Journal of Clinical Research in Pediatric Endocrinology最新文献

{"title":"Long-Term Follow-up of a Case with TBX19 Mutation, a Rare Cause of Isolated ACTH Deficiency and Literature Review.","authors":"Aysegul Ceran, Zehra Aycan, Zeynep Siklar, Elif Ozsu, Sirmen Kizilcan Cetin, Merih Berberoglu","doi":"10.4274/jcrpe.galenos.2025.2024-12-18","DOIUrl":"https://doi.org/10.4274/jcrpe.galenos.2025.2024-12-18","url":null,"abstract":"<p><p>TPIT is a transcription factor required for POMC gene expression and pituitary corticotroph cell differentiation and is encoded by TBX19. Variants in TBX19 cause early onset congenital isolated ACTH insufficiency with a mortality rate of up to 25% in the neonatal period. Mild dysmorphic findings may accompany some cases. Here, we report a case of isolated ACTH deficiency due to a TBX19 variant diagnosed in the neonatal period, which was followed up until adulthood. The patient with hypoglycemia and convulsions on the first day of life were evaluated for hypocortisolemia and low ACTH. While neonatal cholestasis and hyperbilirubinemia were prominent, facial dysmorphism was unremarkable. He was diagnosed with isolated ACTH deficiency, and hydrocortisone replacement therapy was initiated. TBX19 analysis revealed NM 005149 c.512T>C (p.Ile171Thr). Epileptic seizures were observed and antiepileptic treatment was initiated. Cranial MRI revealed an arachnoid cyst, cortical atrophy, and gliotic changes. The patient, which was also included in the first case report describing the gene encoding TPIT, reached the final height. He was 22 years old at the last follow-up, and his physical and mental development was normal. Neuromotor development and growth were normal. TBX19 variants present with hypoglycemic convulsions in the early hours of the neonatal period and may lead to life-threatening neonatal death. Early hydrocortisone replacement therapy is significant for survival without sequelae. Continuing to monitor patients for long-term issues and additional discoveries could be beneficial for elucidating the genotype-phenotype correlation.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144734484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myocardial Performance Index and Carotid Intima-Media Thickness in Children with Metabolically Healthy and Metabolically Unhealthy Obesity.","authors":"Nazlican Civilibal Tang, Kazım Oztarhan, Helen Bornaun, Sumeyra Dogan, Ata Mert Civilibal","doi":"10.4274/jcrpe.galenos.2025.2025-5-4","DOIUrl":"https://doi.org/10.4274/jcrpe.galenos.2025.2025-5-4","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to compare the myocardial performance index (MPI) and carotid intima-media thickness (cIMT) of children who are metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO) with children without obesity.</p><p><strong>Methods: </strong>This study included 62 obese patients between 6 and 17 years of age and 30 age- and gender-matched healthy children. Two groups of obese patients were created: MUO (n=30) and MHO (n=32).</p><p><strong>Results: </strong>Compared to controls, the MPI and cIMT of the obese groups were significantly greater. However, there was no significant difference in MPI and cIMT between the MUO and MHO groups. Additionally, there were independent associations between higher MPI and body mass index-SDS (BMI-SDS) (β=0.312, p=0.002) and between higher cIMT and waist circumference-SDS (WC-SDS) (β=0.371, p=0.003).</p><p><strong>Conclusion: </strong>The primary outcome of the study indicates that while both MPI and cIMT values are elevated in obese children compared to non-obese controls, there is no significant difference between MUO and MHO groups. This suggests that obesity itself, irrespective of metabolic health, is associated with increased cardiovascular risks. BMI-SDS and WC-SDS are useful markers for identifying children at cardiovascular risk, emphasizing the need for early intervention in pediatric obesity.