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Growth disorders resulting in extreme short stature (ESS) are often a result of deficiency in growth hormone (GH) released from the pituitary gland or a defective GH releasing receptor. Genetic defects in the GH1 and GHRHR genes account for around 11.1-20% of ESS cases, resulting in a rare condition called isolated GH deficiency (IGHD). We describe the characterization of a GH1 genetic defect discovered in a 3-year-old male patient with ESS, developmental failure and undetectable serum levels of GH. There was a family history of short stature, with both parents being short. Whole genome sequencing of the patient DNA revealed a large, novel 6 kb homozygous deletion spanning the entire GH1 gene in the patient. While the deletion was homozygous in the proband, it was present in the heterozygous state in the parents. Thus, we report a novel homozygous deletion including the GH1 gene leading to IGHD-type 1A associated with ESS.

Growth disorders resulting in extreme short stature (ESS) are often a result of deficiency in growth hormone (GH) released from the pituitary gland or a defective GH releasing receptor. Genetic defects in the GH1 and GHRHR genes account for around 11.1-20% of ESS cases, resulting in a rare condition called isolated GH deficiency (IGHD). We describe the characterization of a GH1 genetic defect discovered in a 3-year-old male patient with ESS, developmental failure and undetectable serum levels of GH. There was a family history of short stature, with both parents being short. Whole genome sequencing of the patient DNA revealed a large, novel 6 kb homozygous deletion spanning the entire GH1 gene in the patient. While the deletion was homozygous in the proband, it was present in the heterozygous state in the parents. Thus, we report a novel homozygous deletion including the GH1 gene leading to IGHD-type 1A associated with ESS. [ABSTRACT FROM AUTHOR]

Familial short stature (FSS) describes vertically transmitted growth disorders. Traditionally, polygenic inheritance is presumed, but monogenic inheritance seems to occur more frequently than expected. Clinical predictors of monogenic FSS have not been elucidated. The aim of the study was to identify the monogenic etiology and its clinical predictors in FSS children. Of 747 patients treated with growth hormone (GH) in our center, 95 with FSS met the inclusion criteria (pretreatment height ≤−2 SD in child and his/her shorter parent); secondary short stature and Turner/Prader–Willi syndrome were excluded criteria. Genetic etiology was known in 11/95 children before the study, remaining 84 were examined by next-generation sequencing. The results were evaluated by American College of Medical Genetics and Genomics (ACMG) guidelines. Nonparametric tests evaluated differences between monogenic and non-monogenic FSS, an ROC curve estimated quantitative cutoffs for the predictors. Monogenic FSS was confirmed in 36/95 (38%) children. Of these, 29 (81%) carried a causative genetic variant affecting the growth p late, 4 (11%) a variant affecting GH–insulin-like growth factor 1 (IGF1) axis and 3 (8%) a variant in miscellaneous genes. Lower shorter parent’s height (P = 0.015) and less delayed bone age (BA) before GH treatment (P = 0.026) predicted monogenic FSS. In children with BA delayed less than 0.4 years and with shorter parent’s heights ≤−2.4 SD, monogenic FSS was revealed in 13/16 (81%) cases. To conclude, in FSS children treated with GH, a monogenic etiology is frequent, and gene variants affecting the growth plate are the most common. Shorter parent’s height and BA are clinical predictors of monogenic FSS .

The ACAN gene encodes aggrecan, a proteoglycan with important roles in the extracellular matrix of the cartilage tissue. Mutations in this gene are associated with familial and idiopathic short stature, as well as some more severe chondrodysplasias. The variable phenotypic presentations of the ACAN gene mutations are collectively known as aggrecanopathies. The short stature is commonly associated with advanced bone age. We present the first case in our country of ACAN-gene mutation in a girl with familial short stature born small for gestational age. Growth delay was noted after the first year of life but growth velocity declined progressively after 3 years of age. On physical examination some phenotypic features are revealed broad forehead, midfacial hypoplasia, short and broad distal phalanges of the thumbs. The laboratory and imaging studies revealed no abnormalities. Genetic test was performed which proved a mutation in the ACAN gene inherited from the patient’s father. Detailed family history revealed paternal relatives with short stature. The pedigree chart was characteristic of autosomal dominant inheritance pattern. The patient was offered growth hormone treatment but the family refused. [ABSTRACT FROM AUTHOR]

