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BMC Pediatrics Feb 2024Prader-Willi syndrome (PWS) is a rare genetic disease often associated with bone problems, mainly scoliosis and hip dysplasia (HD). This study aimed to analyze the...
BACKGROUND
Prader-Willi syndrome (PWS) is a rare genetic disease often associated with bone problems, mainly scoliosis and hip dysplasia (HD). This study aimed to analyze the clinical characteristics of orthopedic deformities in patients with PWS.
METHODS
A retrospective study was conducted on 175 patients up to March 2023. The Cobb angle(CA) of the spine, the alpha angle of the hip joint, and the acetabular index (AI) were measured. This study aimed to evaluate the relationship between demographic parameters and bone deformities.
RESULTS
Scoliosis was found in 66 patients (43.7%), including 52 (78.8%) with mild scoliosis, 10 (15.2%) with moderate scoliosis, and 4 (6.1%) with severe scoliosis. Only seven patients received orthopedic treatment (10.6%). The median age of scoliosis was 4.5 years old, and the prevalence of scoliosis increased rapidly at the age of 5 years and adolescence. The mean CA in this study increased gradually with age. HD was found in 47 patients (38.2%), and 6 patients received orthopedic treatment (12.7%). The median age at HD was 1.8 years old. The mean AI of the study population decreased with age. The prevalence of HD treated with recombinant human growth hormone (rhGH) was low. No significant differences were observed in sex, genotype, body mass index (BMI), obesity rate, or onset of scoliosis and HD.
CONCLUSION
The prevalence of scoliosis and HD was higher in patients with PWS. The onset age and developmental trends of the different skeletal malformations were different. Early diagnosis and treatment are important for the prognosis and treatment of orthopedic diseases in patients with PWS.
Topics: Child; Adolescent; Humans; Child, Preschool; Infant; Prader-Willi Syndrome; Scoliosis; Retrospective Studies; Human Growth Hormone; Obesity
PubMed: 38355440
DOI: 10.1186/s12887-024-04603-7 -
Journal of Clinical Medicine Jun 2024: Strict regimens of restricted caloric intake and daily physical exercise are life-saving in Prader-Willi syndrome (PWS) but are extremely challenging in home...
: Strict regimens of restricted caloric intake and daily physical exercise are life-saving in Prader-Willi syndrome (PWS) but are extremely challenging in home environments. PWS-specialized hostels (SH) succeed in preventing morbid obesity and in coping with behavioral disorders; however, effects of restricted living environments on quality of life (QOL) have not been described. Evidence on QOL is critical for clinicians involved in placement decisions. : We examined the impact of living in SH versus at home or in non-specialized hostels (H and NSH) on QOL, behavior, and health parameters. All 58 adults (26 males) followed-up in the National Multidisciplinary Clinic for PWS were included: 33 resided in SH, 18 lived at home, and 7 lived in NSH. Questionnaires were administered to primary caregivers to measure QOL, and data were obtained from the medical records. : The H and NSH group were compared with those for adults in SH. Despite strict diet and exercise regimens, QOL was similar for both groups. Eight-year follow-up showed that food-seeking behavior decreased in SH but increased in H and NSH. BMI, cholesterol, and triglyceride levels were lower in SH. : Our results suggest that living in SH is associated with benefits for physical health and behavior without negatively affecting QOL.
PubMed: 38893034
DOI: 10.3390/jcm13113323 -
Journal of Neurodevelopmental Disorders Nov 2023The objective of this study was to identify the age of diagnosis for children with one of three neurogenetic conditions resulting from changes in chromosome 15 (Angelman...
OBJECTIVE
The objective of this study was to identify the age of diagnosis for children with one of three neurogenetic conditions resulting from changes in chromosome 15 (Angelman syndrome [AS], Prader-Willi syndrome [PWS], and duplication 15q syndrome [Dup15q]).
METHODS
Data about the diagnostic process for each condition were contributed by the advocacy organizations. Median and interquartile ranges were calculated for each condition by molecular subtype and year. Comparison tests were run to explore group differences.
