Longitudinal growth trajectories and predictive risk factors for short stature in extremely preterm infants up to six years of age.

Obstetric challenges in suspected fetal macrosomia: Risk factors and assessment.

Chinese adults' and children's heights have grown over two decades, but many parents remain unaware of the main factors affecting their children's height. This study analyzed clinical and early pharmacological interventions for preventing and treating growth disorders and promoting normal growth in children with deviations. This study involves a non-randomized intervention. A retrospective study of 120 children examined at our hospital from March 2023 to February 2025 were divided into four groups based on height and development: short stature group (SS, n=28), less short stature group (LSS, n=32), early development group (ED, n=41) and central precocious puberty group (CPP, n=19). The SS group and LSS group received oral lysine, inositol, vitamin B12 solution + γ-aminobutyric acid (GABA) and the ED group and CPP group received oral Zhi Bai Di Huang Wan and all children were given health guidance. Clinically relevant information, such as baseline information, height growth values, and growth factor levels before and after treatment, was collected and compared among the four groups of children, and pre-treatment factors affecting children's height growth outcomes were also analyzed. Before treatment, the four children's groups differed significantly (P < 0.05). After 3 and 6 months, all children's heights increased, with the fastest growth in the LSS group. Logistic regression showed sex and age before treatment were key factors affecting height. ROC curves revealed AUCs for sex, age and the model of 0.599(95% CI: 0.497-0.701), 0.774(95%CI: 0.686-0.861) and 0.818 (95% CI: 0.735-0.900). Clinical analysis and early intervention for children with growth deviations detected during school physical exams can restore normal growth, slow early bone age advancement, improve height outcomes and prevent or treat growth disorders.

Precocious puberty: An overview of pathogenesis, clinical presentation, and management.

Achondroplasia (ACH) results from a missense mutation in the FGFR3 (fibroblast growth factor receptor 3) gene, representing the primary cause of short stature in humans. This study aims to describe the clinical features, complications, and management outcomes of Saudi patients with achondroplasia. This retrospective study included achondroplasia cases followed at the endocrinology clinic at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia, from (2015-2025). Thirty-three patients were included; 32 were heterozygous and one was homozygous for the FGFR3 c.1138G > A variant. Median age at presentation was 24 months (IQR 7-60), and 54.5% were male. Short stature was universal, with frontal bossing and skeletal deformities present in 93.9%. Developmental delay was observed in 54.5%, while neurological symptoms and hearing loss were each noted in 42.4%. Clinical suspicion of obstructive sleep apnea (OSA) was identified in 17/33 patients (51.5%), with 41.2% (7/17) requiring surgical intervention. Yet, polysomnography was performed in only 10 patients and confirmed OSA in all cases. Radiologic abnormalities were common, with abnormal brain or spine imaging in 96.4% (27/28), foramen magnum stenosis in 50% (14/28), and spinal abnormalities in 71.4% (20/28). Median baseline height SDS was - 5.5. Growth hormone therapy was used in four patients, with only one demonstrating transient benefit. Overall mortality was 9.1% (3/33), including one homozygous infant and two heterozygous patients. This study provides the largest single-center characterization of achondroplasia in Saudi Arabia. The findings highlight the high burden of airway and hearing complications and the limited long-term efficacy of GH therapy, underscoring the need for multidisciplinary and targeted management strategies.

These findings underscore the clinical and genetic heterogeneity of acromelic dysplasias and emphasize that integrated clinical and molecular evaluation is essential for accurate classification and follow-up. • Acromelic dysplasias are rare connective tissue disorders characterized by short stature, brachydactyly, and joint stiffness, caused by variants in genes involved in extracellular matrix organization and TGF-β- related signaling. • Five novel variants in ADAMTSL2, ADAMTS10, and ADAMTS17 expand the molecular spectrum of acromelic phenotypes. • Tiptoe walking, in association with early findings including short stature, acromelia, and broad proximal phalanges on radiographs, may suggest ADAMTSL2-related geleophysic dysplasia.