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144734485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Case of Secondary Pseudohypoaldosteronism in a Neonate not Due to Urinary Tract Issues.","authors":"Ecem İpek Altınok, Yavuz Özer","doi":"10.4274/jcrpe.galenos.2025.2025-4-9","DOIUrl":"https://doi.org/10.4274/jcrpe.galenos.2025.2025-4-9","url":null,"abstract":"<p><p>In this report, we present a case of a female infant diagnosed with secondary PHA who exhibited weight loss, hyponatremia, hyperkalemia, and metabolic acidosis without the presence of UTA or UTI. The patient was a female infant born at 35 weeks gestation who developed electrolyte abnormalities and was diagnosed with secondary pseudohypoaldosteronism (PHA). Initially managed for transient tachypnea of the newborn, she developed respiratory distress requiring mechanical ventilation. Subsequently, she exhibited persistent hyponatremia, hyperkalemia, and metabolic acidosis despite adequate fluid therapy, prompting consideration of adrenal insufficiency and congenital adrenal hyperplasia (CAH). Treatment with hydrocortisone and fludrocortisone was initiated empirically until hormonal analyses excluded CAH. Further evaluation excluded urinary tract anomalies and infections as underlying causes, implicating secondary PHA. The infant responded well to saline and electrolyte replacement therapy, with normalization of electrolyte levels and clinical improvement. Follow-up assessments demonstrated resolution of electrolyte imbalances, and the patient was discharged after 27 days without further complications. Secondary PHA, characterized by renal tubular resistance to aldosterone, typically presents with severe electrolyte disturbances in infancy. It can occur independently of urinary tract abnormalities or infections, highlighting the importance of considering this diagnosis in neonates and infants presenting with hyponatremia, hyperkalemia, and metabolic acidosis that do not respond to conventional therapies. Early recognition and appropriate management, including fluid-electrolyte correction and hormone replacement if indicated, are crucial to prevent life-threatening complications associated with salt-wasting syndromes in this vulnerable population.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144610065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Young Turkish Adults Show a Continuing Positive Secular Change of Height But an Alarming Increase of Overweight in Males: Pilot Study for the Initiation of Updated Growth Charts.","authors":"O Bayrak Demirel, C Koc, N M Sukur, A D Kardelen, M Yildiz, S Poyrazoglu, F Bas, J M Wit, F Darendeliler","doi":"10.4274/jcrpe.galenos.2025.2024-10-4","DOIUrl":"https://doi.org/10.4274/jcrpe.galenos.2025.2024-10-4","url":null,"abstract":"<p><strong>Objective: </strong>Turkish growth reference charts are based on 1989-2002 data. Globally, positive secular trends in height have been observed, and updating growth charts every 20 years is recommended. Additionally, obesity is a rising health issue worldwide. This study investigates if there has been a further increase in young Turkish adults' mean height and BMI compared to previous national data (TK2002) and Turkish-origin young adults in the Netherlands. It also explores the association between adult height and BMI with socioeconomic status (SES) and geographical region.</p><p><strong>Methods: </strong>This cross-sectional study (2023-2024) included 217 females and 248 males, aged 18-26, voluntarily recruited from Istanbul University, representing all regions of Turkey. Height, weight, and SES were recorded. The top two SES groups were combined for analysis.</p><p><strong>Results: </strong>Sample distribution aligned with Turkey's regional population distribution. Mean height was 1.8 cm taller in females (p=0.003) and males (p<0.001) compared to TK2002, and also taller (2.3 and 0.5 cm, respectively, p<0.001 and p=0.03) than in NL2009. BMI was significantly higher in males than in TK2002 and NL2009 (p<0.001).</p><p><strong>Conclusion: </strong>Final height of Turkish students increased by 1.8 cm in both sexes over two decades. Males' BMI was alarmingly high (58% overweight or obese). A population growth study to generate updated growth charts from birth to young adulthood and prevention programs to reduce obesity are needed.