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Objective: Unusual clinical course Background: Osteogenesis imperfecta (OI) is a rare genetic disease that results from mutations in type 1 collagen (COL1) or its interacting proteins. Such mutations lead to defects in bone structure, causing brittle bones, short stature, hearing loss, and dental problems, among others. The current classification system arranges OI into types according to a clinical phenotype that includes the severity of the disease and a combination of specific features, such as blue sclerae and dental abnormalities. Case Report: Here, we present a clinical report of a 3-year-old boy diagnosed with OI in utero who has been followed by our pediatric clinic postnatally. The patient was born with multiple bone fractures, a small head circumference, and blue sclerae and later had a concomitant diagnosis of dentinogenesis imperfecta (DI). Soon after birth, the patient was started on bisphosphonate and calcium/vitamin D treatment. The patient's OI type was inconclusive due to the dramatic difference between perinatal and postnatal phenotypes, the presence of blue sclerae, and the additional diagnosis of DI. The patient experienced only 1 new bone fracture postnatally, had normal anthropometric measurements except for short stature, and was healthy. Conclusions: This clinical case is unique owing to the dramatic perinatal and mild postnatal OI phenotypes. This and the unique combination of postnatal features demonstrate that classical OI typing could be inconclusive in atypical disease presentation. This case may demonstrate a new classification possibility outside the current OI nomenclature. However, the potential beneficial role of pharmacological treatment in the clinical outcome of OI cannot be excluded. [ABSTRACT FROM AUTHOR]

Background: Pituitary stalk interruption syndrome (PSIS) is a congenital disease commonly found in patients with combined pituitary hormone deficiency (CPHD). Most PSIS patients manifest growth retardation and delayed puberty. We report a rare case of PSIS with tall stature, liver cirrhosis and diabetes, possibly caused by an inactivating KCNJ11 gene mutation. Case presentation: A 37-year-old female patient initially presented with liver cirrhosis and diabetes, without any secondary sexual characteristics. Endocrine investigation indicated CPHD. Small anterior pituitary, invisible pituitary stalk and no eutopic posterior lobe hypersignal in the sella turcica viewed in magnetic resonance imaging (MRI) confirmed the diagnosis of PSIS. Despite receiving no growth hormone or sex hormone therapy, she reached a final height of 186 cm. Liver histopathology revealed nonalcoholic fatty cirrhosis. Genetic testing identified a heterozygous p. Arg301Cys mutation in the KCNJ11 gene. Conclusion: This is a rare case of PSIS with liver cirrhosis and diabetes associated with an inactivating KCNJ11 gene mutation. It's supposed that early hyperinsulinism caused by the KCNJ11 gene mutation, as well as delayed epiphyseal closure due to estrogen deficiency, contributed to the patient's exceptionally tall stature. Untreated growth hormone deficiency (GHD) resulted in increased visceral fat, leading to nonalcoholic fatty liver disease (NAFLD) and cirrhosis. The decline in b cell function with age, combined with NAFLD, may have played a role in the development of diabetes. [ABSTRACT FROM AUTHOR]

BRCA1 is involved in the Fanconi anaemia (FA) pathway, which coordinates repair of DNA interstrand cross-links. FA is a rare genetic disorder characterised by bone marrow failure, cancer predisposition and congenital abnormalities, caused by biallelic mutations affecting proteins in the FA pathway. Germline monoallelic pathogenic BRCA1 mutations are known to be associated with hereditary breast/ ovarian cancer, however biallelic mutations of BRCA1 were long predicted to be incompatible with embryonic viability, hence BRCA1 was not considered to be a canonical FA gene. Despite this, several patients with biallelic pathogenic BRCA1 mutations and FA-like phenotypes have been identified -- defining a new FA type (FA-S) and designating BRCA1 as an FA gene. This report presents a scoping review of the cases of biallelic BRCA1 mutations identified to date, discusses the functional effects of the mutations identified, and proposes a phenotypic spectrum of BRCA1 mutations based upon available clinical and genetic data. We report that this FA-S cohort phenotype includes short stature, microcephaly, facial dysmorphisms, hypo/ hyperpigmented lesions, intellectual disability, chromosomal sensitivity to crosslinking agents and predisposition to breast/ovarian cancer and/or childhood cancers, with some patients exhibiting sensitivity to chemotherapy. Unlike most other types of FA, FA-S patients lack bone marrow failure. [ABSTRACT FROM AUTHOR]

Pseudoachondroplasia (PSACH) is a rare, dominant genetic disorder affecting bone and cartilage development, characterized by short-limb short stature, brachydactyly, loose joints, joint stiffness, and pain. The disorder is caused by mutations in the COMP gene, which encodes a protein that plays a role in the formation of collagen fibers. In this study, we present the clinical and genetic characteristics of PSACH in two Chinese families. Whole-exome sequencing (WES) analysis revealed two novel missense variants in the COMP gene: NM_000095.3: c.1319G>T (p.G440V, maternal) and NM_000095.3: c.1304A>T (p.D435V, paternal-mosaic). Strikingly, both the G440V and D435V mutations were located in the same T3 repeat motif and exhibited the potential to form hydrogen bonds with each other. Upon further analysis using Missense3D and PyMOL, we ascertained that thesemutations showed the propensity to disrupt the protein structure of COMP, thus hampering its functioning. Our findings expand the existing knowledge of the genetic etiology underlying PSACH. The identification of new variants in theCOMP gene can broaden the range of mutations linked with the condition. This information can contribute to the diagnosis and genetic counseling of patients with PSACH. [ABSTRACT FROM AUTHOR]

Background: This retrospective study explored the effect on adult height of a combination of recombinant human growth hormone (rhGH) and aromatase inhibitors (AIs), or rhGH and a gonadotropin-releasing hormone analog (GnRHa), and compared their effects with rhGH alone in males at advanced bone age with idiopathic short stature (ISS). Methods: In this retrospective study, rhGH or rhGH combined with GnRHa or rhGH combined with AI therapy was given to males with advanced bone age (13–15 years) and diagnosed with ISS. The patients were followed to assess their adult height. Results: (1) A total of 68 patients were reviewed; 22 males were treated with rhGH for 24.9 ± 4.47 months, 22 males were treated with GnRHa + rhGH for 34.1 ± 3.36 months, and 24 males were treated with AI + RHGH for 22.7 ± 2.49 months. (2) Before treatment, the HtSDS-CA for the three groups were -1.04 ± 0.95, -1.23 ± 1.06, and -0.85 ± 0.98, respectively, and the HtSDS-BA were -2.14 ± 0.29, -2.14 ± 0.21, and-2.26 ± 0.31, respectively. The target heights for each group were 169.7 ± 4.0 cm, 169.7 ± 3.9 cm, and 169.1 ± 3.9 cm, respectively. The predicted adult heights were 161.7 ± 3.35 cm, 162.3 ± 1.75 cm, and 161.6 ± 2.89 cm, respectively. (3) After treatment, the HtSDS-CA for the rhGH group increased by 1.30 ± 0.58, and the HtSDS-BA increased by 2.00 ± 0.27. For the GnRHa + rhGH group, the HtSDS-CA and HtSDS-BA increased by1.42 ± 0.73and 2.74 ± 0.28, respectively. The AI + RHGH group increased by1.39 ± 0.64 and 2.76 ± 0.31, respectively. (4) There was no significant difference between the adult height (170.9 ± 0.7 cm) and target height for the rhGH group (P > 0.05), but the adult heights for the GnRHa + rhGH and AI + RHGH groups (173.2 ± 1.5 cm and 173.5 ± 1.0 cm, respectively, P > 0.05) were higher than the target height (P < 0.05). (5) Compared with the predicted adult height, the adult heights for the three groups improved significantly (P < 0.05). (6) No severe adverse reactions during the treatment occurred in any of the children. However, the total incidence of side effects in the three groups was significant (χ2 = 20.433, P = 0.00). Conclusion: Different therapeutic approaches have been investigated to improve the final adult height of males at advanced bone ages with ISS, and the optimal strategy remains controversial. In children at advanced bone ages with ISS, clinicians should carefully consider the advantages and disadvantages prior to treatment. [ABSTRACT FROM AUTHOR]