To evaluate the long-term safety outcomes of recombinant human growth hormone (rhGH) administered to Korean pediatric patients with growth disorders, including growth hormone deficiency, Turner syndrome, idiopathic short stature, small for gestational age, chronic kidney disease, and Prader-Willi syndrome, using 10-year interim data from the nationwide LG Growth Study registry in the Republic of Korea. Prospective, multicenter, observational registry. This interim analysis included 5,040 patients from 96 centers, representing 19,878 patient-years of treatment between November 2011 and December 2022. Although the registry spans 10 years, follow-up was limited to periods of active GH treatment and therefore varied across patients. Patients received daily or weekly rhGH. Adverse events (AEs), adverse drug reactions (ADRs), serious AEs (SAEs), and serious ADRs (SADRs) were recorded and compared with international registry data. Overall, AEs occurred in 34.2% of patients, ADRs in 7.0%, SAEs in 3.2%, and SADRs in 0.3%. The most frequent AE was scoliosis (1.6%), followed by headache (0.8%) and injection site pain (0.5%). Three malignant neoplasms were reported, yielding a standardized incidence ratio of 1.1 (95% confidence interval, 0.21-2.69), comparable to expected national rates. Craniopharyngioma recurrence occurred in 14.3% of affected patients, consistent with international data. Over 10 years, rhGH therapy in Korean pediatric patients demonstrated a low incidence of ADRs and SADRs, with malignancy and tumor recurrence rates similar to those in global registries. These findings support the long-term safety of rhGH for pediatric growth disorders, with continued surveillance warranted. Using 10 years of real-world data from a pediatric registry, conducted in the Republic of Korea, this study provides one of the largest single-nation safety evaluations of rhGH therapy across multiple etiologies of short stature. The low incidence rates of ADRs and SADRs, in alignment with rates reported for other large-scale international registries, provide reassuring evidence of the safety of rhGH for clinicians and caregivers.

ABSTRACTIntroductionSkeletal complications are common in sickle cell disease (SCD). We previously showed that the prevalence of low areal bone mineral density (aBMD) increased with age in a pediatric SCD cohort, even after adjusting for short stature. Data on age‐related aBMD trends in young adults is lacking.MethodsUsing retrospective data from the Sickle Cell Clinical Research and Intervention Program (SCCRIP), we converted lumbar spine (LS) and total body (TB) aBMD from 713 SCCRIP participants (49.2% females, ages 6–24 years) to age‐, sex‐, ancestry‐, and height‐adjusted Z‐scores, using data from healthy African American controls enrolled in the Bone Mineral Density in Childhood Study.ResultsLow TB bone density prevalence rates increased with age: 29.5% in children (6–< 12 years), 36.7% in adolescents (12–< 18 years), and 42.2% in young adults (18–24 years). LS aBMD followed a similar age‐related trend. Multivariable analysis revealed older age (OR 1.10, 95% CI 1.06–1.16), lower hemoglobin (OR 0.833, 95% CI 0.740–0.936), and higher eGFR (OR 1.01, 95% CI 1.00–1.02) as independent predictors for low TB BMD.ConclusionThese findings highlight the progressive decline of aBMD in SCD and underscore the need for early screening to mitigate morbidity due to SCD‐related skeletal complications.Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission

Progressive short stature in Pearson syndrome and the impact of organ failure.

Individual responses to recombinant human growth hormone (rhGH) therapy vary widely among children with idiopathic growth hormone deficiency (iGHD) and idiopathic short stature (ISS), making accurate prediction of treatment outcomes clinically important. This study aimed to develop and compare machine learning (ML)-based and conventional statistical models to predict short-term growth response and mid-parental height (MPH) attainment following rhGH therapy in iGHD and ISS patients. Retrospective observational cohort study using a nationwide, real-world registry. A total of 2215 children (1877 with iGHD and 338 with ISS) treated with rhGH were identified from the Korean LG Growth Study database. All included patients had at least 1 year of follow-up with available clinical data. Primary outcomes were 1- and 2-year changes in height SDS (ΔHSDS) and achievement of MPH SDS. Predictive models included multiple linear regression, logistic regression, Random Forest, eXtreme Gradient Boosting, and Elastic Net. Model performance was evaluated using R², error metrics and area under the receiver operating characteristic curve. Model interpretability was assessed using SHAP values. In the iGHD group, ensemble ML models modestly outperformed linear regression for predicting 1-year ΔHSDS (R² ≈ 0.19 vs. 0.16), but predictive performance declined at 2 years across all models. Prediction of MPH attainment showed high specificity but very low sensitivity at 1 year, with no clear advantage of ML over logistic regression. In ISS patients, all models demonstrated poor predictive performance for both ΔHSDS and MPH attainment, reflecting substantial clinical heterogeneity. ML approaches provided limited but clinically meaningful improvements in predicting short-term growth response in iGHD, while offering no clear benefit in ISS. These findings highlight both the potential and limitations of ML models based solely on routine clinical variables and underscore the need for integrating multimodal data to improve growth prediction, particularly in heterogeneous ISS populations.

