Statural Growth Research Articles

Successful Anesthetic Management for Mandibular Neoplasm Resection in a Patient with Osteogenesis Imperfecta: A Case Report

Background: Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by bone fragility and deformities. Patients with mandibular neoplasms and suspected OI require careful anesthetic management to avoid complications. This case report describes the successful anesthetic management of a patient with a mandibular neoplasm and suspected OI. Case presentation: A 33-year-old man presented with a large mandibular tumor causing airway obstruction and difficulty eating. He had physical features suggestive of OI, including short stature, bone deformities, and abnormal tooth growth. Preoperative evaluation revealed a difficult airway due to the tumor and potential cervical spine instability. Anesthesia was induced with propofol and atracurium after securing the airway via ultrasound-guided tracheostomy under local anesthesia. The tumor was resected successfully, and the patient recovered without complications. Conclusion: Anesthetic management in patients with suspected OI and mandibular neoplasms requires careful planning and execution. A multidisciplinary approach, including preoperative evaluation, airway management strategies, and close postoperative monitoring, is crucial for successful outcomes.

Associations between growth, maturation and injury in youth athletes engaged in elite pathways: a scoping review

ObjectiveTo describe the evidence pertaining to associations between growth, maturation and injury in elite youth athletes.DesignScoping review.Data sourcesElectronic databases (SPORTDiscus, Embase, PubMed, MEDLINE and Web of Science) searched on 30...

Retrospective study on the diagnosis, treatment, and follow-up of 85 cases of hypophosphatemic rickets in children

To study the diagnosis, treatment, and complications of hypophosphatemic rickets (HR) in children, explore effectiveness evaluation indicators for the disease, and understand the pattern in height growth among these patients. A retrospective analysis of the initial clinical data and five-year follow-up data of 85 children with HR treated at Children's Hospital of Nanjing Medical University from January 2008 to December 2022. Among the 85 children with HR, there were 46 males (54%) and 39 females (46%). The age at initial diagnosis ranged from 6 months to 13 years and 9 months, with a median age of 2.75 years. The average height standard deviation score was -2.0±1.1. At initial diagnosis, children exhibited reduced blood phosphate levels and elevated alkaline phosphatase (ALP), with 99% (84/85) presenting with lower limb deformities. The positive rate for PHEX gene mutations was 93% (55/59). One year post-treatment, there was a significant reduction in ALP levels and the gap between the lower limbs (P<0.05). The fastest height growth occurred in the first year after treatment, at 8.23 cm/year, with a peak height velocity (PHV) phase lasting about two years during puberty. The height increased by 9-20 cm in male children during the PHV stage and 10-15 cm in female children. Major complications included nephrocalcinosis and hyperparathyroidism. The incidence rate of nephrocalcinosis in the first year after treatment was 55% (22/40), which increased with the duration of the disease (P<0.001); an increased urinary phosphate/creatinine ratio was positively associated with a higher risk of nephrocalcinosis (OR=1.740, P<0.001). The incidence of hyperparathyroidism in the first year after treatment was 64% (27/42). For children presenting with lower limb deformities, short stature, and slow growth, early testing for blood levels of phosphate, calcium, and ALP, along with imaging examinations of the lower limbs, can aid in the early diagnosis of HR. Genetic testing may be utilized for definitive confirmation when necessary. ALP combined with improvements in skeletal deformities and annual height growth can serve as indicators of therapeutic effectiveness for HR. Compared to normal children, children with HR demonstrate a lower height increase during the PHV phase, necessitating close follow-up and timely adjustment of treatment plans Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(7): 677-682.

Care pathways in childhood neurodevelopmental disorders: Toward greater awareness of KBG syndrome among pediatricians

IntroductionKBG syndrome is an autosomal dominant, polymalformative genetic syndrome that is mainly associated with neurodevelopmental and learning disorders, intellectual disability, behavioral disorders, and epilepsy as well as characteristic dysmorphic features, short stature, and ENT (ear, nose, and throat) abnormalities. However, the diagnostic pathway of these individuals is an element that has not been broadly evaluated. The main aim of this study was therefore to characterize the diagnostic pathway for these individuals, by assessing the different healthcare professionals involved and the main referral elements. MethodThis was a multicenter, retrospective, descriptive study. A cohort of 30 individuals with KBG syndrome who were followed up at Poitiers University Hospital and Bordeaux University Hospital we recruited. ResultsPediatricians were the main healthcare professionals who referred individuals for genetic consultation, and the main reason for referral was an assessment of learning delays or intellectual disability, in association with other abnormalities. ConclusionPediatricians play a crucial role in the diagnostic guidance of individuals with KBG syndrome, and the main reason for referral remains the assessment of a learning delay or intellectual disability. Healthcare professionals must therefore remain attentive to the child's development and the various anomalies associated with it, in particular characteristic dysmorphic features, behavioral disorders, and statural growth.

