scholarly journals ACAN Gene Mutations in Short Children Born SGA and Response to Growth Hormone Treatment

2016 ◽  
Vol 102 (5) ◽  
pp. 1458-1467 ◽  
Author(s):  
Manouk van der Steen ◽  
Rolph Pfundt ◽  
Stephan J.W.H. Maas ◽  
Willie M. Bakker-van Waarde ◽  
Roelof J. Odink ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Gene Mutation ◽  
Gene Mutations ◽  
Bone Age ◽  
Hormone Treatment ◽  
Gh Treatment ◽  
Midface Hypoplasia ◽  
Short Children ◽  
Hormone Analog

Abstract Background: Some children born small for gestational age (SGA) show advanced bone age (BA) maturation during growth hormone (GH) treatment. ACAN gene mutations have been described in children with short stature and advanced BA. Objective: To determine the presence of ACAN gene mutations in short SGA children with advanced BA and assess the response to GH treatment. Methods: BA assessment in 290 GH-treated SGA children. ACAN sequencing in 29 children with advanced BA ≥0.5 years compared with calendar age. Results: Four of 29 SGA children with advanced BA had an ACAN gene mutation (13.8%). Mutations were related to additional characteristics: midface hypoplasia (P = 0.003), joint problems (P = 0.010), and broad great toes (P = 0.003). Children with one or fewer additional characteristic had no mutation. Of children with two additional characteristics, 50% had a mutation. Of children with three additional characteristics, 100% had a mutation. All GH-treated children with a mutation received gonadotropin-releasing hormone analog (GnRHa) treatment for 2 years from onset of puberty. At adult height, one girl was 5 cm taller than her mother and one boy was 8 cm taller than his father with the same ACAN gene mutation. Conclusion: This study expands the differential diagnosis of genetic variants in children born SGA and proposes a clinical scoring system for identifying subjects most likely to have an ACAN gene mutation. ACAN sequencing should be considered in children born SGA with persistent short stature, advanced BA, and midface hypoplasia, joint problems, or broad great toes. Our findings suggest that children with an ACAN gene mutation benefit from GH treatment with 2 years of GnRHa.

Efficacy of long-term growth hormone therapy in short non-growth hormone-deficient children

2017 ◽  
Vol 30 (2) ◽  
Author(s):  
Lucia Schena ◽  
Cristina Meazza ◽  
Sara Pagani ◽  
Valeria Paganelli ◽  
Elena Bozzola ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Final Height ◽  
Standard Deviation Score ◽  
Bone Age ◽  
Gh Treatment ◽  
Short Children ◽  
Igf I ◽  
Height Gain ◽  
The Cost

AbstractBackground:In recent years, several studies have been published showing different responses to growth hormone (GH) treatment in idiopathic short stature children. The aim of the present study was to investigate whether non-growth-hormone-deficient (non-GHD) short children could benefit from long-term GH treatment as GHD patients.Methods:We enrolled 22 prepubertal children and 22 age- and sex-matched GHD patients, with comparable height, body mass index (BMI), bone age, and insulin-like growth factor 1 (IGF-I) circulating levels. The patients were treated with recombinant human GH (rhGH) and followed until they reach adult height.Results:During GH treatment, the two groups grew in parallel, reaching the same final height-standard deviation score (SDS) and the same height gain. On the contrary, we found significantly lower IGF-I serum concentrations in non-GHD patients than in GHD ones, at the end of therapy (p=0.0055).Conclusions:In our study, the response to GH treatment in short non-GHD patients proved to be similar to that in GHD ones. However, a careful selection of short non-GHD children to be treated with GH would better justify the cost of long-term GH therapy.

scholarly journals Delayed Bone Age Might Accelerate the Response to Human Growth Hormone Treatment in Small for Gestational Age Children with Short Stature

2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
Jung-Eun Moon ◽  
Cheol Woo Ko
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Human Growth ◽  
Bone Age ◽  
Pediatric Endocrinology ◽  
Gh Therapy ◽  
Gh Treatment ◽  
The Impact