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Duplication in the SHOX Gene as a Rare Genetic Cause of Short Stature and/or Skeletal Abnormalities: A Clinical Report and Review of the Literature.","authors":"Benay Turan, Gülçin Arslan, Tayfun Çinleti, Şener Arıkan, İnci Türkan Yılmaz, Merve Saka Güvenç, Bumin Nuri Dündar","doi":"10.4274/jcrpe.galenos.2025.2024-11-20","DOIUrl":"https://doi.org/10.4274/jcrpe.galenos.2025.2024-11-20","url":null,"abstract":"<p><p>The SHOX (short stature homeobox containing gene) haploinsufficiency can result in phenotypes ranging from idiopathic short stature to Leri-Weill dyschondrosteosis (LWD). It has been reported to have been detected in 5-17% of children diagnosed with idiopathic short stature, and in 60-90% of children with LWD. SHOX duplications, although typically associated with tall stature, can result in short stature and/or extremity anomalies in rare cases when partial or complete duplications involving the SHOX region occur. In this case report, two patients with extremity anomalies who were found to have SHOX region duplications with two different clinical features are presented. The first case was an eleven-month-old male, referred to the pediatric endocrinology clinic due to short stature, and skeletal deformities. On physical examination, the patient's weight was 8.6 kilograms (-1.19 standard deviation score; SDS), and his height was 68 cm (-2.57 SDS). The systemic examination was unremarkable, but examination of the extremities revealed the absence of the right thumb and left forearm bones. Radiographic images of the bones revealed possible rudimentary bone tissue of the radius and ulna in the left upper extremity. DNA extracted from the patient's peripheral blood was subjected to multiplex ligation-dependent probe amplification (MLPA) analysis, which revealed a duplication extending from the upstream regulatory regions of the SHOX gene on Xp22.3/Yp11.32 to the downstream CNE8 (conserved noncoding elements) region, including all of the gene's coding regions and upstream regulatory areas. The second case involved a fourteen-month-old male, who was referred after SHOX duplication was detected in a microarray analysis performed due to epilepsy. On physical examination, his weight was 10.3 kg (-0.3 SDS), and his height was 79 cm (-0.11 SDS). Systemic examination was normal, but Madelung deformities were observed in the extremity examination. DNA obtained from the patient's peripheral blood was analyzed using MLPA for deletions and duplications of the SHOX gene and the associated regulatory regions on Xp22.3/Yp11.32. This analysis revealed a heterozygous duplication which extended from the entire SHOX gene and upstream CNE regions to the CNE7/8 regions downstream. SHOX duplications can result in short, normal, or tall stature depending on the size, location, and transcriptional characteristics (such as containing non-coding elements) of the duplicated region. This case report emphasizes that, in the presence of idiopathic short stature and/or extremity anomalies, SHOX duplications should be considered in addition to the other common genetic causes.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Methods Used for Final Height Prediction in Central Precocious Puberty Patients.","authors":"Nisa Nur Turan, Aşan Önder Çamaş, Burçin Çiçek, Merve Nur Hepokur, Hamdi Cihan Emeksiz","doi":"10.4274/jcrpe.galenos.2025.2025-2-1","DOIUrl":"https://doi.org/10.4274/jcrpe.galenos.2025.2025-2-1","url":null,"abstract":"<p><strong>Introduction: </strong>Various methods are used to estimate target height in patients diagnosed with precocious puberty. These methods include the Bayley-Pinneau (BP) and Roche-Wainer-Thissen (RWT) methods. In addition to these methods, in our clinic, we routinely use a practical approach based on the percentiles in growth charts. In this method, the bone age percentile is projected to the end of the percentile curve (at 18 years of age) to estimate the final adult height. We have named this method BAPCPHE (Bone Age Percentile Curve Projected Height Estimation). This study aimed to retrospectively compare the effectiveness of these three methods in predicting target height in patients treated for central precocious puberty and who have reached their final height in our pediatric endocrinology clinic.</p><p><strong>Materials and methods: </strong>50 female patients were included. The predicted adult heights ( PAH) were calculated at treatment initiation, at the end of the first, second, and third years of treatment, and at the time of final height attainment using the BP, RWT, and BAPCPHE methods, based on the patients' heights and bone ages.</p><p><strong>Results: </strong>When the agreement between the PAH calculated by three methods and the final height was analyzed using the Intraclass Correlation Coefficient (ICC), a statistically significant agreement was found for PAH by the BAPCPHE method at the third year. Among the methods, the strongest agreement with final height and PAH was observed with the BP method at the end of treatment, followed by the BAPCPHE method.