Clinical utility of comprehensive gene panel testing for common and rare causes of skeletal dysplasia and other skeletal disorders: Results from the largest cohort to date.

Molecular genetics enables more precise diagnoses of skeletal dysplasia and other skeletal disorders (SDs). We investigated the clinical utility of multigene panel testing for 5011 unrelated individuals with SD in the United States (December 2019-April 2022). Median (range) age was 8 (0-90) years, 70.5% had short stature and/or disproportionate growth, 27.4% had a positive molecular diagnosis (MDx), and 30 individuals received two MDx. Genes most commonly contributing to MDx were FGFR3 (16.9%), ALPL (13.0%), and COL1A1 (10.3%). Most of the 112 genes associated with ≥1 MDx were primarily involved in signal transduction (n = 35), metabolism (n = 23), or extracellular matrix organization (n = 17). There were implications associated with specific care/treatment options for 84.4% (1158/1372) of MDx-positive individuals; >50% were linked to conditions with targeted therapy approved or in clinical development, including osteogenesis imperfecta, achondroplasia, hypophosphatasia, and mucopolysaccharidosis. Forty individuals with initially inconclusive results became MDx-positive following family testing. Follow-up mucopolysaccharidosis enzyme activity testing was positive in 14 individuals (10 of these were not MDx-positive). Our findings showed that inclusion of metabolic genes associated with SD increased the clinical utility of a gene panel and confirmed that integrated use of comprehensive gene panel testing with orthogonal testing reduced the burden of inconclusive results.

Longitudinal Meta-Analysis of Peak Height Velocity in Young Female Athletes.

Growth patterns and biological milestones in youth sports are key to interpreting the development of young athletes. However, there is no analysis of longitudinal meta-analysis describing the growth of young female athletes. This longitudinal meta-analysis estimated growth curves and age at peak height velocity (PHV) in young female athletes based on anthropometric data from longitudinal studies found in the literature. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, studies with repeated measurements in young female athletes were identified from searches of four databases (MEDLINE, Web of Science, SCOPUS, and SPORTDiscus) without date restrictions through August 2023. We adapted our bias assessment criteria using the Cochrane risk of bias tool for randomized controlled trials as a reference. Bayesian multilevel modeling was used to perform a longitudinal meta-analysis to extract stature growth curves and age at PHV. Fourteen studies met our eligibility criteria. Twenty-one independent samples could be included in the analysis. Conditional on the data and models, the predicted mean age at PHV for female athletes was 11.18 years (90% CI: 8.62; 12.94). When studies were aggregated by sport in the models, the models could not capture sport-specific growth curves for stature and estimate a corresponding age at PHV. We provide the first longitudinal meta-analytic summary of pubertal growth and derive age at PHV in young female athletes. The meta-analysis predicted that age at PHV occurs at similar ages to those in the general pediatric population. The data pool was limited in sports and geographic distribution, emphasizing the need to promote longitudinal research in females across different youth sports contexts.

Are There Sensitive Periods for Skill Development in Male Adolescent Basketball Players?

