Screening for imprinting disorders in 58 patients with clinically diagnosed idiopathic short stature

2020 ◽  
Vol 33 (10) ◽  
pp. 1335-1339
Author(s):  
Sayaka Kawashima ◽  
Hiroko Yagi ◽  
Yasuhiro Hirano ◽  
Machiko Toki ◽  
Kei Izumi ◽  
...  
Keyword(s):  
Short Stature ◽  
Clinical Diagnosis ◽  
Standard Deviation Score ◽  
Growth Failure ◽  
Normal Growth ◽  
Postnatal Growth ◽  
Idiopathic Short Stature ◽  
Imprinted Genes ◽  
Imprinting Disorders ◽  
Short Children

AbstractObjectivesImprinted genes have important roles for normal growth and development. Imprinting disorders (IDs) such as Silver-Russell syndrome and Temple syndrome are rare diseases that typically cause short children born small for gestational age (SGA). However, some patients with short stature (SS) caused by IDs were born non-SGA. To date, the contribution of IDs to idiopathic short stature (ISS) has been poorly investigated. The aim of this study was to clarify the contribution of IDs to ISS.MethodsWe conducted methylation analysis for 10 differentially methylated regions using pyrosequencing to detect known IDs in 58 patients (31 male and 27 female children, height standard deviation score −4.2 to −2.0) carrying a clinical diagnosis of ISS.ResultsWe identified no patient with IDs among these patients with ISS.ConclusionsThese results indicate that IDs are rare in patients having ISS, and that imprinted genes affect fetal growth more than postnatal growth. Because patients with IDs born non-SGA usually have clinical features characteristic of each ID, in addition to SS, the patients with ISS as a clinical diagnosis may not be associated with IDs.It is unlikely that cases clinically diagnosed with ISS are caused by IDs leading to growth failure.

scholarly journals MANAGEMENT OF ENDOCRINE DISEASE: Growth and growth hormone therapy in short children born preterm

2017 ◽  
Vol 176 (3) ◽  
pp. R111-R122 ◽  
Author(s):  
Margaret Cristina da Silva Boguszewski ◽  
Adriane de Andre Cardoso-Demartini
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Survival Rates ◽  
Adult Life ◽  
Growth Failure ◽  
Hormone Treatment ◽  
Postnatal Growth ◽  
Childhood Growth ◽  
Short Children ◽  
Postnatal Growth Failure

Approximately 15 million babies are born preterm across the world every year, with less than 37 completed weeks of gestation. Survival rates increased during the last decades with the improvement of neonatal care. With premature birth, babies are deprived of the intense intrauterine growth phase, and postnatal growth failure might occur. Some children born prematurely will remain short at later ages and adult life. The risk of short stature increases if the child is also born small for gestational age. In this review, the effects of being born preterm on childhood growth and adult height and the hormonal abnormalities possibly associated with growth restriction are discussed, followed by a review of current information on growth hormone treatment for those who remain with short stature during infancy and childhood.

scholarly journals Association between serum uric acid and triglycerides in Chinese children and adolescents with short stature

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Yuntian Chu ◽  
Qianqian Zhao ◽  
Mei Zhang ◽  
Bo Ban ◽  
Hongbing Tao
Keyword(s):  
Uric Acid ◽  
Standard Deviation ◽  
Children And Adolescents ◽  
Linear Relationship ◽  
Short Stature ◽  
Serum Uric Acid ◽  
Standard Deviation Score ◽  
Short Children ◽  
Non Linear ◽  
Males And Females