</p><p><strong>Conclusion: </strong>The BAPCPHE method not only measures percentile chart and bone age data, but also allows estimation of PAH quickly, making it a valuable tool in the outpatient setting. Given its simplicity and accuracy, we found the BAPCPHE method preferable.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144576739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Case of Adolescent Girl with Hypercalcemia Resistant to Medical Treatment Due to Giant Breast Fibroadenoma.","authors":"Kürşat Çetin, Berna Singin, Yasemin Funda Bahar, Kerem Karaca, İsmail Zihni, Elif Güler, Hale Tuhan, Mesut Parlak","doi":"10.4274/jcrpe.galenos.2025.2025-3-21","DOIUrl":"10.4274/jcrpe.galenos.2025.2025-3-21","url":null,"abstract":"<p><p>Hypercalcemia in children is a rare condition and can result from various etiologies such as genetic, metabolic, iatrogenic and malignancy. In some malignancies, Parathyroid Hormone Related Protein (PTHrP) can mimic the physiological effects of Parathyroid Hormone (PTH) and cause hypercalcemia. In this report , we present a rare case of hypercalcemia secondary to juvenile fibroadenoma, which is a benign breast tumor. A 14-year-old girl presented with a complaint of solid breast mass. Further evaluation with ultrasonography and trucut biopsy, a diagnosis of 14x8 cm juvenile fibroadenoma was made. Laboratory examination revealed hypercalcemia (13.9 mg/dl) and high PTHrP (>24.8 ng/L) although the patient was asymptomatic. Despite pharmacological treatment, the patient continued to experience persistent hypercalcemia and subsequently underwent a successful surgical excision. Serum calcium and PTHrP levels normalized postoperatively. Hypercalcemia secondary to malignancy in children is rare and calcium elevation is usually mild-moderate and asymptomatic. In this case, PTHrP was elevated in breast fibroadenoma, demonstrating that hypercalcemia can also occur in benign tumors. The follow-up data of our patient after surgical treatment supports the notion that PTHrP-related hypercalcemia does not always indicate a poor prognosis. This case emphasizes the importance of considering benign tumors such as juvenile fibroadenoma as a potential cause of hypercalcemia in adolescents.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel SOX9 Gene Variant Associated with Campomelic Dysplasia: Effects on Sex Phenotypes.","authors":"Nanis S Marzuki, Hannie Dh Kartapradja, Firman P Idris","doi":"10.4274/jcrpe.galenos.2025.2025-3-14","DOIUrl":"https://doi.org/10.4274/jcrpe.galenos.2025.2025-3-14","url":null,"abstract":"<p><p>Campomelic dysplasia (CD) is a rare autosomal dominant genetic disorder primarily caused by mutations in the SOX9 gene. While this condition can affect multiple organ systems, it mainly influences skeletal and sexual development, leading to skeletal malformations and gonadal dysgenesis. We present two cases of campomelic dysplasia diagnosed at an early age. Their clinical presentations were characteristic of this disorder, including bowing of the lower extremities, pretibial dimples, Pierre Robin sequence, and bilateral clubfoot. Both cases exhibited delays in motor skills and speech. The first case involved a 46,XY sex-reversed infant with a novel heterozygous SOX9 gene substitution of p.Arg107Gly (NM_000346.4:c.319C>G). The second case involved a 1.5-year-old boy with typical male external genitalia carrying a heterozygous p.Ala116Val variant (c.347C>T) in the SOX9 gene. Both variants were located in the HMG domain of the gene. Two variants, the novel p.Arg107Gly and the p.Ala116Var, in the SOX9 gene were reported to be associated with campomelic dysplasia. Despite being in the same domain, these variants lead to different sex phenotypes.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nailfold Capillaroscopy: A Non-invasive Tool for Early Detection of Microvascular Alterations in Children with Type 1 Diabetes Mellitus.","authors":"Gözde Akın Kağızmanlı, Tuncay Aydın, Kübra Yüksek Acinikli, Rana İşgüder, Zehra Kızıldağ Karabacak, Korcan Demir, Ece Böber, Şevket Erbil Ünsal, Ayhan Abacı","doi":"10.4274/jcrpe.galenos.2025.2025-2-17","DOIUrl":"https://doi.org/10.4274/jcrpe.galenos.2025.2025-2-17","url":null,"abstract":"<p><strong>Background: </strong>Nailfold capillaroscopy (NC) is a non-invasive tool that can detect microvascular changes in the early stages of vascular disease.</p><p><strong>Objective: </strong>We aimed to assess capillary microarchitecture in children with type 1 diabetes mellitus (T1DM) and its relationship with clinical characteristics, laboratory findings, and glycemic control.