Although spurts in physical capacities during adolescence are well known, little is known about the existence of such spurts in sport-specific skill development, especially during the period of rapid growth in stature. Our aims were to examine the timing, intensity, and sequence of basketball-specific skill spurts aligned with biological (years from peak height velocity (PHV)) rather than chronological age. We then defined putative sensitive periods (windows of optimal development) for each skill aligned to the adolescent growth spurt. Altogether, 160 adolescent male basketballers aged 11-15 yr were tested biannually over 3 consecutive years. The years from attainment of PHV was estimated, and six skill tests were aligned to each year from PHV in 3-month intervals. Skill velocities were estimated using a nonsmooth polynomial model. Maximal gains in slalom dribble occurred 12 months before PHV attainment (intensity, 0.18 m·s -1 ·yr -1 ), whereas in speed shot shooting (intensity, 9.91 pts·yr -1 ), passing (intensity, 19.13 pts·yr -1 ), and slalom sprint (intensity, 0.19 m·s -1 ·yr -1 ), these skill spurts were attained 6 months before PHV attainment. The mean gains in control dribble (intensity, 0.10 m·s -1 ·yr -1 ) and defensive movement (intensity, 0.12 m·s -1 ·yr -1 ) peaks coincided with attainment of PHV. We identified different sized windows for optimal development for each skill. Peak spurts in skill development, for most basketball skills, were attained at the same time as PHV. The multiple peaks observed within the defined windows of optimal development suggest that there is room for skill improvement even if gains might be greater earlier rather than later in practice. Our findings highlight the need to make coaches aware of where their players are relative to the attainment of PHV because different skills appear to develop differently relative to PHV. Such knowledge may help in designing more relevant training regimes that incorporate the athlete's current growth status so that skill development can be maximized.

The effect of gastrostomy tube feeding on growth in children with chronic kidney disease and on dialysis.

Gastrostomy tube (GT) feeding is used to promote nutrition and growth in children with chronic kidney disease (CKD). We explored the relationship between gastrostomy feeding and growth parameters in children with CKD, looking specifically at the nutritional composition of feeds. Children with CKD stages 3-5 or on dialysis in a tertiary children's kidney unit were studied. Data on anthropometry, biochemistry, and nutritional composition of feeds were collected from the time of GT insertion for 3years or until transplantation. Forty children (18 female) were included. Nineteen children were on peritoneal dialysis, 8 on hemodialysis, and 13 had CKD stages 3-5. The median (interquartile range [IQR]) age at GT insertion was 1.26 (0.61-3.58) years, with 31 (77.5%) under 5years of age. The median duration of gastrostomy feeding was 5.32 (3.05-6.31) years. None received growth hormone treatment. Children showed a significant increase in weight standard deviation score (SDS) (p = 0.0005), weight-for-height SDS (p = 0.0007) and body mass index (BMI) SDS (p < 0.0001). None of the children developed obesity. Although not statistically significant, the median height-SDS increased into the normal range (from -2.29 to -1.85). Weight-SDS positively correlated with the percentage of energy requirements from feeds (p = 0.02), and the BMI-SDS correlated with the percentage of total energy intake as fat (p < 0.001). GT feeding improves weight-SDS and BMI-SDS without leading to obesity. GT feeding improved height-SDS but this did not reach statistical significance, suggesting that factors in addition to nutritional optimization need to be considered for statural growth.

Studies on the Effect of Chemical Weed Management on Growth Indices, Yield and Quality of Irrigated Chickpea (Cicer arietinum L.)

Chickpea, characterized by its short stature and slow initial growth, is highly susceptible to a wide range of weed species. The field experiment was designed during the Rabi season of 2021-22 at Agronomy Research Farm, Chaudhary Charan Singh Haryana Agricultural University, Hisar to evaluate the chemical weed management in irrigated chickpea. The experiment was laid out in a Randomised Block Design (RBD) with thirteen treatments replicated thrice. The treatments combinations areT1 (Pendimethalin 30EC @ 1000g a.i ha-1 as PPI), T2 (Imazethapyr 10EC @ 75g a.i ha-1 as PPI), T3 (Imazethapyr 10EC @ 100g a.i ha-1 as PPI), T4 (Pendimethalin 30EC + imazethapyr 2EC (RM) @ 1000g a.i ha-1 as PPI), T5 (Pendimethalin 30EC @ 1000g a.i ha-1 as PRE), T6 (Imazethapyr 10EC @ 75g a.i ha-1 as PRE), T7 (Imazethapyr 10EC @ 100g a.i ha-1 as PRE), T8 (Pendimethalin 30EC + Imazethapyr 2EC (RM) @ 1000g a.i ha-1 as PRE), T9 (Imazethapyr 10EC @ 75g a.i ha-1 as POE), T10 (Imazethapyr 10EC @ 100g a.i ha-1 as POE), T11 (Two hand hoeing at 30 &amp; 50 DAS), T12 (weed free) and T13 (weedy check). The results of this study showed that PPI and PRE application of any herbicide did not cause any phytotoxic effect on chickpea. The Ready mix (RM) herbicide applied as PPI and PRE performed better than sole PPI, PRE, and POE herbicides. Among herbicidal treatments, PPI and PRE application of pendimethalin + imazethapyr (RM) @ 1000 g a.i ha-1 gave excellent control of complex weed flora and increased the yield of chickpea significantly over the weedy check. Different weed control treatments could not bring significant variation in plant population in the initial stage but the plant population declined at maturity. The maximum plant growth attributes were observed with the application of pendimethalin + imazethapyr (RM) @ 1000 g a.i ha-1 as PRE. The POE application of imazethapyr irrespective of the dose recorded the lowest dry matter accumulation throughout the growing season of chickpea. The unchecked growth of weeds in the weedy check caused a 55.2% reduction in seed yield as compared to weed-free treatment. The maximum seed yield (1968 kg ha-1) and yield attributes of chickpea were recorded with weed-free treatment and among herbicidal treatments, maximum seed yield (1827 kg ha-1) was recorded with application of pendimethalin + imazethapyr (RM) @ 1000 g ha-1 PRE.