RESULTS
The median age of diagnosis was 1.8 years for both AS and Dup15q. PWS was diagnosed significantly younger at a median age of 1 month. Deletion subtypes for both PWS and AS were diagnosed earlier than nondeletion subtypes, and children with isodicentric duplications in Dup15q were diagnosed earlier than those with interstitial duplications.
CONCLUSION
Understanding variability in the age of diagnosis for chromosome 15 disorders is an important step in reducing the diagnostic odyssey and improving access to interventions for these populations. Results from this study provide a baseline by which to evaluate efforts to reduce the age of diagnosis for individuals with these conditions.
Topics: Humans; Child; Infant; Prader-Willi Syndrome; Chromosome Disorders; Chromosomes; Angelman Syndrome; Trisomy
PubMed: 37936142
DOI: 10.1186/s11689-023-09504-x -
Frontiers in Endocrinology 2024Anti-Müllerian hormone (AMH) is a Sertoli cell-secreted glycoprotein involved in male fetal sex differentiation: it provokes the regression of Müllerian ducts, which... (Review)
Review
Anti-Müllerian hormone (AMH) is a Sertoli cell-secreted glycoprotein involved in male fetal sex differentiation: it provokes the regression of Müllerian ducts, which otherwise give rise to the Fallopian tubes, the uterus and the upper part of the vagina. In the first trimester of fetal life, AMH is expressed independently of gonadotropins, whereas from the second trimester onwards AMH testicular production is stimulated by FSH and oestrogens; at puberty, AMH expression is inhibited by androgens. AMH has also been suggested to participate in testicular descent during fetal life, but its role remains unclear. Serum AMH is a well-recognized biomarker of testicular function from birth to the first stages of puberty. Especially in boys with nonpalpable gonads, serum AMH is the most useful marker of the existence of testicular tissue. In boys with cryptorchidism, serum AMH levels reflect the mass of functional Sertoli cells: they are lower in patients with bilateral than in those with unilateral cryptorchidism. Interestingly, serum AMH increases after testis relocation to the scrotum, suggesting that the ectopic position result in testicular dysfunction, which may be at least partially reversible. In boys with cryptorchidism associated with micropenis, low AMH and FSH are indicative of central hypogonadism, and serum AMH is a good marker of effective FSH treatment. In patients with cryptorchidism in the context of disorders of sex development, low serum AMH is suggestive of gonadal dysgenesis, whereas normal or high AMH is found in patients with isolated androgen synthesis defects or with androgen insensitivity. In syndromic disorders, assessment of serum AMH has shown that Sertoli cell function is preserved in boys with Klinefelter syndrome until mid-puberty, while it is affected in patients with Noonan, Prader-Willi or Down syndromes.
Topics: Female; Humans; Male; Anti-Mullerian Hormone; Cryptorchidism; Androgens; Follicle Stimulating Hormone; Peptide Hormones
PubMed: 38501100
DOI: 10.3389/fendo.2024.1361032 -
Gait & Posture Jul 2024Prader-Willi syndrome (PWS) is characterized by a complex clinical condition, whose typical features lead to impaired motor and functional skills. To date, limited data...
BACKGROUND
Prader-Willi syndrome (PWS) is characterized by a complex clinical condition, whose typical features lead to impaired motor and functional skills. To date, limited data is available as regards symmetry of gait in PWS.
RESEARCH QUESTION
The aim of this study was to characterize lower-limb asymmetry during gait in a group of Prader-Willi Syndrome (PWS) individuals by using the synchronized cyclograms and to compare it with those of two different control groups, a normal-weight group and an obese group.
METHODS
A total of 18 PWS, 30 normal weight (NW) and 28 obese individuals (OG) matched for age, sex and height were assessed via 3D gait analysis. Gait spatio-temporal parameters were computed together with angle-angle diagrams, characterized in terms of their geometric features (i.e. area, orientation, and trend symmetry index).