Introduction: Natriuretic peptide receptor 2 (NPR2 or NPR-B) plays a central role in growth development and bone morphogenesis and therefore loss-of-function variations in NPR2 gene have been reported to cause Acromesomelic Dysplasia, Maroteaux type 1 and short stature. While several hypotheses have been proposed to underlie the pathogenic mechanisms responsible for these conditions, the exact mechanisms, and functional characteristics of many of those variants and their correlations with the clinical manifestations have not been fully established. Methods: In this study, we examined eight NPR2 genetic missense variants (p.Leu51Pro, p.Gly123Val, p.Leu314Arg, p.Arg318Gly, p.Arg388Gln, p.Arg495Cys, p.Arg557His, and p.Arg932Cys) Acromesomelic Dysplasia, Maroteaux type 1 and short stature located on diverse domains and broadly classified as variants of uncertain significance. The evaluated variants are either reported in patients with acromesomelic dysplasia in the homozygous state or short stature in the heterozygous state. Our investigation included the evaluation of their expression, subcellular trafficking and localization, N-glycosylation profiles, and cyclic guanosine monophosphate (cGMP) production activity. Results and Discussion: Our results indicate that variants p.Leu51Pro, p.Gly123Val, p.Leu314Arg, p.Arg388Gln have defective cellular trafficking, being sequestered within the endoplasmic reticulum (ER), and consequently impaired cGMP production ability. Conversely, variants p.Arg318Gly, p.Arg495Cys, and p.Arg557His seem to display a non-statistically significant behavior that is slightly comparable to WT-NPR2. On the other hand, p.Arg932Cys which is located within the guanylyl cyclase active site displayed normal cellular trafficking profile albeit with defective cGMP. Collectively, our data highlights the genotype-phenotype relationship that might be responsible for the milder symptoms observed in short stature compared to acromesomelic dysplasia. This study enhances our understanding of the functional consequences of several NPR2 variants, shedding light on their mechanisms and roles in related genetic disorders which might also help in their pathogenicity re-classification. [ABSTRACT FROM AUTHOR]

In the intricate world of botanical life, an often-overlooked menace lurks - plant viruses. Viruses invade their target and hijack the plant cell's mechanisms to multiply and reproduce. The impact of these microscopic assailants is profound, affecting food security, food safety, national economies, biodiversity, and the rural environment. Plant viruses, although small in stature, wield immense influence in the plant kingdom. They are sub-microscopic entities comprised of genetic material, either DNA or RNA, encased within a protective protein coat. They need a medium of transmission for survival and spread, which can be air, water, contaminated tools, or certain other organisms known as vectors. These vectors, often insects, fungi, or nematodes, serve as intermediaries between the virus and its plant host, facilitating transmission and infection. Understanding the intricate interactions between plant viruses and their vectors is vital for developing effective control strategies that can mitigate the devastating impact of these diseases on crops. This relationship between a plant virus and a vector is a testament to the complexity of the natural world, where microscopic organisms wield enormous influence over the health and fate of plants, impacting ecosystems and even human agriculture. This review delves into the world of plant virus vectors, un-ravelling their roles in disease transmission, their biological mechanisms, and the pivotal role they play in shaping agricultural landscapes worldwide. It also explores the types of virus transmission and their effects on vector behaviour. This knowledge is essential for developing strategies to mitigate the impact of plant viruses and protect global food security. [ABSTRACT FROM AUTHOR]

In-vivo bone microstructure measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) is gaining importance in research and clinical practice. Second-generation HR-pQCT (XCT2) shows improved image quality and shorter measurement duration compared to the first generation (XCT1). Predicting and understanding the occurrence of motion artifacts is crucial for clinical practice. We retrospectively analyzed data from HR-pQCT measurements at the distal radius and tibia of 1,000 patients (aged 20 to 89) evenly distributed between both generations of HR-pQCT. Motion artifacts were graded between 1 (no motion) and 5 (severe motion), with grades greater 3 considered unusable. Additionally, baseline characteristics and patients' muscle performance and balance were measured. Various group comparisons between the two generations of HR-pQCT and regression analyses between patient characteristics and motion grading were performed. The study groups of XCT1 and XCT2 did not differ by age (XCT1: 64.9 vs. XCT2: 63.8 years, p = 0.136), sex (both 74.5% females, p > 0.999), or BMI (both 24.2 kg/m2, p = 0.911) after propensity score matching. XCT2 scans exhibited significantly lower motion grading in both extremities compared to XCT1 (Radius: p < 0.001; Tibia: p = 0.002). In XCT2 motion-corrupted scans were more than halved at the radius (XCT1: 35.3% vs. XCT2: 15.5%, p < 0.001), and at the tibia the frequency of best image quality scans was increased (XCT1: 50.2% vs. XCT2: 63.7%, p < 0.001). The strongest independent predictor for motion-corrupted images is the occurrence of high motion grading at the other scanning site during the same consultation. The association between high motion grading in one scan and a corresponding high motion grading in another scan within the same session suggests a non-resting patient. Additionally, aged, female, and patients with smaller stature tend towards higher motion grading, requiring special attention to a correct extremity fixation. [ABSTRACT FROM AUTHOR]

A coincidental occurrence of severe haemophilia A and Turner syndrome in a female person is extremely rare (less than 10 cases published). In such challenging cases, a multidisciplinary approach based on medicine of precision with full access to genetic and bio-molecular exploration is indispensable. The article presents an eight-year-old girl, with a family history of haemophilia, without significant disease signs (only post-dental extraction bleeding and a shorter stature). Discordantly, however, the investigations revealed a challenging condition: a genotype of 46,X,i(Xq), with an Isochromosome Xq responsible for the Turner syndrome and simultaneously, for the detrimental transformation, interfering with X chromosome inactivation, of an obligate hemophilia carrier into a severe hemophilia case—two distinct and provocative diseases. [ABSTRACT FROM AUTHOR]

Objective: Scarce data exist regarding obstetric complications of short‐stature patients. This study aimed to investigate obstetric and perinatal outcomes in women with short stature; specifically, to investigate whether short‐stature patients are at an increased risk for cesarean delivery. Methods: A population‐based cohort study was conducted, including all singletons born between the years 1991 and 2021 at a tertiary medical center. Obstetric and perinatal outcomes of short‐stature patients were compared with those of non‐short patients. A generalized estimation equation binary logistic model was constructed to adjust for confounders and maternal recurrence in the cohort. Results: The study population included 356 356 parturient; among them, 14 035 (3.9%) were short‐stature patients. Short‐stature patients had significantly higher rates of cesarean delivery (20.7% vs 13.7%, odds ratio = 1.64, 95% confidence interval 1.57–1.71, P < 0.001), induction of labor, pathologic presentations, prolonged second stage of labor, non‐reassuring fetal monitoring, and meconium‐stained amniotic fluid. Newborns of short‐stature patients had a significantly higher risk of being small for gestational age as compared with those of non‐short patients. In the generalized estimation equation models, the association between short stature and risk of cesarean delivery remained significant (adjusted odds ratio = 1.32, 95% confidence interval 1.27–1.38, P < 0.001), as well as the risk of small for gestational age newborns (adjusted odds ratio = 1.51, 95% confidence interval 1.40–1.63, P < 0.001), but not for the other adverse outcomes. Conclusions: Maternal short stature is an independent risk factor for cesarean delivery and is associated with small for gestational age newborns. Synopsis: Maternal short stature is an independent risk factor of cesarean delivery and is associated with a higher risk of small for gestational age newborns. [ABSTRACT FROM AUTHOR]

