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The genotype–phenotype relationship in PWS patients is important for a better understanding of the clinical phenotype and clinical characteristics of different genotypes of PWS in children. We aimed to explore the influence of specific gene changes on the clinical symptoms of PWS and the value of early screening and early intervention of the condition. All data in this study were extracted from the database of the XiaoPang Weili Rare Disease Care Center. The collected information included basic demographics, maternal pregnancy information, endocrine abnormalities, growth and development abnormalities, and other clinical phenotypes. The relationships between genotypes and phenotypes in the major categories of PWS were analyzed. A total of 586 PWS cases with confirmed molecular diagnosis and genotyping were included in this study. Among them, 83.8% belonged to the deletion type, 10.9% the uniparental disomy (UPD) type, and 5.3% the imprinting defect (ID) type. Age‐wide comparison among the three groups: The rate of hypopigmentation in the deletion group was higher than that in the UPD group (88.8% vs. 60.9%; p < 0.05); A total of 62 patients (14.2%) had epilepsy; and no statistical significance was found among the three groups (p = 0.110). Age‐wide comparison between the deletion and non‐deletion types: the rate of skin hypopigmentation and epilepsy in the deletion group was significantly higher than that in the non‐deletion group (88.8% vs. 68.4%, p < 0.001; 15.9% vs. 7.6%, p = 0.040). The intergroup comparison for the >2‐year age group: there were significant intergroup differences in the language development delay among the three groups (p < 0.001). The incidence of delayed language development was the highest in the deletion group, followed by the UPD group, and the lowest in the ID group. The rates of obesity and hyperphagia in the deletion group were also higher than those in the non‐deletion group (71.1% vs. 58.9%, p = 0.041; 75.7% vs. 62.0%, p = 0.016). There are significant differences in the rates of skin hypopigmentation and language developmental delay among the deletion, UPD, and ID genotypes. The patients with deletion type had significantly higher rates of lighter skin color, obesity, hyperphagia, language developmental delay, and epilepsy. The results of this study will help clinicians better understand the impact of different PWS molecular etiologies on specific phenotypes. [ABSTRACT FROM AUTHOR]

Background: To investigate hypothalamic-pituitary-thyroid function in children of different ages, nutritional phases, and genotypes that were diagnosed with Prader-Willi syndrome (PWS), as well as the effects of recombinant human growth hormone (rhGH) treatment on thyroid hormones in PWS patients.Methods: One hundred and thirty PWS patients (87 boys and 43 girls) aged from newborn to 15 years (y) (median 1.25 y, mean, SD: 2.95 ± 3.45 y), were surveyed in this study. Serum thyroid hormone levels were examined at least once per3-6 months during the 2 years follow-up study. Central hypothyroidism (C-HT) was identified as low/normal thyroid-stimulating hormone (TSH) and low free thyroxine 4 (FT4).Results: All study participants had normal neonatal TSH screening test results. The prevalence of C-HT is 36.2% (47/130). No C-HT cases were diagnosed in PWS either below 1 month (m) or above 12 y. The prevalence of C-TH would be increased with age before 3 y until reaching the peak, followed by a gradual decline over the years. The prevalence of C-HT varies significantly at different ages (Pearson's χ2 = 19.915; p < 0.01). However, there is no correlation between the C-HT prevalence and nutritional phases (Pearson's χ2 = 4.992; p = 0.288), genotypes (Pearson's χ2 = 0.292; p = 0.864), or rhGH therapy (Pearson's χ2 = 1.799; p = 0.180).Conclusions: This study suggests the prevalence of C-TH was increased with the age before 3 y, and reached the peak in the 1 to 3 y group, then gradually declined over the years. There is no correlation between C-HT prevalence and nutritional phases, genotypes, or rhGH treatment. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the application of BACs‐on‐Beads (BoBs™) assay for rapid detection of chromosomal abnormalities for prenatal diagnosis (PND). Methods: A total of 1520 samples, including seven chorionic villi biopsy samples, 1328 amniotic fluid samples, and 185 umbilical cord samples from pregnant women were collected to detect the chromosomal abnormalities using BoBs™ assay and karyotyping. Furthermore, abnormal specimens were verified by chromosome microarray analysis (CMA) and fluorescence in situ hybridization (FISH). Results: The results demonstrated that the success rate of karyotyping and BoBs™ assay in PND was 98.09% and 100%, respectively. BoBs™ assay was concordant with karyotyping for Trisomy 21, Trisomy 18, and Trisomy 13, sex chromosomal aneuploidy, Wolf–Hirschhorn syndrome, and mosaicism. BoBs™ assay also detected Smith–Magenis syndrome, Williams–Beuren syndrome, DiGeorge syndrome, Miller–Dieker syndrome, Prader–Willi syndrome, Xp22.31 microdeletions, 22q11.2, and 17p11.2 microduplications. However, karyotyping failed to show these chromosomal abnormalities. A case of 8q21.2q23.3 duplication which was found by karyotyping was not detected by BoBs™ assay. Furthermore, all these chromosomal abnormalities were consistent with CMA and FISH verifications. According to the reports, we estimated that the detection rates of karyotyping, BoBs™, and CMA in the present study were 4.28%, 4.93%, and 5%, respectively, which is consistent with the results of a previous study. The respective costs for the three methods were about $135–145, $270–290, and $540–580. Conclusion: BoBs™ assay is considered a reliable, rapid test for use in PND. A variety of comprehensive technological applications can complement each other in PND, in order to maximize the diagnosis rate and reduce the occurrence of birth defects. [ABSTRACT FROM AUTHOR]