</p><p><strong>Subjects and methods: </strong>We included 55 children with T1DM (aged 6-18 years, diagnosed for at least one year) and 55 age- and sex-matched healthy controls. For all patients with T1DM, data on diabetes duration were collected, and the average HbA1c values were calculated by taking the mean of the HbA1c levels measured at three-month intervals during routine clinical assessments over the past year. In patients using 24-hour continuous glucose monitoring (CGM) devices, glycemic data from the previous 3 months were analyzed. The capillaroscopic findings were evaluated by two different researchers with experience in the field of pediatric rheumatology. Capillaroscopic parameters were compared based on glycemic control (HbA1c ≥7.5% vs. <7.5%), disease duration (<5 vs. ≥5 years), time in range (TIR ≥70% vs. <70%), and glucose variability (CV ≤36% vs. >36%).</p><p><strong>Results: </strong>The median age of patients with T1DM was 14.5 (11.3-17.2) years, with a median disease duration of 3.8 (2.3-6.7) years. Compared to controls, patients with T1DM had significantly lower capillary density and more frequent dilated, tortuous, cross-linked, and abnormal capillaries (p<0.001, p<0.001, p<0.001, p=0.01, and p=0.03, respectively). Capillary density was significantly lower in patients with poor glycemic control (p<0.001) and those with longer disease duration (p=0.02). A negative correlation was observed between capillary density and disease duration (r=-0.3, p=0.02). After adjusting for age, gender, BMI, and diabetes duration, capillary density remained negatively correlated with average HbA1c (r= -0.4, p=0.004). Among CGM users (n=22), capillary density showed a positive correlation with TIR (r=0.5, p=0.04), even after adjustment for confounders.</p><p><strong>Conclusion: </strong>Children with T1DM exhibited significantly higher microvascular changes, mostly associated with poor glycemic control, compared to healthy controls. NC can be a useful technique for detecting early alterations in the capillary structures of children with T1DM, even in the absence of microvascular complications.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Founder Pathogenic Variant in <i>LMNA</i> and Its Diverse Phenotypic Manifestations in Mandibuloacral Dysplasia: Insights from a Turkish Cohort.","authors":"Zehra Manav Yigit, Mustafa Altan, Goksel Tuzcu, Gokay Bozkurt, Ahmet Anik","doi":"10.4274/jcrpe.galenos.2025.2025-3-27","DOIUrl":"https://doi.org/10.4274/jcrpe.galenos.2025.2025-3-27","url":null,"abstract":"<p><strong>Objective: </strong>Mandibuloacral dysplasia (MAD) is a rare genetic disorder characterized by distinctive skeletal abnormalities, metabolic issues, and skin changes, often linked to pathogenic variants in the LMNA gene, which encodes lamin A/C. This study investigates a specific founder mutation within a Turkish cohort and explores its impact on phenotypic expressivity.</p><p><strong>Methods: </strong>We conducted a comprehensive analysis involving genetic testing for LMNA variants in patients diagnosed with MAD. Clinical evaluations documented a wide range of phenotypic features, including facial dysmorphism, skeletal anomalies, and metabolic abnormalities. We also collected family histories to assess inheritance patterns and potential environmental influences.</p><p><strong>Results: </strong>Our findings identified a common founder mutation in the LMNA gene among the cohort, which was present in a significant percentage of participants. Notably, phenotypic expressivity varied significantly, with some individuals exhibiting classic MAD features, while others showed atypical manifestations, such as additional endocrine disorders and variable severity of skeletal anomalies. This variability underscores the complexity of the genotype-phenotype relationship.</p><p><strong>Conclusion: </strong>This study highlights the significance of the founder mutation in LMNA and its diverse phenotypic outcomes in MAD. Our results contribute to the understanding of how genetic mutations can lead to a spectrum of clinical presentations, emphasizing the necessity for personalized clinical approaches in managing this condition. Further research is warranted to elucidate the underlying mechanisms of phenotypic variability and to improve diagnostic and therapeutic strategies.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}