Approximately 80% of children with short stature are classified as having Idiopathic Short Stature (ISS). While growth hormone (GH) treatment received FDA approval in the United States in 2003, its long-term impact on final height remains debated. Other treatments, like aromatase inhibitors, metformin, and insulin-like growth factor-1 (IGF-1), have been explored, but there is no established standard treatment for ISS. In South Korea and other Asian countries, East Asian Traditional Medicine (EATM) is sometimes employed by parents to potentially enhance their children's height growth, often involving herbal medicines. One such product, Astragalus membranaceus extract mixture HT042, claims to promote height growth in children and has gained approval from the Korean Food and Drug Administration (KFDA). Research suggests that HT042 supplementation can increase height growth in children without skeletal maturation, possibly by elevating serum IGF-1 and IGF-binding protein-3 levels. Preclinical studies also indicate the potential benefits of natural products, including of EATM therapies for ISS. The purpose of this review is to offer an overview of bone growth factors related to ISS and to investigate the potential of natural products, including herbal preparations, as alternative treatments for managing ISS symptoms, based on their known efficacy in in vivo studies. [ABSTRACT FROM AUTHOR]

Hypophosphatasia (HPP) is a rare condition characterized by abnormal bone mineralization. The manifestations of HPP vary from no symptoms to intrauterine fetal death; short stature is another indication of HPP. A 3 1/2-year-old boy presented with short stature, transient hypercalcemia, and mild gait disturbance without definite bony deformity. Laboratory examination revealed transient hypercalcemia, normal phosphorous and 25-hydroxy vitamin D levels, and mildly low alkaline phosphatase levels. A targeted next-generation sequencing panel associated with inborn errors of metabolism revealed a pathogenic heterozygous mutation in the ALPL gene, c.979T>C (p.Phe327Leu). When a child visits a hospital with short stature, decreased height velocity, and low alkaline phosphatase level, clinicians should consider the possibility of HPP even if definite skeletal dysplasia is not evident. [ABSTRACT FROM AUTHOR]

Cornelia de Lange syndrome is a genetic and clinically heterogeneous entity, caused by at least five genes. It is characterized by short stature, gestalt facies, microcephaly, neurodevelopmental disorders, and other anomalies. In this report, we present a 13-year-old female patient with microcephaly, cleft palate, polydactyly, short stature, triangular facies, frontal bossing, a bulbous nose, an overfolded helix, limited pronosupination, and an anomalous uterus. No neurodevelopmental disorders were reported. A chromosomal microarray analysis of 6.5 million markers was performed in the proband and her parents. The results showed a de novo heterozygous microdeletion of exons 9–14 within RAD21, which confirmed the diagnosis of Cornelia de Lange syndrome type 4. Our patient did not show any neurologic phenotype (until the time of diagnosis), although neurodevelopmental disorders are frequently present in patients with Cornelia de Lange syndrome type 4, and despite carrying a deletion that was larger than previously reported. Therefore, unknown genetic modifiers or intrinsic mechanisms of RAD21 variants may exist and should be studied. [ABSTRACT FROM AUTHOR]

Large-scale genomic structural variations can have significant clinical implications, depending on the specific altered genomic region. Briefly, 2q37 microdeletion syndrome is a prevalent subtelomeric deletion disorder characterized by variable-sized deletions. Affected patients exhibit a wide range of clinical manifestations, including short stature, facial dysmorphism, and features of autism spectrum disorder, among others. Conversely, isolated duplications of proximal chromosome 2q are rare and lack a distinct phenotype. In this report, we provide an extensive molecular analysis of a 15-day-old newborn referred for syndromic features. Our analysis reveals an 8.5 Mb microdeletion at 2q37.1, which extends to the telomere, in conjunction with an 8.6 Mb interstitial microduplication at 2q34q36.1. Our findings underscore the prominence of 2q37 terminal deletions as commonly reported genomic anomalies. We compare our patient's phenotype with previously reported cases in the literature to contribute to a more refined classification of 2q37 microdeletion syndrome and assess the potential impact of 2q34q36.1 microduplication. We also investigate multiple hypotheses to clarify the genetic mechanisms responsible for the observed genomic rearrangement. [ABSTRACT FROM AUTHOR]

Purpose: Doses of spinal bupivacaine adjusted to patient height or height/weight have been shown to provide hemodynamic stability during cesarean section. However, their effects in short stature parturients are unknown. Methods: In this double-blind, randomized clinical trial, we randomly assigned short parturients (height < 150 cm) undergoing elective cesarean section, to receive doses of intrathecal hyperbaric bupivacaine either height or height/weight-adjusted, in a 1:1 ratio. The primary outcome was post-spinal hypotension (defined as systolic blood pressure [SBP] < 90% of baseline between spinal administration and delivery of the baby). Secondary outcomes included severe post-spinal hypotension (SBP < 80% of baseline), post-delivery hypotension (SBP < 90% and < 80% of baseline), intraoperative bradycardia, nausea and vomiting, shivering, rescue analgesic needed, and spinal block characteristics. Results: A total of 112 patients underwent randomization. Post-spinal hypotension (SBP < 90% of baseline) occurred in 52% of the patients in the height/weight group and in 55% in the height group (difference − 3.5%: 95% confidence interval [CI] − 22 to 14.8, P = 0.705). There was no significant difference between the two groups in the occurrences of post-spinal severe hypotension (SBP < 80% of baseline), post-delivery hypotension, and spinal block characteristics. Six patients (11%) in the height/weight group needed intraoperative rescue analgesic compared to none in the height group (P = 0.027). Conclusion: We found that height-based dosing in short parturients provides the optimal trade-off between intraoperative hemodynamic instability and provision of pain-free anesthesia. Trial registration: clinicaltrial.gov-NCT04082676. https://clinicaltrials.gov/ct2/show/NCT04082676. [ABSTRACT FROM AUTHOR]

The Graciosa donkey has been associated with husbandry and social activities in Graciosa Island for decades. Although donkeys played an essential role in the development of the island, their numbers are severely reduced. The Graciosa donkey is characterised by its small stature, strong bony constitution and strong hooves. They are extremely gentle, patient and submissive fully integrated into the island's ecosystem. As so they must be considered as elements of an environmentally sustainable ecosystem. This study aimed to define the morphotype of the Graciosa donkey and to access its genetic diversity using microsatellite markers. Biometric data consisted of 15 morphological traits from 39 individuals. The Graciosa donkey is dolichocephalic, hypermetric according to the dactilothoracic index, hypometric regarding the approximate live weight and far from ground. Twenty-four individuals, which showed no kinship, based on results of 13 markers were considered as founders and were genotyped for two additional markers and further analysed in this study. All microsatellites used were polymorphic, but low levels of genetic diversity were identified. As the Graciosa donkey gains popularity, the information obtained from this study will be very useful for conservation and management purposes by safeguarding its genetic diversity. [ABSTRACT FROM AUTHOR]