RESULTS
Individuals with PWS exhibit reduced speed, stride length and cadence and increased duration of both stance and double support phase than the other groups. OG was characterized by the same pattern when compared to NW. With respect to inter-limb symmetry, individuals with PWS exhibited significantly larger cyclogram areas at hip joint with respect to the other two groups (203.32 degrees vs. 130.73 degrees vs. 111.59 degrees) and significantly higher orientation angle (4.17° vs. 2.11° vs. 1.22°) and Trend Symmetry (3.72 vs. 2.02 vs. 1.21) with respect to the other two groups at knee joint; no differences were found at ankle joint. Both individuals with PWS and those of OG exhibited reduced ROM at knee and ankle joints with respect with normal weight, but no statistically significant differences were observed between PWS and OG.
SIGNIFICANCE
The obtained results may provide novel and useful insights to understand better the impairments in motor control associated with this pathological state, supporting clinics in the identification of the best rehabilitation program for this rare pathological state, aimed to improve stability and motor control.
Topics: Humans; Prader-Willi Syndrome; Female; Male; Adult; Gait; Young Adult; Adolescent; Case-Control Studies; Gait Analysis; Obesity; Biomechanical Phenomena; Lower Extremity; Hip Joint; Knee Joint; Child; Ankle Joint
PubMed: 38805861
DOI: 10.1016/j.gaitpost.2024.05.026 -
BioRxiv : the Preprint Server For... Mar 2024Epigenome editing with DNA-targeting technologies such as CRISPR-dCas9 can be used to dissect gene regulatory mechanisms and potentially treat associated disorders. For...
Epigenome editing with DNA-targeting technologies such as CRISPR-dCas9 can be used to dissect gene regulatory mechanisms and potentially treat associated disorders. For example, Prader-Willi Syndrome (PWS) is caused by loss of paternally expressed imprinted genes on chromosome 15q11.2-q13.3, although the maternal allele is intact but epigenetically silenced. Using CRISPR repression and activation screens in human induced pluripotent stem cells (iPSCs), we identified genomic elements that control expression of the PWS gene from the paternal and maternal chromosomes. We showed that either targeted transcriptional activation or DNA demethylation can activate the silenced maternal and downstream PWS transcripts. However, these two approaches function at unique regions, preferentially activating different transcript variants and involving distinct epigenetic reprogramming mechanisms. Remarkably, transient expression of the targeted demethylase leads to stable, long-term maternal expression in PWS iPSCs. This work uncovers targeted epigenetic manipulations to reprogram a disease-associated imprinted locus and suggests possible therapeutic interventions.
PubMed: 38496583
DOI: 10.1101/2024.03.03.583177 -
Endocrine Reviews May 2024Since hypothalamic obesity (HyOb) was first described over 120 years ago by Joseph Babinski and Alfred Fröhlich, advances in molecular genetic laboratory techniques... (Review)
Review
Since hypothalamic obesity (HyOb) was first described over 120 years ago by Joseph Babinski and Alfred Fröhlich, advances in molecular genetic laboratory techniques have allowed us to elucidate various components of the intricate neurocircuitry governing appetite and weight regulation connecting the hypothalamus, pituitary gland, brainstem, adipose tissue, pancreas, and gastrointestinal tract. On a background of an increasing prevalence of population-level common obesity, the number of survivors of congenital (eg, septo-optic dysplasia, Prader-Willi syndrome) and acquired (eg, central nervous system tumors) hypothalamic disorders is increasing, thanks to earlier diagnosis and management as well as better oncological therapies. Although to date the discovery of several appetite-regulating peptides has led to the development of a range of targeted molecular therapies for monogenic obesity syndromes, outside of these disorders these discoveries have not translated into the development of efficacious treatments for other forms of HyOb. This review aims to summarize our current understanding of the neuroendocrine physiology of appetite and weight regulation, and explore our current understanding of the pathophysiology of HyOb.
Topics: Humans; Obesity; Hypothalamic Diseases; Appetite; Neurosecretory Systems; Animals; Hypothalamus; Body Weight
PubMed: 38019584
DOI: 10.1210/endrev/bnad033 -
BioRxiv : the Preprint Server For... Aug 2023Angelman Syndrome (AS) and Prader-Willi Syndrome (PWS), two distinct neurodevelopmental disorders, result from loss of expression from imprinted genes in the chromosome...
