IntroductionHypochondroplasia (HCH) is a disproportionate short-statured skeletal dysplasia condition caused by gain-of-function pathogenic variants in the fibroblast growth receptor 3 gene (FGFR3). Although HCH typically becomes clinically apparent after the first year of life, when height discrepancy compared with the general population becomes more pronounced, diagnosis is often delayed by several years. Early recognition of HCH is challenging because of wide phenotypic variability and subtle clinical and radiographic features, leading to delayed or missed diagnosis. Furthermore, wide variant heterogeneity and restrictive testing criteria can contribute to diagnostic delays. Early diagnosis may facilitate timely clinical management and psychosocial support. However, no standardized diagnostic criteria for HCH currently exist, nor are diagnostic pathways well described in the literature.MethodsIn October 2024, 14 experts across multiple specialties completed an online survey on current clinical practices for diagnosing HCH. A subset convened in person to discuss strategies to optimize clinical diagnostic pathways, which were subsequently refined by the collective group.ResultsAge-specific diagnostic opportunities were identified. Prenatally, sonographic features of HCH may be detectable from approximately 20 weeks' gestation. Postnatally, features suggestive of HCH include a sustained fall in length/height centiles over the first 2 years of life, relative macrocephaly, neonatal seizures, and specific radiographic and neuroimaging findings. Between ages 2-3 years, a characteristic growth pattern including limb shortening and body disproportion may become evident. Neurocognitive involvement including neurodevelopmental challenges may become apparent. HCH should be considered in the differential diagnosis of idiopathic or isolated short stature. Genetic testing panels that include FGFR3 and evaluation of short-statured parents can support diagnosis.ConclusionEarly diagnosis of HCH is achievable when age-specific key clinical and radiologic features are recognized and supported by molecular testing using appropriate diagnostic platforms. This work represents an important first step towards developing consensus-based diagnostic guidelines for HCH.

CONTEXT:Although the safety and effectiveness of recombinant human growth hormone therapy (rhGH) has been reported for several years, the level of consensus on the outcomes that should be reported is unclear. OBJECTIVE:This work aims to understand the frequency and trends in reported outcomes of safety and effectiveness for rhGH therapy for growth hormone deficiency (GHD) in childhood. METHODS:A systematic review was performed in 7 English- and Chinese-language databases. Eligibility criteria included all studies published between 2003 and 2022, with participants who started rhGH before age 16 years for GHD. RESULTS:The 219 eligible studies that were identified included 171 cohort studies, 39 controlled trials, and 9 case-control studies. The median age of the participants at start of rhGH was 9.5 years (10th-90th: 7.1-11.9). The most commonly reported outcomes included change in height SDS in 117 (53%), height velocity in 105 (48%), insulin-like growth factor-1 (IGF-1) in 66 (30%), height in 63 (29%), bone age in 58 (26%), IGF-1 SDS in 45 (21%), injection site adverse events in 44 (20%), glucose concentration in 42 (19%), insulin-like growth factor-binding protein 3 in 34 (16%), and thyroid function in 30 (14%). Of the 342 different outcomes, 178 (52%) were considered as outcomes that were mainly focused on safety, 94 (28%) on efficacy, and 70 (20%) on both. Over the two decades, height SDS and height velocity remained the most frequently reported outcomes. Of the 342 outcomes, 9 (3%) were on quality of life and these were reported in 29 of 219 (13%) studies. CONCLUSION:The results of this systematic review allow the development of a core outcome set that is recommended for routine use in all children receiving rhGH for childhood GHD.

FOXP4 is a transcription factor belonging to the FOX subfamily P, which acts as a multifunctional regulator in cardiac morphogenesis, lung development, and gut development. Six heterozygous missense and loss-of-function (LoF) variants in FOXP4 were reported in a few cases to cause neurodevelopmental phenotypes with multiple congenital abnormalities. Larger studies are needed to further confirm and delineate FOXP4-related disease. In this study, exome/genome sequencing was used to identify variants in 13 participants with short stature, dysmorphic features, neurodevelopmental disorders (NDD), and congenital heart disease (CHD). Additionally, we reviewed the data of 12 published cases. Among 25 participants with FOXP4 variants, 23 carried heterozygous variants, and two were homozygous for LoF variants. Most cases presented with short stature, failure-to-thrive, and dysmorphic features. Other common features included NDD, skeletal anomalies, and CHD. All heterozygous variants recruited in this study were absent from controls, confirmed to be de novo or inherited from affected parents, and predicted to undergo nonsense-mediated decay (NMD) or disrupt canonical splicing. The two homozygous LoF variants were predicted to undergo NMD. This study provides clinical and genetic evidence to confirm the autosomal dominant disease and characterizes the recessive form of FOXP4-related disease.