Idiopathic short stature is a common reason for referral to the general paediatric or endocrine clinic. It can negatively impact the quality of life for the child and young person, extending into adulthood for some. However, these children are healthy individuals and treatment is not usually indicated. Whilst those with constitutional delay in growth and puberty can be given hormonal supplementation to induce puberty, there is no treatment available in the UK for the remaining children and young people as growth hormone is not approved for idiopathic short stature. It is important to emphasise to the child, young person and family that they are following a normal pattern of growth to reduce the perception that there is a problem. Growth charts plotted with bone age and a target range for family size are useful for predicting adult height and managing patient and parental expectations. [ABSTRACT FROM AUTHOR]

Introduction: Familial Short stature is considered one of the most common causes of Short Stature along with the constitutional delay in growth and puberty (CDGP) from which it can easily be distinguish. The core parameters of anthropometry represent diagnostic criteria for obesity and other non-communicable diseases. To measure the anthropometric parameters in the patients with idiopathic clinically non-syndromic familial short-stature and to correlate those parameters with their height and compare them with the control group. Material and Methods: A cross-sectional study was conducted among Familial Short Stature females of 5-18 years age group referred from Paediatric and Genetic OPD of AIIMS, Rishkesh. Non-parametric tests were applied for comparing the variables and correlation coefficients were obtained. Results: There was a significant difference between the groups in terms of Standing Height (cm) (W = 376.000, P = <0.001), BMI (Kg/m2) (W = 1128.500, P = 0.002), with the median BMI (Kg/m2) and Waist/Height Ratio (W = 1164.500, P = <0.001), with the median Waist/Height Ratio being highest in the Short-Stature group. There was moderate to strong positive correlation between standing height and other anthropometric parameters. The mean waist to height ratio of 0.6 among short stature and 0.5 among the control group, with short stature having more odds of getting overweight and also shows a greater predilection of short-stature group for developing Cardio-vascular diseases. Discussion and Conclusion: Familial short stature though being a manifestation of some underlying cause, can fall in a non-syndromic group until further studies including karyotyping, next-generation sequencing etc. Extensive research for appropriate categorization and how this can effectively help combat the burden of malnutrition and non-communicable diseases should be done. [ABSTRACT FROM AUTHOR]

Abstract Objective To verify the prevalence of novel definitions of familial short stature on a cross-sectional cohort of children referred for short stature when their height and that of both parents were measured. Methods We consecutively enrolled 65 individuals referred for short stature when both parents were present. We defined “target height-related short stature” (TH-SS) when child’s height is ≤ − 2 SDS and included in the range of target height; suspected “autosomal dominant short stature” (AD-SS) when child height and at least one parent height are ≤ − 2 SDS; “constitutional familial short stature” (C-FSS) when a child with TH-SS does not have any parents with height ≤ − 2 SDS. Results Of 65 children referred for SS, 48 individuals had a height ≤ − 2 SDS. Based on the parents’ measured heights, 24 children had TH-SS, 16 subjects AD-SS, and 12 individuals C-FSS. If we had considered only the parents’ reported height, 3 of 24 children with TH-SS, 9 of 16 with AD-SS, and 10 of 12 with C-FSS would have been lost. Conclusion We suggest novel definitions to adequately detect and approach the cases of FSS since C-FSS (25%) might not need any specific investigation, while on the contrary, AD-SS (33%) should undergo genetic evaluation. Moreover, this study underlines that adequate measurement and consideration of children’s and parents’ heights (individually and together) are crucial in the clinical evaluation of every child with short stature.

Context: The delayed growth of a child is a major cause of concern for the parents. There is a multitude of etiological factors which must be considered in relation to this common aspect of healthcare. Aim: The study was done to evaluate the etiological profile of short stature in children and adolescents. Settings and Design: The cross-sectional study was conducted for 12 months including 111 cases of short stature (out of the 1,058 cases screened), at the endocrinology outpatient department (OPD) of a tertiary care institute in Haryana. Subjects and Methods: As per the inclusion criteria, cases with age

