Safety and effectiveness of growth hormone therapy in infants with Prader-Willi syndrome younger than 2 years: a prospective study

2019 ◽  
Vol 32 (8) ◽  
pp. 879-884 ◽  
Author(s):  
Raquel Corripio ◽  
Carla Tubau ◽  
Laura Calvo ◽  
Carme Brun ◽  
Núria Capdevila ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Prospective Study ◽  
Mixed Model ◽  
Standard Deviation Score ◽  
Uniparental Disomy ◽  
Chromosome 15 ◽  
Prader Willi Syndrome ◽  
Gh Treatment ◽  
Maternal Uniparental Disomy ◽  
A Prospective Study

Abstract Background There is little evidence of the effects of early treatment with growth hormone (GH) in infants with Prader-Willi syndrome (PWS). A prospective study was conducted to assess the safety of GH therapy in infants younger than 2 years of age with PWS. Methods A total of 14 patients with PWS started treatment with GH under the age of 2 years and were followed over a 2-year period. A deletion of chromosome 15 was present in nine infants (64.3%) and maternal uniparental disomy 15 in five infants (35.7%). The median age at start of GH treatment was 9.6 months (interquartile range [IQR] 9.0–18.3 months). Changes in height standard deviation score (SDS), body mass index (BMI) SDS and subcapsular and tricipital skinfolds in the follow-up period were evaluated with a mixed-model regression analysis using the Package R. Results There were no fatal adverse events. A significant decrease (p < 0.001) in tricipital and subcapsular skinfold thickness, with an upward trend of height SDS and a downward trend of BMI SDS, was observed. Infants who started GH before 15 months of age started walking at a median of 18.0 [17.0–19.5] months vs. 36.6 [36.3–37.8] months for those who began treatment with GH after 15 months of age (p = 0.024). Conclusions GH treatment in infants with PWS less than 2 years of age is safe and improved body composition. Infants who received GH before the age of 15 months started to walk earlier.

scholarly journals Benefits and challenges in conducting long-term growth hormone therapy in patients with Prader-Willi syndrome

Genetika ◽  
2020 ◽  
Vol 52 (1) ◽  
pp. 149-160
Author(s):  
Olga Antonova ◽  
Hadil Kathom ◽  
Evgeni Grigorov ◽  
Rada Staneva ◽  
Savina Hadjidekova ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Statistical Analysis ◽  
Uniparental Disomy ◽  
Prader Willi Syndrome ◽  
Gh Treatment ◽  
Maternal Uniparental Disomy ◽  
Significant Difference ◽  
Genetic Mechanisms ◽  
Post Hoc

The purpose of this report is to comment the results from long-term growth hormone (GH) treatment of Bulgarian patients suffering from rare genetic disease-Prader-Willi syndrome (PWS) with reference to the age, body composition, complications and genetic etiology. Statistical analysis was performed by ANOVA with post hoc Kruskal-Wallis test and Dunn's multiple comparison tests. In 90% of the patients maternal uniparental disomy (mUPD) was found to be the cause of the disease. No cases due to imprinting defects are found. The BMI data shows no statistically significant difference between BMI at diagnosis (21.850), at the beginning of the GH therapy (21.852) and current BMI (24.09) - measured under the GH background. Early GH treatment allows to overcome arising obstacles in time and to improve the quality of life for PWS children and their families. During the fourteen years study period only ten patients were diagnosed with the disease. Ninety percent (n=9) of the children were found to be with maternal UPD (mUPD) and only one case was due to deletion in 15q11-13. These results are in agreement with other studies in the field which shows the need for reassessment and new robust statistical analysis of the frequency of genetic mechanisms for PWS.

scholarly journals Quantitative Analysis of SRNPN Gene Methylation by Pyrosequencing as a Diagnostic Test for Prader–Willi Syndrome and Angelman Syndrome

2006 ◽  
Vol 52 (6) ◽  
pp. 1005-1013 ◽  
Author(s):  
Helen E White ◽  
Victoria J Durston ◽  
John F Harvey ◽  
Nicholas CP Cross
Keyword(s):  
Diagnostic Test ◽  
Angelman Syndrome ◽  
Uniparental Disomy ◽  
Chromosome 15 ◽  
Prader Willi Syndrome ◽  
Maternal Uniparental Disomy ◽  
Cpg Sites ◽  
Specific Pcr ◽  
Small Nuclear Ribonucleoprotein ◽  
Maternal Contribution