INTRODUCTION:Evidence for growth hormone therapy in Indian hedgehog (IHH)-related short stature is limited. The aim of present study was to assess growth outcomes in children with heterozygous pathogenic IHH variants treated with recombinant human growth hormone (rhGH). METHODS:This is a retrospective cohort of 19 children with short stature carrying heterozygous deleterious IHH variants treated with daily rhGH (33-50 µg/kg/day); 10 attained adult height. Outcomes were height SD score (SDS), height velocity, and adult height SDS. RESULTS:At treatment start, median height SDS was -2.6 (IQR: -3.0; -2.2) and height velocity 5.1 cm/year (IQR: 4.3; 6.2). After 1 year, height velocity increased to 9.2 cm/year (IQR: 7.9; 10.3) and height SDS to -1.9 (IQR: -2.3; -1.6), with Δheight SDS 0.7 (IQR: 0.5; 1.0). Over a median of 4.0 years of therapy (IQR: 3.4; 5.7), total Δheight SDS was 1.2 (IQR: 0.8; 1.5), and 16/19 (84%) had height SDS ≥ -2.0 at last follow-up. At last follow-up, patients with predicted loss-of-function variants (n = 6) showed higher height SDS than those with missense variants (n = 13) (-0.8 [IQR: -0.9; -0.7] vs. -1.7 [IQR: -1.9; -1.6]) and greater Δheight SDS (1.4 [IQR: 1.2; 1.9] vs. 0.8 [IQR: 0.7; 1.3]). Among those reaching adult height, adult height SDS was -1.7 (IQR: -1.9; -1.6) after a median of 5.8 years of therapy (IQR: 4.0; 7.3), with Δheight SDS 0.8 (IQR: 0.7; 1.4). CONCLUSIONS:rhGH therapy was associated with clinically meaningful height gains, including adult height improvement, in children with IHH-related short stature; variant class may modify response.

INTRODUCTION:Idiopathic short stature (ISS) refers to children whose height falls substantially below the mean for sex and age relative to a reference population, despite the absence of an identifiable endocrine, genetic, syndromic, or systemic disorder. Clinical management remains challenging because no dedicated ICD-11 code exists and no universally accepted diagnostic criteria have been established. This has led to variability in how the condition is classified, inconsistency in access to testing, and uncertainty around eligibility for growth-promoting therapies. To address these inconsistencies and support broader global alignment in the recognition and management of ISS, an international consensus initiative was undertaken. METHODS:A Steering Committee of 10 internationally recognized experts with extensive clinical and academic expertise in ISS supported the development of a structured modified Delphi process. An Expert Panel of 22 key opinion leaders participated in a three‑round survey conducted between November 2025 and February 2026. Panelists evaluated draft statements related to ISS definition, diagnostic criteria, burden of disease, and decision to treat. Consensus thresholds were predefined at 70%, and statements were refined between rounds, as needed. RESULTS:A total of 44 statements achieved consensus, with final agreement levels ranging from 77% to 100%. The statements establish a standardized clinical definition of ISS, propose evidence-based diagnostic criteria applicable across diverse healthcare settings, describe the impact of ISS on patients and caregivers, and suggest when to consider growth-promoting treatment for patients with ISS. For example, consensus was reached on the definition of ISS (a condition in which an individual has a height more than a standard deviation score of 2 below the mean for sex, age, and population, corresponding to below the 2.3 percentile, without identifiable underlying pathology) and on key elements of diagnostic evaluation (include the child's medical, developmental, and medication background, including prenatal and perinatal course, chronic illnesses or infections, and neurodevelopmental milestones, alongside family history and environmental exposures; perform a physical examination to identify clinical signs of underlying pathology, including assessment of body proportions, dysmorphic body features, head circumference, body mass index, and pubertal development). Key areas requiring future research were also highlighted. CONCLUSION:This international consensus offers the first globally derived, ISS‑focused guidance developed using a formal Delphi methodology for identifying and managing children and adolescents with ISS. Adoption of these recommendations may reduce regional variability, improve diagnostic clarity, and ultimately enhance outcomes for individuals affected by ISS.