Purpose. Growth hormone (GH) treatment is recommended to improve growth and psychosocial problems in short stature children born small for gestational age (SGA). Although GH therapy in these patients has been extensively studied, the impact of therapy according to delays in bone age (BA) is not known well. Objective. To investigate the effects of GH therapy in SGA patients with short stature according to BA delay. Methods. We retrospectively analyzed changes in height SD score (SDS) and BA/chronological age (CA) after 6 and 12 months of GH therapy in patients grouped according to BA delay. We studied 27 SGA children with short stature in the pediatric endocrinology clinic of Kyungpook National University Children’s Hospital. Results. Of the 27 patients, 9 had <2 years of BA delay, while 18 had >2 years of delay. There were no significant differences between the two groups in terms of gestational age and weight at birth, height SDS, IGF-1 SDS, and growth hormone dosage at the beginning of therapy. However, height SDS increased significantly in the group with >2 years of BA delay after 6 months of GH therapy (−2.50 ± 0.61 vs −1.87 ± 0.82; p=0.037) and 12 months (−2.27 ± 0.70 vs −1.63 ± 0.65; p=0.002). When height SDS was compared between with and without GHD, there were no significant differences. Conclusions. Delayed BA (>2 years) may impact the response to GH treatment in SGA children with short stature.

scholarly journals A high proportion of novel ACAN mutations and their prevalence in a large cohort of Chinese short stature children

2021 ◽  
Author(s):  
Li Lin ◽  
Mengting Li ◽  
Jingsi Luo ◽  
Pin Li ◽  
Shasha Zhou ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Family History ◽  
Short Stature ◽  
Bone Age ◽  
Hormone Treatment ◽  
Pathogenic Variants ◽  
Common Causes ◽  
History Of ◽  
The Common ◽  
Next Generation Sequencing Ngs

Abstract Context Aggrecan, encoded by ACAN gene, is the main proteoglycan component in the extracellular cartilage matrix. Heterozygous mutations in ACAN have been reported to cause idiopathic short stature. However, the prevalence of ACAN pathogenic variants in Chinese short stature patients and clinical phenotypes remain to be evaluated. Objective We sought to determine the prevalence of ACAN pathogenic variants among Chinese short stature children and characterize the phenotypic spectrum and their responses to growth hormone (GH) therapies. Patients and Methods Over 1000 unrelated short stature patients ascertained across China were genetically evaluated by Next-generation sequencing (NGS)-based test. Result We identified 10 novel likely pathogenic variants and 2 recurrent pathogenic variants in this cohort. None of ACAN mutation carriers exhibited significant dysmorphic features or skeletal abnormities. The prevalence of ACAN defect is estimated to be 1.2% in the whole cohort, it increased to 14.3% among those with advanced bone age and to 35.7% among those with both advanced bone age and family history of short stature. Nonetheless, five out of eleven ACAN mutation carries had no advanced bone age. Two individuals received growth hormone therapy with variable levels of height SDS improvement. Conclusion Our data suggested that ACAN mutation is one of the common causes of Chinese pediatric short stature. Although it has a higher detection rate among short stature patients with advanced bone age and family history, part of affected probands presented with delayed bone age in Chinese short stature population. The growth hormone treatment was moderately effective for both individuals.

Growth Hormone Treatment for Short Stature in the USA, Germany and France: 15 Years of Surveillance in the Genetics and Neuroendocrinology of Short-Stature International Study (GeNeSIS)

2018 ◽  
Vol 90 (3) ◽  
pp. 169-180 ◽  
Author(s):  
Roland Pfäffle ◽  
Christof Land ◽  
Eckhard Schönau ◽  
Paul-Martin Holterhus ◽  
Judith L. Ross ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Standard Deviation Score ◽  
Measurement Data ◽  
International Study ◽  
Hormone Treatment ◽  
Height Velocity ◽  
Growth Disorders ◽  
Gh Treatment ◽  
The Usa

Background/Aims: To describe characteristics, auxological outcomes and safety in paediatric patients with growth disorders treated with growth hormone (GH), for cohorts from the USA, Germany and France enrolled in GeNeSIS, a post-authorisation surveillance programme. Methods: Diagnosis and biochemical measurement data were based on reporting from, and GH treatment was initiated at the discretion of, treating physicians. Auxological outcomes during the first 4 years of GH treatment and at near-adult height (NAH) were analysed. Serious and treatment-emergent adverse events were described. Results: Children in the USA (n = 9,810), Germany (n = 2,682) and France (n = 1,667) received GH (dose varied between countries), most commonly for GH deficiency. Across diagnostic groups and countries, mean height velocity standard deviation score (SDS) was > 0 and height SDS increased from baseline during the first 4 years of treatment, with greatest improvements during year 1. Most children achieved NAH within the normal range (height SDS >−2). No new or unexpected safety concerns were noted. Conclusion: GH treatment improved growth indices to a similar extent for patients in all three countries despite variations in GH doses. Data from these three countries, which together contributed > 60% of patients to GeNeSIS, indicated no new safety signals and the benefit-risk profile of GH remains unchanged.