ABSTRACT Body dissatisfaction drives compensatory behaviors in modifiable domains like weight, but less is known about dissatisfaction with fixed traits such as height. This study examined how height and height dissatisfaction relate to appearance management strategies. A community sample of 328 Australian adults (72.89% female) completed measures of height, height dissatisfaction, and six compensatory behaviors, including footwear use, body composition changes, and concealment. Shorter height and greater dissatisfaction were linked to more frequent compensatory behaviors, particularly among males. Height dissatisfaction predicted most strategies more strongly than actual height and fully mediated the link between height and fat-reduction behaviors, while partially mediating footwear use. A suppression effect emerged: shorter dissatisfied individuals compensated more, but when controlling for dissatisfaction, taller individuals also reported higher compensatory behaviors. Males more often pursued muscularity and height-enhancing strategies, while taller females reported concealment behaviors like slouching. Findings align with gendered height norms and highlight height dissatisfaction as an overlooked body image concern with behavioral consequences, underscoring the need for inclusive body image frameworks.

Perceived leg length discrepancy (pLLD) is a common source of dissatisfaction after total hip arthroplasty (THA), even in the absence of significant radiographic discrepancies. While spinopelvic factors have been increasingly recognized, most previous studies have focused on sagittal alignment or lumbar mobility, and the impact of preoperative global spinopelvic coronal flexibility on pLLD has remained unclear. We retrospectively reviewed 114 patients who underwent primary unilateral THA for osteoarthritis between January and December 2023. pLLD was assessed using a four-point scale at 6 months postoperatively. Patients who reported no perception of discrepancy were classified as the non-pLLD group, while those reporting mild, clear, or strong perception were grouped as the pLLD cohort. Preoperative spinal flexibility was measured on coronal radiographs during maximal lateral bending, calculating changes in spinopelvic angle (ΔSPA), reflecting thoracic-to-pelvic coronal flexibility, and lumbosacral angle (ΔLSA), reflecting lumbar-to-pelvic coronal flexibility. Secondary parameters included radiographic leg length discrepancy, leg lengthening, and sagittal spinopelvic alignment. Multivariable logistic regression analysis was used to identify independent predictors of pLLD. pLLD was reported in 47 patients (41.2%). The pLLD group exhibited significantly lower ΔSPA values (16.6° vs. 21.9°, P = 0.001) compared to the non-pLLD group, although ΔLSA did not differ significantly. Multivariable analysis revealed that lower ΔSPA (P = 0.006) and shorter height (P = 0.037) were independently associated with pLLD. Radiographic leg length discrepancy did not differ significantly between the two groups. Reduced preoperative global spinopelvic coronal flexibility, particularly diminished ΔSPA, was associated with the perception of leg length discrepancy following THA. Assessment of coronal spinopelvic flexibility may provide additional insight for preoperative evaluation and patient counseling. Further studies are warranted to better understand whether perioperative rehabilitation aimed at improving coronal spinopelvic mobility may help to mitigate pLLD after THA.