Noonan syndrome (NS) is a genetic disorder which belongs to the RASopathy family, characterized by craniofacial dysmorphisms, short stature, congenital heart defects, and an increased predisposition to malignancies. Although hematologic malignancies, neuroblastomas and certain solid tumors have been documented in NS, the co-occurrence of dysembryoplastic neuroepithelial tumor (DNET) and Hodgkin's lymphoma, has not been previously reported in the literature. We present the case of an 11-year-old boy with NS caused by a pathogenic variant in the PTPN11 gene who developed both a DNET and Hodgkin's Lymphoma. Notably, the patient had been receiving recombinant human growth hormone (rhGH) therapy prior to tumor diagnosis, raising concerns about potential contributing factors. Through a literature review, we identified reports of DNETs and lymphomas in patients with NS, highlighting the variability in genetic mutations and clinical presentations. However, no predominant PTPN11 variant was associated with a specific tumor predisposition. This case underscores the complex relationship between NS and tumor development, reinforcing the importance of individualized surveillance strategies, particularly in patients undergoing rhGH therapy. Further studies are needed to clarify the oncogenic potential of specific NS-associated mutations and to establish evidence-based guidelines for cancer surveillance in these patients.

The role of the cohesin complex depends on the cohesin loader proteins NIPBL and MAU2. While NIPBL variants are a major cause of Cornelia de Lange Syndrome (CdLS), the role of MAU2 in disease is unclear. We describe 18 individuals carrying 15 heterozygous MAU2 variants and demonstrate pathogenicity through functional analyses. MAU2 in-frame variants predominantly impair NIPBL-MAU2 interaction, whereas truncating variants cause MAU2 haploinsufficiency and lead to NIPBL reduction. Most patients exhibit a DNA methylation profile compatible with the CdLS episignature. We also identified two MAU2-specific episignatures that reflect variant-dependent molecular consequences. Affected individuals display a wide range of phenotypes, from classic CdLS to milder presentations, with short stature and microcephaly as consistent features. A heterozygous Mau2 knockout mouse model recapitulated these traits, confirming the causal role of MAU2 disruption in vivo. Our study establishes MAU2 as a new CdLS-associated gene and delineates a MAU2-related chromatinopathy with variable expressivity.

Introduction and Objective: Mutations in the ABCC8 gene, encoding the SUR1 subunit of the ATP-sensitive potassium channel, are classically associated with neonatal diabetes (NDM). However, some variants in this gene can result in MODY (Maturity-Onset Diabetes of the Young), with milder phenotypes and variable age of onset. This study aims to describe the phenotypic variability in a Brazilian family with MODY diabetes due to an ABCC8 gene mutation. Methods: This is a descriptive study of a Brazilian family with multiple members affected by diabetes. Next-generation sequencing was used to perform genetic sequencing and the identified pathogenic variant was confirmed through Sanger sequencing and classified according to ACMG criteria. Clinical data, including age at diagnosis, HbA1c, presence of diabetes complications, and sulfonylurea treatment, were analyzed. Results: Genetic sequencing of the proband identified the pathogenic variant c.2473C>T/p.R825W in ABCC8. This variant was also identified in four other family members (two offspring and two sisters). Despite the shared genetic etiology, significant phenotypic variability was observed. Age at diagnosis ranged from 16-51y. HbA1c levels at initial evaluation varied from 5.8 to 9.2%. Two offspring and one sister were asymptomatic at diagnosis, while the other sister had pre-diabetes. Only the proband exhibited diabetes-related complications (diabetic retinopathy, myocardial dysfunction). The sulfonylurea treatment response was heterogeneous, with variable doses required for glycemic control. The proband used glibenclamide 1.25 mg, while the sisters used gliclazide 30 mg and glibenclamide 5 mg. The two offspring did not require antidiabetic medication. Conclusion: The location of the pathogenic variant within the ABCC8 gene influences the disease phenotype, resulting in either MODY or NDM. Our study highlights the phenotypic variability associated with ABCC8 mutations and underscores precise molecular diagnosis's importance in guiding appropriate treatment strategies. A.C. Santomauro Junior: None. A.D. Costa-Riquetto: None. T.G. Amorim: None. F.R. Barros: None. E.B. Val: None. A. Jorge: None. M.G. Teles: None. FAPESP (#2013/19920-2)