IGSF1 deficiency is a rare X-linked condition characterized by central hypothyroidism and a wide variety of other clinical features with variable prevalence, including a delayed pubertal testosterone rise and growth spurt in the context of normal or accelerated testicular growth, and adult macroorchidism with relatively low serum testosterone concentrations. Other features include increased waist circumference, attention deficit, prolactin deficiency and transient partial growth hormone (GH) deficiency in childhood, contrasting with an increased GH secretion in adulthood. Patients with this disorder are not detected shortly after birth if neonatal screening programs are based on thyroid-stimulating hormone (TSH) concentrations. A 13.2-year-old male patient was referred to pediatric endocrinology for evaluation of short stature. He was born large for gestational age into a nonconsanguineous family. During work-up for short stature, deficiencies of TSH, prolactin and GH were detected, leading to treatment with levothyroxine and GH. At 16.9 years, GH treatment was stopped and during transition to adult care, his insulin-like growth factor 1 level was above the normal range. This prompted an analysis of IGSF1, in which a novel hemizygous variant causing a stop codon at c.3559C>T (p.Q1187*) was found, confirming the diagnosis of IGSF1 deficiency syndrome. In this report, we describe his clinical and hormonal characteristics at presentation and during long-term follow-up. [ABSTRACT FROM AUTHOR]

Objective: Recent reports have indicated the role of the prokineticin receptor 2 gene (PROKR2) in the etiology of pituitary hormone deficiencies, suggesting a potential role for the PROK2 pathway in pituitary development, in addition to its role in gonadotropin releasing hormone-expressing neuron development. Here, we present the clinical and molecular findings of four patients with PROKR2 mutations. Methods: Next-generation targeted sequencing was used to screen 25 genes in 59 unrelated patients with multiple pituitary hormone deficiency (MPHD), isolated growth hormone (GH) deficiency, or idiopathic short stature. Results: Two different, very rare PROKR2 missense alterations classified as pathogenic (NM_144773.4:c.518T>G; NP_658986.1:p. (Leu173Arg)) and likely pathogenic (NM_144773.4:c.254G>A; NP_658986.1:p.(Arg85His)) were identified in four patients in heterozygous form. Patient 1 and Patient 2 presented with short stature and were diagnosed as GH deficiency. Patient 3 and Patient 4 presented with central hypothyroidism and cryptorchidism and were diagnosed as MPHD. No other pathogenic alterations were detected in the remaining 24 genes related to short stature, MPHD, and hypogonadotropic hypogonadism. Segregation analysis revealed asymptomatic or mildly affected carriers in the families. Conclusion: PROKR2 dominance should be kept in mind as a very rare cause of GH deficiency and MPHD. Expressional variation or lack of penetrance may imply oligogenic inheritance or other environmental modifiers in individuals who are heterozygous carriers. [ABSTRACT FROM AUTHOR]

Background. Mutations in the growth hormone (GH) gene cause various forms of biologically inactive growth hormone (BIGH) syndrome. Ghrelin potentiates the secretion of GH. Adenohypophysis hormones take part in human growth mechanisms. Insulin-like growth factor 1 (IGF-1) level is a criterion of GH activity. The purpose of the study was to assess the adenohypophysis functions and to determine the role of ghrelin in patients with BIGH syndrome to optimize the diagnosis and treatment. Materials and methods. Anthropometric parameters were evaluated in 158 children with BIGH syndrome whose average age was 7.83 ± 1.23 years. The function of the adenohypophysis was evaluated according to the levels of somatotropin, thyroid-stimulating, adrenocorticotropic, luteinizing, follicle-stimulating hormone and their corresponding peripheral hormones, which were determined by radioimmunological methods and chemiluminescent immunoassay. A statistical analysis of the results was carried out. Results. The release of GH against the background of clonidine and insulin tests in patients with BIGH syndrome was higher than 10 ng/ml, the basal level of IGF-1 was significantly lower than the reference values. After a 4-day test for sensitivity to GH, the level of IGF-1 increased more than 2 times. Against the background of treatment with recombinant GH, serum thyroid-stimulating, adrenocorticotropic hormone, and cortisol indicators changed significantly, but their levels fluctuated within the reference values. Significant changes in ghrelin content were detected 120 minutes after falling asleep. Most children with BIGH syndrome had timely sexual development, precocious puberty was revealed in 19 children, the smallest was the group with delayed puberty (5 children). Gonadotropin-releasing hormone analogues were added to the GH treatment in case of unsatisfactory final growth. Conclusions. Normal/high levels of GH and reduced IGF-1 are characteristic of children with BIGH syndrome. In addition, these children have a significant increase in ghrelin in the first hours after falling asleep. The test for sensitivity to GH is a reliable diagnostic method. Thyroid and adrenal disorders were not found in patients with BIGH syndrome. Children with BIGH syndrome have normal sexual development with a tendency to precocious puberty. The simultaneous use of gonadotropin-releasing hormone analogues in combination with GH preparations significantly improves patients’ final growth. [ABSTRACT FROM AUTHOR]

Context Numerous reports of suicide among individuals who received cadaver-derived human growth hormone (c-hGH) through the National Hormone Pituitary Program (NHPP) raised the alarm for potentially increased suicide risk. Objective We conducted a study to assess suicide risk in the NHPP cohort and identify contributing factors to facilitate early recognition and intervention. Methods The study population consisted of patients receiving NHPP c-hGH starting from 1957, and cohort deaths with an ICD code consistent with suicide or possible suicide through 2020 were evaluated. Descriptive data were extracted from medical records. Standardized mortality ratios (SMRs) to compare the observed number of suicide deaths in the cohort to the expected number were calculated using general population suicide rates by sex, age group, and time period. Results Among 6272 patients there were 1200 all-cause cohort deaths, of which 55 (52 male, 3 female) were attributed to suicide. Of these, 47 were identified by ICD code alone compared to an expected count of 37.8 (SMR = 1.25, 95% CI 0.91-1.66). Among male cohort members, the SMR was 1.33 (95% CI 0.97-1.78). Elevated risk of suicide was detected for cohort members aged 25-34 (SMR = 1.79, 95% CI 1.06-2.83) and during the period from September 19, 1985, to December 31, 1998 (SMR = 1.70, 95% CI 1.02-2.65). Conclusion Overall, the observed number of suicides among NHPP c-hGH recipients was not significantly higher than expected. However, certain subgroups may be at elevated risk of suicide. Studies are needed to better understand the nature and magnitude of suicide risk among c-hGH recipients to facilitate early intervention to prevent suicide deaths. [ABSTRACT FROM AUTHOR]

Gender-based institutions influence resource allocation within the household and when other measures for economic welfare are scarce or unreliable, the use of biological measures are now standard in economics. This study uses late nineteenth and early twentieth century BMI, statures, and weight to assess how net nutrition accumulated to women and men during U.S. economic development. Throughout the late nineteenth and early twentieth centuries, female and male BMIs, statures, and weight remained constant over time. Unskilled laborers' BMIs were higher, their statures were taller, and their weights heavier than workers in other occupations. Women and men from the Northeast and Middle Atlantic had higher BMIs and shorter statures, while their counterparts from the South were taller and had lower BMIs, indicating that it was superior Southern cumulative net nutrition associated with lower BMIs [ABSTRACT FROM AUTHOR]

Multiple endocrine neoplasia 2B (MEN2B) is a rare syndrome with prevalence estimated at approximately 0.2 per 100,000; it is caused by mutation of the RET proto-oncogene. MEN2B is characterized by early-onset medullary thyroid carcinoma (MTC), ganglioneuromatosis of the aerodigestive tract, marfanoid habitus, ophthalmologic abnormalities, and pheochromocytoma in adulthood. Mutations in the RyR1 gene manifest clinically in congenital myopathies and/or malignant hyperthermia susceptibility. We present a case of a 4-year-old boy with an accidentally detected RET and RyR1 mutations in the course of diagnostic approach of short stature and delayed motor development. Due to a poor and blurred clinical picture of MEN2B syndrome, accompanied by RyR1 mutation symptoms, the diagnostic path was extended. Our patient had no family history of MTC. In the imaging studies of the thyroid gland, no abnormalities were found, whereas the serum level of calcitonin was elevated to 34 pg/mL (N < 5.0). The patient qualified for total thyroidectomy, and the histopathological examination confirmed the diagnosis of MTC. The postoperative serum calcitonin level dropped to normal ranges. This case shows how new genetic diagnostic procedures could be crucial in accidentally diagnosing rare endocrine disease with atypical symptoms, giving an opportunity for relatively early intervention. [ABSTRACT FROM AUTHOR]