scholarly journals First report on growth hormone treatment response in a patient with spondylodysplastic type of Ehlers-Danlos syndrome with normal growth hormone secretion

2021 ◽  
Vol 50 (1) ◽  
pp. 47-56
Author(s):  
Katarina Božić ◽  
Tatjana Milenković ◽  
Srđan Pašić ◽  
Katarina Mitrović ◽  
Slađana Todorović ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Case Report ◽  
Short Stature ◽  
Treatment Response ◽  
Growth Hormone Treatment ◽  
Hormone Treatment ◽  
Gh Treatment ◽  
Ehlers Danlos Syndrome ◽  
Gh Secretion ◽  
First Case

Introduction/Aim: Spondylodysplastic Ehlers-Danlos Syndrome (sdEDS) is a rare genetic disorder of collagen synthesis, caused by a mutation in the B4GALT7, B3GALT6, or SLC39A13 gene. Features of this very rare disorder are short stature, hypotonia, hyperflexible joints, soft, thin, and overly stretchable skin, sparse hair and eyebrows, elderly face, wide forehead and prolonged wound healing. Molecular genetic analysis is needed for definite confirmation of the diagnosis. So far, only three case reports describing growth hormone treatment response in patients with sdEDS have been published. All of these patients had growth hormone (GH) deficiency. We present the first case report regarding growth hormone treatment response in a patient with sdEDS and normal GH secretion (without GH deficiency). Case report: Patient was a girl with short stature and normal GH secretion. Having in mind that the girl was born small for the gestational age, due to her short stature, she started using HR, before the diagnosis of sdEDS was made. Based on the lack of improvement in growth velocity as well as the girl's phenotype, genetic analyses were performed and the diagnosis of sdEDS due to biallelic mutations of the B4GALT7 gene was established. After the diagnosis of sdEDS was made and due to suboptimal response in growth velocity to the GH treatment, the GH therapy was stopped at the age of 11 years. Conclusion: This is a first case report regarding GH treatment in a child with sdEDS and normal GH secretion, demonstrating a very limited therapeutic effect of GH on linear growth in the presented patient.

scholarly journals Racial/Ethnic Disparities in US Pediatric Growth Hormone Treatment

2018 ◽  
Vol 90 (2) ◽  
pp. 102-108 ◽  
Author(s):  
Adda Grimberg ◽  
Anders Lindberg ◽  
Michael Wajnrajch ◽  
Andrew J. Cucchiara ◽  
Cecilia Camacho-Hübner
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Census Data ◽  
Treatment Initiation ◽  
Ethnic Disparities ◽  
Hormone Treatment ◽  
Gh Treatment ◽  
Male Predominance ◽  
Relative Risks ◽  
Racial Ethnic

Background/Aims: To compare racial/ethnic proportions of subjects receiving growth hormone (GH) treatment to the expected proportions, and secondarily, to assess racial/ethnic differences in subject characteristics at GH treatment initiation. Methods: Race/ethnicity-based expected frequencies of height <–2.25 SD were determined by applying relative risks for short stature, calculated from a regional population of 189,280 pediatric primary care patients, to US census data, and compared to racial/ethnic proportions of US subjects enrolled in the Pfizer International Growth Study (KIGS) using the χ2 test. Characteristics of white and black subjects at GH treatment initiation were presented as medians and compared by the Wilcoxon rank sum test (significant p < 0.01). Results: White subjects exceeded the expected frequency (63%) for all indications (83%) and each separately, ranging from 73% for congenital GH deficiency (GHD) to 85% for idiopathic short stature (p < 0.001). Compared to white subjects, black subjects treated for idiopathic GHD had greater height deficits relative both to the population (–2.97 vs. –2.56 SD) and to their mid-parental heights (–2.47 vs. –1.89 SD), lower stimulated GH peak levels (4.9 vs. 6.0 ng/mL), and lower birth weights (–0.86 vs. –0.48 SD). Black subjects with congenital GHD had lower stimulated GH peaks (2.1 vs. 3.2 ng/mL) and started GH treatment at younger ages (2.9 vs. 4.8 years), while those with acquired GHD had lower birth weights (–1.12 vs. –0.08 SD). Male predominance did not differ by race for any or all indications. Conclusion: Overrepresentation of white children among those receiving GH treatment in the US KIGS registry reflects racial/ethnic treatment biases, not just differences in growth rates.

