Molecular Syndromology最新文献

{"title":"Cytomolecular Analysis of a Ring X Chromosome in a Patient with Turner Syndrome: A Case Report.","authors":"Evellyn Karine Cruz da Silva, Ruan Barboza Rocha, Paloma de Sousa Passos, Edivaldo Herculano Correa de Oliveira, Thomas Liehr, Daria Barroso Serrão das Neves, Denise Côrrea Benzaquem, Cleiton Fantin","doi":"10.1159/000551346","DOIUrl":"10.1159/000551346","url":null,"abstract":"<p><strong>Introduction: </strong>Turner syndrome (TS) is a genetic disorder caused by the complete or partial absence of one of the X chromosomes. Its clinical features include short stature, gonadal dysgenesis, primary amenorrhea, and infertility. The condition presents significant phenotypic variability, especially in cases involving chromosomal mosaicism and structural abnormalities.</p><p><strong>Case presentation: </strong>A 21-year-old female patient from Tapauá, Amazonas, Brazil, was evaluated due to irregular bleeding followed by secondary amenorrhea. Cytogenetic analysis of peripheral blood lymphocytes was performed using conventional G-banding, followed by fluorescence in situ hybridization (FISH) for molecular characterization. Cytogenetic analysis revealed 2 cell lines: one with monosomy X (45,X) and another with 46 chromosomes including a ring X chromosome. The final karyotype was mos45,X[170]/46,X,r(X)(p11.22q13.23)[30]. The presence of a ring X chromosome was confirmed by FISH.</p><p><strong>Conclusion: </strong>This case illustrates the relevance of combining classical and molecular cytogenetic techniques to identify structural X chromosome abnormalities. Such analysis is essential for accurate diagnosis, understanding genotype-phenotype correlations, and guiding clinical management and genetic counseling in patients with TS.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":"545-550"},"PeriodicalIF":0.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"One-Carbon Metabolism and Midbrain Dopaminergic Cells in Lesch-Nyhan Disease.","authors":"Shaima Alsuwaidi, Carl Ernst","doi":"10.1159/000549247","DOIUrl":"10.1159/000549247","url":null,"abstract":"<p><strong>Background: </strong>Lesch-Nyhan disease (LND) is characterized by severe motor problems, self-injury, and gout. LND is caused by loss of function of HPRT which functions to salvage purine nucleotides, but the link between purine recycling and the neurological phenotypes remains unknown. One-carbon metabolism (OCM) is the utilization of single-carbon units for important cellular pathways such as de novo purine synthesis, the methionine cycle, and the transsulfuration pathway. Since purine salvage is lost in LND and one-carbon groups are required for de novo purine synthesis, there is an obligate need to re-route one-carbon flux in LND. Midbrain dopaminergic neurons have been associated with LND and may represent an important intersection point for OCM and LND.</p><p><strong>Summary: </strong>In this review, we analyze the relationships between HPRT loss, OCM, and the unique metabolic features of midbrain dopaminergic cells. Our hope is to better understand how changes to metabolic flux in OCM might affect midbrain dopaminergic cells and ultimately lead to the neurological phenotypes of LND.</p><p><strong>Key messages: </strong>OCM provides important components for different processes and pathways including de novo purine synthesis, methionine cycle, transsulfuration pathway, and polyamine synthesis. Changes in flux toward de novo purine synthesis in LND may affect these interconnected processes and have potential effects on dopaminergic cells as discussed in this review.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":"441-454"},"PeriodicalIF":0.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12707950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>PIK3CA</i>-Related Phenotypes due to Germline and Somatic Mosaic Variants: A two-Case Report.","authors":"Nazli Busra Acikgoz, Damla Yildiz, Gizem Urel-Demir, Gulen Eda Utine, Pelin Ozlem Simsek-Kiper","doi":"10.1159/000549757","DOIUrl":"10.1159/000549757","url":null,"abstract":"<p><strong>Objective: </strong>Somatic mosaic activating <i>PIK3CA</i> variants are a well-established cause of segmental overgrowth phenotypes, whereas germline <i>PIK3CA</i> variants are rare and clinically heterogeneous. We report 2 unrelated patients - 1 with a somatic mosaic and 1 with a de novo germline <i>PIK3CA</i> variant - with longitudinal clinical follow-up.</p><p><strong>Case presentation: </strong>Patient 1 carried NM_006218.4:c.1412C>T; p.