Abstract Background Elevated triglyceride (TG) levels are a biomarker for cardiovascular disease (CVD) risk. The correlation between serum uric acid (SUA) and TG concentrations in adults or obese children is well established. However, studies on SUA and TG in children with short stature are limited. Aim To determine the relationship between SUA and TG levels in short children and adolescents. Method This was a cross-sectional evaluation of a cohort of 1095 patients with short stature (720 males and 375 females). The related clinical characteristics, including anthropometric and biochemical parameters, were determined. Results Smooth curve fitting, adjusted for potential confounders was performed, which indicated the existence of a non-linear relationship between these measures. Piecewise multivariate linear analysis revealed a significant positive relationship between SUA and TG at SUA concentrations over 7 mg/dL (β = 0.13, 95% CI: 0.05–0.22, P = 0.002) but no significant correlation at lower SUA levels (β = 0.01, 95% CI: 0.01–0.04, P = 0.799). Furthermore, a stratified analysis was performed to appraise changes in this relationship for different sexes and standard deviation levels of body mass index (BMI). The non-linear relationship remained consistent in males and females with BMI standard deviation scores (BMI SDS) ≥ 0, with inflection points of 6.71 mg/dL and 3.93 mg/dL, respectively. Within these two groups, SUA and TG levels showed a positive association when SUA levels were higher than the inflection point (β = 0.21, 95% CI: 0.11–0.31, P < 0.001 for males and β = 0.1, 95% CI: 0.03–0.17, P = 0.005 for females). However, a specific relationship was not observed at lower SUA levels. No significant relationships were found between SUA and TG levels in males and females with BMI SDS < 0. Conclusion The present study identified the non-linear association of SUA and TG levels with short children and adolescents. This relationship was based on BMI status. This finding suggests that health status should be considered for short stature children with high SUA levels, especially in children with a high BMI standard deviation score.

Short Children and Growth Hormone

PEDIATRICS ◽  
1984 ◽  
Vol 73 (1) ◽  
pp. 112-113
Author(s):  
KENNETH C. COPELAND
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Growth Rates ◽  
Plasma Concentrations ◽  
Normal Growth ◽  
Somatomedin C ◽  
Short Children ◽  
Provocative Testing

To the Editor.— The article by Bright et al1 was a provocative description of two subjects with short stature, normal growth hormone (GH) responses to provocative testing, and low somatomedin-C (SM-C) concentrations, which increased after administration of GH. The authors conclude that the short stature in these individuals may be due to a biologically inactive GH molecule or to decreased dose responsiveness to GH of SM-producing cells. Their data also seem compatible with a third possibility: normal short children respond to GH administration with increases in SM-C plasma concentrations and growth rates.

scholarly journals Clinical spectrum and management of imprinting disorders

2020 ◽  
Vol 32 (4) ◽  
pp. 321-334
Author(s):  
Miriam Elbracht ◽  
Gerhard Binder ◽  
Olaf Hiort ◽  
Cordula Kiewert ◽  
Christian Kratz ◽  
...  
Keyword(s):  
Clinical Diagnosis ◽  
Maternal Effect ◽  
Mendelian Inheritance ◽  
Clinical Spectrum ◽  
Imprinted Genes ◽  
Congenital Disorders ◽  
Molecular Changes ◽  
Imprinting Disorders ◽  
Pathogenic Variants ◽  
Accelerated Growth

Abstract Imprinting disorders are exceptional within the group of monogenic syndromes. They are associated with molecular changes affecting imprinted regions and usually do not follow the rules of Mendelian inheritance. They account for a relevant proportion of congenital disorders, especially within the syndromal growth entities with endocrine, neurological, and skeletal characteristics. In patients with imprinting disorders and accelerated growth, significant tumor risks have to be considered. The number of known imprinting disorders increases with the identification of new regions in which parentally imprinted genes are located. Imprinting disorders are caused by genomic pathogenic variants affecting imprinted genes, as well as by aberrant imprinting marks (epimutations) in the patients themselves. Additionally, maternal effect mutations have recently been identified that trigger secondary epimutations in the offspring. These maternal effect mutations explain not only imprinting disorders in their children, but also recurrent reproductive failure in the families. This review aims to provide an overview of the recent findings in 13 well-known imprinting disorders relating to clinical diagnosis, management and counseling.