scholarly journals Mortality in Children Receiving Growth Hormone Treatment of Growth Disorders: Data From the Genetics and Neuroendocrinology of Short Stature International Study

2017 ◽  
Vol 102 (9) ◽  
pp. 3195-3205 ◽  
Author(s):  
Charmian A Quigley ◽  
Christopher J Child ◽  
Alan G Zimmermann ◽  
Ron G Rosenfeld ◽  
Leslie L Robison ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Turner Syndrome ◽  
International Study ◽  
Hormone Treatment ◽  
Idiopathic Short Stature ◽  
Growth Disorders ◽  
Gh Treatment ◽  
Increased Risk ◽  
History Of

Abstract Context Although pediatric growth hormone (GH) treatment is generally considered safe for approved indications, concerns have been raised regarding potential for increased risk of mortality in adults treated with GH during childhood. Objective To assess mortality in children receiving GH. Design Prospective, multinational, observational study. Setting Eight hundred twenty-seven study sites in 30 countries. Patients Children with growth disorders. Interventions GH treatment during childhood. Main Outcome Measure Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) using age- and sex-specific rates from the general population. Results Among 9504 GH-treated patients followed for ≥4 years (67,163 person-years of follow-up), 42 deaths were reported (SMR, 0.77; 95% CI, 0.56 to 1.05). SMR was significantly elevated in patients with history of malignant neoplasia (6.97; 95% CI, 3.81 to 11.69) and borderline elevated for those with other serious non–GH-deficient conditions (2.47; 95% CI, 0.99-5.09). SMRs were not elevated for children with history of benign neoplasia (1.44; 95% CI, 0.17 to 5.20), idiopathic GHD (0.11; 95% CI, 0.02 to 0.33), idiopathic short stature (0.20; 95% CI, 0.01 to 1.10), short stature associated with small for gestational age (SGA) birth (0.66; 95% CI, 0.08 to 2.37), Turner syndrome (0.51; 95% CI, 0.06 to 1.83), or short stature homeobox-containing (SHOX) gene deficiency (0.83; 95% CI, 0.02 to 4.65). Conclusions No significant increases in mortality were observed for GH-treated children with idiopathic GHD, idiopathic short stature, born SGA, Turner syndrome, SHOX deficiency, or history of benign neoplasia. Mortality was elevated for children with prior malignancy and those with underlying serious non–GH-deficient medical conditions.

scholarly journals SAT-109 Utilizing Pituitary Volume (PV) and the Growth Hormone Stimulation Test (GHST) to Jointly Define the Etiology of Short Stature (SS): An Improved Diagnostic Criteria for Growth Hormone Treatment

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Tara Prasanna Patale ◽  
Liam McGuirk ◽  
Nicholas Andrew Krasnow ◽  
Alice Alexandrov ◽  
Tavia Buysse ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Hormone Treatment ◽  
Roc Curve Analysis ◽  
Poor Growth ◽  
Short Children ◽  
Number Of Patients ◽  
The Mean ◽  
The Difference ◽  
Normal Controls

