Hormone Research in Paediatrics最新文献

{"title":"Transition between Pediatric and Adult Diabetes Healthcare Services: An Online Global Survey of Experiences and Perceptions of Young People with Diabetes and Their Carers.","authors":"Laura Cudizio, Steven James, Nisa M Maruthur, Sze May Ng, Sarah Lyons, Aleksandra Araszkiewicz, Apoorva Gomber, Frank Snoek, Eva Toft, Jill Weissberg-Benchell, Carine de Beaufort","doi":"10.1159/000545118","DOIUrl":"10.1159/000545118","url":null,"abstract":"<p><strong>Introduction: </strong>Young adults with diabetes face many challenges during emerging adulthood. Our study aimed to identify experiences and perceptions of people with diabetes (PwD) (aged 14-25 years) and their carers, around transition planning, and the actual transfer from pediatric to adult diabetes healthcare services.</p><p><strong>Methods: </strong>Data were collected via an online global survey (seven language options), broadly advertised by the scientific societies ISPAD, EASD, patient advocates, team members and partners, via newsletters, websites, e-mails, and social media.</p><p><strong>Results: </strong>There were 146 respondents from 29 countries. Of these, 90 (61.6%) were PwD age 18.5 (±3.6 years), diagnosed at 9.0 (±4.4 years), and 56 (38.3%) carers. Respondents receiving care in pediatric units (vs. adult) (58.2%) had higher care satisfaction and more frequent appointments (p < 0.05); 65.1% of respondents reported a fixed transfer age (≥18 years). Overall, 45.2% detailed transfer-related concerns; 44.3% felt their psychosocial needs were adequately addressed, 24.7% felt unprepared for areas of self-management. Combined pediatric and adult diabetes clinics (56.2%), and psychologist support (50.7%) were most desired.</p><p><strong>Conclusion: </strong>Findings highlight the urgent need to improve the transition process. A joint ISPAD, EASD, and ADA consensus report is in preparation.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-13"},"PeriodicalIF":2.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Endocrine Disruptors in Childhood Obesity: Unraveling the Obesogens.","authors":"Aikaterini Kapama, Charikleia Stefanaki, George Mastorakos, Maria Papagianni","doi":"10.1159/000545043","DOIUrl":"10.1159/000545043","url":null,"abstract":"<p><strong>Background: </strong>Obesity is a disease, acknowledged by WHO, characterized as an epidemic in a worldwide range, particularly in Western countries. Childhood obesity, lately, has raised major concerns. Among the complex factors contributing to obesity, environmental factors, such as endocrine disruptors, are gaining attention as emerging contributors to obesity.</p><p><strong>Summary: </strong>Toxicants, such as bisphenol A, phthalates, perfluoroalkyl and polyfluoroalkyl substances, heavy metals, and pesticides, have been associated with increases in the incidence of obesity in human populations, animals, and cellular models. These EDCs, called obesogens, disrupt the endocrine system across multiple pathways. They influence appetite, promote inflammation, disrupt the ecology and function of the gut microbiome, and induce transgenerational epigenetic changes. At the cellular level, they act as agonists of peroxisome proliferator-activated receptor γ, steroid, and aryl hydrocarbon receptors.</p><p><strong>Key messages: </strong>Children are exposed to obesogens through multiple metabolic pathways, which contribute directly and indirectly to the development of obesity. Despite the increasing evidence, more studies are needed to identify additional obesogens and elucidate their mechanisms of action to minimize exposure to pediatric and adolescent populations.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-14"},"PeriodicalIF":2.