Case Reports in Genetics最新文献

{"title":"From Diagnosis to Disclosure: Navigating Genetic Counseling Dilemmas in <i>BRCA2</i>-Associated Prostate Cancer in the Middle East.","authors":"Chantel van Wyk, Reem Abdulrahim, Ilse Crous, Abeer Al Saegh, Amira Al Balushi, Bushra Al Muhairi, Sara Al Kiyumi, Suad Al Malki, Munjid Al Harthy","doi":"10.1155/crig/2823337","DOIUrl":"10.1155/crig/2823337","url":null,"abstract":"<p><strong>Background: </strong>Germline genetic testing is integral to precision oncology in prostate cancer (PCa), particularly for men with pathogenic or likely pathogenic (P/LP) <i>BRCA1/2</i> variants, where results have therapeutic and hereditary implications. However, data from the Middle East remain limited regarding real-world implementation of genetic counseling and its influence on family communication and cascade testing.</p><p><strong>Aim: </strong>To describe the role and challenges of genetic counseling for <i>BRCA2</i>-associated PCa in Omani patients, focusing on family communication, risk awareness, and cascade testing uptake.</p><p><strong>Methods: </strong>This descriptive, retrospective case series included nine men with PCa carrying P/LP <i>BRCA2</i> variants identified between September 2021 and December 2025. Clinical and genetic data were extracted from electronic records, and genetic counseling documentation was reviewed for family history, psychosocial context, communication patterns, and cascade testing. Quantitative data were summarized descriptively. Qualitative content analysis of counseling records identified recurring sociocultural and communication-related factors.</p><p><strong>Findings and discussion: </strong>Patients were aged 60-76 years at the time of PCa diagnosis, with varied educational backgrounds and disease stages, and all carried <i>BRCA2</i> variants. Awareness of diagnosis differed, with some patients partially informed or unaware. These findings underscore the pivotal role of genetic counseling in translating <i>BRCA2</i> molecular results into actionable strategies for patients and families. Family-mediated protective nondisclosure and decision-making were prominent. Cascade testing uptake was higher in families with younger or medically informed relatives and lower where stigma or fear prevailed.</p><p><strong>Conclusion: </strong>In this single-center Omani case series, effective counseling for <i>BRCA2</i>-associated PCa required navigating complex cultural dynamics related to family-mediated communication and decision-making. Integrating culturally sensitive, family-centered genetic counseling into routine oncology care may save lives by empowering families to act earlier on inherited risk.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2026 ","pages":"2823337"},"PeriodicalIF":0.0,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13392218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Case of Malan Syndrome With Pulmonary Artery Dilatation due to a Novel Frameshift Variant in Exon 2 of the <i>NFIX</i> Gene.","authors":"Toshihiko Mori, Mayu Hirano, Shigeto Fuse, Maki Katai, Hiroko Shigetomi","doi":"10.1155/crig/4265185","DOIUrl":"10.1155/crig/4265185","url":null,"abstract":"<p><p>Malan syndrome is a rare overgrowth disorder caused by deletions or pathogenic variants in the <i>NFIX</i> gene. Here, we present the case of a Japanese male infant with Malan syndrome, which was caused by a novel frameshift variant resulting from an eight-base insertion in Exon 2 of the <i>NFIX</i> gene. Echocardiography revealed dilatation of the pulmonary artery without hemodynamic abnormalities. Malan syndrome shares many clinical features with Sotos syndrome, including overgrowth, macrocephaly, developmental delay, and intellectual disability. Therefore, molecular genetic testing is required for diagnosis. Pathogenic variants in the <i>NFIX</i> gene have also been reported in individuals with Marshall-Smith syndrome. Some individuals exhibit phenotypic overlap between Malan syndrome and Marshall-Smith syndrome. Our patient was diagnosed with Malan syndrome because he had a frameshift variant in Exon 2, resulting in haploinsufficiency, and exhibited macrocephaly, but not proptosis or micrognathia. To our knowledge, this is the second reported case in the literature of concomitant pulmonary artery dilatation in Malan syndrome.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2026 ","pages":"4265185"},"PeriodicalIF":0.0,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13270412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148273221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Case of Pallister-Killian Syndrome in a Newborn.","authors":"Giulia Di Donato, Chiara Cauzzo, Paola Cicioni, Teresa Topazio, Valentina Chiavaroli, Chiara Palka Bayard De Volo, Elisena Morizio, Francesco Chiarelli, Susanna Di Valerio","doi":"10.1155/crig/8819010","DOIUrl":"10.1155/crig/8819010","url":null,"abstract":"<p><strong>Background: </strong>Pallister-Killian syndrome (PKS) is a rare disorder caused by tissue-limited mosaicism tetrasomy of chromosome 12p. Affected newborns show a typical dysmorphic pattern: macrosomia, coarse facies, hypertelorism, small nose with long philtrum, V-shaped upper lip, low set ears, frontotemporal alopecia, and patchy pigmentary skin and hair anomalies. Seizures and developmental delay, cardiac defects, diaphragmatic hernia, and renal/anal malformations may be associated.</p><p><strong>Case: </strong>Here, we report the case of a newborn with multiple congenital malformations, later diagnosed with PKS.