Changes in Resting-State Networks in Children with Growth Hormone Deficiency.

Purpose: Growth hormone deficiency (GHD) refers to the partial or complete lack of growth hormone. Short stature and slow growth are characteristic of patients with GHD. Previous neuroimaging studies have suggested that GHD may cause cognitive and behavioral impairments in patients. Resting-state networks (RSNs) are regions of the brain that exhibit synchronous activity and are closely related to our cognition and behavior. Therefore, the purpose of the current study was to explore cognitive and behavioral abnormalities in children with GHD by investigating changes in RSNs. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) data of 26 children with GHD and 15 healthy controls (HCs) were obtained. Independent component analysis was used to identify seven RSNs from rs-fMRI data. Group differences in RSNs were estimated using two-sample t-tests. Correlation analysis was employed to investigate the associations among the areas of difference and clinical measures. Results: Compared with HCs, children with GHD had significant differences in the salience network (SN), default mode network (DMN), language network (LN), and sensorimotor network (SMN). Moreover, within the SN, the functional connectivity (FC) value of the right posterior supramarginal gyrus was negatively correlated with the adrenocorticotropic hormone and the FC value of the left anterior inferior parietal gyrus was positively correlated with insulin-like growth factor 1. Conclusions: These results suggest that alterations in RSNs may account for abnormal cognition and behavior in children with GHD, such as decreased motor function, language withdrawal, anxiety, and social anxiety. These findings provide neuroimaging support for uncovering the pathophysiological mechanisms of GHD in children. Impact statement Children with growth hormone deficiency (GHD) generally experience cognitive and behavioral abnormalities. However, there are few neuroimaging studies on children with GHD. Moreover, prior research has not investigated the aberrant brain function in patients with GHD from the perspective of brain functional networks. Therefore, this study employed the independent component analysis method to investigate alterations within seven commonly observed resting-state networks due to GHD. The results showed that children with GHD had significant differences in the salience network, default mode network, language network, and sensorimotor network. This provides neuroimaging support for revealing the pathophysiological mechanisms of GHD in children.

Growth of Extremely Low Birth Weight Infants (ELBW) born at a Tertiary Hospital: Statural catch-up growth continues during the 3rd year of life

Background: Extremely low birth weight (ELBW) infants, with birth weights less than 1000 g, often experience challenges in postnatal growth. This study aimed to assess the growth patterns of ELBW infants over a 3-year period, focusing on statural catch-up growth. Methods: Anthropometric measures (z-scores) were obtained at birth, 2, 4, 6, 12, 18, 24, and 36 months for 87 ELBW infants born between September 2016 and September 2018. Their growth data was compared to WHO growth standards without adjusting for gestational age. All preterm infants received preterm formula for an average of 4-6 months. Results: ELBW infants showed significant catch-up growth in weight-for-age (WAZ) and length-for-age (LAZ) during the first two years of life, while weight-for-length (WLZ) showed an initial increase followed by a mild decline. By age 3, a substantial proportion of infants achieved normal growth parameters. Specifically, 78% had normal WAZ, 90% had normal LAZ, 87% had normal WLZ, and 91.5% had normal head circumference z-scores (HCZ). Overweight was observed in 7.4% of ELBW infants at age 3. Conclusion: ELBW infants fed preterm formula for 4-6 months demonstrated significant catch-up growth during the first 12-18 months of life, with continued catch-up in LAZ during the third year. A high percentage of these infants achieved normal growth parameters by age 3, emphasizing the effectiveness of early interventions in improving postnatal growth in ELBW infants.