OBJECTIVE:Self-limited delayed puberty (SLDP) is the most common cause of delayed puberty and exhibits high heritability, although few causal genes have been identified. This study aims to identify potential candidate genes associated with SLDP. METHODS:Whole-exome sequencing was conducted in 71 children with SLDP, most of whom presented with short stature. Rare coding variants were prioritized through comprehensive bioinformatics analyses and classified as high-impact or moderate-impact based on predicted functional effects. Candidate genes were selected based on the absence of human phenotype data, recurrence within the cohort, intolerance to mutation, and prior identification in genome-wide association studies. Burden tests compared the frequency of rare high-impact variants in these candidate genes between SLDP patients and the gnomAD v2.0 control group. Gene-phenotype associations were further explored using UK Biobank data. RESULTS:Fourteen high-impact and 7 moderate-impact variants were identified in 19 candidate genes, suggesting a potential role in SLDP. Variants in 8 candidate genes (GPS1, INHBB, SP3, NAMPT, ARID3B, NASP, FNBP1, PRDM2) were significantly enriched in cases compared to controls in the burden test analysis. INHBB was additionally linked to delayed menarche in UK Biobank data. Furthermore, 3 pathogenic variants (CDK13, GDF5, ANRKD11) and 6 likely pathogenic variants (TYMP, DPF2, KMT2C, TP63, MC3R, GHSR) previously associated with growth or pubertal human disorders were identified. CONCLUSION:These findings suggest that SLDP involves both monogenic and polygenic mechanisms, with novel candidate genes contributing to its genetic basis. The association of INHBB with pubertal timing underscores its potential role in SLDP pathophysiology.

BACKGROUND:To improve the precision of molecular diagnosis by means of a comprehensive bidirectional phenotypic and genotypic reanalysis in cases of unresolved monogenic diabetes previously investigated using a targeted next-generation sequencing (tNGS) panel. METHODS:Molecular and clinical data from 128 unresolved cases referred between 2011 and 2019 were analyzed. These included 92 cases of suspected maturity-onset diabetes of the young (MODY), 12 of neonatal diabetes, 16 of familial partial lipodystrophy (FPLD), 7 of mitochondrial diabetes, and 1 of Wolfram syndrome. All cases were initially investigated using a tNGS panel consisting of 51 nuclear genes and the complete mitochondrial genome. RESULTS:This extensive reanalysis process increases molecular diagnosis from 9 to 22%. Phenotypic reevaluation, entailing in-depth phenotyping, is instrumental in excluding 62 atypical cases (48.4%). Genotypic reanalysis identifies 5 previously overlooked molecular defects: two mutations in regulatory regions (one in the HNF1A promoter and another in the PTF1A enhancer); one in the MTTK mitochondrial gene; one in the MFN2 gene; and one in the GCK gene. CONCLUSIONS:Our findings indicate that a combined approach of genotypic and, mainly, phenotypic reanalysis is an effective strategy for improving the accuracy of molecular diagnosis in individuals with suspected monogenic diabetes.

This study aimed to evaluate a cohort of patients with syndromic tall stature of unknown etiology via exome sequencing (ES) to identify novel candidate genes for overgrowth conditions. We enrolled 37 patients with heights greater than the 97.7th percentile and syndromic features. The ES analysis first focused on rare deleterious single nucleotide and copy number variants in genes previously associated with overgrowth conditions. For patients in whom diagnosis of a known tall stature disorder could not be achieved, we performed analysis for candidate genes. The search considered deleterious variants in constrained genes that were linked with height in association studies, animal models consistent with the proposed phenotype, and/or variants recurrent in the literature or our cohort. Genetic diagnosis was established in 11 patients. Pathogenic or likely pathogenic variants were identified in FBN1, PTEN, NSD1, SUZ12, CDH8, and DEPDC5. One patient carried a likely pathogenic mutation in FBN2 and a pathogenic mutation in COL5A1. Furthermore, in two patients, we identified large pathogenic deletions confirmed by chromosomal microarray analysis. Candidate gene analysis uncovered four genes potentially associated with tall stature in five patients: PTCH1, SST, KDM4A, and GRB10. PTCH1 and SST were identified in patients with whole gene deletions. Two unrelated patients were found to have the same rare missense variant in KDM4A. In conclusion, exome sequencing analysis had a diagnostic yield of 29.7% in a cohort of patients with syndromic tall stature and we identified four novel candidate genes that are involved in overgrowth conditions.