</p><p><strong>Conclusions: </strong>Phenotypic and cytogenetic variability of PKS, together with the lack of correlation between tetrasomic cells' proportion and disease severity, may be challenging for diagnosis. Therefore, a detailed physical examination is mandatory for early clinical suspicion and to guide further investigations. The usefulness of array-CGH performed on peripheral blood should also be emphasized as a sensitive diagnostic tool.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2026 ","pages":"8819010"},"PeriodicalIF":0.0,"publicationDate":"2026-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13240379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148200249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Case of Nonimmune Hydrops Fetalis With a Duct-Dependent Systemic Circulation and a Novel Mutation of Kabuki Syndrome.","authors":"Rameshwar Prasad, Sudipta Sahoo, Richie Dalai, Keshav Kumar Pathak, Bhabesh Kant Chowdhary","doi":"10.1155/crig/8898702","DOIUrl":"10.1155/crig/8898702","url":null,"abstract":"<p><strong>Introduction: </strong>Nonimmune hydrops fetalis (NIHF) has numerous etiologies, the most common of which are cardiac anomalies and fetal infection. However, genetic disorders are also being increasingly recognized as a cause of NIHF. Here, we report a case of a neonate presenting with polyhydramnios, NIHF, structural heart disease, and diaphragmatic defect who was found to have a previously unreported mutation in the <i>KMT2D</i> gene.</p><p><strong>Case presentation: </strong>A female neonate with antenatally detected NIHF was born at 35 weeks of gestation via cesarean section. At birth, she was noted to have dysmorphic features, scoliosis, and a single umbilical artery. Further investigations revealed a left-sided obstructive cardiac lesion and a right-sided Morgagni hernia. She required invasive ventilation, inotropes, and prostaglandin E1 for preductal coarctation of the aorta with hypoplastic left heart syndrome. Genetic analysis was warranted due to multiple anomalies in the neonate. Whole exome sequencing (WES) showed a previously unreported truncating mutation in the <i>KM2TD</i> gene, confirming the diagnosis of Kabuki syndrome type 1.</p><p><strong>Conclusion: </strong>Kabuki syndrome is rare, and its presentation with hydrops is extremely rare. Our case presented with polyhydramnios, antenatal hydrops, hypoplastic left heart, right-sided Morgagni hernia, and scoliosis with a novel mutation, thus potentially expanding the genotype-phenotype spectrum of this syndrome. This case highlights that a pediatrician should have a high index of suspicion for inherited genetic syndromes in a case of nonimmune hydrops with multiple congenital anomalies. Genetic tests are valuable for identifying rare syndromes and novel mutations.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2026 ","pages":"8898702"},"PeriodicalIF":0.0,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13240378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148200223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Case Highlighting the Importance of Timely Intervention for a Male With AZFb + c Microdeletion.","authors":"Rahul Atodaria, Randa Abdelmasih","doi":"10.1155/crig/2832648","DOIUrl":"10.1155/crig/2832648","url":null,"abstract":"<p><p>Male infertility can be caused by various microdeletions of the azoospermia factor (AZF) gene, some of which require sperm retrieval techniques for treatment. Yet, the likelihood of success with such techniques depends partly on the affected AZF gene segment. For patients with select AZF microdeletions, other options such as in vitro fertilization, sperm donation, and adoption may be more appropriate. We present a case about a 32-year-old male diagnosed with infertility due to azoospermia from a complete AZFb + c deletion, which is unlikely to be successfully treated with sperm retrieval techniques. The goal of this case report is to highlight the significance of earlier diagnosis of AZF microdeletions in infertile males to facilitate earlier genetic counseling and pursuit of the most appropriate intervention.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2026 ","pages":"2832648"},"PeriodicalIF":0.0,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13191823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148017706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Heterogeneity of a <i>TP53</i> Variant in a Consanguineous Omani Family: A Case Report Featuring a Homozygous Pathogenic Variant.","authors":"Mariya Al Hinai, Chantel Van Wyk, Manal Al Kharusi, Nishath Hamza, Abeer Al Batashi, Abeer Al Sayegh, Maryam Al Shihhi","doi":"10.1155/crig/1809799","DOIUrl":"10.1155/crig/1809799","url":null,"abstract":"<p><strong>Background: </strong>Li-Fraumeni syndrome (LFS) is a rare, autosomal dominant cancer predisposition syndrome caused by germline mutations in the <i>TP53</i> gene. While heterozygous <i>TP53</i> variants are well-characterized, homozygous germline mutations are extremely rare, and their clinical significance remains poorly understood. Such cases are more likely to arise in consanguineous families, where shared genetic ancestry increases the risk of homozygosity.</p><p><strong>Case presentation: </strong>We report a consanguineous Omani family with a homozygous <i>TP53</i> missense variant, in a male infant who presented with multiple hypopigmented skin macules and a strong family history of childhood and adult-onset cancers. Several relatives were identified as heterozygous carriers of the same pathogenic variant. A deceased older sibling exhibited similar cutaneous findings and early malignancy, suspecting he may also have carried the homozygous variant. These skin manifestations may represent a novel phenotypic feature not previously associated with LFS.