Development and validation of a mobile application for point of care evaluation of growth failure

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Riddhi V. Patel ◽  
Anurag T. Bajpai ◽  
Hemangkumar V. Mendpara ◽  
Chetankumar C. Dave ◽  
Sajili S. Mehta ◽  
...  
Keyword(s):  
Standard Deviation ◽  
Short Stature ◽  
Clinical Diagnosis ◽  
Mobile Application ◽  
Point Of Care ◽  
Standard Deviation Score ◽  
Operating Characteristics ◽  
Deviation Score ◽  
Work Up ◽  
Care Evaluation

Abstract Objectives Lack of systematic evaluation of short stature results in unnecessary work-up on one hand while missing pathology on the other. We have developed a mobile application that guides work-up based on age, auxology (height, BMI, and corrected standard deviation score), and skeletal maturation with an aim of reducing the diagnostic errors. Aim of this study is to develop and validate a mobile application for point of care evaluation of short stature. Methods The application was developed (n=400) and validated (n=412) on children and adolescents (2–18 years of age) presenting to our Pediatric Endocrinology Clinic with short stature. Height standard deviation score thresholds determining the need for workup were derived from Receiver Operating Characteristics (ROC) curve. Student’s t-test and ROC curves were used to identify the most appropriate parameter differentiating constitutional delay of growth and puberty (CDGP) from pathological and nutritional from endocrine causes. The validation of the application involved comparing the application predicted and clinical diagnosis at each step of the algorithm. Results The mobile application diagnosis was concordant with clinical diagnosis in 408 (99.0%) with discordance in four (two with CDGP labeled as growth hormone deficiency [GHD] and two with GHD labeled as CDGP). Conclusions Mobile application guided short stature assessment has a high concordance with the clinical diagnosis and is expected to help point of care short stature evaluation.

scholarly journals The prevalence and volumetry of pituitary cysts in children with growth hormone deficiency and idiopathic short stature

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Nicholas Krasnow ◽  
Bradley Pogostin ◽  
James Haigney ◽  
Brittany Groh ◽  
Winston Weiler ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Short Stature ◽  
Growth Failure ◽  
Brain Magnetic Resonance Imaging ◽  
Idiopathic Short Stature ◽  
Hormone Deficiency ◽  
Gh Treatment ◽  
Cyst Volume ◽  
Pituitary Cysts

AbstractBackgroundPituitary cysts have been speculated to cause endocrinopathies. We sought to describe the prevalence and volumetry of pituitary cysts in patients with growth hormone deficiency (GHD) and idiopathic short stature (ISS).MethodsSix hundred and eighteen children evaluated for growth failure at the Division of Pediatric Endocrinology at New York Medical College between the years 2002 and 2012, who underwent GH stimulation testing and had a brain magnetic resonance imaging (MRI) prior to initiating GH treatment were randomly selected to be a part of this study. High resolution MRI was used to evaluate the pituitary gland for size and the presence of a cyst. Cyst prevalence, cyst volume and percentage of the gland occupied by the cyst (POGO) were documented.ResultsFifty-six patients had a cyst, giving an overall prevalence of 9.1%. The prevalence of cysts in GHD patients compared to ISS patients was not significant (13.5% vs. 5.7%, p=0.46). Mean cyst volume was greater in GHD patients than ISS patients (62.0 mm3vs. 29.4 mm3, p=0.01). POGO for GHD patients was significantly greater (p=0.003) than for ISS patients (15.3%±12.8 vs. 7.1%±8.0). Observers were blinded to patient groups.ConclusionsGHD patients had a significantly greater volume and POGO compared to ISS patients. This raises the question of whether cysts are implicated in the pathology of growth failure.

Management of Puberty for Optimal Auxological Results in β-Thalassaemia Major

2001 ◽  
Vol 14 (s2) ◽  
Author(s):  
Manuela Caruso-Nicoletti ◽  
V. De Sanctis ◽  
L. Cavallo ◽  
G. Raiola ◽  
L. Ruggiero ◽  
...  
Keyword(s):  
Short Stature ◽  
Final Height ◽  
Growth Failure ◽  
Normal Growth ◽  
Growth Spurt ◽  
Endocrine Disorders ◽  
Thalassaemia Major ◽  
Pubertal Growth Spurt ◽  
Pubertal Growth ◽  
Height Gain