Background: Childhood stunting is one of our community's most prevalent public health nutrition problems. Many factors may lead to the development of stunning. Growth hormones and diet might play a role in the treatment. This study aims to investigate the effect of nutritional status on the growth rate among children with short stature who underwent growth hormone therapy the previous year. Methods: A one-year retrospective, cross-sectional study was carried out among 4-10-year-old children with stunting. Laboratory tests, anthropometric measurements, and dietary intake were measured at the start of the research and one year after the application of growth hormone therapy. Results: A significantly higher growth rate was observed among males than females (P = 0.040). Also, males had significantly higher calorie intake (P). This study found that the patients had a less than 8.5% difference in energy intake vs. total energy requirement. There is a significant association between food consumption from two food groups (milk and meat) (P = 0.04 and 0.021, respectively. Conclusion: Diet plays a significant role in the improvement of growth velocity. [ABSTRACT FROM AUTHOR]

Background and Objectives: Stable fixation is essential for successful healing after medial open wedge high tibial osteotomy (MOWHTO) to minimize the risk of non-union and correction loss. In Asians, potential complications such as D-hole screw osteotomy plane violation (D-hole violation) and inadequate plate fitting arise due to improper plate size. This study aimed to evaluate the risk factors for D-hole violation and compare the conventional anatomic (CA) plate with an individualized anatomic (IA) plate in MOWHTO procedures. Materials and Methods: A simulation study on D-hole violation using the CA plate was conducted, involving preoperative radiographs and CT scans of 64 lower extremities from 47 MOWHTO patients. Additionally, a randomized controlled study compared CA and IA plates in MOWHTO procedures with 34 patients (17 in the CA plate group; 18 in the IA plate group). Patient demographics, patient-reported outcome measures (PROMs), and radiological measures were analyzed. Results: In the simulation study, the rates of D-hole violation ranged from 20.3% to 59.4%, with an increase observed as the plate was distalized from 5 mm to 10 mm away from the joint line. Short stature was identified as an independent risk factor for D-hole violation (p < 0.001), with a cutoff value of 155.3 cm. In the randomized controlled study, no significant difference in PROMs and D-hole violation was observed between the CA plate and IA plate groups. However, the IA plate group showed better plate fitting compared to the CA plate group (p = 0.041). Conclusions: This study identified a high risk of D-hole screw osteotomy plane violations in MOWHTO procedures, particularly when the plate is positioned more distally and in individuals with a stature below 155.3 cm. It also revealed that individualized plates provide better tibial fitting compared to conventional anatomic plates, particularly in Asian populations where tibial morphology tends to be shorter than in Western populations. Therefore, evaluating patient stature and selecting tailored plates are essential to optimize plate positioning and minimize plate-related complications in MOWHTO procedures. [ABSTRACT FROM AUTHOR]

Background: Short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis is a rare, autosomal recessive, skeletal disorder first described in 2018. This syndrome starts with pre- and postnatal developmental delay, and gradually presents with variable facial dysmorphisms, a short stature, amelogenesis imperfecta, and progressive skeletal dysplasia affecting the limbs, joints, hands, feet, and spine. Case presentation: We identified a homozygous novel nonsense mutation in exon 1 of SLC10A7 (NM_001300842.2: c.100G > T / p.Gly34*) segregating with the typical disease phenotype in a Han Chinese family. We reviewed the 12-year surgical treatment history with seven interventions on spine. Conclusion: To date, only 12 cases of the SLC10A7 mutation have been reported, mainly from consanguineous families. Our patient showed a relatively severe and broad clinical phenotype compared with previously reported cases. In this patient, annual check-ups and timely surgeries led to a good outcome. [ABSTRACT FROM AUTHOR]

Background: Partial duplications involving the long arm of the X chromosome are associated with mental retardation, short stature, microcephaly, and a wide range of physical findings. Female carriers usually have no clinical phenotype. Occasionally, they may also have heterogeneous features due to non-random inactivation of the X chromosome. Methods: The peripheral blood sample was collected from the patient and subjected to a few genetic testing, including chromosomal karyotyping, Chromosomal microarray analysis (CMA), Optical genome mapping, short tandem repeat (STR) analysis for Determination of parental origin, and X chromosome inactivation (XCI) analysis. Results: We have identified a de novo Xq23-Xq26.3 duplication in an adult female featuring extremely short stature and mild mental deficiency. Chromosome analysis detected a duplication on Xq23-q26.3 with a size of approximately 20 Mb. The duplication region has encompassed a number of genes, among which ARHGEF6, PHF6, HPRT1 and SLC9A6 are associated with X-linked mental retardation. Further analysis suggested that the duplication has derived from her father, was of the inversion duplication type and involved various degrees of skewed X chromosome inactivation. Conclusion: Correlation with her phenotypes might indicate new mechanisms by which the X chromosome may lead to short stature and mental retardation. Our findings thereby may shed more light on the phenotypic implication of functional disomy of X-chromosome genes. [ABSTRACT FROM AUTHOR]

Objective: Hypothalamic-pituitary axis dysfunction is a common complication in post-operative craniopharyngioma(CP) patients, and it greatly impacts the longterm quality of life of such patients. To better understand the effects of postoperative hypothalamic-pituitary dysfunction and long-term hormone replacement therapy in patients with childhood CP, we assessed approximately 200 patients with childhood-onset CP postoperatively. Methods: Clinical details of patients with childhood-onset CP who underwent sellar tumor resection in Beijing Children’s Hospital and Beijing Tiantan Hospital from 2018 to 2019 were retrieved retrospectively. The participants were followed up to assess the effects of post-operative long-term hormone replacement therapy and assess the tumor recurrence rate. Results: The median age of admission was 8.1 (1.8, 14.3) years. Headache (45.5%), visual impairment (39.5%), and nausea (33.0%) were the most common clinical manifestations. ACP accounted for 95% of all CP cases. The incidence of central adrenal insufficiency and central hypothyroidism within the first week after surgery was 56.2% and 70.3%, respectively. At the same time 85.5% of the patients required at least one dose of desmopressin to control urine output. Total survival and tumor recurrence rates were 98.6% and 26.1%, respectively, with a median follow-up time of 29.7 (19.0, 40.3) months. During the follow-up period, 28.1% patients met the diagnostic criteria for short stature, while 54.4% fit the criteria for obesity. In addition, 94.4% of the patients were taking at least one kind of hormone substitution, and 74.7% were taking three or more. The prevalence of levothyroxine, glucocorticoid, desmopressin, and growth hormone replacement therapy was 87.3%, 77.5%, 78.9% and 31.0%, respectively. The proportion of patients treated with the substitutive combination of levothyroxine, hydrocortisone, and desmopressin was 54.9%. Conclusion: This study is a large-sample systematic postoperative endocrine function evaluation of patients with childhood-onset CP. Due to the high prevalence of post-operative hypothalamic-pituitary dysfunction, patients with CP usually require long-term multiple hormone substitution therapy. Individualized management and accurate hormone replacement dosage for postoperative childhood-onset CP patients are of great importance. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the relationship between serum uric acid (SUA) and the triglyceride-glucose (TyG) index, which is a more effective indicator of insulin resistance. The study participants included 1700 children and adolescents with short stature who were recruited at the Affiliated Hospital of Jining Medical University in China between March 2013 and April 2021. A positive association between SUA levels and the TyG index was detected by univariate analysis (p < 0.001). Furthermore, a nonlinear relationship was detected between SUA and the TyG index, whose point was 6.55 mg/dL. There was a positive association between SUA and the TyG index when the SUA level was greater than 6.55 mg/dL (β 0.17, 95% CI: 0.07, 0.27; P < 0.001). However, we did not observe a significant relationship between SUA and the TyG index when the SUA level was less than 6.55 mg/dL (β 0.02, 95% CI: − 0.01, 0.05; P = 0.091). In addition, a stratified analysis was performed to appraise changes in this relationship for different sexes. The relationship between SUA and the TyG index in males and females is consistent with that in the general population, showing a nonlinear relationship. However, the inflection points of SUA level were significantly higher in males than in females, and the inflection points were approximately 6.72 and 5.88 mg/dL, respectively. This study revealed a nonlinear relationship between SUA and the TyG index in children with short stature. The nonlinear relationship remained in gender stratification analysis, but the inflection point of SUA level was higher in men. Further studies are needed to establish a causal relationship between SUA levels and the TyG index in children with short stature. [ABSTRACT FROM AUTHOR]