Anomalies du récepteur de l’hormone de croissance hypophysaire et de son effecteur de l’axe somatotrope, l’Insulin-Like Growth Factor I

Postnatal statural growth is under the hormonal control of the somatotropic axis: hypothalamus-pituitary-liver-bone. Numerous gene abnormalities have been described, located at the hypothalamus and especially at the pituitary levels. Rarer damages are located downstream at the level of the pituitary growth hormone (GH) receptor, as in Laron's syndrome or in post-receptor signaling, Stat5b or the terminal effector of growth, the Insulin-Like Growth Factor I (IGF I). For several decades now, these severe statural growth retardations can benefit from recombinant IGF I treatment, with variable efficacy depending on the genetic abnormality.

Beyond Growth Hormone: Association of Short Stature Types and Growth Hormones With Scoliosis.

Cross-sectional and retrospective cohort study. We investigated the effect of 3 types of short stature [partial growth hormone deficiency (GHD), GHD, and idiopathic short stature (ISS)] and recombinant human growth hormone (rhGH) therapy on scoliosis. In short stature, rhGH is widely used and the concentration of growth hormone varies among types. The epidemiologic characteristics of scoliosis and the role of rhGH in scoliosis remain unclear. A cross-sectional study was conducted among 3896 patients with short stature (partial GHD, GHD, and ISS), and a 1:1 age and sex-matched control group with preexisting whole-spine radiographs. The cohort study included 2605 subjects who underwent radiography more than twice to assess scoliosis development, progression, and the need for bracing and surgery. Adjusted logistic regression was used to assess differences in the prevalence of scoliosis among patients with partial GHD, GHD, ISS, and controls. The Kaplan-Meier method was used to analyze the time course of scoliosis development and progression. Cox regression was applied to assess the independent factors related to scoliosis development and progression. Mendelian randomization analyses were also performed. Compared with controls, patients with short stature had a higher incidence of scoliosis (34.47% in partial GHD, 31.85% in GHD, 32.94% in ISS vs . 8.83% in control, P < 0.001), a higher risk of scoliosis development [hazard ratio (HR) = 1.964 in partial GHD, P < 0.001; HR = 1.881 in GHD, P = 0.001; HR = 1.706 in ISS, P = 0.001), but not a higher risk of progression, brace, or surgery. Among the 3 types of short stature, there were no differences in the incidence, development, and progression of scoliosis or the need for bracing or surgery. RhGH treatment increased the risk of scoliosis development in each short-stature group (HR = 2.673 in partial GHD, P < 0.001; HR = 1.924 in GHD, P = 0.049; HR = 1.564 in ISS, P = 0.004). Vitamin D supplementation was protective against scoliosis development (HR = 0.456 in partial GHD, P = 0.003; HR = 0.42 in GHD, P = 0.013; HR = 0.838 in ISS, P = 0.257). More attention should be paid to the spinal curve in patients with partial GHD, GHD, or ISS. For short stature treated with rhGH, the risk of scoliosis development was increased. Vitamin D supplementation may be beneficial for prevention. Level III.

Short Stature and Distinct Growth Characteristics in Angelman Syndrome

Introduction: Angelman syndrome (AS) is a rare, genetic, neurodevelopmental disorder characterized by severe impairments in speech, cognition, and motor skills accompanied by unique behaviors, distinct facial features, and high prevalence of epilepsy and sleep problems. Despite some reports of short stature among AS patients, this feature is not included in the clinical criteria defined in 2005. We investigated growth patterns among AS patients with respect to mutation type, growth periods, family history, and endocrine abnormalities. Methods: Data were collected from patients’ medical files in AS National Clinic. Mutation subtypes were divided to deletion and non-deletion. Four growth periods were defined: preschool, childhood, peak height velocity, and final height. Results: The cohort included 88 individuals (46 males), with 54 (61.4%) carrying deletion subtype. A median of 3 observations per individual produced 280 data points. Final height SDS was significantly lower compared to general population (−1.23 ± 1.26, p < 0.001), and in deletion group versus non-deletion (−1.67 ± 1.3 vs. −0.65 ± 0.96, p = 0.03). Final height SDS was significantly lower compared to height SDS in preschool period (−1.32 vs. −0.47, p = 0.007). Patient’s final height SDS was significantly lower than the parents’ (∆final-height SDS = 0.94 ± 0.99, p = 0.002). IGF1-SDS was significantly decreased compared to general population (−0.55 ± 1.61, p = 0.04), with lower values among deletion group (−0.70 ± 1.44, p = 0.01). Conclusions: AS patients demonstrate specific growth pattern with deceleration during childhood and adolescence, resulting in significantly decreased final height compared to normal population, and even lower among deletion subgroup, which could be attributed to reduced IGF1 levels. We propose adding short stature to the clinical criteria and developing adjusted growth curves for AS population.