Introduction: RASopathies are a heterogeneous group of conditions of the RAS/mitogen-activated protein kinase pathway presenting with overlapping features such as growth deficiency, neurodevelopmental disorders, cardiac defects, craniofacial dysmorphisms, cutaneous and ocular abnormalities, and increased cancer risk. Methods: This retrospective study analyzed the medical records regarding clinical and molecular data from 2018 to 2024 in a single center for rare diseases of individuals diagnosed with Noonan syndrome and related disorders previously submitted to diagnostic molecular analysis through next-generation sequencing techniques. Results: Twenty-four patients were enrolled with an even sex ratio distribution and ages ranging from 1 month to 16 years at first evaluation. The main reason for referral was diagnostic assessment due to a combination of dysmorphic features (24/24; 100%), growth deficiency (18/24; 75%), neurodevelopmental disorders (15/24; 62.5%), and/or heart disease (13/24; 54.1%). Final diagnoses included 15 individuals with Noonan syndrome (nine with variants in PTPN11, two in SOS1, and one each in LZTR1, A2ML1, and MRAS, besides one with variants in both LZTR1 and SOS1), two with Noonan syndrome with multiple lentigines (both with variants in PTPN11), two with Neurofibromatosis-Noonan (NF1), two with cardiofaciocutaneous syndrome (BRAF), and one each with Noonan syndrome-like with loose anagen hair (PPP1CB), Noonan syndrome-like (CBL), and Costello syndrome (HRAS); one individual presented with a double diagnosis of Noonan and Klinefelter syndromes. Conclusion: Three pairs of unrelated patients presented recurrent variants in the PTPN11 gene, partially concordant in phenotypic correlation among the pairs but not fully concordant compared to previously described cases in the literature. Undescribed features in this group included myopathy and megacolon in a patient with Noonan syndrome-like, hypogonadotropic hypogonadism, and azoospermia in a patient with Noonan syndrome-like with loose anagen hair, and schizophrenia in a patient with Costello syndrome. One patient with Noonan syndrome had a novel variant of the A2ML1 gene (c.1829G>A), but the variant was strictly of uncertain significance, while c.2033G>A in the LZTR1 gene and c.1A>G in the NF1 gene are variants for the first time associated with features of Noonan syndrome.

Noonan Syndrome (NS) is a clinically and genetically heterogeneous condition characterized by typical facial dysmorphisms, short stature, congenital heart defects, and developmental delays. While variants in genes such as PTPN11, SOS1, and RAF1 account for most genetically confirmed cases, diagnosis is challenging due to phenotypic overlap with other syndromes. In this retrospective study, we reviewed 192 patients with a clinical diagnosis of NS at a single tertiary center. Genetic diagnosis of NS was confirmed in 133 patients (69.4%) and diagnosis of non-NS RASopathies was confirmed in 5 patients via targeted RASopathy panels. Exome sequencing (ES) was performed in 20 of the undiagnosed patients. In six cases, alternative genetic diagnoses were established due to variants in SETD5, BRPF1, DPH1, ACTB, CREBBP, and GATA4, genes associated with syndromes presenting overlapping phenotypes with NS. Our findings emphasize the utility of a hypothesis-free approach that uses phenotypic features to prioritize variants in resolving diagnostic uncertainty in NS-like presentations. These findings also highlight the need to broaden differential diagnoses beyond RASopathies when genetic confirmation of NS cannot be established.

Cell number is a major determinant of organism size in mammals. In humans, gene mutations in cell cycle components result in restricted growth through reduced cell numbers. Here we identified biallelic mutations in CDK4 as a cause of microcephaly and short stature. CDK4 encodes a key cell cycle kinase that associates with D-type cyclins during G1 of the cell cycle to promote S-phase entry and cell proliferation through retinoblastoma (RB) phosphorylation. CDK4 and CDK6 are believed to be functionally redundant and are targeted jointly by chemotherapeutic CDK4/6 inhibitors. Using molecular and cell biology approaches, we show that functional CDK4 protein is not detectable in cells with CDK4 mutations. Cells display impaired RB phosphorylation in G1, leading to G1/S-phase transition defects and reduced cell proliferation, consistent with complete loss of cellular CDK4 enzymatic activity. Together, these findings demonstrate that CDK4 is itself required for cell proliferation, human growth, and brain size determination during development.