Growth Hormone therapy has been shown to induce transient insulin resistance in children, and there is concern regarding the diabetogenic potential of GH therapy in children born small for gestational age (SGA). In this case, female patient born SGA with a weight of 2,750 g (−1.73 standard deviation (SD)) and length of 45.5 cm (−2.6 SD). The patient's father and paternal grandfather were diagnosed with type 2 diabetes mellitus. At 3 years of age, the patient presented with short stature; height and weight were 85 cm (−2.5 SD) and 13 kg (−0.19 SD), respectively. She was placed on GH therapy. At 11 years of age, her fasting blood glucose and hemoglobin A1c levels were 116 mg/dL and 7.4%, respectively. Blood test results were negative for anti-glutamic acid decarboxylase and anti-islet antigen-2 antibodies. The patient discontinued GH therapy and started diet therapy and oral metformin (500 mg/day) administration. Five months later, the hemoglobin A1c level was 5.3% and glycemic control further improved. To our knowledge, family history may be an important risk factor for GH-induced diabetes. So, the GH dosage for patients born SGA with family history of diabetes should be adjusted so as not to be too excessive, and long-term follow-up studies will be required to evaluate fully the effects of GH therapy for them. [ABSTRACT FROM AUTHOR]

Noonan, Costello and Cardio-facio-cutaneous syndromes belong to a group of disorders named RASopathies due to their common pathogenetic origin that lies on the Ras/MAPK signaling pathway. Genetics has eased, at least in part, the distinction of these entities as they are presented with overlapping clinical features which, sometimes, become more pronounced with age. Distinctive face, cardiac and skeletal defects are among the primary abnormalities seen in these patients. Skeletal dysmorphisms range from mild to severe and may include anterior chest wall anomalies, scoliosis, kyphosis, short stature, hand anomalies, muscle weakness, osteopenia or/and osteoporosis. Patients usually have increased serum concentrations of bone resorption markers, while markers of bone formation are within normal range. The causative molecular defects encompass the members of the Ras/MAPK/ERK pathway and the adjacent cascades, important for the maintenance of normal bone homeostasis. It has been suggested that modulation of the expression of specific molecules involved in the processes of bone remodeling may affect the osteogenic fate decision, potentially, bringing out new pharmaceutical targets. Currently, the laboratory imprint of bone metabolism on the clinical picture of the affected individuals is not clear, maybe due to the rarity of these syndromes, the small number of the recruited patients and the methods used for the description of their clinical and biochemical profiles. [ABSTRACT FROM AUTHOR]

Matrix Gla protein (MGP) is a vitamin K-dependent post-translationally modified protein, highly expressed in vascular and cartilaginous tissues. It is a potent inhibitor of extracellular matrix mineralization. Biallelic loss-of-function variants in the MGP gene cause Keutel syndrome, an autosomal recessive disorder characterized by widespread calcification of various cartilaginous tissues and skeletal and vascular anomalies. In this study, we report four individuals from two unrelated families with two heterozygous variants in MGP, both altering the cysteine 19 residue to phenylalanine or tyrosine. These individuals present with a spondyloepiphyseal skeletal dysplasia characterized by short stature with a short trunk, diffuse platyspondyly, midface retrusion, progressive epiphyseal anomalies and brachytelephalangism. We investigated the cellular and molecular effects of one of the heterozygous deleterious variants (C19F) using both cell and genetically modified mouse models. Heterozygous 'knock-in' mice expressing C19F MGP recapitulate most of the skeletal anomalies observed in the affected individuals. Our results suggest that the main underlying mechanism leading to the observed skeletal dysplasia is endoplasmic reticulum stress-induced apoptosis of the growth plate chondrocytes. Overall, our findings support that heterozygous variants in MGP altering the Cys19 residue cause autosomal dominant spondyloepiphyseal dysplasia, a condition distinct from Keutel syndrome both clinically and molecularly. Biallelic loss-of-function variants in the gene encoding Matrix Gla Protein (MGP) are known to cause a recessive disorder called Keutel syndrome. Here, the authors report that heterozygous missense variants affecting one particular cysteine residue of MGP can cause a clinically distinct, dominant disorder, likely via impaired signal peptide processing leading to cellular stress and apoptosis. [ABSTRACT FROM AUTHOR]

Currently, no published cases report concomitant X-linked hypophosphatemia (XLH) and adult hypophosphatasia (HPP). Both diseases share clinical phenotypes that are almost indistinguishable. The correct diagnosis may be missed without a standardized laboratory and genetic testing approach. Pathogenic variants in the phosphate regulating endopeptidases homolog X-linked gene (PHEX) and the tissue-nonspecific alkaline phosphatase gene (ALPL) are genes that cause XLH and HPP, respectively. We describe a concomitant yet undescribed genetic pathogenic variant in a family. A 61-year-old woman was referred by orthopedic surgery for the presence of bilateral leg bowing and short stature during the assessment of knee surgery. The patient had a biochemical workup relevant for low serum phosphorus and 1,25-dihydroxy vitamin D and normal alkaline phosphatase (ALP). Genetic analysis revealed pathogenic variants in PHEX and ALPL. Her 42-year-old daughter shared identical symptoms and genetic variants with her mother. Both patients started conventional treatment for XLH with phosphorus and vitamin D, and the daughter later switched to burosumab-twza. Adult XLH and HPP may have similarities in clinical presentation but differ in some essential laboratory findings. Normal ALP levels helped direct our diagnosis toward XLH. However, the diagnosis was challenging due to the presence of concurrent variants in the genes involved. These variants illustrate the significant heterogeneity of the clinical expression. [ABSTRACT FROM AUTHOR]

Objective: To analyze the clinical data and genetic characteristics of Noonan syndrome, both the effect and side effects of recombinant human growth hormone (rhGH) treatment. Methods: We collected clinical data from 8 children with Noonan syndrome diagnosed from November 2017 to June 2021. The diagnosis was clarified by exome second‐generation sequencing and parental PCR‐NGS validation and interpretation of the preceding evidence, and growth hormone therapy was administered. Of the cases, four males and four females were seen for slow height growth and the median age at diagnosis was 8 years 7 months (1 year 7 months to 12 years 6 months). Results: Here, 7 children were treated with rhGH. Compared to the pre‐treatment period, the growth rate increased after rhGH treatment [3.7 ± 0.5 cm/year before treatment and 8.0 ± 1.0 cm/year after treatment, p < 0.01], with the maximum growth rate between 3 and 6 months of treatment and decreasing with the duration of treatment thereafter. The growth hormone treatment was discontinued and the orthopedic consultation was ordered with regular follow‐up, which was considered to be related to the PTPN11 mutation. Conclusion: Noonan syndrome is characterized by slow growth, short stature, mental retardation, peculiar facial features, structural heart abnormalities and abnormal bone metabolism. and osteochondroma was found after case 2 rhGH treatment. Genetic examination is mostly caused by PTPN11 mutation. It is recommended to pay attention to bone metabolism abnormalities before growth hormone treatment, especially in children with PTPN11 mutations. We analyze the clinical data and genetic characteristics of Noonan syndrome, both the effect and side effects of recombinant human growth hormone (rhGH) treatment. [ABSTRACT FROM AUTHOR]