Etiology, histology, and long-term outcome of bilateral testicular regression: a large Belgian series

Abstract STUDY QUESTION What is the long-term outcome of individuals born with bilateral testicular regression (BTR) in relation to its underlying etiology? SUMMARY ANSWER Statural growth and pubertal development are adequate with incremental doses of testosterone replacement therapy (TRT); however, penile growth is often suboptimal, especially in those with a suspected genetic etiology (i.e. heterozygous DHX37 variants) or a micropenis at birth. WHAT IS KNOWN ALREADY BTR is a rare and poorly understood condition. Although a vascular origin has been postulated, heterozygous missense variants in DHX37 have been attributed to the phenotype as well. How these various etiologies impact the clinical phenotype, gonadal histology and outcome of BTR remains unclear. STUDY DESIGN, SIZE, DURATION For this cross-sectional study, individuals with BTR were recruited in eight Belgian pediatric endocrinology departments, between December 2019 and December 2022. A physical exam was performed cross-sectionally in all 17 end-pubertal participants and a quality of care questionnaire was completed by 11 of them. Exome-based panel testing of 241 genes involved in gonadal development and spermatogenesis was performed along with a retrospective analysis of presentation and management. A centralized histological review of gonadal rests was done for 10 participants. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 35 participants (33 with male, 1 with female, and 1 with non-binary gender identity) were recruited at a mean age of 15.0 ± 5.7 years. MAIN RESULTS AND THE ROLE OF CHANCE The median age at presentation was 1.2 years [0–14 years]. Maternal gestational complications were common (38.2%), with a notably high incidence of monozygotic twin pregnancies (8.8%). Heterozygous (likely) pathogenic missense variants in DHX37 (p.Arg334Trp and p.Arg308Gln) were found in three participants. No other (likely) pathogenic variants were found. All three participants with a DHX37 variant had a microphallus at birth (leading to female sex assignment in one), while only six of the remaining 31 participants without a DHX37 variant (19.4%) had a microphallus at birth (information regarding one participant was missing). Testosterone therapy during infancy to increase penile growth was more effective in those without versus those with a DHX37 variant. The three participants with a DHX37 variant developed a male, female, and non-binary gender identity, respectively; all other participants identified as males. TRT in incremental doses had been initiated in 25 participants (median age at start was 12.4 years). Final height was within the target height range in all end-pubertal participants; however, 5 out of 11 participants (45.5%), for whom stretched penile length (SPL) was measured, had a micropenis (mean adult SPL: 9.6 ± 2.5). Of the 11 participants who completed the questionnaire, five (45.5%) reported suboptimal understanding of the goals and effects of TRT at the time of puberty induction. Furthermore, only 6 (54.5%) and 5 (45.5%) of these 11 participants indicated that they were well informed about the risks and potential side effects of TRT, respectively. Histological analysis of two participants with DHX37 variants suggested early disruption of gonadal development due to the presence of Müllerian remnants in both and undifferentiated gonadal tissue in one. In eight other analyzed participants, no gonadal remnants were found, in line with the BTR diagnosis. LIMITATIONS, REASONS FOR CAUTION The limitations of this study include the relatively small sample size (n = 35) and the few individuals with DHX37 variants (n = 3). Furthermore, data on the SPL were often missing, due to this being undocumented or refused by participants. WIDER IMPLICATIONS OF THE FINDINGS TRT provides adequate statural growth, even when initiated in late adolescence, thus providing time for physicians to explore the patients’ gender identity if needed. However, sufficient and understandable information regarding the effects and side effects of TRT is required throughout the management of these patients. SPL remains suboptimal in many individuals and could be improved by TRT during infancy to mimic the physiological mini-puberty. An environmental origin in some participants is supported by the high incidence of gestational complications (38.2%) and by the three monozygotic twin pregnancies discordant for the BTR phenotype. Individuals with a heterozygous DHX37 variant have a more severe phenotype with severely restricted penile growth until adulthood. Histological analysis confirmed DHX37 as a gonadal development, rather than a BTR-related, gene. STUDY FUNDING/COMPETING INTEREST(S) Funding was provided by the Belgian Society for Pediatric Endocrinology and Diabetology (BESPEED) and by Ghent University Hospital under the NucleUZ Grant (E.D.B.). M.C. and E.D.B. are supported by an FWO senior clinical investigator grant (1801018N and 1802220N, respectively). The authors report no conflicts of interest. TRIAL REGISTRATION NUMBER N/A.

