Growth patterns of Chinese patients with Prader‐Willi syndrome

The aim of the present study was to investigate the spontaneous development of growth and weight gain of patients with Prader‐Willi syndrome (PWS) in Mainland China. We retrospectively analyzed 120 cases of PWS diagnosed from 1994 to 2014 in Mainland China. Scatter diagram of the growth data was compared to standardized growth curve. The length at birth was similar to the normal population and the mean birthweight is under the 50th centile of normal population. Heights in 43% (27/62) of patients had dropped off below the 3^rd centile of their peers after 5 years of age. Weights in 65.9% (58/88) of patients had exceeded the 97^th centile of their peers after 3 years of age. Early obesity is obvious in 92.9% (66/71) of patients with body mass index (BMI) up the 97^th centile of their peers from 2–3 years of age. Final mean height is 149.3 ± 11.2 cm for females (n = 7) and 146.2 ± 9.8 cm for males (n = 6), showing 11.3 cm and 26.6 cm below the average height for normal Chinese girls and boys. The growth pattern of PWS in Mainland China is comparable to those in Caucasians. Early intervention with recombinant human growth hormone is warranted considering the early onset of growth retardation and obesity.     

Changeability of the fully methylated status of the 15q11.2 region in induced pluripotent stem cells derived from a patient with Prader‐Willi syndrome

Prader‐Will syndrome (PWS) is characterized by hyperphagia, growth hormone deficiency and central hypogonadism caused by the dysfunction of the hypothalamus. Patients with PWS present with methylation abnormalities of the PWS‐imprinting control region in chromosome 15q11.2, subject to parent‐of‐origin‐specific methylation and controlling the parent‐of‐origin‐specific expression of other paternally expressed genes flanking the region. In theory, the reversal of hypermethylation in the hypothalamic cells could be a promising strategy for the treatment of PWS patients, since cardinal symptoms of PWS patients are correlated with dysfunction of the hypothalamus. The genome‐wide methylation status dramatically changes during the reprograming of somatic cells into induced pluripotent stem cells (iPSCs) and during the in vitro culture of iPSCs. Here, we tested the methylation status of the chromosome 15q11.2 region in iPSCs from a PWS patient using pyrosequencing and a more detailed method of genome‐wide DNA methylation profiling to reveal whether iPSCs with a partially unmethylated status for the chromosome 15q11.2 region exhibit global methylation aberrations. As a result, we were able to show that a fully methylated status for chromosome 15q11.2 in a PWS patient could be reversed to a partially unmethylated status in at least some of the PWS‐iPSC lines. Genome‐wide DNA methylation profiling revealed that the partial unmethylation occurred at differentially methylated regions located in chromosome 15q11.2, but not at other differentially methylated regions associated with genome imprinting. The present data potentially opens a door to cell‐based therapy for PWS patients and, possibly, patients with other disorders associated with genomic imprinting.     

Long‐term effects of growth hormone therapy on patients with Prader–Willi syndrome

Aim: To assess the effects of recombinant human growth hormone (rhGH) treatment in children with Prader–Willi syndrome. Design: A 1‐year study and an observational follow‐up visit 10 years later. Methods: In 20 patients with Prader–Willi syndrome (PWS): clinical assessment, laboratory tests, body composition analysis by dual energy X‐ray absorptiometry, sleep polygraphy, health‐related quality of life assessed by 16D. Results: Only two patients had normal growth hormone secretion at baseline. All patients were significantly shorter than their expected heights, but experienced catch‐up growth during growth hormone treatment. At follow‐up, 13 patients had reached adult heights and were markedly taller than historical controls. The cumulative dose of rhGH over 10 years correlated inversely with the total body fat percentage (p = 0.033). However, patients remained severely obese at 10 years. Sleep polygraphy was abnormal in more than half of the patients. Health‐related quality of life of the patients remained substantially below that of normal population. Conclusion: Growth hormone markedly improved adult height in subjects with PWS when compared to historical data. The cumulative dose of growth hormone correlated with reduction in body fat; nevertheless, patients remained severely obese.     