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nonmalignant Adrenocorticotrophic Hormone-Independent Cushing's Syndrome in Pediatric Patients: A Retrospective Observational Cohort Study.","authors":"Myriam Hassan, Dinane Samara-Boustani, Alix Besançon, Anya Rothenbuhler, Caroline Storey, Graziella Pinto, Athanasia Stoupa, Marc Nicolino, Laura Gabriela González-Briceño, Adrien Nguyen Quoc, Gaelle Vermillac, Sibylle Rovani, Isabelle Flechtner, Caroline Thalassinos, Yamina Dassa, María Beatriz Arrom Brañas, Magali Viaud, Jacques Beltrand, Virginie Ribault, Laetitia Martinerie, Agnès Linglart, Jérôme Bertherat, Thomas Blanc, Michel Polak, Dulanjalee Kariyawasam","doi":"10.1159/000545265","DOIUrl":"10.1159/000545265","url":null,"abstract":"<p><strong>Introduction: </strong>Adrenocorticotrophic hormone (ACTH)-independent Cushing's syndrome (CS) is a rare cause of pediatric CS. Our objective was to describe the features of pediatric ACTH-independent CS and to compare groups defined by etiology.</p><p><strong>Methods: </strong>We conducted a retrospective observational study of patients aged 0-18 years at diagnosis between 1992 and 2022 for ACTH-independent CS in three Paris pediatric hospitals. Additionally, we compared the outcomes of McCune-Albright syndrome (MCAS) patients with CS and without CS.</p><p><strong>Results: </strong>Of the 15 patients with CS, 7 had MCAS, 7 had primary pigmented nodular adrenocortical disease (PPNAD) as part of CNC (Carney complex), and 1 had CS with no etiology found. Age at CS diagnosis was 0.3 years old (0.17; 1) in MCAS and 9 years old (5; 15) in PPNAD. The MCAS group had more impaired growth retardation (-4.75 SDS in MCAS vs. -1 SDS in CNC, p = 0.006) and higher prevalences of intrauterine growth retardation (p = 0.01) and liver dysfunction at diagnosis (p = 0.04). All 7 MCAS patients had learning disabilities vs. only 2 CNC patients. 12 out of 15 had bilateral adrenalectomy. None of the MCAS patients received growth hormone therapy, while 4 CNC patients benefited from growth hormone therapy. At the end of follow-up, growth recovered in both groups, albeit less in the MCAS group (-1.5 SDS in MCAS vs. -0.5 SDS in CNC), in which liver dysfunction often persisted.</p><p><strong>Conclusion: </strong>ACTH-independent CS is rare but can lead to significant burden in children. Early diagnosis and management are essential. New drugs targeting adrenal steroid synthesis are awaited.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-12"},"PeriodicalIF":2.6,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SKIN-PEDIC: A Worldwide Assessment of Skin Problems in Children and Adolescents Using Diabetes Devices.","authors":"Anna Korsgaard Berg, Stefano Passanisi, Thekla von dem Berge, Agata Chobot, Nancy Samir Elbarbary, Julie Pelicand, Franco S Giraudo, Rosaline Mentink, Floris Levy-Khademi, Ana L Creo, Malene Søborg Heidemann, Claudia Piona, Emrullah Arslan, Didem Gunes Kaya, Theo C J Sas, Lars Krogvold, Stefano Tumini, Cari Berget, Tiago Jeronimo Dos Santos, Beate Karges, Mariana Zorron, Jannet Svensson","doi":"10.1159/000545428","DOIUrl":"10.1159/000545428","url":null,"abstract":"<p><strong>Introduction: </strong>Children and adolescents with diabetes are increasingly using technological devices to maintain normoglycemia. However, skin problems associated with these devices are becoming a significant issue. This study aimed to investigate prevalence of skin issues in children and adolescents with diabetes globally and identify important factors associated with these skin problems.</p><p><strong>Methods: </strong>This multinational study involved 22 pediatric diabetes centers. Over a 4-week period, pseud anonymized data were collected on children and adolescents using diabetes devices, including demographic factors, visual skin problems, type of devices and products being used. Univariate logistic regression was applied to identify associations with skin problems.</p><p><strong>Results: </strong>A total of 1,719 children and adolescents were included. Skin problems were present in 52% of pump users compared to 30% of sensor users. Eczema was found in 9% of participants at both insulin pump and glucose sensor sites, whereas scars, wounds, and lipodystrophies were significantly more frequent at insulin pump sites than at glucose sensor sites. Both xerosis cutis and keratosis pilaris were strongly associated with almost all types of skin problems, increasing the risk 2 to fivefold.