Abstract Background: Angelman syndrome (AS) and Prader–Willi syndrome (PWS) are 2 distinct neurodevelopmental disorders caused primarily by deficiency of specific parental contributions at an imprinted domain within the chromosomal region 15q11.2-13. In most cases, lack of paternal contribution leads to PWS either by paternal deletion (∼70%) or maternal uniparental disomy (UPD; ∼30%). Most cases of AS result from the lack of a maternal contribution from this same region by maternal deletion (∼70%) or by paternal UPD (∼5%). Analysis of allelic methylation differences at the small nuclear ribonucleoprotein polypeptide N (SNRPN) locus can differentiate the maternally and paternally inherited chromosome 15 and can be used as a diagnostic test for AS and PWS. Methods: Sodium bisulfite–treated genomic DNA was PCR-amplified for the SNRPN gene. We used pyrosequencing to individually quantify the resulting artificial C/T sequence variation at CpG sites. Anonymized DNA samples from PWS patients (n = 40), AS patients (n = 31), and controls (n = 81) were analyzed in a blinded fashion with 2 PCR and 3 pyrosequencing reactions. We compared results from the pyrosequencing assays with those obtained with a commonly used methylation-specific PCR (MS-PCR) diagnostic protocol. Results: The pyrosequencing assays had a sensitivity and specificity of 100% and provided quantification of methylation at 12 CpG sites within the SNRPN locus. The resulting diagnoses were 100% concordant with those obtained from the MS-PCR protocol. Conclusions: Pyrosequencing is a rapid and robust method for quantitative methylation analysis of the SNRPN locus and can be used as a diagnostic test for PWS and AS.

Growth hormone treatment and bone mineral density in pediatric patients with Prader–Willi syndrome

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Yuji Oto ◽  
Nobuyuki Murakami ◽  
Takeshi Inoue ◽  
Keiko Matsubara ◽  
Sohei Saima ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Growth Hormone ◽  
Bone Mineral ◽  
Pediatric Patients ◽  
Standard Deviation Score ◽  
Hormone Treatment ◽  
Prader Willi Syndrome ◽  
Mineral Density ◽  
Gh Treatment ◽  
Total Body

Abstract Objectives Previous reports indicate that growth hormone (GH) treatment for Prader–Willi syndrome (PWS) improves bone mineral density (BMD) only when initiated at a young age and not when initiated in adulthood. However, there are no data on BMD during long-term GH treatment of Japanese children and adolescents with PWS. Thus, this study aimed to investigate BMD changes among patients with PWS, who were undergoing GH treatment from childhood to adolescence. Methods Sixty-seven pediatric patients with PWS who had GH treatment initiated during childhood between January 2003 and June 2020 were evaluated. To avoid underestimation, we used total body BMD, which was evaluated using dual-X-ray absorptiometry adjusted for the BMD z-score using patient height, sex, and age. Results In both sexes, age was negatively correlated with the BMD-standard deviation score (SDS) (male: r=−0.156 [p=0.042]; female: r=−0.197 [p=0.043]), which started to decrease in childhood. Conclusions The BMD-SDS of patients with PWS decreases gradually despite GH treatment. As there are no clear recommendations about monitoring of bone health in patients with PWS, further studies are needed to improve the guidelines for screening of BMD and treatment of patients with PWS.

Prader-Willi syndrome due to maternal uniparental disomy of chromosome 15 in a boy with a balanced 3;21 translocation

2001 ◽  
Vol 100 (1) ◽  
pp. 85-86 ◽  
Author(s):  
Lori L. Bassett ◽  
Ron C. Michaelis ◽  
Mary Holland Geiger ◽  
Jack Tarleton ◽  
C. Lynn Moore ◽  
...  
Keyword(s):  
Uniparental Disomy ◽  
Chromosome 15 ◽  
Prader Willi Syndrome ◽  
Maternal Uniparental Disomy

Mosaic maternal uniparental disomy of chromosome 15 in Prader-Willi syndrome: Utility of genome-wide SNP array

2012 ◽  
Vol 161 (1) ◽  
pp. 166-171 ◽  
Author(s):  
Kosuke Izumi ◽  
Avni B. Santani ◽  
Matthew A. Deardorff ◽  
Holly A. Feret ◽  
Tanya Tischler ◽  
...  
Keyword(s):  
Snp Array ◽  
Uniparental Disomy ◽  
Chromosome 15 ◽  
Prader Willi Syndrome ◽  
Maternal Uniparental Disomy ◽  
Genome Wide

scholarly journals Correlation of Genotype and Perinatal Period, Time of Diagnosis and Anthropometric Data before Commencement of Recombinant Human Growth Hormone Treatment in Polish Patients with Prader–Willi Syndrome

Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 798
Author(s):  
Agnieszka Lecka-Ambroziak ◽  
Marta Wysocka-Mincewicz ◽  
Katarzyna Doleżal-Ołtarzewska ◽  
Agata Zygmunt-Górska ◽  
Teresa Żak ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Human Growth Hormone ◽  
Recombinant Human Growth Hormone ◽  
Uniparental Disomy ◽  
Genetic Diagnosis ◽  
Human Growth ◽  
Prader Willi Syndrome ◽  
Maternal Uniparental Disomy ◽  
Group 3 ◽  
Group 1

Genotype–phenotype correlation in patients with Prader–Willi syndrome (PWS) has still not been fully described. We retrospectively analysed data of 147 patients and compared groups according to genetic diagnosis: paternal deletion of chromosome 15q11-q13 (DEL 15, n = 81), maternal uniparental disomy (UPD 15, n = 10), excluded DEL 15 (UPD 15 or imprinting centre defect, UPD/ID, n = 30). Group DEL 15 had an earlier genetic diagnosis and recombinant human growth hormone (rhGH) start (p = 0.00), with a higher insulin-like growth factor 1 (IGF1) level compared to group UPD/ID (p = 0.04). Among perinatal characteristics, there was only a tendency towards lower birth weight SDS in group UPD 15 (p = 0.06). We also compared data at rhGH start in relation to genetic diagnosis age—group 1: age ≤9 months, group 2: >9 months ≤ 2 years, group 3: > 2 years. Group 1 had the earliest rhGH start (p = 0.00), with lower body mass index (BMI) SDS (p = 0.00) and a tendency towards a higher IGF1 level compared to group 3 (p = 0.05). Genetic background in children with PWS is related to time of diagnosis and rhGH start, with a difference in IGF1 level before the therapy, but it seems to have little impact on perinatal data. Early genetic diagnosis leads to early rhGH treatment with favourable lower BMI SDS.

scholarly journals Early treatment with GH alone in Turner syndrome: prepubertal catch-up growth and waning effect

2004 ◽  
pp. 567-572 ◽  
Author(s):  
M Wasniewska ◽  
F De Luca ◽  
R Bergamaschi ◽  
MP Guarneri ◽  
L Mazzanti ◽  
...  
Keyword(s):  
Prospective Study ◽  
Turner Syndrome ◽  
Standard Deviation Score ◽  
Height Velocity ◽  
Bone Maturation ◽  
Gh Treatment ◽  
Height Gain ◽  
Catch Up ◽  
Growth Promoting ◽  
A Prospective Study

OBJECTIVE: In order to ascertain the advantages of early GH treatment in Turner syndrome (TS), we started a prospective study aimed at evaluating prepubertal height gain in a cohort of 29 girls who were treated with the same pro-kilo GH dose (1.0 IU/kg per week) since they were less than 6 years old and for at least 5 years before entering puberty. PATIENTS AND DESIGN: Following a minimum of 6 months of baseline observations, 29 girls with TS were enrolled for this prospective study provided that they (a) were less than 6 years old, (b) were below -1.0 standard deviation score (SDS) for height, (c) had a projected adult height (PAH) lower than the respective target height (TH) and (d) had a height velocity (HV) lower than -1.0 SDS. All the selected girls underwent a 5-year treatment with biosynthetic GH at a stable dose of 1.0 IU/kg per week and were periodically measured during the treatment period in order to evaluate height, HV and PAH. RESULTS: After a dramatic acceleration during the 1st year, HV was attenuated during the subsequent years, reaching its nadir at the 5th year. Height deficiency under therapy progressively decreased from entry onwards, shifting from -2.4+/-0.7 to -1.0+/-1.2 SDS. In the same period, mean PAH progressively increased, although after 5 years it remained lower than the average TH. CONCLUSIONS: (a) An effective growth-promoting strategy in TS should be based on early GH treatment, as suggested by our results. (b) This strategy could result in a prepubertal normalization of height, thus allowing the appropriate timing for the induction of puberty. (c) An initial GH dose of 1.0 IU/kg per week may be suitable during the first years of therapy, as shown by our data documenting an important waning effect of GH therapy only after the 4th year of treatment. (d) No acceleration of bone maturation was observed under this treatment regimen.

scholarly journals Molecular Changes in Prader-Willi Syndrome Neurons Reveals Clues About Increased Autism Susceptibility.