(Pro471Leu) in the C2 domain and presented with macrocephaly, generalized overgrowth, epilepsy, and structural brain anomalies; mosaicism was supported by an attenuated mutant signal on Sanger sequencing. Patient 2 harbored a de novo NM_006218.4:c.323G>A; p.(Arg108His) in the N-terminal p85-binding region and showed macrocephaly, attention-deficit/hyperactivity disorder, and mitral annular disjunction/mitral valve prolapse with aortic root dilatation.</p><p><strong>Conclusion: </strong>These 2 cases illustrate <i>PIK3CA</i>-related phenotypes arising from somatic mosaic and germline contexts and document their clinical course over time. Larger, well-characterized cohorts and complementary functional assays are needed to refine genotype-phenotype relationships, inform clinical care, and evaluate targeted therapies.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":"519-528"},"PeriodicalIF":0.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12721807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145821523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Novel and Recurrent <i>FBN1</i> Gene Mutations in Two Unrelated Turkish Families with Isolated Ectopia Lentis: A Case Report with Insights from a Literature Review.","authors":"G Somayyeh Heidargholizadeh, Shahrashoub Sharifi, Sukru Palanduz, Ali Nazemi","doi":"10.1159/000549172","DOIUrl":"10.1159/000549172","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to identify the potential genetic defects underlying familial clustering of lens dislocation in two unrelated Turkish families, consistent with the clinical features of isolated ectopia lentis (IEL). The investigation seeks to determine whether the detected findings overlap with those observed in other syndromic conditions that present with lens dislocation. Additionally, a focused review of IEL within the scientific literature was conducted to contextualize the molecular and phenotypic spectrum associated with lens abnormalities. The results of this study are expected to contribute to a deeper understanding of the molecular basis of IEL and to enhance diagnostic precision, genetic counseling, and clinical management strategies for affected individuals.</p><p><strong>Case presentation and conclusion: </strong>Comprehensive family histories and clinical evaluations revealed lens dislocation and associated ocular manifestations without systemic abnormalities or extraocular features suggestive of connective tissue disorders. Whole-exome sequencing (WES) in affected individuals identified two heterozygous <i>FBN1</i> missense variants. The first variant, ENST00000316623.5:c.2920C>T, which has been previously reported in the literature, is located within the TB5 domain and was identified in ten affected members of family 1. The second variant, ENST00000316623.5:c.7018T>C, located within the TB9 domain, was identified in a single affected individual from family 2 and is reported here for the first time in association with IEL. Segregation analysis demonstrated that both variants co-segregated with the ectopia lentis phenotype and were completely absent in unaffected family members as well as in WES data from 200 ophthalmologically normal in-house controls. Besides, our study focused review of the literature on <i>FBN1</i>-associated IEL revealed that approximately 66.7% of reported variants involve missense substitutions affecting cysteine residues. Our study further reinforces this pattern by identifying two rare <i>FBN1</i> missense variants that co-segregate with the phenotype, thereby expanding the known mutational spectrum of IEL. These findings also underscore the phenotypic heterogeneity of IEL, as reflected by the variable age of onset among affected individuals, and emphasize the critical role of domain-specific cysteine-altering mutations in the pathogenesis of IEL.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":"475-483"},"PeriodicalIF":0.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12707959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145775968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two Unrelated Witteveen-Kolk Syndrome Patients Presenting with Unusual Clinical Features: Dual Diagnosis and Atypical Rare Manifestation.","authors":"Mustafa Yilmaz, Ayse Ozden, Hakan Doneray, Oguzhan Bahadır, Tuna Apuhan, Ayberk Turkyilmaz","doi":"10.1159/000549497","DOIUrl":"10.1159/000549497","url":null,"abstract":"<p><strong>Introduction: </strong>Witteveen-Kolk syndrome (WITKOS, OMIM 613406) is a rare autosomal dominant neurodevelopmental disorder caused by heterozygous loss-of-function variants in the <i>SIN3A</i> gene or microdeletions involving <i>SIN3A</i> at 15q24. We aimed to present new clinical and genetic findings of 2 patients diagnosed with WITKOS.