ObjectiveACAN gene variants are an important cause of familial short stature (FSS). Appropriate growth-promoting therapies effectively improve the patient height. Here, we report a therapeutic assessment of cases of seven families of FSS patients with heterozygous ACAN variants. Our findings provide a valuable theoretical basis for the clinical diagnosis and treatment of this disease.MethodsFrom December 2020 to June 2021, 32 FSS patients were examined in Tianjin Medical University General Hospital (Tianjin, China) by whole-exome sequencing to determine whether ACAN variants were present. Their clinical data were summarized and scrupulously analyzed.ResultsWe found seven novel heterozygous ACAN variants: c.1051 + 2T > A, c.313T > C (p.S105P), c.2660C > G (p.S887X), c.2153C > A (p. T718K), c.7243delG (p.D2415Tfs*4), c.2911G > T (p.G971X), c.758-7T > C. All seven patients had proportionate short stature and mild skeletal dysplasia. Endocrine examination results were normal. Only one of the patients had an advanced bone age (1.1 years older than chronological age), whereas the other patients had normal bone ages. All of them had a family history of short stature, with or without osteoarthritis or intervertebral disc disease. All seven patients accepted treatment with recombinant human growth hormone (rhGH) and were regularly followed up. One patient did not come at the follow-up visit. The height of the remaining six patients before and after the treatment was −2.89 ± 0.68 SDS, −1.91 ± 0.93 SDS, respectively, with a treatment course of 1.85 ± 1.91 years. A good therapeutic response was observed in all of them.ConclusionsIn this study, seven novel heterozygous variants in ACAN were discovered, which expanded the spectrum of the already established ACAN pathogenic variants. In FSS cohort, the proportion of ACAN variants accounted was large. The treatment with rhGH effectively increased the patient height, but further studies with longer follow-up periods and more extensive observations are required to elucidate the long-term effect.

NPR2 variants are associated with various short stature and bone dysplasia, such as acromesomelic dysplasia Maroteaux tyoe, individuals with a phenotype similar to Léri–Weill syndrome (LWD), and idiopathic short stature (ISS). However, few studies have reported on the relationship between familial short stature (FSS) and NPR2 variants. This study aimed to explore the relationship between FSS and NPR2 variants through the detection and identification of NPR2 variants in children with FSS, phenotypic description, clear treatment plan, and follow-up of treatment effect. Children who met the FSS diagnostic criteria and had informed consent were included in the study. The trio whole-exome sequencing method (trio-WES) was used to detect and evaluate the NPR2 variants. A total of 16 children with short stature were included in this study (pretreatment height ≤ −2 standard deviation (SD) in both the patient and the shorter parent, unknown genetic etiology). NPR2 variants were identified in 12.5%(2/16) of the participants. Patient A was a 6-year-old male and 103.7 cm tall (−3.11SD), while Patient B was a 9-year-old female and 123.2 cm tall (−1.88SD). However, their heights increased after recombinant human growth hormone (rhGH) treatment. The height of patient A increased by 0.36SD six months after treatment while that of patient B increased by 1.22SD after one and a half years of treatment. NPR2 variant causes FSS. The growth rate of children significantly improved after rhGH treatment. However, further follow-up study is needed to determine the final height after long-term treatment. [ABSTRACT FROM AUTHOR]

Introduction Midparental height (MPH) can be used as a crude prediction of the child's adult height. Familial short stature (FSS) is a condition in which the final adult height achieved is less than the third percentile for the patient's age, sex, and population. Nevertheless, it is consistent with parental height in the absence of nutritional, hormonal, acquired, genetic, and iatrogenic causes. The rationale for treating childhood short stature includes increasing height and alleviating psychosocial disability while maintaining favorable risk/benefit and cost/benefit ratios. Selection among management options may therefore depend on the degree to which each meets these goals. Inappropriately, ascribing a child's extreme shortness to relatively short parents could thus result in delayed investigations or failure to appreciate the seriousness of a child's situation. Aim The aim of this study is to evaluate the response to growth hormone (GH) therapy when the decision of treatment was made based on their relation to MPH whether FSS or much shorter than their MPH standard deviation score (SDS). Patients and methods This is a retrospective study; we studied the auxologic data of 21 children with FSS [height SDS (HtSDS) <-2, MPHSDS <-2 SD] and 14 children who were not short [HtSDS >-2, but =1 SD shorter than their MPHSDS who were treated with recombinant GH (somatropin/norditropin] 0.03-0.05 mg/kg/day daily for more than 1 year, and the dose was adjusted to keep the insulin-like growth factor-1 (IGF-1) level in the upper quartile of normal for age. Results In the FSS group, after an average of 3.27 years on GH treatment, the HtSDS increased by 0.92 SD, and IGF-1 SD increased by 2.87 SD. Difference between the HtSDS and MPHSDS improved significantly from -0.18 to 0.74 SD. In the other group, after GH therapy the HtSDS increased by 0.5 and IGFSDS increased by 3.24 SD. Difference between the HtSDS and MPHSDS improved significantly from -1.26 to -0.72 SD. However, the HtSDS was still more than 0.5 or more lower than the MPHSDS. In both groups, the HtSDS gain was positively correlated with the duration of GH therapy (r=0.52, P=0.01) and negatively correlated with the age at the start of treatment (r=-0.34, P=0.01) and the pretreatment IGF-1 level (r=-0.37, P=0.04). Conclusion GH therapy improved HtSDS even to exceed MPHSDS in children with FSS. Children with normal stature while far below MPHSDS had their HtSDS improved with GH therapy while did not reach their MPHSDS. The duration and age at the start of GH therapy are important parameters for the favorable outcome. MPHSDS is an important parameter in GH therapy decision. [ABSTRACT FROM AUTHOR]

