regulates fundamental aspects of physiological homeostasis and behavior, including stress response, reproduction, growth, sleep, and feeding, several of which are affected in patients with Prader-Willi (PWS) and Schaaf-Yang syndrome (SYS). PWS is caused by paternal deletion, maternal uniparental disomy, or imprinting defects that lead to loss of expression of a maternally imprinted region of chromosome 15 encompassing non-coding RNAs and five protein-coding genes; SYS patients have a mutation in one of them, MAGEL2. Throughout life, PWS and SYS patients suffer from musculoskeletal deficiencies, intellectual disabilities, and hormonal abnormalities, which lead to compulsive behaviors like hyperphagia and temper outbursts. Management of PWS and SYS is mostly symptomatic and cures for these debilitating disorders do not exist, highlighting a clear, unmet medical need. Research over several decades into the molecular and cellular roles of PWS genes has uncovered that several impinge on the neuroendocrine system. In this review, we will discuss the expression and molecular functions of PWS genes, connecting them with hormonal imbalances in patients and animal models. Besides the observed hormonal imbalances, we will describe the recent findings about how the loss of individual genes, particularly MAGEL2, affects the molecular mechanisms of hormone secretion. These results suggest that MAGEL2 evolved as a mammalian-specific regulator of hypothalamic neuroendocrine function.
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Ansiedade , Hipotálamo , Animais , Síndrome , Mamíferos/genética , Sistemas NeurossecretoresRESUMO
BACKGROUND: Although leptin/melanocortin pathway pathologies in hypothalamus are thought to be the main cause of early-onset obesity and hyperphagia in PWS and BBS, the exact mechanism is still not known. OBJECTIVE: To measure serum concentrations of a-MSH, BDNF and AGRP in a group of children with BBS or PWS. METHODS: We recruited 12 subjects with PWS, 12 subjects with BBS, 28 obese controls (OC) and 26 lean controls (LC) matched for age, sex and puberty. Serum a-MSH, BDNF and AGRP levels were measured by the ELISA method. RESULTS: The mean a-MSH level was lower in PWS than those of OC and LC (3729 ± 1319, 5211 ± 829 and 5681 ± 565 pg/ml, respectively, p < 0.001), and mean a-MSH was lower in OC than LC (p < 0.05). The mean BDNF level of PWS was higher than those of OC and LC (565 ± 122, 482 ± 102 and 391 ± 74 pg/ml, respectively, p < 0.001). On the other hand, mean a-MSH level of BBS was lower than those of OC and LC (4543 ± 658, 5211 ± 829 and 5681 ± 565 pg/ml, respectively, p < 0.001), and mean a-MSH was lower in OC than LC (p < 0.05). The mean BDNF level of BBS was higher than those of OC and LC (583 ± 115, 482 ± 102 and 391 ± 74 pg/ml, respectively, p < 0.001). Additionally, both in PWS and BBS, the mean BDNF level was higher in OC than LC (p < 0.01). Regarding AGRP level, there was no difference both in BBS and PWS compared to OC. CONCLUSION: We found that the serum a-MSH levels of PWS and BBS groups are significantly lower compared to those of obese and lean controls. Therefore, we can speculate that the circulating a-MSH level does properly reflect its central production, and the serum a-MSH level might be a good biomarker to detect a-MSH deficiency in individuals suspected to have BBS or PWS, and also in those with POMC, PCSK1, and LEPR deficiency.
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Fator Neurotrófico Derivado do Encéfalo , alfa-MSH , Proteína Relacionada com Agouti/metabolismo , Criança , Humanos , Obesidade/metabolismo , Síndrome , alfa-MSH/metabolismoRESUMO
Sno-lncRNAs are intron-derived long noncoding RNAs (lncRNAs) with snoRNA ends. Sno-lncRNAs were first discovered in the human Prader-Willi (PWS)/Angelman (AS) imprinted domain. Here, we report the identification and characterization of four sno-lncRNA types (sno-lncRNA1, sno-lncRNA2, sno-lncRNA3, and sno-lncRNA4) in the bovine PWS/AS imprinted domain. Reverse transcription-PCR first determined the cDNA sequences of the four bovine sno-lncRNAs. A gene structure analysis showed that sno-lncRNA1 lacks introns, but sno-lncRNA2 and sno-lncRNA3 have one and two introns respectively. The three sno-lncRNAs have similar snoRNA ends. Moreover, the three have similar snoRNAs at their 5' and 3' ends. The head-to-tail orientation has six sno-lncRNA copies arranged between bovine SNORD116-6 and SNORD116-12. Moreover, only a copy of sno-lncRNA4 was located between SNORD116-3 and SNORD116-4. The expression of the four sno-lncRNAs was analyzed in the bovine heart, liver, spleen, lung, kidney, muscle, fat, brain, and placenta tissues. The monoallelic expression of sno-lncRNA4 was determined in bovine tissues. The results showed that the four sno-lncRNAs are widely expressed in the nine tissues, although sno-lncRNA3 and sno-lncRNA4 were undetected in the placenta. Moreover, an informative single nucleotide polymorphism (rs448706424) revealed the allelic expression of sno-lncRNA4 in exon 2 of sno-lncRNA4. The bovine genome had six copies of sno-lncRNA1, sno-lncRNA2, and sno-lncRNA3, but their allelic expression was not identified.