</p><p><strong>Conclusion: </strong>Skin problems are a serious concern that limits the use of diabetes devices in children and adolescents, consequently increasing risk for long-term complications. This study highlights the extent of the problem in a real-world setting of unselected participants despite the use of preventive strategies. Consequently, the development of more skin-friendly devices is needed to ensure that all children and adolescents with diabetes can effectively use these devices in the long term.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-14"},"PeriodicalIF":2.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physical Activity in Very Young Children Living with Type 1 Diabetes.","authors":"Rowen Seckold, Michelle Fuery, Stewart G Trost, Tony Huynh, Carmel E Smart, Bruce R King","doi":"10.1159/000545316","DOIUrl":"10.1159/000545316","url":null,"abstract":"<p><strong>Introduction: </strong>Physical activity has health benefits for people living with type 1 diabetes (T1D); however, there are barriers limiting their ability to meet minimum recommended levels of moderate-to-vigorous physical activity (MVPA). We aimed to measure physical activity levels and barriers to physical activity in children <7 years of age living with T1D and compare to general population data and guidelines.</p><p><strong>Methods: </strong>Children <7 years of age with T1D were recruited from two paediatric diabetes centres in Australia. Physical activity was measured for 7 days using an accelerometer. Parents completed questionnaires related to barriers to physical activity (Barriers to Physical Activity in Diabetes [BAPAD1]) and fear of hypoglycaemia (Hypoglycaemia Fear Survey-Parents of Young Children [HFS-PYC]). Continuous glucose monitor (CGM) data were collected. MVPA was compared to the general population.</p><p><strong>Results: </strong>Thirty-three children, mean age 4.5 years (SD 1.2), mean HbA1c 7.1% (SD 1.1) (55 mmol/mol [SD 13]), and mean diabetes duration 35 months (SD 21), participated. Children with and without T1D did not meet daily MVPA recommendations and mean MVPA was not significantly different between groups (42.6 min [SD 26.02] vs. 42.8 min [SD 17.05], p = 0.972). CGM time in range 3.9-10 mmol/L correlated with MVPA (Tau-b = 0.396, p = 0.19). The median (Q1, Q3) for BAPAD1 average score was 2.4 (2, 4) and median HFS behaviour and worry sub-scores were both low at 2.3 (2, 3).</p><p><strong>Conclusions: </strong>Children <7 years of age did not meet the recommended daily MVPA level independent of diabetes. Parental concern regarding diabetes-related barriers to physical activity was low.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-11"},"PeriodicalIF":2.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parental Perception of Quality of Life and Impact of Short Stature in Children with Hypochondroplasia and Other Genetic Causes of Short Stature.","authors":"Despoina Galetaki, Anqing Zhang, Nicole Rangos, Nadia Merchant, Roopa Kanakatti Shankar, Kimberly Pitner, Niusha Shafaei, Raheem Seaforth, Andrew Dauber","doi":"10.1159/000545318","DOIUrl":"10.1159/000545318","url":null,"abstract":"<p><strong>Introduction: </strong>Short stature can lead to physical limitations and socioemotional effects limiting a child and parents' quality of life (QoL). This study investigates the impact of hypochondroplasia and other genetic causes (ACAN, NPR2 mutations, and RASopathy) of short stature on QoL.</p><p><strong>Methods: </strong>Parents of participants in an ongoing phase II clinical trial of vosoritide in children with selected genetic causes of short stature completed the Quality of Life in Short Stature Youth (QoLISSY) survey. Results from the survey domains (Total, Physical, Social, Emotional, Coping, Beliefs, Future, and Effects on parents) were compared to a reference population with idiopathic short stature (ISS) and growth hormone deficiency (GHD).</p><p><strong>Results: </strong>The cohort had lower mean total QoL scores compared to the reference population (54.0+/- 19.7 vs. 70.0+/- 22.0, p value <0.001), along with lower Physical (44.8+/- 21.2 vs. 71.8+/-23.2, p value <0.001) and Social scores (54.0+/-22.2 vs. 69.4+/-25.2, p value <0.001), and worse Effects on parents (52.3+/- 20.0 vs. 65.68 +/- 24.5, p value <0.0001). Older age and lower baseline height were associated with lower scores. Lower QoL scores were more prominent in males compared to the reference. When comparing genetic diagnoses, patients with NPR2 mutations had the lowest QoL scores.