This retrospective study aimed to clarify the characteristics of bone maturation using longitudinal data in short-stature prepubertal children. Children with chronological ages (CAs) of 4.5-10.5 yr with nonfamilial idiopathic short stature (ISS, n = 95), familial ISS (FSS, n = 21), and short-stature children born small for gestational age (SGA, n = 23) were selected, of which 435 left-hand plain radiographic images were evaluated. Bone age (BA) delay was defined as BA minus CA. In the ISS group, there was a statistically significant difference in median BA delay among the CA groups (P < 0.001), as median BA delay gradually increased from 5- to 9-yr-old groups (-1.06 [range, -2.17 to 0.27] and -2.45 [range, -4.35 to -0.32] yr, respectively). In the FSS group, median BA delays were approximately -1 yr in all CA groups. In the SGA group, median BA delay gradually decreased from 7- to 10-yr-old groups (-1.96 [range, -2.99 to 0.56] and -0.04 [range, -2.44 to 0.92] yr, respectively), but with no significant difference (P = 0.647). The heavier weight of children with FSS and the probable earlier onset of adrenarche in children born SGA compared to those with ISS could have affected bone maturation. [ABSTRACT FROM AUTHOR]

Objectives: The objective of my study was to determine the frequency of familial short height in children aged 3 to 14 years with short height. Study Design: Descriptive study. Setting: Department of Pediatric Endocrinology at The Children Hospital & Institute of Child health Multan (CH& ICH). Period: November 2018 to October 2019. Material & Methods: Eighty four patients were enrolled after taking informed consent from parents/guardians. Heights of all patients, parental heights, mid parental heights were plotted on CDC growth charts. Patients having familial short stature were noted down. Results: Out of 84 patients, 59 (70.2%) were males and 25 (29.85%) were females. Age range was 3-14 years. Mean age of the population was 8.68 ± 3.42 years and mean height and weight were 114.29 ± 24.62cm and 28.95±10.01 kg, respectively. Mean height for mother and father of the patients were 154.39 ±4.56cm and 171.10 ± 3.52cm, respectively. Out of 84 children, 21 (25%) patients had FSS. In our study population FSS was more seen in children < 8 years of age, female gender and families with income of > 20K/months with p value of 0.879, 0.129 and 0.592 respectively. Conclusion: Majority of children presenting with short stature have FSS and CDG and do not have an endocrine disorder. In our study, frequency of familial short stature in children aged 3 to 14 years was 25%. The results should be validated in multicenter studies. [ABSTRACT FROM AUTHOR]

Context: Collagens are the most abundant proteins in the human body. In a growth plate, collagen types II, IX, X, and XI are present. Defects in collagen genes cause heterogeneous syndromic disorders frequently associated with short stature. Less is known about oligosymptomatic collagenopathies.Objective: This work aims to evaluate the frequency of collagenopathies in familial short stature (FSS) children and to describe their phenotype, including growth hormone (GH) treatment response.Methods: Eighty-seven FSS children (pretreatment height ≤ -2 SD both in the patient and his or her shorter parent) treated with GH were included in the study. Next-generation sequencing was performed to search for variants in the COL2A1, COL9A1, COL9A2, COL9A3, COL10A1, COL11A1, and COL11A2 genes. The results were evaluated using American College of Medical Genetics and Genomics guidelines. The GH treatment response of affected children was retrospectively evaluated.Results: A likely pathogenic variant in the collagen gene was found in 10 of 87 (11.5%) children. Detailed examination described mild asymmetry with shorter limbs and mild bone dysplasia signs in 2 of 10 and 4 of 10 affected children, respectively. Their growth velocity improved from a median of 5.3 cm/year to 8.7 cm/year after 1 year of treatment. Their height improved from a median of -3.1 SD to -2.6 SD and to -2.2 SD after 1 and 3 years of therapy, respectively. The final height reached by 4 of 10 children differed by -0.67 to +1.0 SD and -0.45 to +0.5 SD compared to their pretreatment height and their affected untreated parent's height, respectively.Conclusion: Oligosymptomatic collagenopathies are a frequent cause of FSS. The short-term response to GH treatment is promising. [ABSTRACT FROM AUTHOR]