The popular Joha rice cultivar Kon Joha, cultivated throughout the state, was used to induce mutations. Kon Joha is short-grain aromatic rice with excellent cooking quality. The cultivar is tall and late maturing with an average yield of less than 2 tons ha−1 and is susceptible to lodging The investigation through M1 to M3 generation aimed at improving the morpho-agronomic traits of the popular Joha rice cultivar Kon Joha. The experiments were carried out during the Sali season (winter rice) from 2017 to 2019 at Instruction-cum-Research (ICR) Farm of Assam Agricultural University, Jorhat (Assam). Dry uniform seeds of Kon Joha were subject to irradiation with 100–400 Gy of gamma rays from a 60Co source. The M1 generation used a randomized complete block design with four replications during Sali 2017. A total of 5998 M1 plant progenies were subject to screening in the M2 during Sali 2018. The M3 included 662 morpho-agronomic variants raised in the plant rows during Sali 2019, and 66 mutants were confirmed. The M1 of Kon Joha registered a reduction in germination, seedling height, pollen/spikelet fertility and plant survival at 400 Gy. All the traits showed highly significant differences among the doses in the M2 generation. The shift in trait means was in both directions as influenced by the genotype and mutagen dose. The 66 mutants exhibited significant differences for all traits in the M3 generation. Fifty mutants were shorter than the parent Kon Joha. The GCV and PCV estimates were high (>20%) for grain yield, biological yield, productive tillers, filled grains, and average panicle weight. All the traits except panicle length exhibited high heritability coupled with high genetic advance, suggesting the predominance of additive gene action and the effectiveness of simple selection. Grain yield showed a significant positive correlation with plant height, panicle length, filled grains, spikelet fertility, the average panicle weight and harvest index in the mutant population. Thus, mutation induction in Kon Joha proved useful in inducing desirable changes in plant architectural traits. The study further emphasized the short stature high yielding mutants with strong aroma for wide-scale testing in the state. [ABSTRACT FROM AUTHOR]

Background: Hypogonadism is a significant late complication in childhood cancer survivors (CCS). The aim of this study was to elucidate the advantages and limitations of estrogen replacement therapy (ERT) for CCS with hypogonadism. Methods: Seventeen CCS were divided into two groups: gonadal hypogonadism (GH) group (n = 8) and central hypogonadism (CH) group (n = 9). Pearson correlation coefficients were used to investigate the impact of cancer management on final height, bone density, and uterine development. Results: Seven of GH group had hematologic malignancies, and all of them underwent total body irradiation before bone marrow transplantation. The GH group showed significant positive correlations between the onset age of disease treatment and final height (p < 0.05, R = 0.712) and uterine size following ERT (p < 0.05, R = 0.775). All CCS in the CH group had brain tumors, and seven of them received chemotherapy. There were trends towards positive and negative correlations between the onset age of disease treatment and final height (p = 0.09, R = 0.598) or uterine size (p = 0.07, R = − 0.669), respectively. A negative correlation trend was observed between the age at ERT initiation and final height (p = 0.07, R = − 0.769) or bone density (p = 0.18, R = − 0.626) in six CH patients who received growth hormone therapy. Five CCS in both groups experienced osteoporosis, despite receiving ERT. Conclusion: Individualized management strategies beyond ERT are essential to reduce long-term complications in CCS with hypogonadism, considering the type and timing of cancer treatment. [ABSTRACT FROM AUTHOR]

Background: Daily recombinant human growth hormone (rhGH) is approved and marketed worldwide to treat children and adults with GH deficiency and other conditions. Efficacy of rhGH therapy is influenced by several variables. Drop of treatment adherence over time has been recognized as a cause of reduced rhGH efficacy and has driven considerable efforts from pharmaceutical companies and scientists to develop long-acting rhGH (LAGH) formulations in order to relieve patients and their families from the burden of daily injections. Summary: Different technologies to manipulate drug release have been produced allowing weekly, biweekly, or monthly rhGH administration. The LAGH formulations developed at present have demonstrated a comparable or even higher efficacy as compared with daily rhGH in most of the cases and no major safety issues in phase 3 studies. A greater incidence of injection-site reactions has been reported but mainly of mild and transient nature. Key Messages: Despite LAGH analogs appearing promising, potential drawbacks still need to be addressed. Long-term consequences of nonphysiological GH profile and its consequences on metabolism and risk of cancer, optimal therapeutic monitoring, immunogenicity of LAGH molecules, and potential novel side effects related to the technologies used to develop these molecules are among the major concerns that require answers from long-term surveillance. Finally, increased acceptance of LAGH formulations from patients and their caregivers is yet to be demonstrated and cost-effectiveness evaluated consequently. [ABSTRACT FROM AUTHOR]

Global change drivers that modify the quality and quantity of litter inputs to soil affect greenhouse gas fluxes, and thereby constitute a feedback to climate change. Carbon cycling in the Yukon–Kuskokwim (Y–K) River Delta, a subarctic wetland system, is influenced by landscape variations in litter quality and quantity generated by herbivores (migratory birds) that create 'grazing lawns' of short stature, nitrogen-rich vegetation. To identify the mechanisms by which these changes in litter inputs affect soil carbon balance, we independently manipulated qualities and quantities of litter representative of levels found in the Y–K Delta in a fully factorial microcosm experiment. We measured CO2 fluxes from these microcosms weekly. To help us identify how litter inputs influenced greenhouse gas fluxes, we sequenced soil fungal and bacterial communities, and measured soil microbial biomass carbon, dissolved carbon, inorganic nitrogen, and enzyme activity. We found that positive correlations between litter input quantity and CO2 flux were dependent upon litter type, due to differences in litter stoichiometry and changes to the structure of decomposer communities, especially the soil fungi. These community shifts were particularly pronounced when litter was added in the form of herbivore feces, and in litter input treatments that induced nitrogen limitation (i.e., senesced litter). The sensitivity of carbon cycling to litter quality and quantity in this system demonstrates that herbivores can strongly impact greenhouse gas fluxes through their influence on plant growth and tissue chemistry. [ABSTRACT FROM AUTHOR]

Turner syndrome is a multisystem disease with varied clinical features influenced by genetic composition and possibly ethnicity. To review local data and identify the clinical features more common in our population. A retrospective review of the clinical, biochemical features and karyotype of all patients with a confirmed diagnosis of Turner syndrome receiving treatment at the adult endocrinology clinic, Steve Biko Academic Hospital, was performed. Seventeen patients with complete data sets were identified. Our population group had a higher percentage of mosaic Turner syndrome than that described in the literature. The clinical features also differed significantly from the classic features described, with the exception of the universal presence of short stature and hypogonadism. This may explain the delayed age of diagnosis. Screening programmes are necessary, and the consistent finding of short stature can be used as a screening tool in early childhood to identify more patients who will benefit from referral. [ABSTRACT FROM AUTHOR]