Prevalence of refractoriness when testing growth hormone levels in children

ObjectiveLate night spontaneous growth hormone (GH) pulses may influence the pituitary GH response to provocation tests. We evaluated GH response during arginine-insulin-tolerance test (AITT) after a GH peak during a short spontaneous nocturnal profile (SSNP) in children with short stature or low growth velocity. DesignUsing SSNP and subsequent AITT, we examined 257 children 4–18 years old (138 (53.7%) males) recruited from three hospitals. Medical records were reviewed retrospectively. Refractory children were defined as a GH peak ≥7 μg/L during SSNP but no GH peak ≥7 μg/L during AITT. ResultsIn total, 201/257 children had a GH peak ≥7 μg/L at SSNP and/or AITT. Of these, 21.9% were refractory. The proportion of males (p = 0.033) and body mass index (BMI) standard deviation score (SDS) (p = 0.037) were higher in the refractory group than in children with a GH peak ≥7 μg/L during AITT. The median period between last GH peak ≥7 μg/L during SSNP and GHmax at AITT was 210 (30–390) minutes. The GHmax at AITT occurred 30 min earlier for children without a peak ≥7 μg/L during the SSNP (p = 0.004). The number of refractoriness differed somewhat between the hospitals (p = 0.025). ConclusionsMany children with short stature were refractory at testing; among them we found few clinical characteristics. Refractoriness might be influenced by some differences in procedure, but needs to be considered when evaluating GH response in children.

Views on Short Stature of Female vs Male Endocrine Pediatric Patients Undergoing Provocative Growth Hormone Testing and Their Parents

ObjectiveBoys outnumber girls in short stature evaluations and growth hormone treatment despite absence of gender differences in short stature prevalence. Family views on short stature influence medical management, but gender-based analysis of these views is lacking. This study explored endocrine patients’ and their parents’ perceptions of short stature and its impact on quality of life by patient gender. MethodsPatients aged 8 to 14 years undergoing provocative growth hormone testing and 1 parent each completed semistructured interviews. Clinical data were extracted by chart review. ResultsTwenty-four patient-parent dyads (6 female patients, 22 mothers; predominantly non-Hispanic White) participated. Six major themes emerged: (1) patients’ perceptions of their short stature were similar by gender, (2) physical experiences of short stature were similar by gender, (3) social experiences of short stature were both similar and different by gender, (4) parental perceptions of short stature as a factor limiting their child’s functionality were similar by gender, (5) concern about societal stigma related to short stature arose for both genders, and (6) patients’ perceptions of parental messaging about the import of their short stature were similar by gender. ConclusionOur data reveal more similarities than differences between genders in patient perceptions and patient and parent-reported experiences of short stature. Worry about stature-related stigma was noted for patients of both genders. Parental messaging about short stature emerged as an important area to explore further by patient gender. Our findings suggest that clinicians should be wary of making gender or stigma-based assumptions when evaluating children with short stature.

Longitudinal growth of stature in boys according to age and puberty: Prediction of adult stature from the age of 13 years.