Abstract Background Genetic factors, dysregulation in the endocrine system, cytokine and paracrine factors are implicated in the pathogenesis of familial short stature (FSS). Nowadays, the treatment choice for FSS is limited, with only recombinant human growth hormone (rhGH) being available. Methods Herein, starting from the identification of 122 genetic loci related to FSS, we adopted a genetic-driven drug discovery bioinformatics pipeline based on functional annotation to prioritize crucial biological FSS-related genes. These genes were suggested to be potential targets for therapeutics. Results We discovered five druggable subnetworks, which contained seven FSS-related genes and 17 druggable targerts. Conclusions This study provides a valuable drug repositioning accompanied by corresponding targetable gene clusters for FSS therapy.

Context: The delayed growth of a child is a major cause of concern for the parents. There is a multitude of etiological factors which must be considered in relation to this common aspect of healthcare. Aim: The study was done to evaluate the etiological profile of short stature in children and adolescents. Settings and Design: The cross-sectional study was conducted for 12 months including 111 cases of short stature (out of the 1,058 cases screened), at the endocrinology outpatient department (OPD) of a tertiary care institute in Haryana. Subjects and Methods: As per the inclusion criteria, cases with age <18 years were enrolled. The examination and anthropometric measurements were performed in the presence of parents/guardians. Results: Out of the 1,058 cases screened; 111 cases of short stature were recruited as per the inclusion and exclusion criteria. The prevalence was about 10.49% of the total population. The mean age of the sample was 12.34 ± 3.19 years. The endocrine causes were the most common followed by normal variants of growth and delay, chronic systemic illness, and nutritional and skeletal causes. Among the endocrine causes, hypothyroidism was the most common followed by growth hormone deficiency and type 1 diabetes mellitus (T1DM). Conclusions: The mean chronological age of 12.34 ± 3.19 years suggests the delayed detection of short stature in the population. This highlights the importance of educating parents so that timely therapeutic intervention can be done to achieve the potential height. [ABSTRACT FROM AUTHOR]

Objective: To verify the prevalence of novel definitions of familial short stature on a cross-sectional cohort of children referred for short stature when their height and that of both parents were measured. Methods: We consecutively enrolled 65 individuals referred for short stature when both parents were present. We defined "target height-related short stature" (TH-SS) when child's height is ≤ − 2 SDS and included in the range of target height; suspected "autosomal dominant short stature" (AD-SS) when child height and at least one parent height are ≤ − 2 SDS; "constitutional familial short stature" (C-FSS) when a child with TH-SS does not have any parents with height ≤ − 2 SDS. Results: Of 65 children referred for SS, 48 individuals had a height ≤ − 2 SDS. Based on the parents' measured heights, 24 children had TH-SS, 16 subjects AD-SS, and 12 individuals C-FSS. If we had considered only the parents' reported height, 3 of 24 children with TH-SS, 9 of 16 with AD-SS, and 10 of 12 with C-FSS would have been lost. Conclusion: We suggest novel definitions to adequately detect and approach the cases of FSS since C-FSS (25%) might not need any specific investigation, while on the contrary, AD-SS (33%) should undergo genetic evaluation. Moreover, this study underlines that adequate measurement and consideration of children's and parents' heights (individually and together) are crucial in the clinical evaluation of every child with short stature. [ABSTRACT FROM AUTHOR]