We set out to delineate the phenotypic and genotypic characteristics of Prader-Willi syndrome (PWS), a congenital neurodevelopmental disorder caused by the lack of expression of the paternally inherited imprinted genes on chromosome 15q11-13 in 31 Chinese patients. They were genotyped to identify deletions using methylation-specific polymerase chain reaction analysis and subsequent methylation-specific multiplex ligation-dependent probe amplification analysis. Microsatellite linkage analysis was performed to distinguish maternal uniparental disomy (UPD) from imprinting defect. Clinical manifestations were recorded and compared between patients with paternal 15q11-13 deletion and UPD. Deletions in the 15q11-13 region were present in 26 (83.9 %) patients, and UPD was observed in 5 (16.1 %) patients. The mean maternal age at the time of childbirth for mUPD children (32.8 ± 5.1 years) was significantly higher than that of children with paternal 15q11-13 deletion (27.1±3.2 years, P < 0.05). All patients had neonatal hypotonia, feeding difficulties in infancy, and decreased fetal activity, but only 12.9 % of the patients showed short stature, 54.8 % presented typical facial features, and 35.5 % showed skin picking lesions. Conclusion: Significant heterogeneity in clinical phenotypes and genotypes in PWS were observed between Chinese and Western populations in this study. This suggests that ethnic differences may be relevant to the diagnostic criteria for PWS. [ABSTRACT FROM AUTHOR]

The article presents abstracts on pediatrics which include stillbirth and newborn mortality after helping babies breathe training in India, toddler's developmental functions with sickle cell anemia and risk factors for renal injury for children with solitary functioning kidney.

Prader-Willi syndrome (PWS) is a complex and multisystem neurobehavioral disease, which is caused by the lack of expression of paternally inherited imprinted genes on chromosome15q11.2-q13.1. The clinical manifestations of PWS vary with age. It is characterized by severe hypotonia with poor suck and feeding difficulties in the early infancy, followed by overeating in late infancy or early childhood and progressive development of morbid obesity unless the diet is externally controlled. Compared to Western PWS patients, Chinese patients have a higher ratio of deletion type. Although some rare disease networks, including PWS Cooperation Group of Rare Diseases Branch of Chinese Pediatric Society, Zhejiang Expert Group for PWS, were established recently, misdiagnosis, missed diagnosis and inappropriate intervention were usually noted in China. Therefore, there is an urgent need for an integrated multidisciplinary approach to facilitate early diagnosis and optimize management to improve quality of life, prevent complications, and prolong life expectancy. Our purpose is to evaluate the current literature and evidences on diagnosis and management of PWS in order to provide evidence-based guidelines for this disease, specially from China., (© 2022. The Author(s).)