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Doenças dos Bovinos , Síndrome de Prader-Willi , RNA Longo não Codificante , Alelos , Animais , Bovinos/genética , Doenças dos Bovinos/genética , Impressão Genômica , Humanos , Íntrons , Síndrome de Prader-Willi/genética , RNA Longo não Codificante/genética , RNA Nucleolar Pequeno/genética , RNA Nucleolar Pequeno/metabolismoRESUMO
Obesity is a global medical problem; its common form is known as diet-induced obesity (DIO); however, there are several rare genetic disorders, such as Prader-Willi syndrome (PWS), that are also associated with obesity (genetic-induced obesity, GIO). The currently available therapeutics for treating DIO and GIO are very limited, and they result in only a partial improvement. Cannabidiolic acid (CBDA), a constituent of Cannabis sativa, gradually decarboxylates to cannabidiol (CBD). Whereas the anti-obesity properties of CBD have been reasonably identified, our knowledge of the pharmacology of CBDA is more limited due to its instability. To stabilize CBDA, a new derivative, CBDA-O-methyl ester (HU-580, EPM301), was synthesized. The therapeutic potential of EPM301 in appetite reduction, weight loss, and metabolic improvements in DIO and GIO was tested in vivo. EPM301 (40 mg/kg/d, i.p.) successfully resulted in weight loss, increased ambulation, as well as improved glycemic and lipid profiles in DIO mice. Additionally, EPM301 ameliorated DIO-induced hepatic dysfunction and steatosis. Importantly, EPM301 (20 and 40 mg/kg/d, i.p.) effectively reduced body weight and hyperphagia in a high-fat diet-fed Magel2null mouse model for PWS. In addition, when given to standard-diet-fed Magel2null mice as a preventive treatment, EPM301 completely inhibited weight gain and adiposity. Lastly, EPM301 increased the oxidation of different nutrients in each strain. All together, EPM301 ameliorated obesity and its metabolic abnormalities in both DIO and GIO. These results support the idea to further promote this synthetic CBDA derivative toward clinical evaluation in humans.
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Obesidade , Síndrome de Prader-Willi , Animais , Antígenos de Neoplasias/metabolismo , Canabinoides , Dieta Hiperlipídica/efeitos adversos , Camundongos , Camundongos Knockout , Obesidade/tratamento farmacológico , Síndrome de Prader-Willi/genética , Proteínas/metabolismo , Redução de PesoRESUMO
Prader−Willi syndrome (PWS) is a complex neurodevelopmental disorder caused by the deletion or inactivation of paternally expressed imprinted genes at the chromosomal region 15q11−q13. The PWS-critical region (PWScr) harbors tandemly repeated non-protein coding IPW-A exons hosting the intronic SNORD116 snoRNA gene array that is predominantly expressed in brain. Paternal deletion of PWScr is associated with key PWS symptoms in humans and growth retardation in mice (PWScr model). Dysregulation of the hypothalamic−pituitary axis (HPA) is thought to be causally involved in the PWS phenotype. Here we performed a comprehensive reverse transcription quantitative PCR (RT-qPCR) analysis across nine different brain regions of wild-type (WT) and PWScr mice to identify stably expressed reference genes. Four methods (Delta Ct, BestKeeper, Normfinder and Genorm) were applied to rank 11 selected reference gene candidates according to their expression stability. The resulting panel consists of the top three most stably expressed genes suitable for gene-expression profiling and comparative transcriptome analysis of WT and/or PWScr mouse brain regions. Using these reference genes, we revealed significant differences in the expression patterns of Igfbp7, Nlgn3 and three HPA associated genes: Pcsk1, Pcsk2 and Nhlh2 across investigated brain regions of wild-type and PWScr mice. Our results raise a reasonable doubt on the involvement of the Snord116 in posttranscriptional regulation of Nlgn3 and Nhlh2 genes. We provide a valuable tool for expression analysis of specific genes across different areas of the mouse brain and for comparative investigation of PWScr mouse models to discover and verify different regulatory pathways affecting this complex disorder.