</p><p><strong>Conclusion: </strong>Patients with hypochondroplasia and other genetic causes of short stature had lower scores in multiple domains of QoL compared to ISS/GHD. Older age, male sex, and shorter stature may exacerbate effects on QoL. Additional studies to further explore these associations can clarify the unique challenges and facilitate appropriate medical and psychosocial support for children and their families.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-9"},"PeriodicalIF":2.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired Dietary Decision-Making in Children and Adolescents with Congenital Adrenal Hyperplasia.","authors":"L Nate Overholtzer, Shan Luo, Seung-Lark Lim, Trevor A Pickering, Nicole R Fraga, Elaine Kim, Megan M Herting, Veeraya K Tanawattanacharoen, Mitchell E Geffner, Mimi S Kim","doi":"10.1159/000545117","DOIUrl":"10.1159/000545117","url":null,"abstract":"<p><strong>Introduction: </strong>Children and adolescents with congenital adrenal hyperplasia (CAH) are at increased risk for obesity and exhibit differences in brain regions associated with food reward and decision-making. We aimed to understand differences in dietary decision-making between youth with CAH compared to controls.</p><p><strong>Methods: </strong>A total of 37 youth with CAH (12.2 ± 3.1 y, 59.5% female) and 100 controls (11.7 ± 2.4 y, 57% female) rated 30 low- and 30 high-calorie foods for health, taste, and liking. Participants then chose between 100 food pair trials using a mouse-tracking paradigm; 75 were discordant for health and taste ratings. Self-control success was measured as the percentage of trials in which the healthier food was chosen instead of the tastier food. Area under the curve (AUC) and maximum deviation (MD) are used as real-time indices of decision-making.</p><p><strong>Results: </strong>Patients with CAH exhibited higher AUCs (CAH: 9.48 ± 8.08, control: 6.40 ± 7.33; p < 0.05) and MDs (CAH: 0.20 ± 0.13, control: 0.15 ± 0.12; p < 0.05) in self-control trials. However, patients with CAH and controls did not differ in their self-control success (CAH: 28.47 ± 24.27%, control: 35.16 ± 25.01%; p = 0.16). In youth with CAH, testosterone was correlated with AUC (R = 0.46, p < 0.01) and MD (R = 0.38, p = 0.02) during successful self-control trials.</p><p><strong>Conclusions: </strong>Children and adolescents with CAH exhibit more cognitive conflict when choosing between healthy and tasty foods. Two indicators of disease severity were associated with cognitive conflict during food choice in patients with CAH. Our findings suggest impaired dietary decision-making in CAH could contribute to obesity risk.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-10"},"PeriodicalIF":2.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12353772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fertility in Non-Classic Lipoid CAH: A Case Report and Review of the Literature.","authors":"Emre Murat Altinkilic, Camilla Mains Balle, Clarissa Daniela Voegel, Therina du Toit, Amit V Pandey, Claus H Gravholt, Christa E Flück","doi":"10.1159/000545063","DOIUrl":"10.1159/000545063","url":null,"abstract":"<p><strong>Introduction: </strong>Non-classic lipoid congenital adrenal hyperplasia (LCAH) presents with adrenal insufficiency but typically lacks a gonadal phenotype or features a delayed-onset gonadal presentation. Information on fertility outcomes in affected individuals is limited.</p><p><strong>Case presentation: </strong>We describe an adult male with severe, early onset primary adrenal insufficiency, yet normal fertility, diagnosed in mid-adulthood with compound heterozygous STAR gene variants, including both known and novel mutations. The identified variants, c.814C>T (p.Arg272Cys) and c.743A>C (p.Lys248Thr), underwent structural and functional analysis, revealing partial enzymatic activity. A review of existing reports on the gonadal phenotype and fertility in non-classic LCAH identified only nine adult males. Among these, five exhibited normal gonadal function, but none had documented paternity.