We share our experiences of instructing three patients with severe upper limb dysfunction on how to self‐adjust CPAP/NPPV masks. In Case 1, we simplified the procedure by suturing a part of the headband as the left forearm was amputated. In Case 2, the patient had congenitally short limbs with short stature; thus, we provided an additional belt to the headband to maintain the headband's configuration while wearing the mask. In Case 3, the patient had left hemiplegia due to stroke and, repetitive coaching was conducted during the recovery phase rehabilitation program. Difficulties with self‐adjusting NPPV/CPAP masks can occur whenever there is limited hand mobility above the head, including upper limb dysfunction. Simplifying procedures and providing sufficient time for instruction could help achieve independence. There have been no previous reports describing similar training details. We believe that sharing this knowledge will be helpful to both patients and healthcare professionals. [ABSTRACT FROM AUTHOR]

Short stature is a global problem in children. It's important to make early identification and treatment according their causes with participation of parents in the treatment plan to improve their quality of life of their children. The study aimed to assess mothers' knowledge and perception toward short stature of their children and its effect on quality of life. Subjects and Method: A descriptive research design was used. Setting: It was carried out at Pediatric Endocrine Outpatient Clinic of Tanta Main University Hospital. Subjects: All of mothers and their children (106) with short stature. The study was conducted at pediatric endocrine outpatient clinic of Tanta Main University Hospital. Three Tools were used to collect the required data: Tool I: Structure Questionnaire sheet of mothers' knowledge, Tool II: Mothers' perception regarding short stature and Tool III: Quality of Life in Short Stature Youth. Results revealed that mothers had low level of knowledge and perception and half of children had poor quality of life. The study concluded that short stature children had poor quality of life that prevent him from doing things, exposed to negative comparison, and affect on their parents. The study recommended that establishing educational programs for mothers to improve their knowledge toward short stature of their children. [ABSTRACT FROM AUTHOR]

Objective To investigate the changes in the serum levels of Klotho, fibroblast growth factor 23 (FGF23), and insulin-like growth factor-1 (IGF-1) in children with idiopathic short stature (ISS) before and after recombinant human growth hormone (rhGH) treatment, as well as the correlation of Klotho and FGF23 with the growth hormone (GH)/IGF-1 growth axis in these children. Methods A prospective study was conducted on 33 children who were diagnosed with ISS in the Department of Pediatrics, Hebei Provincial People's Hospital, from March 10, 2021 to December 1, 2022 (ISS group). Twenty-nine healthy children, matched for age and sex, who attended the Department of Child Healthcare during the same period, were enrolled as the healthy control group. The children in the ISS group were treated with rhGH, and the serum levels of Klotho, FGF23, and IGF-1 were measured before treatment and after 3, 6, and 9 months of treatment. A correlation analysis was conducted on these indexes. Results There were no significant differences in the serum levels of IGF-1, Klotho, and FGF23 between the ISS and healthy control groups (P>0.05). The serum levels of Klotho, FGF23, and IGF-1 increased significantly in the ISS group after 3, 6, and 9 months of rhGH treatment (P<0.05). In the ISS group, Klotho and FGF23 levels were positively correlated with the phosphate level before treatment (P<0.05). Before treatment and after 3, 6, and 9 months of rhGH treatment, the Klotho level was positively correlated with the IGF-1 level (P<0.05), the FGF23 level was positively correlated with the IGF-1 level (P<0.05), and the Klotho level was positively correlated with the FGF23 level (P<0.05), while Klotho and FGF23 levels were not correlated with the height standard deviation of point (P>0.05). Conclusions The rhGH treatment can upregulate the levels of Klotho, FGF23, and IGF-1 and realize the catch-up growth in children with ISS. Klotho and FGF23 may not directly promote the linear growth of children with ISS, but may have indirect effects through the pathways such as IGF-1 and phosphate metabolism. The consistent changes in Klotho, FGF23 and IGF-1 levels show that there is a synergistic relationship among them in regulating the linear growth of ISS children. [ABSTRACT FROM AUTHOR]

Short stature is a common physical developmental abnormality in children. Without timely and accurate diagnosis, as well as early intervention, it can impose a heavy burden on the children and their families. There are numerous causes for short stature, and the diagnostic process essentially involves identifying its underlying causes. Based on a thorough understanding of the regular patterns of child physical development and the characteristics of individuals at high risk of short stature, a scientific definition of short stature needs to be established, along with standardized diagnostic and treatment protocols, to achieve early diagnosis or referral for short stature. Furthermore, it is necessary to enhance scientific awareness of short stature among parents and primary care pediatricians, in order to avoid over-treatment, missed diagnoses, and misdiagnoses arising from "misconceptions", and to improve the scientific assessment of short stature. [ABSTRACT FROM AUTHOR]

Intellectual functioning studies carried out amongst children indicate that chronic diseases like type 1 diabetes and growth hormone deficiency (GHD), may, but do not necessarily, result in intellectual loss. Cognitive functions may decline as a child becomes older, as a disease persists over time and/or due to non-compliance with treatment recommendations or high stress levels. This study aimed to assess the cognitive functioning of children and youths with T1D and GHD-related short stature compared to healthy children. Methods: The study was carried out on 88 children with type 1 diabetes, 38 children suffering from short stature caused by (GHD), as well as a control group comprising 40 healthy children. Weschler's tests were applied to measure intellectual and cognitive functions. Results: The results suggest that for children suffering from type 1 diabetes and short stature, their chronic childhood diseases per se do not impair cognitive development. It was observed that the higher the age of chronically ill children and the longer the disease persists, the lower their scores in individual cognitive subtests. For healthy children, age is correlated with the acquisition of particular skills and higher scores in specific subtests. Conclusions: On the basis of qualitative analysis of the cognitive functions subject to the study and close clinical observation of chronically ill children, we have been able to conclude that chronic diseases may alter cognitive functioning. [ABSTRACT FROM AUTHOR]

The most common causes of short stature (SS) in children are familial short stature (FSS) and idiopathic short stature (ISS). Recently, growth plate dysfunction has been recognized as the genetic cause of FSS or ISS. The aim of this study was to investigate monogenic growth failure in patients with ISS and FSS. Targeted exome sequencing was performed in patients categorized as ISS or FSS and the subsequent response to growth hormone (GH) therapy was analyzed. We found 17 genetic causes involving 12 genes (NPR2, IHH, BBS1, COL1A1, COL2A1, TRPS1, MASP1, SPRED1, PTPTN11, ADNP, NADSYN1, and CERT1) and 2 copy number variants. A genetic cause was found in 45.5% and 35.7% of patients with FSS and ISS, respectively. The genetic yield in patients with syndromic and non-syndromic SS was 90% and 23.1%, respectively. In the 11 genetically confirmed patients, a gain in height from −2.6 to −1.3 standard deviations after 2 years of GH treatment was found. The overall diagnostic yield in this study was 41.7%. We identified several genetic causes involving paracrine signaling, the extracellular matrix, and basic intracellular processes. Identification of the causative gene may provide prognostic evidence for the use of GH therapy in non-SGA children. [ABSTRACT FROM AUTHOR]

Background: Noonan syndrome (NS) is characterized by typical facial features, short stature, congenital heart defects and other comorbidities. Lymphedema and chylous pleural effusions are also common in NS, but protein-losing enteropathy (PLE) is rarely reported. Case presentation: We present the case of a 19-year-old Chinese woman presenting with PLE. Small intestine biopsy showed obvious expansion of lymphatic vessels. The gene mutation results of the patient indicated a c.184T>G missense mutation (p. Tyr62Asp) in the PTPN11 gene (NM_002834.3). Conclusion: NS accompanied by PLE is not common, but hypoproteinemia attributable to PLE may be more common in patients with NS than previously thought. It remains uncertain whether mutation of the PTPN11 gene is related to PLE, indicating that further research is needed. [ABSTRACT FROM AUTHOR]