Angelman Syndrome (AS) and Prader-Willi Syndrome (PWS), two distinct neurodevelopmental disorders, result from loss of expression from imprinted genes in the chromosome 15q11-13 locus most commonly caused by a megabase-scale deletion on either the maternal or paternal allele, respectively. Each occurs at an approximate incidence of 1/15,000 to 1/30,000 live births and has a range of debilitating phenotypes. Patient-derived induced pluripotent stem cells (iPSCs) have been valuable tools to understand human-relevant gene regulation at this locus and have contributed to the development of therapeutic approaches for AS. Nonetheless, gaps remain in our understanding of how these deletions contribute to dysregulation and phenotypes of AS and PWS. Variability across cell lines due to donor differences, reprogramming methods, and genetic background make it challenging to fill these gaps in knowledge without substantially increasing the number of cell lines used in the analyses. Isogenic cell lines that differ only by the genetic mutation causing the disease can ease this burden without requiring such a large number of cell lines. Here, we describe the development of isogenic human embryonic stem cell (hESC) lines modeling the most common genetic subtypes of AS and PWS. These lines allow for a facile interrogation of allele-specific gene regulation at the chromosome 15q11-q13 locus. Additionally, these lines are an important resource to identify and test targeted therapeutic approaches for patients with AS and PWS.
PubMed: 37693591
DOI: 10.1101/2023.08.30.555563 -
Human Movement Science Oct 2023Prader-Willi Syndrome (PWS) is a rare neurodevelopmental disorder affecting multiple functional parameters. This study examined postural stability and associated gait...
BACKGROUND
Prader-Willi Syndrome (PWS) is a rare neurodevelopmental disorder affecting multiple functional parameters. This study examined postural stability and associated gait and neuromuscular factors in young adults with PWS.
METHODS
Participants included 10 adults with PWS [7 M/3F; Body Fat % 40.61 ± 7.79]; ten normal weight (NW) adults [7 M/3F; Body Fat % 23.42 ± 7.0]; ten obese (OB) adults [7 M/3F; Body Fat % 42.40 ± 5.62]. Participants completed the Sensory Organization Test (SOT)®. Condition (C) specific and a composite equilibrium score (CES) were calculated (maximum = 100). Quadriceps strength was assessed using an isokinetic dynamometer. Three-dimensional gait analyses were completed along a 10 m walkway using a motion capture system and two force plates. A gait stability ratio (GSR) was computed from gait speed and step length (steps/m).
RESULTS
The PWS group had lower scores for C1, C3, C4 and CES compared to the NW (p < .039 for all) and lower scores for C4 and CES than the OB (p < .019 for both) groups, respectively. In C5 (eyes closed, sway-referenced support) and C6 (sway-referenced vision and support), 33.3% of participants with PWS fell during the first trial in both conditions (X [2] 7.436, p = .024) and (X [2] 7.436, p = .024) but no participant in the other groups fell. Those with PWS showed higher GSR than participants with NW (p = .005) and those with obesity (p = .045).
CONCLUSION
Individuals with PWS had more difficulty maintaining standing balance when relying on information from the somatosensory (C3), visual-vestibular (C4) and vestibular systems (C5, C6). A more stable walk was related to shorter steps, slower velocity and reduced peak quadriceps torque. Participation in multisensory activities that require appropriate prioritization of sensory system(s) input for controlling balance in altered sensory environments should be routinely included. In addition, exercises targeting muscular force and power should be included as part of exercise programming in PWS.
Topics: Young Adult; Humans; Prader-Willi Syndrome; Obesity; Gait; Walking; Exercise
PubMed: 37515958
DOI: 10.1016/j.humov.2023.103125 -
International Journal of Molecular... Aug 2023The hypothalamus regulates fundamental aspects of physiological homeostasis and behavior, including stress response, reproduction, growth, sleep, and feeding, several of... (Review)
Review
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, . 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 , affects the molecular mechanisms of hormone secretion. These results suggest that evolved as a mammalian-specific regulator of hypothalamic neuroendocrine function.
Topics: Animals; Syndrome; Anxiety; Hypothalamus; Mammals; Neurosecretory Systems
PubMed: 37685915
DOI: 10.3390/ijms241713109