</p><p><strong>Case presentation: </strong>This study presents 2 cases: patient 1 had genomic variations caused by a multilocus disease, including pathogenic variations in the <i>SIN3A</i> gene and paternal mosaic uniparental disomy 11 (UPD(11)p), and showed syndromic symptoms. Patient 2 was followed up with a preliminary diagnosis of hypogonadotropic hypogonadism (HH) and a new de novo pathogenic variation in the <i>SIN3A</i> gene.</p><p><strong>Conclusions: </strong>These findings expand the phenotypic spectrum associated with <i>SIN3A</i> variants and highlight the importance of comprehensive genetic testing in atypical presentations of rare diseases. The inclusion of <i>SIN3A</i> in HH gene panels may aid molecular diagnosis in cases without apparent syndromic findings. This study contributes to the understanding of the phenotypic and genotypic heterogeneity of WITKOS.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":"484-490"},"PeriodicalIF":0.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12707922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Replication-Based Mechanism Underlies a Complex dup(18p)/del(18q) Rearrangement Not Derived From Parental Inversion.","authors":"Bruna Burssed, Malú Zamariolli, Bianca Pereira Favilla, Décio Brunoni, Leslie Domenici Kulikowski, Fernanda Teixeira Bellucco, Maria Isabel Melaragno","doi":"10.1159/000551668","DOIUrl":"10.1159/000551668","url":null,"abstract":"<p><strong>Introduction: </strong>Most intrachromosomal rearrangements characterized by terminal monosomy and trisomy concomitantly seen in different arms of the same chromosome usually arise due to pericentric inversions in parents. Forty-seven patients have been described with such alteration in chromosome 18.</p><p><strong>Methods: </strong>We investigated a patient with dup(18p)/del(18q) whose rearrangement was characterized by karyotype, catalog and custom chromosomal microarrays, fluorescence in situ hybridization (FISH), whole genome sequencing, and Sanger sequencing.</p><p><strong>Results: </strong>The patient presents a 9.7 Mb terminal duplication in 18p and a 25.8 Mb terminal deletion in 18q. The duplicated segment is inserted into the long arm of chromosome 18 in an inverted position. At the junction point, we found a 19-nucleotide segment insertion derived from a downstream 18q sequence and the presence of microhomology with both the breakpoint from the long-arm region and the one from the inverted duplicated segment from the short arm.</p><p><strong>Conclusion: </strong>We described, to the best of our knowledge, the fifth confirmed case of concomitant terminal trisomy and monosomy in different arms of chromosome 18 which is not due to a pericentric parental inversion, and the first with breakpoints determined at the nucleotide level. The combination of various techniques enabled us to infer the rearrangement's likely mechanism of formation. The structural features observed are consistent with replication-based mechanisms, including Fork Stalling and Template Switching and Microhomology-Mediated Break-Induced Replication. The detailed rearrangement characterization also allowed for a more detailed karyotype-phenotype correlation, which indicates that the 18q deletion is likely the cause of most of the patient's phenotypical alterations.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":"455-464"},"PeriodicalIF":0.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13218727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148139447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Candidate Gene for Cerebro-Oculo-Nasal Syndrome: A Zinc-Finger Gene <i>ZNF185</i> Located at Xq28.","authors":"Filiz Hazan, Ceren Yılmaz Uzman, Durdugül Ayyıldız Emecen, Murat Muhtar Yılmazer, Taylan Öztürk, Mertkan Mustafa Bilen, Anıl Hüvez, Recep İlhan, Ferah Genel, Petek Ballar","doi":"10.1159/000549375","DOIUrl":"10.1159/000549375","url":null,"abstract":"<p><strong>Introduction: </strong>Cerebro-oculo-nasal syndrome (CONS) is characterized by ocular alterations ranging from anophthalmia/microphthalmia to normal eyes, structural anomalies of the central nervous system, and proboscis-like nares. This syndrome was first described more than 30 years ago, but only 21 patients have been reported to date.