AbstractShort stature is present in a significant percentage of patients affected by β-thalassaemia major. Growth failure of patients with thalassaemia is multifactorial. The most important contribution is attributed to the toxic effect desferrioxamine and to endocrine disorders, due to iron overload. The commonest endocrine complication is hypogonadism. The growth pat- tern of patients with thalassaemia is characterized by normal growth during childhood, a deceleration of growth velocity around age 9-10 years, and a reduced pubertal growth spurt. In addition, reduced growth of the trunk is often present. Short stature and short trunk are more evident at pubertal age. Hypogonadism is usually considered responsible for the pubertal growth failure, as well as the aggravation of body disproportion at pubertal age. However, data suggest that pubertal height gain and final height are reduced in both patients with spontaneous puberty and patients with induced puberty. It is concluded that several aspects of peripubertal growth in patients with thalassaemia remain to be clarified.

scholarly journals Once-Weekly Administration of Sustained-Release Growth Hormone in Korean Prepubertal Children with Idiopathic Short Stature: A Randomized, Controlled Phase II Study

2018 ◽  
Vol 90 (1) ◽  
pp. 54-63 ◽  
Author(s):  
Jin Soon Hwang ◽  
Hae Sang Lee ◽  
Kee-Hyoung Lee ◽  
Han-Wook Yoo ◽  
Dae-Yeol Lee ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Sustained Release ◽  
Short Stature ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Recombinant Human Growth Hormone ◽  
Standard Deviation Score ◽  
Idiopathic Short Stature ◽  
Height Velocity ◽  
Prepubertal Children

Background/Aims: To determine the optimal dose of LB03002, a sustained-release, once-weekly formulation of recombinant human growth hormone (rhGH), and to compare its efficacy and safety with daily rhGH in children with idiopathic short stature (ISS). Methods: This multicenter, randomized, open-label, phase II study included GH-naïve, prepubertal children with ISS, randomized to receive daily rhGH 0.37 mg/kg/week (control, n = 16), LB03002 0.5 mg/kg/week (n = 14), or LB03002 0.7 mg/kg/week (n = 16). The primary endpoint was height velocity (HV) change at week 26. Results: At week 26, the least square (LS) means for HV change (cm/year) with control, LB03002 0.5 mg/kg/week, and LB03002 0.7 mg/kg/week were 5.08, 3.65, and 4.38, and the LS means for the change in height standard deviation score were 0.65, 0.49, and 0.58, respectively. The lower bound of the 90% confidence interval for the difference between LB03002 0.7 mg/kg/week and the control in the LS mean for HV change (–1.72) satisfied the noninferiority margin (–1.75). Adverse events were generally mild and short-lived. Conclusion: A once-weekly regimen of LB03002 0.7 mg/kg demonstrated noninferiority to the daily regimen of rhGH 0.37 mg/kg/week in terms of HV increments. LB03002 was well tolerated and its safety profile was comparable with that of daily rhGH.

scholarly journals Growth Restriction and Genomic Imprinting-Overlapping Phenotypes Support the Concept of an Imprinting Network

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 585
Author(s):  
Thomas Eggermann ◽  
Justin H. Davies ◽  
Maithé Tauber ◽  
Erica van den Akker ◽  
Anita Hokken-Koelega ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Personalised Medicine ◽  
Human Growth ◽  
Postnatal Growth ◽  
Paternal Allele ◽  
Diagnostic Tools ◽  
Imprinted Genes ◽  
Imprinting Disorders ◽  
Molecular Alterations ◽  
Maternal Resources

Intrauterine and postnatal growth disturbances are major clinical features of imprinting disorders, a molecularly defined group of congenital syndromes caused by molecular alterations affecting parentally imprinted genes. These genes are expressed monoallelically and in a parent-of-origin manner, and they have an impact on human growth and development. In fact, several genes with an exclusive expression from the paternal allele have been shown to promote foetal growth, whereas maternally expressed genes suppress it. The evolution of this correlation might be explained by the different interests of the maternal and paternal genomes, aiming for the conservation of maternal resources for multiple offspring versus extracting maximal maternal resources. Since not all imprinted genes in higher mammals show the same imprinting pattern in different species, the findings from animal models are not always transferable to human. Therefore, human imprinting disorders might serve as models to understand the complex regulation and interaction of imprinted loci. This knowledge is a prerequisite for the development of precise diagnostic tools and therapeutic strategies for patients affected by imprinting disorders. In this review we will specifically overview the current knowledge on imprinting disorders associated with growth retardation, and its increasing relevance in a personalised medicine direction and the need for a multidisciplinary therapeutic approach.

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