El crecimiento es un fenómeno biológico continuo resultante del equilibrio entre la cantidad, calidad y función de la materia, que permite adquirir de forma paulatina una conformación estable y un desempeño maduro, que se debe expresar en forma plena y óptima en todos los humanos. Su expresión debe considerarse un signo de salud y por ello debe ser analizado por todos los médicos en la vigilancia de cada paciente desde el nacimiento hasta el término de la pubertad, ya que al ser un indicador objetivo nos permite cuantificar y calificar las variaciones en las dimensiones físicas y la composición corporal a las diferentes edades, y refleja el equilibrio entre la expresión de las condiciones genéticas y los factores permisivos o restrictivos del medio ambiente. El método más recomendable es comparar las medidas auxológicas de una población con la expresión individual, aunque debe considerarse que los estudios poblacionales señalan solo lo que es “habitual” en una población, lo que no forzosamente es sinónimo de normal ni de óptimo, ya que: varones y mujeres muestran diferencias en la edad e intensidad del crecimiento, el crecimiento prenatal puede afectar al crecimiento posnatal, existen variaciones étnicas o raciales en la expresión del crecimiento posnatal, hay variaciones entre familias de la misma etnia en el crecimiento posnatal, y existen variaciones en la velocidad de maduración incluso dentro de miembros de la misma familia. Se describen las principales medidas antropométricas, las características de los instrumentos que las cuantifican y cómo se debe analizar el resultado. PALABRAS CLAVE: Crecimiento, antropometría, talla, peso, índice de masa corporal, proporcionescorporales, velocidad de crecimiento

Abstract Disclosure: M. Alimussina: None. J. Bryce: None. M. Chen: None. S. Koley: None. A. Al-Agha: None. N. Amin: None. N. Atapattu: None. J. Chen: None. Y. Deyanova: None. A. Fu: None. C. Gong: None. V. Iotova: None. D. Janus: None. A. Jorge: Consulting Fee; Self; Novo Nordisk. Grant Recipient; Self; BioMarin. R. Markosyan: None. S. Seneviratne: None. M.G. Shaikh: None. S. Shenoy: None. S. Shepherd: None. L. Tack: None. M. Wasniewska: None. S. Chen: Research Investigator; Self; Pfizer, Inc. S.F. Ahmed: Grant Recipient; Self; GenSci, Novo Nordisk, Pfizer, Inc.. Speaker; Self; Ipsen. Introduction: The Global Registry For Novel Therapies In Rare Bone & Endocrine Conditions (GloBE-Reg, https://globe-reg.net/) project was launched in 2022 with the aim of supporting studies that focus on effectiveness and long-term safety of specific therapies. The project’s initial focus has been on recombinant human growth hormone therapy (rhGH). Although safety information on rhGH therapy has now been collected for several years, there are still existing gaps in our knowledge, especially with the introduction of new indications and novel forms of rhGH. Methods: The GloBE-Reg registry has three layers of datasets, with the first dataset consisting of internationally agreed core data elements that can apply to any rare condition, another set of data elements that allows the selection of a specific therapy and diagnosis, a third set of additional data elements that is made up of the therapy and diagnosis-specific minimum dataset (MDS) and an option to have a more extended dataset. The minimum dataset collects information on the diagnosis, therapy, clinician reported outcomes, patient reported outcomes and adverse events. The platform and the registry received ethics/IRB approval in the UK and is now extending internationally. The fields within the MDS are developed following guidance from short-life expert working groups (EWG). Results: Since its launch in November 2022, 51 centres from 29 countries have registered their interest to use the platform and of these, 14 centres from 11 countries in 3 continents have already included 444 (M:F, 282:162) patients with a median age of 11 yr (range <1, 29). Of these, 317 (71%) were on daily rhGH, 126 (28%) were on long-acting rhGH, one was on daily rhGH as an adult and in one, rhGH therapy had been discussed but not started. Nine different brands of rhGH were being used across these centres for 9 groups of indications, whereas long-acting rhGH was being used for only 4 indications. In addition, there were 11 (3%) cases receiving rhGH for other conditions associated with short stature or growth retardation. The largest indication group was GHD (65%) followed by SGA (10%), TS (7%), PWS (7%), ISS (5%) and others. Of the 444 cases, 67 (15%) had also been entered in other disease registries and 18 (27%) of these 67 had been entered by one centre into the GloBE-Reg through its bulk upload facility. A Childhood GHD MDS is now fully operational and MDS for other conditions are under development. Conclusion: Since its launch, GloBE-Reg has shown that a relatively low-cost platform operated through an academic institution can have sufficient stakeholder acceptability and versatility for collecting information that can support the development of long-term safety and effectiveness studies. The preliminary data that have been collected on rhGH show the long-term utility of the platform for collecting global brand and diagnosis-specific data. Presentation: 6/2/2024