Background and Objectives: Height growth is one of the indicators of health level in a society that affect children'shealth. This study aimed to determine the prevalence of short stature and some related factors in 6-year-old childrenin Rafsanjan. Materials and Methods: In this cross-sectional study, 521 children aged 6 years referring to health centers ofRafsanjan in 2018, were studied by cluster random sampling. Demographic characteristics and anthropometricvariables for children and their parents were collected and their short stature was studied based on the stansards ofCDC (Centers for disease control and prevention). In short children serum levels of electrolytes, thyroid hormones,growth hormone, and 25-Hydroxy vitamin D3 were measured and bone age determination was performed. Data wereanalyzed using chi-square test, independent t-test and Pearson's correlation coefficient. Results: The prevalence of short stature was 4% (21 children) with 95% confidence interval 1.3% to 6.7%. Eleven(52.4%) were boy. The main cause of short stature in 52.4% of children (11 cases) was genetic. One case had growthhormone deficiency (4.8%) and one had hypothyroidism (4.8%). No cause for short stature was found for 38% ofcases (8 cases). There was a significant positive correlation between child height and father's height (r=0.361;p<0.001) and mother's height (r=0.269; p<0.001) Conclusion: In this study, the main cause of short stature in children was genetic causes. Knowing the causes ofshort stature is necessary to take timely action to correct this defect. [ABSTRACT FROM AUTHOR]

Familial short stature (FSS) describes vertically transmitted growth disorders. Traditionally, polygenic inheritance is presumed, but monogenic inheritance seems to occur more frequently than expected. Clinical predictors of monogenic FSS have not been elucidated. The aim of the study was to identify the monogenic etiology and its clinical predictors in FSS children. Of 747 patients treated with growth hormone (GH) in our center, 95 with FSS met the inclusion criteria (pretreatment height ≤-2 SD in child and his/her shorter parent); secondary short stature and Turner/Prader-Willi syndrome were excluded criteria. Genetic etiology was known in 11/95 children before the study, remaining 84 were examined by next-generation sequencing. The results were evaluated by American College of Medical Genetics and Genomics (ACMG) guidelines. Nonparametric tests evaluated differences between monogenic and non-monogenic FSS, an ROC curve estimated quantitative cutoffs for the predictors. Monogenic FSS was confirmed in 36/95 (38%) children. Of these, 29 (81%) carried a causative genetic variant affecting the growth plate, 4 (11%) a variant affecting GH-insulin-like growth factor 1 (IGF1) axis and 3 (8%) a variant in miscellaneous genes. Lower shorter parent's height (P = 0.015) and less delayed bone age (BA) before GH treatment (P = 0.026) predicted monogenic FSS. In children with BA delayed less than 0.4 years and with shorter parent's heights ≤-2.4 SD, monogenic FSS was revealed in 13/16 (81%) cases. To conclude, in FSS children treated with GH, a monogenic etiology is frequent, and gene variants affecting the growth plate are the most common. Shorter parent's height and BA are clinical predictors of monogenic FSS.

Background: Our objectives were to evaluate the etiology of short stature, assess the prevalence of idiopathic short stature (ISS) and assess the growth hormone (GH)-insulin-like growth factor (IGF) axis in children with ISS. Methods: A stepwise diagnostic evaluation was done in 394 children aged 4–16 years with short stature. Children with no definitive etiology were labeled as ISS. In these children, baseline IGF-1, IGF binding protein-3 (IGFBP-3) and stimulated IGF-1 after administration of GH for 4 days were measured. Results: Hypothyroidism (in 18.1%) and ISS (in 15.5%) were the commonest causes of short stature. In children with ISS (n=61), the mean baseline and stimulated IGF-1 standard deviation scores (SDSs) were −1.2±1.0 and −0.3±1.4, respectively, with levels below −2 SDS in 13 (21%) and six (10%) children, respectively. In 33 (54%) of the ISS patients, response to GH was suboptimal (increment in the IGF-1 level <40%). There was no difference in the mean peak GH, IGFBP-3 and baseline and stimulated IGF-1 levels between children with familial and non-familial ISS. A significant positive correlation of height SDS with baseline IGF-1 SDS (r=0.28, p=0.026), stimulated IGF-1 SDS (r=0.32, p=0.010) and ΔIGF-1 SDS (r=0.26, p=0.036) was observed in children with ISS. Conclusions: Hypothyroidism and ISS were the commonest etiologies for short stature. The baseline IGF-1 was below −2 SDS in 21% and the increment after GH stimulation was suboptimal in 54% of children, indicating that a substantial proportion of children with ISS had an impaired GH-IGF axis. [ABSTRACT FROM AUTHOR]