The purpose of this study was to cross-validate and demonstrate how adult stature can be predicted in 13-year-old teenager's boys by using a new reference specific growth curve obtained from chronological age and maturity. Stature measurements of 125 boys aged from 12 to 17.5 years were obtained over a period of five consecutive years. The maturity was based on the age of peak height velocity (APHV). An assessment of secondary pubertal stages using a simplification of the Tanner stages was also carried out. We found a connection between the secondary pubertal stage and the APHV. We carried out a prediction of the adult stature of 67 teenagers aged from 160 and 164 months. Significant differences between APHV enabled us to classify the adolescents into three categories according to their biological maturity: 19% of adolescents with advanced puberty, 62% with standard puberty and 19% with delayed puberty. The mean growth curves were used to predict the adult stature of 67 individuals with a good accuracy (±3cm). The mean differences between predicted and real adult stature are -0.11 cm with 95% limits of agreement of [-3.2; + 2.8cm]. The new stature growth curves developed from age and maturation enables us to accurately track individual growth kinetics.

Long-acting PEGylated growth hormone in children with idiopathic short stature: time to reconsider our diagnostic and treatment policy?

Idiopathic short stature (ISS) is a diagnosis of exclusion, and therefore each child with short stature or slow growth referred to a paediatrician deserves a full medical history and physical examination, as well as radiological and laboratory screening tests. In patients with an increased likelihood of a genetic cause, genetic testing is indicated. Idiopathic short stature is an approved indication for recombinant human growth hormone (rhGH) in the USA but not in most other parts of the world. In a recent article published in this journal, Luo et al reported on the 1-year's results of a multicentre randomized controlled trial (n = 360) on the efficacy and safety of two dosages of long-acting PEGylated rhGH (PEG-rhGH, Jintrolong®) (0.1 or 0.2 mg/kg body weight per week, respectively) in children with ISS compared with an untreated control group. The growth response to the higher dosage was similar to reported data on daily rhGH. In this commentary, we discuss whether the recent data on genetic causes of short stature in children who initially were labelled ISS, and data on the long-term safety of daily rhGH, may influence the balance between risks and benefits of rhGH treatment in children with ISS. We further discuss the pharmacokinetic and -dynamic profile of PEG-rhGH and its potential consequences for long-term safety.

Accelerazione improvvisa dell’età ossea nel bambino prepubere. Quali le possibili cause?

George is referred at age 6 years 6 months from family pediatrician to a pediatric endocrinologist for poor statural growth and some facial dysmorphic notes. Second child of non consanguineous parents. Older sister is in good health. Father 177 cm tall, mother 161 cm, menarche 11 1/2 years. Genetic target cm 175.5 (50° pc). No major pathologies in family history. Pregnancy passed regularly, induced delivery at 39 weeks due to fetal distress; neonatal period progressed without complications. At birth kg 2650, cm 49. Head circumference unknown. According to the mother, growth in the first years of life was regular. Modest delay in psychomotor development: first words after one year, independent walking at 17 months. He is followed in Child Neuropsychiatry for “developmental delay and mild intellectual disability (IQ :63) and behavioral problems” and is undergoing psycho-motor physiotherapy treatment. He is also being followed in Broncho Pneumology for episodes of bronchial asthma and by ophthalmologists for modest strabismus. The parents report that George, seen at age 5 years and 6 months, had a stature of 101.9 cm (3° pc), a weight of 17.5 kg, and a bone age 4 years and 6 months. Given the dysmorphic facial notes, two geneticists had been consulted who did not make a diagnostic suspicion. CGH array was negative. On objective examination (6 years and 6 months), general and nutritional conditions are good, preserved limb/trunk ratio. Some modest facial dysmorphia, mild strabismus and modest delay in cognitive development are noted. Examination of the various organs and apparatuses is negative. Height 107 cm (3° pc, 10 cm below genetic target), weight 21 kg, BMI 15 (25° pc). Bone age found to be 5 1/2 years (1 year below chronological age). The pediatric endocrinologist decides to recheck statural growth at 6 to 12 months. In fact, the child is revisited at ages 8 and 4 months. The period between the two visits has progressed without any particular events. Dysmorphia persists, regular trunk/limb ratio, prepubertal genitalia. Height 123 cm (10° pc, within genetic target), weight 25 kg, BMI 16.6 (25°-50° pc), head circumference 52.5 cm (50° pc). Bone age: 10 years, almost 2 years higher than chronological age. Conclusions: stature at low limits of normal, some dysmorphic notes, modest psychomotor and cognitive delay, rapid acceleration of bone age, which at age 5 ½ years and at 6 years 6/12) 1 year lower than chronological became at 8 years 4 months almost 2 years higher resulting in worsening prognosis of final stature (see Figure 1).