</p><p><strong>Conclusion: </strong>STAR variants may be present in adults with unresolved primary adrenal insufficiency and normal gonadal function. Infertility is not an inevitable outcome, as demonstrated by this case.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-8"},"PeriodicalIF":2.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of Obesity following Treatment for Childhood Malignancies.","authors":"Elpis Athina Vlachopapadopoulou","doi":"10.1159/000545045","DOIUrl":"10.1159/000545045","url":null,"abstract":"<p><strong>Background: </strong>Obesity, long viewed as a reversible outcome of personal choices, is influenced by a complex interplay of genetic, physiological, socioeconomic, and environmental factors. A special group of children and adolescents are the childhood cancer survivors (CCSs), as obesity and its comorbidities have been recognized as long-term effects following treatment for childhood malignancies and craniopharyngioma. The aim of this literature review was to report the epidemiological data, pathophysiology and risk factors regarding obesity development in CCS and the possible mediators. The possible mechanisms contributing to increased body mass index (BMI) include hypothalamic hyperphagia and hypothalamic-pituitary insufficiency, corticosteroid therapy, constitutional factors including genetic predisposition and variable sensitivity to corticosteroids. The risk factors are divided into two categories: those related to the initial diagnosis and the treatment modalities implicated and independent factors such as sex, age at diagnosis, ethnic origin, socioeconomic status and BMI at diagnosis.</p><p><strong>Summary: </strong>Higher risk for developing overweight/obesity face the CCS who had increased BMI at diagnosis, were younger than 6 years of age, received cranial radiation therapy even as low as 6 Gys, had tumors and surgery of the hypothalamic-pituitary region, craniopharyngioma and those who were treated with dexamethasone. They also have high likelihood of developing metabolic syndrome.</p><p><strong>Key messages: </strong>Obesity is one of the most prevalent long-term sequelae of treatment for childhood malignancies. CCSs already face a heightened risk of chronic diseases. Thus, it is crucial to prevent additional avoidable risk factors, such as obesity. All CCS should have height and weight measurements and BMI calculation, as well as being counseled annually on the importance of regular physical activity and heart-healthy diet.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-7"},"PeriodicalIF":2.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Variant in an Intron Splicing Enhancer Associated with Familial Growth Hormone Deficiency.","authors":"Sally Radovick, Mariam Gangat, Bethany Murphy, Jennifer L Miller, Youn Hee Jee","doi":"10.1159/000545037","DOIUrl":"10.1159/000545037","url":null,"abstract":"<p><strong>Introduction: </strong>Variants in the intron splicing enhancer (ISE) of intron 3 in the GH1 gene are implicated in the etiology of isolated growth hormone deficiency type 2 (type II IGHD).</p><p><strong>Methods: </strong>Exome sequencing was performed to screen variants that co-segregated with IGHD in an extended family with type II IGHD. The causality of the candidate variant was assessed using bioinformatic tools and previous in vitro studies.</p><p><strong>Results: </strong>Exome sequencing identified a rare intronic variant (NM_000515.5, c.291+34 G>A) in the second XGGG repeat of ISE in intron 3 of GH1, which occurred de novo in the mother with IGHD and was passed onto her two affected children. The variant was previously shown in vitro to cause exon 3 skipping in 50% of the mRNAs and was predicted to create a new binding site for exonic splicing enhancer binding proteins (SR proteins).</p><p><strong>Conclusion: </strong>Our familial case reiterates the importance of intronic variants in the splicing enhancer region as a cause of IGHD. Consideration should be given to sequencing the splicing enhancer region in intron 3 of GH1 for patients who undergo genetic testing for growth hormone deficiency.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-11"},"PeriodicalIF":2.7,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12353847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}