Background: Prader-Willi syndrome (PWS) is a rare and complex genetic disorder caused by lacking expression of imprinted genes on the paternally derived chromosome 15q11-q13 region. This study aimed to characterize the perinatal features of 134 Chinese individuals with PWS., Methods: This study included the patients of a PWS registry in China. Anonymous data of 134 patients were abstracted. Perinatal and neonatal presentations were analyzed, and compared between the two PWS genetic subtypes. We also compared the perinatal features of PWS patients with the general population and other previous reported large cohorts from France, UK and USA., Results: This study included 134 patients with PWS (115 patients with 15q11-q13 deletion and 19 with maternal uniparental disomy). Higher mean maternal age was found in this cohort (30.5 vs. 26.7), particularly in the maternal uniparental disomy (UPD) group (36.0 vs. 26.7) comparing with the general population. 88.6% of mothers reported a decrease of fetal movements. 42.5 and 18.7% of mothers had polyhydramnios and oligohydramnios during pregnancy, respectively. 82.8% of the patients were born by caesarean section. 32.1% of neonates had birth asphyxia, 98.5% had hypotonia and 97.8% had weak cry or even no cry at neonatal period. Feeding difficulty existed in 99.3% of the infants, 94.8% of whom had failure to thrive. 69.4% of the infants ever used feeding tube during hospitalization, however, 97.8% of them discontinued tube feeding after discharge. Maternal age and pre-pregnancy weight were significantly higher in the UPD group (both P < 0.05)., Conclusions: Differential diagnosis of PWS should be highlighted if infants having following perinatal factors including polyhydramnios, decreased intrauterine fetal movements, caesarean section, low birth weight, feeding difficulty, hypotonia and failure to thrive. Higher maternal age may be a risk factor of PWS, especially for UPD. Further studies are needed for elucidating the mechanism of PWS.

Background: Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are clinically distinct neurodevelopmental disorders caused by absence of paternally or maternally expressed imprinted genes on chromosome 15q11.2-q13.3 region. Methods: 3331 individuals was recruited from June 2013 to December 2016 under an institutional review board-approved protocol of informed consent. The methylation-specific PCR was employed as a first-tier screening test. The multiplex-fluorescent-labeled STR linkage analysis was carried out to define the underlying genetic mechanisms. The chromosomal microarray analysis was employed to identify chromosomal breakpoints in confirmed cases, and to detect other chromosomal abnormalities in undiagnosed cases. Genetic counseling and recurrence risk assessment were provided to families with affected individuals. Results: The methylation-specific PCR identified 36 PWS suspected patients and 13 AS suspected patients. UBE3A sequence analysis identified another 1 patient with AS. The STR linkage analysis define the underlying genetic mechanisms. Thirty PWS patients were with paternal deletions on chromosome region 15q11-q13, 5 with isodisomic uniparental disomy and 1 with mixed segmental isodisomic/ heterodisomic uniparental disomy of maternal chromosome 15. Twelve AS patients were with maternal deletions, 1 with isodisomic uniparental disomy and 1 with UBE3A gene mutation. The chromosomal microarray analysis identified chromosomal breakpoints in confirmed cases, and detected chromosomal abnormalities in another 4 patients with clinically overlapped features but tested negative for PWS/AS. Genetic counseling was offered to all families with affected individuals. Conclusions: Identifying the disorders at early age, establishing the molecular mechanisms, carrying out treatment intervention and close monitoring can significantly improve the prognosis of PWS/AS patients. [ABSTRACT FROM AUTHOR]

High rates of misdiagnosis and delayed intervention in neonatal PWS are leading to poor prognoses. To determine the clinical and image characteristics of newborns with Prader-Willi syndrome (PWS). A total of 102 cases of newborns definitively diagnosed with PWS at the Children's Hospital of Fudan University from 02/2014 to 12/2017 were retrospectively analyzed. We analyzed the modulated voxel-based morphology (VBM) of gray matter in PWS by T2 weighted imaging. Of 102 cases, 75 (73.5%) have paternal deletion of 15q11.2-q13, whereas 27 (26.5%) have maternal uniparental disomy (UPD). Of the 75 deletion cases, 75 (100%) week crying, 71 (94.7%) hypotonia, 70 (93.3%) poor feeding, 46 (61.3%) hypopigmentation, 43 (57.3%) male cryptorchidism, 10 (13.3%) female labia minora, 48 (64%) characteristic facial features. Of 27 UPD cases, 27 (100%) week crying and hypotonia, 25 (92.6%) hypophagia, 20 (74.1%) male cryptorchidism, 1 (3.7%) female labia minora, 19 (70.4%) characteristic facial features, 12 (44.4%) hypopigmentation. The modulated VBM analysis shows that the middle frontal gyrus, orbitofrontal cortex (middle), and inferior frontal gyrus are the most variable brain regions that determine the endo-phenotype difference between the two genotypes. Hypotonia, hypophagia, and maldevelopment of sexual organs are general characteristics of newborns with PWS in Chinese population. In UPD cases, the proportions of premature newborns, elderly parturient women and congenital malformations were higher than for paternal deletion cases. The differences in the gray matter volume of these three regions between the two genotypes may explain the differences in maladaptive behaviors and emotions.