</p><p><strong>Case presentation: </strong>In the present report, we present a 20-year-old CONS patient who exhibited anophthalmia, microphthalmia, cleft lip-palate, and proboscis-like nares. Exome sequencing (ES) analysis was performed for clinical diagnosis for the index case; her parents were evaluated with Sanger sequence analysis methods in terms of the variation detected in the index case. The ES analysis of the patient identified a novel heterozygous frameshift variant in the <i>ZNF185</i> gene. This variant was not detected in her parents, whose biological relationship to the patient was confirmed through identity testing. According to the American College of Medical Genetics and Genomics (ACMG) criteria, this novel de novo variant was assessed as likely pathogenic. Peripheral blood mononuclear cells were isolated from peripheral blood of the patient and her parents. Protein was extracted and analyzed by Western blot using antibodies against <i>ZNF185</i> and GAPDH as control. Western blot analysis detected an ∼80 kDa protein in both the patient and her healthy parents. Additionally, extra bands (∼20-25 kDa) were observed in the patient using the anti-<i>ZNF185</i> antibody.</p><p><strong>Conclusion: </strong>We aimed to evaluate all CONS patients based on their clinical features. Furthermore, we propose that the <i>ZNF185</i> gene may play a role in the etiology of CONS.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":"500-509"},"PeriodicalIF":0.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12705139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145769645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAPOS and Beyond: <i>ATP1A3</i> Variants in Pediatric Movement Disorders - Case Reports.","authors":"Mehpare Sarı Yanartaş, Özlem Yayıcı Köken, Ahmet Cevdet Ceylan, Ayşe Ergül Bozacı, Tuğçe Tural Kara, Şenay Haspolat","doi":"10.1159/000549755","DOIUrl":"10.1159/000549755","url":null,"abstract":"<p><strong>Introduction: </strong><i>ATP1A3</i>-related disorders encompass a clinically heterogeneous spectrum that includes previously defined dominantly inherited phenotypes such as alternating hemiplegia of childhood (AHC), rapid-onset dystonia-parkinsonism, and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) syndrome, as well as more complex and overlapping presentations.</p><p><strong>Case presentation: </strong>In this study, we present 2 pediatric cases that expand the phenotypic and genotypic spectrum of <i>ATP1A3</i>-associated disease. Both patients presented with \"Guillain-Barré syndrome (GBS)-like episodes\" characterized by acute-onset encephalopathy, ataxia, areflexia, and sensorimotor deterioration following febrile infections. Prominent paroxysmal postural abnormalities and dystonia were noted in both cases; however, the overall clinical features blurred the classical boundaries between CAPOS and other <i>ATP1A3</i>-associated phenotypes. The first patient carried the previously reported heterozygous <i>ATP1A3</i>(NM_001256214.2):c.2491G>A(p.Glu831Lys) variant, classically associated with CAPOS, and also exhibited sensorineural hearing loss with a positive family history. The second patient harbored a novel <i>ATP1A3</i>(NM_152296.5):c.2266C>T p.(Arg756Cys)(Clinvar: VCV000425189.38) variant and displayed oculomotor apraxia and chorea during episodes.</p><p><strong>Conclusion: </strong>These cases underscore the importance of considering <i>ATP1A3</i> variants in children presenting with GBS-like features, infection-triggered neurological attacks, and mixed movement disorders. Our findings highlight the diagnostic value of genetic testing in atypical neuroregression syndromes and contribute to the recognition of \"blended\" <i>ATP1A3</i> phenotypes beyond classical diagnostic entities. The novel pathogenic variant further supports ongoing efforts to refine genotype-phenotype correlations within this evolving group of neurological disorders.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":"536-544"},"PeriodicalIF":0.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12755908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arg339Gln Is a Recurrent Variant in Rare Combined Oxidative Phosphorylation Deficiency 4: A New Patient with Biallelic <i>TUFM</i> Gene Variant.","authors":"Aysel Tekmenuray-Unal, Muhammet Tas, Murat Kangin, A Ergul Bozaci","doi":"10.1159/000549573","DOIUrl":"10.1159/000549573","url":null,"abstract":"<p><strong>Introduction: </strong>Combined oxidative phosphorylation deficiency 4 (COXPD4, OMIM #610678) is a very rare mitochondrial disorder caused by biallelic variants in <i>TUFM</i> gene. The condition is characterized by microcephaly, severe early-onset lactic acidosis, and progressive, often fatal, infantile encephalopathy. To date, only 8 patients with biallelic <i>TUFM</i> variants have been reported.