Familial short stature (FSS) is characterised by body height lower than -2 SD if compared with mean height for age, sex and background population, that occurs in two or more subsequent generations. Although the cause for FSS remains not clarified in many individual cases, it may result from autosomal dominantly inherited growth plate disorders. The spectrum of clinical features of growth plate disorders ranges from very mildly expressed forms with proportional short stature up to potentially lethal severe skeletal dysplasia with limb deformities. Growth plate disorders include subgroups according to underlying mechanisms at molecular level - impaired paracrine signalisation, defects of cartilaginous extracellular matrix, or defective fundamental intracellular functions. FGFR3or NPR2 gene mutations lead to impaired paracrine signalisation. The defects of cartilaginous extracellular matrix include mutations in genes ACAN, FNB1 or in genes encoding individual types collagen (e.g. COL2A1). Heterozygous mutations of SHOX gene cause 2-15 % of idiopathic short stature. Clarification of specific diagnosis allows a more precise estimation of final body height, for targeted follow-up with regard to potential complications, for appropriate management and relevant genetic counselling. Team collaboration of paediatric endocrinologist, anthropologist, radiologist and genetician is helpful for both diagnosis and management of affected children. [ABSTRACT FROM AUTHOR]

Objective. Short stature can be caused by a great variety of congenital and acquired conditions, some of which present with additional symptoms and signs. Overall, the number of patients seeking medical attention for short stature may be considered as the tip of the iceberg. The objective of this study was to determine the pattern and etiological factors of short stature in children. Methodology. A cross-sectional study was carried out in the Department of Endocrinology at a tertiary care health center in north India from August 2012 to June 2015. Four hundred and fifty one children (280 boys and 171 girls), ranging from 4 to 18 years presenting with short stature were studied. Anthropometric measurements were plotted on Indian standard growth charts. Results. In this study, the male to female ratio was found to be 1.6:1, with mean chronological age of 11.6+3.2 years, and mean bone age of 7.8+2.8 years. The common etiologic factors in the order of frequency were constitutional delay in growth and puberty (41.2%), familial short stature (15.9%), type 1 diabetes mellitus (9.9%), and hypothyroidism (8.6%) while growth hormone deficiency (2.4%) was a relatively uncommon cause. The most common pathological cause for proportionate short stature was type 1 diabetes and for disproportionate short stature was hypothyroidism. Hypothyroidism caused the maximum retardation of bone age while the least bone age retardation was noticed in familial short stature. Conclusion. Physiological/normal variants outnumbered the pathological causes of short stature. Endocrinological causes were found in almost one fourth of children with short stature; however, growth hormone deficiency was found in only 2.4% of the children.

Childhood short stature comprises Varity of endocrinal, systemic, Skeletal & genetic disorders of pediatrics and is not just confined for endocrinal disorder only. A systemic approach often reduces the need for test which is often expensive &unnecessary. Use growth chart & asses bone age during evaluation. Short & heavy child are generally due to Endocrine causes, Short & thin are due to systemic disease, Short with normal velocity are may be due to Constitutional delay in growth &puberty or Familial short stature, differentiation can be done by Bone Age. In Girls Turner syndrome has to be kept in mind. Purpose of evaluation to find out the child who does not need treatment, who cannot be treated & the child who can be benefited from treatment.

Background: Familial short stature (FSS) and constitutional delay of growth (CDG) are the most frequent norm variants in children presenting with short stature. Knowing the growth patterns of these entities in the first years of life might be helpful to distinguish them from growth hormone deficiency (GHD) or other chronic diseases. Methods: We studied the height in the first 5 years of life in 26 children with FSS, in 38 children with CDG and in 14 children with idiopathic GHD. Results: Height standard deviation scores (SDS) did not change between birth and 6 months of life, while height SDS decreased significantly afterwards in GHD, FSS, and CDG. The loss of height SDS was higher in the first 2 years of life than between 2 and 5 years of life in children with CDG (-0.92 vs. -0.11; p = 0.003) or FSS (-0.79 vs. -0.01; p = 0.002). In idiopathic GHD, the loss of height SDS did not differ between the first 2 years of life and the next 3 years (-0.78 vs. -0.77; p = 0.821). Conclusion: Children with FSS and CDG showed a decline in height SDS mainly in the first 2 years of life, whereas the height SDS of children with idiopathic GHD decreased almost continuously over the first 5 years of life. [ABSTRACT FROM AUTHOR]