Objective: To investigate cognitive function and brain MRI characteristics in children aged 7~18 years with phenylketonuria (PKU) and their association with blood phenylalanine (Phe) control levels. Methods: This was a cross-sectional study. Clinical data including general characteristics, random blood Phe levels, Wechsler intelligence scale for children scores, and MRI scores were collected from 29 PKU patients aged 7-18 years treated at Guangzhou Women and Children's Medical Center from July 2024 to July 2025. Patients were divided into two groups by random blood Phe>600 μmol/L and ≤600 μmol/L and by historical Phe target attainment rate into relatively well-controlled (≥50%) and poorly-controlled (<50%). Independent-samples t-test, Mann-Whitney U test and multiple linear regression were used to examine the effects of blood Phe control, clinical phenotype and other factors on full scale intelligence quotient (FSIQ) and MRI scores. Results: Among the 29 patients, 17 were males and 12 females, including 17 with classic PKU and 12 with mild PKU. Twenty-seven (93%) were diagnosed early via newborn screening. Physical development was generally normal in 27 patients except for 1 with short stature and 1 with obesity. The random blood Phe level was (634±262) μmol/L. The random blood Phe level in the relatively well-controlled group (19 cases) was significantly lower than that in the poorly-controlled group (10 cases) ((550±266) vs. (794±171) μmol/L, t=2.17, P=0.039). The FSIQ was 90±14 points. The overall abnormality rate on brain MRI was 86% (25/29), with predominant white matter lesions in the parieto-occipital lobe. The MRI score was 4 (2, 16) points, and 10 cases (34%) had a score ≥10 points. Diffusion restriction was observed in 16 cases (55%), of whom 13 cases had random blood Phe>600 μmol/L. The >600 μmol/L group (18 cases) had lower FSIQ, verbal comprehension and working memory scores (all P<0.05), and higher MRI scores (6 (3, 20) vs. 2 (0, 4), Z=2.26, P=0.024) than the ≤600 μmol/L group (11 cases). FSIQ and the scores for verbal comprehension, perceptual reasoning, working memory, and processing speed were all significantly lower in the poorly-controlled group than in the relatively well-controlled group (all P<0.05). Multiple linear regression indicated that long-term Phe metabolic control status (β=0.63, P=0.003) was an independent predictor of FSIQ (F=3.18, P=0.022, adjusted R²=0.33), whereas age (β=0.44, P=0.015) and random blood Phe level (β=0.42, P=0.044) were independent predictors of MRI score (F=4.34, P=0.006, adjusted R²=0.37). Conclusions: In early-diagnosed PKU patients aged 7~18 years, FSIQ is within the average range, often accompanied by varying degrees of white matter abnormalities. Poor long-term metabolic control of blood Phe is closely associated with cognitive decline. Recent blood Phe level >600 μmol/L correlates with more extensive white matter lesions, frequently accompanied by acute brain injury with restricted diffusion.

To develop and evaluate a simplified method for skeletal age assessment in adolescents as a rapid alternative to the Greulich-Pyle (GP) method. Retrospective methodological study comparing the simplified method with the GP atlas, with duplicate readings by experienced and inexperienced raters. One hundred and seventeen hand and wrist radiographs (67 boys, 50 girls) from adolescents referred for short stature but otherwise healthy. Radiographs with GP-assessed bone age ≥ 9 years in girls and ≥ 11 years in boys were included. Bone age was scored independently using GP and simplified methods in two rounds by two paediatric endocrinologists and, for the simplified method, two residents. Outcomes included measures of agreement between methods, the proportion of readings within ±1 year of GP, and inter- and intra-rater reliability. Among experienced raters, the simplified method showed minimal bias relative to GP, with about 91% of readings within ±1 year. Reliability coefficients for both methods exceeded 0.9. Repeatability of the simplified method was slightly lower than GP but remained within clinically acceptable limits and close to predefined acceptability thresholds for inexperienced raters. The simplified method offers a transparent, standardised, and reproducible approach to adolescent skeletal age assessment. Although not intended to replace the GP method, it is particularly suited to research involving large datasets or resource-limited environments and to population-level skeletal analyses. In busy clinics, it may also serve as a quick check of radiologists' GP-based interpretations, allowing review of reported bone ages without repeating a full atlas assessment.