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Síndrome de Prader-Willi , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Encéfalo/metabolismo , Modelos Animais de Doenças , Éxons , Impressão Genômica , Humanos , Camundongos , Síndrome de Prader-Willi/genética , Síndrome de Prader-Willi/metabolismo , Pró-Proteína Convertase 1/genética , Pró-Proteína Convertase 1/metabolismo , RNA Nucleolar Pequeno/genética , RNA Nucleolar Pequeno/metabolismoRESUMO
OBJECTIVE: Despite clear benefits in the management of children with Prader-Willi syndrome (PWS), the role of growth hormone (GH) in adults is unclear. The aim of this study was to conduct a systematic review to evaluate the effects of GH on body composition, bone health and cardiovascular health in adults with PWS. DESIGN: A systematic computerized literature search of the PubMed database was conducted by two independent reviewers. Inclusion criteria were individuals over the age of 16 years with a genetic diagnosis of PWS who had received GH therapy, together with assessment of body composition, bone health or cardiovascular health. RESULTS: Twenty full-text papers met the inclusion criteria, encompassing 364 unique patients. No differences in body mass index (BMI) were noted, although 2 studies reported increased BMI after GH cessation. Data demonstrated statistically significant increases in lean body mass and reductions in percentage fat mass. Studies reported inconsistent effects of GH on cholesterol and echocardiography parameters. No studies reported differences in bone mineral density, although one reported improved bone geometry. Minor adverse events including pretibial oedema, headache and transient impaired glucose tolerance were reported in 7 studies. CONCLUSIONS: These data suggest that GH is safe and well tolerated in adults with PWS, with evidence of improvement in body composition. Further longitudinal studies are still required to investigate the effects of GH on bone and cardiovascular health. Where GH is used in adults with PWS, this should be managed by a specialist multidisciplinary team with regular monitoring initiated.
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Hormônio do Crescimento Humano , Síndrome de Prader-Willi , Adolescente , Adulto , Composição Corporal , Densidade Óssea , Criança , Hormônio do Crescimento , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Síndrome de Prader-Willi/tratamento farmacológicoRESUMO
BACKGROUND: High-flow vascular stains (HFVS) are lesions that have the appearance of capillary malformations/port wine stains but are associated with increased arterial flow. OBJECTIVE: To identify features of HFVS that differentiate them from typical "slow-flow" port wine stains. METHODS: Retrospective multicenter cohort study of HFVS evaluated across 7 centers was conducted. HFVS were characterized by clinical features (warmth, thrill, rapid capillary refill), radiologic findings (fast flow), or mutations associated with capillary malformation-arteriovenous malformation syndrome. Investigators reviewed photographs. RESULTS: The study reviewed 70 patients with HFVS (47 multifocal and 23 solitary). Most were flat (77%), warm to the touch (60%), and red or pink-red in color (35%), with heterogeneous color saturation (73%) and well-defined borders (71%). Regional soft tissue swelling/overgrowth was common (47%). Head and neck location was most common (38%). Among 34 HFVS with photographic review over time, all demonstrated changes in appearance. LIMITATIONS: Retrospective design, recall bias, lack of standardized time points or visual analog scale, and image variability. CONCLUSION: Heterogeneity of stain color saturation, warmth to touch, peripheral pallor, and overgrowth/soft tissue swelling help distinguish HFVS from port wine stains. Darkening of color and increased border demarcation may develop over time. These findings raise suspicion for HFVS and provide an indication to assess for extracutaneous involvement.