Failure to thrive in a child is defined as 'lack of expected normal physical growth' or 'failure to gain weight'. Diagnosis requires repeated growth measurements over time using local, age-appropriate growth centile charts. Premature babies with appropriate growth velocity and children with 'catch-down' growth, constitutional growth delay or familial short stature show normal growth variants, and usually do not require further evaluation. In Singapore, the most common cause of failure to thrive in children is malnutrition secondary to psychosocial and caregiver factors. 'Picky eating' is common in the local setting and best managed with an authoritative feeding style from caregivers. Other causes are malabsorption and existing congenital or chronic medical conditions. Child neglect or abuse should always be ruled out. Iron deficiency is the most common complication. The family doctor plays a pivotal role in early detection, timely treatment, appropriate referrals and close monitoring of 'catch-up' growth in these children. [ABSTRACT FROM AUTHOR]

Aim: To investigate whether there is a change in bone turnover-related biochemical markers and bone mineral density of children with constitutional delay of growth and puberty (CDGP) in the prepubertal period. Methods: We measured serum calcium, phosphorus, alkaline phosphatase, parathormone, 25-OH vitamin D, osteocalcin, osteoprotogerin and urinary deoxypyridinoline levels (D-pyd), and bone mineral density (BMD) in 31 prepubertal boys with CDGP. These children were compared with 22 prepubertal boys with familial short stature (FSS) and 27 normal prepubertal boys. Results: Urinary D-pyd was significantly high in CDGP group as compared to control group (p=0.010). Volumetric BMD did not significantly differ between CDGP, FSS, and control groups (p=0.450). Volumetric BMD and urinary D-pyd levels of FSS and control groups were similar. Mean or median levels of calcium, phosphorus, alkaline phosphatase, parathormone, and osteoprotegerin did not significantly differ between CDGP, FSS, and control groups. Conclusions: Our data suggest that prepubertal boys with CDPG have normal bone turnover. However, their significantly higher urinary D-pyd levels relative to those of FSS and control groups might be an indicator of later development of osteoporosis. Therefore, long-term follow-up studies monitoring bone mineral status of prepubertal boys with CDPG from prepuberty to adulthood are needed to better understand bone metabolism of these patients. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency of etiological factors in short statured patients presenting at endocrine clinic of National Institute of Child Health, Karachi. Methods: This descriptive cross sectional study was conducted at Endocrine clinic of National Institute of Child Health, Karachi. One hundred children (48 boys and 52 girls) aged 3-15 years (mean 9.9±3.4) with short stature from January 2007 to July 2007 were evaluated during that period. Results: Constitutional growth delay (CGD) and familial short stature (FSS) were identified as the most common, 55% of all short stature cases. Non-endocrinal causes as a single entity was detected in 17 children. Most common etiological factors in order of frequency were normal variant of growth (CGD, FSS), Hypothyroidism, Growth Hormone deficiency (GHD), and Celiac disease. GHD was found in 13% of total cases and it comprises 44% among endocrinal causes. Boys outnumbered girls with ratio of 2.7:1 (p < 0.05). Conclusion: Most common cause of short stature was normal variants of growth as a group. Children with height falling below 0.4th percentile are more likely to have pathological cause. [ABSTRACT FROM AUTHOR]

BACKGROUND/OBJECTIVES: In 2001, a chart review of children referred to the authors' endocrine clinic because of short stature revealed that many were referred with insufficient baseline data, had normal height velocity and were within genetic target height. Therefore, a two-way fax communication system was implemented between referring physicians and the authors' service before the first visit. Aspects that were assessed included whether this system increased the information accompanying the patient at referral, resulted in children with nonpathological shortness not being seen in the clinic, and was used differently by paediatricians and general practitioners. STUDY DESIGN: Between January and December 2006, 138 referrals for short stature, diagnosed with familial short stature, constitutional delay or idiopathic short stature, were audited (69 with and 69 without previous fax communication). Data collected included source of referral, clinical information provided, available growth measurements, and results from laboratory and imaging studies. RESULTS: Fax communication resulted in growth curves being provided more often (95.6% of cases versus 40.5% of cases without fax communication [P<0.001]) and more investigations being performed by the referring physician (median [range]: six [zero to 13] investigations versus one [zero to 11]; P<0.001), as well as a diagnosis of nonpathological short stature being given to 31 children based on the growth curve, laboratory and imaging results, without the children being seen in the endocrine clinic. Fax communication was also used more frequently by paediatricians (84%) than by general practitioners (15%). CONCLUSION: The fax communication system resulted in a more complete evaluation of referred patients by their physicians and reduced the number of unnecessary visits to the authors' specialty clinic while promoting medical education. [ABSTRACT FROM AUTHOR]