There are few studies comparing the impact of different bone age (BA) assessment methods on treatment follow-up cycles. This study aimed to analyze the value of artificial intelligence-assisted multiple BA assessment methods in evaluating the efficacy of idiopathic short stature (ISS) in traditional Chinese medicine treatment. We selected 388 cases of healthy children’s BA data from November 2021 to August 2024 in a single center as the control group, and 190 cases of female pediatric patients with ISS admitted in the same period as the treatment group, which were divided into 120 cases in the effective group and 70 cases in the ineffective group according to the final therapeutic efficacy. They were divided into 3 periods of 6, 9, and 12 months according to the interval of follow-up. All the children underwent left hand X-ray examinations before treatment and after follow-up, all the X-rays were taken using artificial intelligence-assisted Greulich and Pyle atlas (G&P), Tanner Whitehouse 3 (TW3), and Tanner Whitehouse China 05 (TW C) methods for assessment. We analyzed the initial and follow-up BA assessment results and their differences and compared the relationship between the BA difference and the efficacy of each method. The results showed that the overall difference in BA follow-up was significantly higher in the treatment-effective group than in the ineffective group (P < .01). The assessment value of BA difference based on TW3 and TW C methods was better than that of the G&P method in the follow-up of the 6th, 9th and 12th months (P < .01). The TW C and TW3 methods could evaluate the efficacy of the treatment early in the 6-month follow-up, while the G&P method had a diagnostic value in the 12-month follow-up. Both TW3 and TW C methods of BA assessment can be used to evaluate the treatment effect as early as the 6-month follow-up period, and the TW C method had a higher diagnostic value of efficacy in Chinese girls with ISS compared with the TW3 and G&P methods.

Structural variants (SVs) are genomic rearrangements of 50bp or more and contribute substantially to human genetic disorders. They are often incompletely resolved using cytogenetic and short-read sequencing approaches. Emerging technologies such as long-read sequencing (LRS) and optical genome mapping (OGM) provide complementary advantages for SV detection. This study aimed to evaluate the combined utility of OGM and LRS for the precise delineation of clinically relevant chromosomal rearrangements. Five patients with suspected chromosomal abnormalities were investigated using karyotyping, fluorescence in situ hybridisation (FISH), chromosomal microarray (CMA), and triplet repeat-primed PCR (TP-PCR), followed by integrative analysis using OGM and LRS. In Case 1 (short stature and recurrent miscarriages), OGM identified two insertions in addition to a balanced translocation, whereas LRS revealed disruptions in the NBAS and VTI1A genes. In Case 2 (Fragile X syndrome), LRS precisely determined the exact size of FMR1 CGG repeats, supported by OGM. In Case 3, LRS resolved inversion breakpoints with associated microdeletions and insertions associated with recurrent miscarriages. In Case 4, OGM identified an additional intrachromosomal rearrangement on chromosome 18. In Case 5, OGM detected an intrachromosomal fusion underlying intellectual disability. Overall, OGM provided genome-wide structural insights, while LRS enabled nucleotide-level breakpoint resolution. Except for case 2, all rearrangements are novel. Our study concludes that the combined application of technologies enables comprehensive characterisation of complex SVs that remain unresolved by standard methods. This integrative approach improves diagnostic yield, facilitates genotype-phenotype correlation, and supports the implementation in SV detection for patients.

Case seriesPatients: Female, 20-year-old • Female, 28-year-oldFinal Diagnosis: Turner syndromeSymptoms: Primary amenorrheaClinical Procedure: —Specialty: GeneticsObjective: Congenital defects/diseasesBackgroundFamilial Turner syndrome (TS) is an uncommon sex chromosome abnormality, typically characterized by the transmission of identical X-chromosomal aberrations (eg, partial or complete deletions) within a lineage. The occurrence of familial TS involving distinct karyotypes within the same generation is exceptionally rare and presents unique challenges for genetic counseling and mechanistic understanding.Case ReportsTwo cousins (aged 20 and 28) from a nonconsanguineous family presented with primary amenorrhea, hypergonadotropic hypogonadism, and short stature. Despite striking phenotypic convergence, karyotyping demonstrated 46,X,i(X)(q10) in the proband (III-17) and 45,X in the cousin (III-13). Pelvic ultrasonography showed absent or underdeveloped internal genital organs and gonadal dysgenesis in both patients. Systematic cardiac and renal screening revealed no structural abnormalities. Whole-exome sequencing and copy number variation analysis performed on 11 relatives (including both patients) ruled out pathogenic variants in known TS-associated loci under American College of Medical Genetics and Genomics 2015/2019 criteria; low-level or tissue-restricted mosaicism could not be definitively excluded. A structured literature review was conducted to compare previously reported familial TS patterns.ConclusionsThis report documents a rare instance of intrafamilial phenotypic uniformity despite genotypic heterogeneity. The findings support the hypothesis that functional haploinsufficiency of the X-chromosome short arm (Xp) acts as the convergent pathogenic mechanism for the core TS phenotype, regardless of the specific chromosomal error. Clinicians should recognize that familial clustering can occur via distinct cytogenetic mechanisms, requiring broad prenatal screening rather than targeted testing for recurrence, along with careful counseling regarding the uncertainties of heritability versus coincidental de novo events.