2021 ◽  
Author(s):  
Anna Kaitlyn Victor ◽  
Martin Donaldson ◽  
Daniel Johnson ◽  
Winston Miller ◽  
Lawrence Reiter
Keyword(s):  
Behavioral Problems ◽  
Neurodevelopmental Disorder ◽  
Uniparental Disomy ◽  
Autism Spectrum ◽  
Chromosome 15 ◽  
Prader Willi Syndrome ◽  
Maternal Uniparental Disomy ◽  
Mitochondrial Defects ◽  
Mitochondrial Transcripts ◽  
Global Reduction

Background: Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by hormonal dysregulation, obesity, intellectual disability, and behavioral problems. Most PWS cases are caused by paternal interstitial deletions of 15q11.2-q13.1, while a smaller number of cases are caused by chromosome 15 maternal uniparental disomy (PW-UPD). Children with PW-UPD are at higher risk for developing autism spectrum disorder (ASD) than the neurotypical population. In this study, we used expression analysis of PW-UPD neurons to try to identify the molecular cause for increased autism risk. Methods: Dental pulp stem cells (DPSC) from neurotypical control and PWS subjects were differentiated to neurons for mRNA sequencing. Significantly differentially expressed transcripts among all groups were identified. Downstream protein analysis including immunocytochemistry and immunoblots were performed to confirm the transcript level data and pathway enrichment findings. Results: We identified 9 transcripts outside of the PWS critical region (15q11.2-q13.1) that may contribute to core PWS phenotypes. Moreover, we discovered a global reduction in mitochondrial transcripts in the PW-UPD +ASD group. We also found decreased mitochondrial abundance along with mitochondrial aggregates in the cell body and neural projections of +ASD neurons. Conclusions: The 9 transcripts we identified common to all PWS subtypes may reveal PWS specific defects during neurodevelopment. Importantly, we found a global reduction in mitochondrial transcripts in PW-UPD +ASD neurons versus control and other PWS subtypes. We then confirmed mitochondrial defects in neurons from individuals with PWS at the cellular level. Quantification of this phenotype supports our hypothesis that the increased incidence of ASD in PW-UPD subjects may arise from mitochondrial defects in developing neurons.

scholarly journals Molecular Changes in Prader-Willi Syndrome Neurons Reveals Clues About Increased Autism Susceptibility

2021 ◽  
Vol 14 ◽  
Author(s):  
A. Kaitlyn Victor ◽  
Martin Donaldson ◽  
Daniel Johnson ◽  
Winston Miller ◽  
Lawrence T. Reiter
Keyword(s):  
Behavioral Problems ◽  
Neurodevelopmental Disorder ◽  
Uniparental Disomy ◽  
Autism Spectrum ◽  
Chromosome 15 ◽  
Prader Willi Syndrome ◽  
Maternal Uniparental Disomy ◽  
Mitochondrial Defects ◽  
Mitochondrial Transcripts ◽  
Global Reduction

Background: Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by hormonal dysregulation, obesity, intellectual disability, and behavioral problems. Most PWS cases are caused by paternal interstitial deletions of 15q11.2-q13.1, while a smaller number of cases are caused by chromosome 15 maternal uniparental disomy (PW-UPD). Children with PW-UPD are at higher risk for developing autism spectrum disorder (ASD) than the neurotypical population. In this study, we used expression analysis of PW-UPD neurons to try to identify the molecular cause for increased autism risk.Methods: Dental pulp stem cells (DPSC) from neurotypical control and PWS subjects were differentiated to neurons for mRNA sequencing. Significantly differentially expressed transcripts among all groups were identified. Downstream protein analysis including immunocytochemistry and immunoblots were performed to confirm the transcript level data and pathway enrichment findings.Results: We identified 9 transcripts outside of the PWS critical region (15q11.2-q13.1) that may contribute to core PWS phenotypes. Moreover, we discovered a global reduction in mitochondrial transcripts in the PW-UPD + ASD group. We also found decreased mitochondrial abundance along with mitochondrial aggregates in the cell body and neural projections of +ASD neurons.Conclusion: The 9 transcripts we identified common to all PWS subtypes may reveal PWS specific defects during neurodevelopment. Importantly, we found a global reduction in mitochondrial transcripts in PW-UPD + ASD neurons versus control and other PWS subtypes. We then confirmed mitochondrial defects in neurons from individuals with PWS at the cellular level. Quantification of this phenotype supports our hypothesis that the increased incidence of ASD in PW-UPD subjects may arise from mitochondrial defects in developing neurons.

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