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Malformações Arteriovenosas/diagnóstico , Capilares/anormalidades , Mancha Vinho do Porto/diagnóstico , Adolescente , Malformações Arteriovenosas/genética , Criança , Pré-Escolar , Análise Mutacional de DNA , Diagnóstico Diferencial , Feminino , Humanos , Angiografia por Ressonância Magnética , Masculino , Mutação , Mancha Vinho do Porto/genética , Pele/irrigação sanguínea , Pele/diagnóstico por imagem , Ultrassonografia Doppler , Adulto JovemRESUMO
INTRODUCTION: Prader-Willi syndrome (PWS) is a rare, genetic, neurodevelopmental syndrome associated with hyperphagia and early onset obesity, growth and sex hormone insufficiencies, mild-to-moderate intellectual disability, and behavioral challenges such as compulsivity, anxiety, skin picking, social skills deficits and temper outbursts. Given high rates of psychiatric comorbidity and potential risk factors for suicide in PWS, this study sought a first estimate of the prevalence of suicidal ideation (SI) and attempts (SA) in the PWS population and any characteristics associated with suicidality in this population. METHODS: Using the Global Prader-Willi Syndrome Registry, we included all participants who had answered a question about SI. We examined the most recent data from the surveys about social, economic, and demographic factors, genetic subtype, and psychiatric symptoms and treatments. A chi-square analysis was used to compare registry participants who reported SI to those without reported SI. RESULTS: From 750 included survey respondents, 94 (12.5%) endorsed some history of SI. Of these, 25 (26.6%) also reported a history of SA, with an average age of 16.25 years at their first attempt. Those with a history of SI were predominantly male and adult age, and had higher rates of aggression and psychiatric comorbidities, therapies, and medications. CONCLUSIONS: This study indicates that the rate of SI and SA in PWS is comparable to the general population, and that suicide attempts in PWS typically begin in middle-teenage years. Despite unique challenges, individuals with PWS and their caregivers should be included in screens and psychoeducation for suicide and mental health concerns.
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Síndrome de Prader-Willi , Suicídio , Adolescente , Adulto , Ansiedade , Humanos , Masculino , Síndrome de Prader-Willi/epidemiologia , Sistema de Registros , Inquéritos e QuestionáriosRESUMO
Prader-Willi syndrome is a complex condition requiring constant care and supervision of the affected child. AIM: To evaluate quality of life and caregiver burden in children with Prader-Willi syndrome. METHODS: All children with Prader-Willi syndrome, attending a tertiary referral centre, were invited to participate (n = 44). Quality of life was evaluated using the PedsQL questionnaire. Family impact modules and parent proxy reports evaluated the impact on the quality of life of the child and family. Additional challenges were captured using a burden questionnaire. RESULTS: Nineteen children participated. Median age was 7.9 years (0.6-18.1 years). Majority were female (n = 14, 74%). Median age at diagnosis was 2.5 weeks (range birth-2 years 8 months). Growth hormone treatment was in place for the majority (n = 14, 74%). Increased weight and age were identified as significantly impacting on family functioning and relationships. Parents perceived increased weight and age to have a significant negative impact on their child's psychosocial health and social functioning. Caregivers of children >12 years reported an increased burden of care. Disruption to routines, restriction of social activities and psychological difficulties were reported as increasing caregiver burden. CONCLUSION: Prader-Willi syndrome impacts significantly on quality of life for both the affected child and the family.
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Síndrome de Prader-Willi , Qualidade de Vida , Sobrecarga do Cuidador , Cuidadores , Criança , Feminino , Humanos , Recém-Nascido , Masculino , Inquéritos e QuestionáriosRESUMO
Port-wine stains (PWS) are frequently refractory to laser treatments. Although previous data highlight prognostic factors and biological events related to poor outcomes, no previous publications correlate their capillaroscopic and architectural features. The aim of the present study is to describe refractory port-wine stains performing capillaroscopy and reflectance confocal microscopy (RCM) to describe their morphological and microscopic aspects. This is a prospective cohort study. All the consecutive patients with PWS poor responsive to previous treatment were included. Clinical assessment, capillaroscopy, and reflectance confocal microscopy were performed. A total of 65 patients were included, 12 with a capillaroscopic Type II pattern patients and 53 with Type III. At RCM examination, PWS with a capillaroscopic Type III pattern showed deeper-located blood vessels (p < 0.001) with a higher diameter (p < 0.042) compared with Type II. At the dynamic evaluation, 3 RCM patterns can be distinguished: Subset A, characterized by linear vessels with reduced diameter; Subset B, formed by enlarged vessels; and Subset C, characterized by deep and large aneurysmatic dilatation connected to small vessels. We defined 3 RCM patterns of refractory PWS.