Health‐related correlates of psychological well‐being among girls and boys 6–8 years of age: The Physical Activity and Nutrition in Children study

Aim

Due to limited knowledge on the differences in the correlates of psychological well‐being (PSWB) between girls and boys, we compared the correlates of PSWB between primary school girls and boys.

Methods

A population sample of 412 children participated in the Physical Activity and Nutrition in Children study. Parents completed a questionnaire that included 19 questions on the components of PSWB, and a PSWB score was computed. We assessed correlates of PSWB, including physical activity, sedentary behaviour, cardiorespiratory fitness, diet quality, body fat content, sleep duration, sleep disordered breathing, prevalent diseases and parental characteristics. We used logistic regression to analyse the risk of being in the lowest third of the PSWB scores.

Results

Low parental education was associated with increased risk (odds ratio (OR) 2.34, P = 0.039) and high cardiorespiratory fitness with decreased risk (OR 0.26, P = 0.006) of poor PSWB in girls. At least 2 h of screen‐based sedentary behaviour per day (OR 1.93, P = 0.037), daily parental smoking (OR 2.10, P = 0.034) and sleep disordered breathing (OR 4.24, P = 0.003) were related to increased risk of poor PSWB in boys.

Conclusions

There are large differences in the correlates of PSWB between girls and boys. Most of these correlates are modifiable and related to the health behaviour of children and their parents.     

1p36 deletion syndrome associated with Prader–Willi‐like phenotype

Background: 1p36 deletion syndrome is one of the most common subtelomeric deletion syndromes, characterized by moderate to severe mental retardation, characteristic facial appearance, hypotonia, obesity, and seizures. The clinical features often overlap with those of Prader–Willi syndrome (PWS). To elucidate the phenotype–genotype correlation in 1p36 deletion syndrome, two cases involving a PWS‐like phenotype were analyzed on molecular cytogenetics. Methods: Two patients presenting with the PWS‐like phenotype but having negative results for PWS underwent fluorescence in situ hybridization (FISH). The size of the chromosome 1p36 deletions was characterized using probes of BAC clones based on the University of California, Santa Cruz (UCSC) Genome Browser. Results: PWS was excluded on FISH and methylation‐specific polymerase chain reaction. Subsequent FISH using the probe D1Z2 showed deletion of the 1p36.3 region, confirming the diagnosis of 1p36 deletion syndrome. Further analysis characterized the 1p36 deletions as being located between 4.17 and 4.36 Mb in patient 1 and between 4.89 and 6.09 Mb in patient 2. Conclusion: Patients with 1p36 deletion syndrome exhibit a PWS‐like phenotype and are therefore probably underdiagnosed. The possible involvement of the terminal 4 Mb region of chromosome 1p36 in the PWS‐like phenotype is hypothesized.     

Physical and emotional well‐being of survivors of childhood and young adult allo‐SCT – A Danish national cohort study

The aim of this investigation was to examine, within a population‐based study of a national cohort comprising Danish survivors of allo‐SCT (n = 148), the long‐term effects of allo‐SCT in children and young adults. Physical and emotional well‐being was assessed using the Short Form 36 (SF‐36) and the HADS. Allo‐SCT‐related data were obtained from the participants' medical records. The study includes 148 patients, with an 89% response rate (n = 132). For comparison purposes, norm data from Danish (1994, n = 6000), Swedish (2006, n = 285), and British (2001, n = 1792) population samples were used. Factors negatively influencing the SF‐36 subscales included female gender; TBI; stem cells derived from PB; older age at time of questioning; and living alone. Factors significantly (p < 0.05) influencing HADS were transplantation with stem cells derived from PB and being underweight at time of questioning (median values were within normal range). Overall scores of allo‐SCT patients were similar to norm data. In conclusion, this national cohort study shows that patients treated with SCT in early life (<25) and whose survival period extended beyond 10 yr (mean) from SCT, showed similar levels of anxiety, depression, and physical and emotional well‐being to those of the normal population.