Abstract Background: We have previously shown that short children have significantly reduced PVs. In this study, we further define the etiology of SS in a larger cohort of siblings (SBs). Objective: To further investigate the efficacy of PV as an indicator of poor growth. Patients and Methods:Methods: The database of a peds endo center was queried for SBs aged 6–18 yrs who underwent a GHST and subsequent MRI between 2013–19. Their MRI results were compared to randomly selected normal controls (NCs) aged 6–18 yrs seen at a neuroradiology center between 2010–16. Patients with MRI abnormalities were excluded. PVs were calculated using the ellipsoid formula (LxWxH/2). Our previous ROC curve analysis has defined 215.02mm3 and 315.00mm3 as cutoffs for small PVs in prepubertal and pubertal (PB) SBs, respectively (RSP). Growth hormone levels &lt;10 ng/ml or &gt;10 ng/ml diagnosed patients as growth hormone deficient (GHD) or idiopathic short stature (ISS), RSP. Patients: 77 SBs of 37 families were compared to 170 NCs. SBs &lt;11 yrs and &gt;11 yrs were considered pre-PB and PB, RSP. Results: The mean (MN) and median (MD) ages of SBs were 11.6 ± 2.2 and 11.9 yrs, RSP, and the MN and MD ages of the NCs were 12.6 ± 3.4 and 13.2 yrs, RSP. The difference (DIF) in MN age was significant (SG) (p&lt;0.05). The pre-PB SBs and pre-PB NCs had MN and MD ages of 9.3 ± 1.2 and 9.7 yrs, RSP and 8.6 ± 1.4 and 8.6 yrs, RSP. The DIF in MN pre-PB age was SG (p&lt;0.05). The PB SBs and PB NCs had MN and MD ages of 13.0 ± 1.4 and 12.7 yrs, RSP and 14.7 ± 1.9 and 14.6 yrs, RSP. The DIF in MN PB age was not SG (p&lt;0.05). The MN and MD PVs for SBs (n=77) were 220.1 ± 94.0 and 204mm3, RSP. The MN and MD PVs for NCs (n=170) were 364.0 ± 145.2 and 346.0mm3, RSP. The DIF in MN PVs was SG (p &lt;0.001). Stratified by age, the MN and MD PVs for SBs ages 6–11 yrs (n=29) were 166.1 ± 46.8 and 160mm3, RSP, and the MN and MD PVs for NCs ages 6–11 yrs (n=58) were 246.8 ± 63.7 and 241.6mm3, RSP. The DIF in MN PV was SG (p &lt;0.001). The MN and MD PVs for SBs &gt;11 yrs (n=48) were 252.7 ± 100.5 and 227mm3, RSP and the MN and MD PVs for NCs &gt;11 yrs (n=112) were 424.6 ± 138.4 and 403.3mm3, RSP. The DIF in MN PV was SG (p &lt;0.001). 86% of pre-PB SBs had small PVs, while 93% were GHD. 79% of PB SBs had small PVs, while 79% of PB SBs were GHD. 81.8% of all SBs had small PVs, while 84.4% were GHD. When combined, GHST and PV identify the etiology for SS in 96.1% of subjects. Discussion: The GHST recognized the etiology for SS in 84.4% of the SBs, while PV identified 81.8%. Using both criteria together, the etiology for SS was identified in 96.1% of the SBs. 3 of the 4 pre-PB SBs, who did not meet the PV cutoff had PVs within 10% of the cutoff. Conclusion: We have shown that PV is not inferior to the GHST in the diagnosis of SS. Combining the GHST and PV defines the etiology of SS in 96.1% of patients. Jointly, the GHST and PV should be considered the new gold standard for identifying children who qualify for GH therapy. This criteria will significantly diminish the number of patients diagnosed with ISS.

Successful treatment of short stature with growth hormone replacement therapy in a patient with anorexia nervosa

2015 ◽  
Vol 29 (4) ◽  
Author(s):  
Yuji Koike ◽  
Masaya Akibayashi ◽  
Yukako Yokouchi
Keyword(s):  
Growth Hormone ◽  
Anorexia Nervosa ◽  
Replacement Therapy ◽  
Short Stature ◽  
Hormone Replacement ◽  
Bone Age ◽  
Delayed Puberty ◽  
Primary Amenorrhea ◽  
Gh Treatment ◽  
Igf I

Abstract A 19-year-old woman visited our outpatient clinic requesting treatment for short stature. She had been repeatedly hospitalized at a psychiatric unit and was subsequently diagnosed with anorexia nervosa (AN). She was 139.3 cm (–3.6 SD) tall and weighed 25.5 kg (23% lower than standard weight). She had primary amenorrhea and her bone age (BA) was 11.8 years. She had low insulin-like growth factor (IGF)-I (80 ng/mL) and a basal growth hormone (GH) level of 1.47 ng/mL. Treatment with recombinant GH was initiated. At 22 years of age, she was 152.2 cm (–1.1 SD) tall and weighed 39.7 kg. As she had shown a favorable response to GH treatment, therapy was discontinued. We suggest that it is worthwhile treating AN patients with GH replacement therapy for short stature, once low IGF-I levels without GH resistance, delayed puberty, delay in BA, and nutritional stabilization are taken into consideration.

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