</p><p><strong>Case presentation: </strong>We present a case of a female infant with microcephaly who died from severe lactic acidosis at 7 months of age. Genetic analysis revealed homozygous c.1016G>A (p.Arg339Gln) variant in the <i>TUFM</i> gene, which has previously been reported in three other COXPD4 cases. This is the fourth publication describing the same variant in this rare disorder, suggesting that it is a recurrent variant in COXPD4 patients.</p><p><strong>Conclusion: </strong>Arg339Gln variant was found in all patients from Turkey and is considered a potential founder mutation. This report aims to contribute to the phenotypic spectrum of COXPD4, explore the frequency and clinical presentation of the reported variants, enhance the understanding of genotype-phenotype correlations, and raise awareness of rare mitochondrial disorders.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":"491-499"},"PeriodicalIF":0.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12707923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145775985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prenatally Diagnosed De Novo Interstitial Duplication in 2p21p24.3 with Unique Manifestations: Case Report.","authors":"Ahmet Kablan, Abdullah Sezer, Abdüllatif Bakir, Abdülkerim Kolkiran, Hanife Saat","doi":"10.1159/000549693","DOIUrl":"10.1159/000549693","url":null,"abstract":"<p><strong>Introduction: </strong>Partial duplications involving chromosome 2p are rare genomic events associated with variable phenotypic outcomes, ranging from craniofacial abnormalities, organ malformations to developmental delays. Prenatal identification of such duplications has become increasingly common with advances in chromosomal microarray technology, but predicting postnatal manifestations remains challenging. This report presents a de novo 32 Mb duplication of 2p21p24.3, detected prenatally, in a male patient who demonstrated unique clinical features and multisystem involvement postnatally.</p><p><strong>Case presentation: </strong>A 29-year-old pregnant female was referred for genetic evaluation following prenatal detection of flat nasal bridge, frontal bossing, short extremities, micropenis, and suspected hypospadias. Chromosomal microarray analysis revealed a 32 Mb duplication of 2p21p24.3, confirmed as de novo by parental testing. Postnatally novel features such as subglottic haemangioma, preauricular pit, and behavioural symptoms related to facial contact were noted. Growth delay, craniofacial dysmorphism, congenital heart defects, and genital anomalies were also observed. A multidisciplinary approach involving clinical genetics was critical for addressing the patient's complex medical needs. Despite ongoing supportive care, the patient continues facing significant developmental and medical challenges, underscoring the need for long-term follow-up as well as genotype-phenotype correlations.</p><p><strong>Conclusion: </strong>This case broadens the clinical spectrum of partial trisomy 2p by documenting unique features, including subglottic haemangioma, behavioural symptoms, and preauricular pit. It highlights the value of integrating prenatal diagnostics with detailed postnatal phenotypic assessment to improve understanding of genotype-phenotype correlations in rare chromosomal duplications. Although the <i>PPP1CB</i> gene within the region is considered a plausible candidate for explaining some of the patient's cardinal features, dysmorphism (prominent forehead, preauricular ear pits, low-set, posteriorly rotated ears), cardiac-neurological problems, other genes associated with defined syndromes - whose clinical manifestations overlap to varying degrees - were also considered as potential contributors to the clinical picture, such as <i>MYCN</i>, <i>DNMT3A</i>, <i>DPYSL5</i>, and <i>SOS1</i>. These insights can aid clinicians in genetic counselling, anticipatory guidance, and management of similar cases in the future.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":"510-518"},"PeriodicalIF":0.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12711258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}