Hemifacial microsomia (HFM) is a congenital craniofacial anomaly characterized by mandibular hypoplasia and facial asymmetry. Kissing molars (KM) represent a rare dental anomaly in which the occlusal surfaces of impacted molars are in contact with each other. The aim of this case report is to present the coexistence of KM in a patient diagnosed with HFM. A 28-year-old male patient presented with discomfort in the left posterior mandibular region. Clinical examination revealed facial asymmetry associated with mandibular growth deficiency on the left side. Panoramic radiography demonstrated a KM configuration in the left mandibular posterior region and mandibular hypoplasia on the affected side. The mandibular deformity was classified as Type II A according to the Pruzansky–Kaban classification. Due to symptoms and potential complications, the impacted teeth were surgically removed. Postoperative healing was uneventful, and bone healing was observed at the six-month follow-up. Atypical impacted tooth configurations may occur in patients with HFM. This case contributes to the literature by presenting the coexistence of HFM and KM.

Pseudohypoparathyroidism (PHP) is a rare disorder characterized by hypocalcemia and elevated PTH. Although short stature is a key feature, especially in PHP type 1 (PHP1), growth data in Chinese patients remain limited. Clinical data, including height, age, and biochemical indices, were retrospectively collected from PHP1 patients at Peking Union Medical College Hospital. Molecular diagnosis was performed using MS-MLPA, Sanger sequencing, and WES. Growth charts for height, weight, and BMI in underage patients were constructed. A total of 92 PHP1 patients (58 males, 34 females) including 32 pseudohypoparathyroidism type 1A (PHP-1A), 49 sporadic pseudohypoparathyroidism type 1B (PHP-S1B), and 11 autosomal dominant pseudohypoparathyroidism type 1B (PHP-AD1B) were recruited. Growth velocity peaked at 12 years in males and 5 years in females, with height plateau at 14 and 13 years. Adult height was 166.6 cm (SDS -1.04) in males and 155.0 cm (SDS -0.52) in females. PHP-1A patients had significantly shorter adult height than PHP-1B (male: 157.0±6.9 vs. 171.9±8.9, P=0.004; female: 146.8±10.2 vs. 156.2±4.9, P=0.007). PHP-1A showed early-onset weight gain from age 1, persisting into adulthood. Adult Wt-SDS was 1.67 vs. 1.55 in males and 2.00 vs. 3.10 in females (PHP-1A vs. PHP-1B). Weight curves exceeded population P50 in most groups, with no significant differences in adult weight, Wt-SDS, BMI, or obesity prevalence between subtypes. Chinese PHP1 patients show early growth plateau and short stature, more severe in PHP-1A. Obesity varies by subtype and sex, with earlier and more persistent weight gain in PHP-1A. These growth charts may aid clinical management.

Most symptoms resolved within the first year of diagnosis. The lower resolution rate for constipation compared to other GIs suggests a functional etiology, while the delayed recovery of anemia and short stature likely reflects their complex etiology. Serological normalization and GFD adherence are confirmed as predictors of clinical remission. •Time to clinical remission in celiac children after starting a gluten-free dietmay vary between different symptoms. •Clinical remission is associated with serological normalization and adherence to diet. •Constipation has a significantly poorer rate of resolution among other gastrointestinal symptoms, due to its functional etiology, while anemia and short stature resolve slightly slower. •Most patients reach clinical remission within the first year on a gluten-free diet; serological normalization and diet adherence are confirmed to be predictors of clinical remission.