</p><p><strong>Discussion: </strong>This case adds to the limited literature on homozygous <i>TP53</i> variants and raises the possibility of a link between cutaneous features and homozygosity. While heterozygous carriers often exhibit variable penetrance, the homozygous state may be associated with earlier and more severe phenotypes. Genetic counseling in such families is complex due to uncertainty in predicting clinical outcomes and the psychosocial burden of decision-making, particularly in children. Challenges in family communication further hinder risk awareness and testing uptake.</p><p><strong>Conclusion: </strong>This is the first reported case of a homozygous <i>TP53</i> p.Arg158His variant in the Omani population, expanding the phenotypic spectrum of LFS. Our findings underscore the importance of genetic counseling, cascade testing, and long-term surveillance in consanguineous families with hereditary cancer syndromes, and call for further research into genotype-phenotype correlations and associated dermatological findings.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2026 ","pages":"1809799"},"PeriodicalIF":0.0,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13112418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147783424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prolonged Survival With Homozygous Deletion of Exon 9 in Perlman Syndrome: A Case Report.","authors":"Esther Levy, Leighton Elliott, Michal A Miller, Mackenzie Kramer","doi":"10.1155/crig/9916711","DOIUrl":"10.1155/crig/9916711","url":null,"abstract":"<p><p>Perlman syndrome is a rare autosomal recessive overgrowth disorder characterized by macrosomia, nephromegaly, renal dysplasia, and characteristic facial features. It has both similarities and differences to other more common overgrowth syndromes. Pathogenic homozygosity is extremely rare in nonconsanguineous relationships. Survival is predicted by differences among various germline mutations in the DIS3L2 gene on chromosome 2q37.1, with prolonged survival documented in heterozygous mutations allowing partial exoribonuclease function. Although homozygous deletions of exon 9 are rare and have been associated with poor survival, we describe a case report of the only known patient with Perlman syndrome to live past 2 years old with this deletion. Diligent management and surveillance may be associated with prolonged survival in Perlman syndrome.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2026 ","pages":"9916711"},"PeriodicalIF":0.0,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13109714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147783358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complete Androgen Insensitivity Syndrome (CAIS) Genetic Counseling: Navigating Germline Mosaicism Concerns.","authors":"Lauren M Iacono, Paul A Levy, Tamar G Baer","doi":"10.1155/crig/1224893","DOIUrl":"10.1155/crig/1224893","url":null,"abstract":"<p><p>Complete androgen insensitivity syndrome (CAIS) is caused by pathogenic variants in the androgen receptor (AR) gene that lead to a phenotypically female appearance in XY individuals. It is almost always inherited as an X-linked recessive condition. Here, we present two sisters with different clinical courses. AR gene sequencing revealed identical hemizygous pathogenic variants in both sisters but not in the mother. This rare occurrence of germline mosaicism is the first described in CAIS. Germline mosaicism should be considered when \"<i>de novo</i>\" AR gene variants are identified. Despite the low recurrence risk, counseling would be beneficial to families so they can make well-informed prenatal and reproductive plans.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2026 ","pages":"1224893"},"PeriodicalIF":0.0,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13069466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147676634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Generation-Skipping Inheritance Pattern of Marfan Syndrome Due to <i>FBN1</i> Insertional Translocation: Diagnostic Utility of FISH and Implications for Genetic Counseling.","authors":"Breanna Beers, Hamilton Wexler, Gretchen MacCarrick","doi":"10.1155/crig/1611720","DOIUrl":"10.1155/crig/1611720","url":null,"abstract":"<p><p>Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder caused by pathogenic variants in the fibrillin-1 (<i>FBN1</i>) gene on Chromosome 15q21.1. A 3-year-old female presented to the clinic with MFS and a family history of an affected maternal uncle and maternal great-aunt. The proband and the uncle had a positive thoracic aortic aneurysm and dissection (TAAD) panel for MFS revealing an <i>FBN1</i> deletion. This was confirmed on proband's chromosome microarray; however, the mother was negative for the <i>FBN1</i> deletion. Fluorescence in situ hybridization (FISH) was used in this case to show a unique chromosome rearrangement in the unaffected mother with an insertional translocation of the 15q21.1 loci (<i>FBN1</i>) to Chromosome 7p. This led to an affected child who inherited the nontranslocated Chromosome 7 and the 15q21 (<i>FBN1</i>) deletion. Thus, individuals in the family inheriting Chromosome 7 with the <i>FBN1</i> insertional translocation are protected from the MFS phenotype. This supports the known autosomal dominant inheritance pattern while allowing for uncharacteristic skipping of generations of MFS in this family.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2026 ","pages":"1611720"},"PeriodicalIF":0.0,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12972207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147436263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Rare Case of Concurrent SNRPB Mutation and 22q11.2 Microduplication in a Child With Cerebro-Costo-Mandibular Syndrome.","authors":"Elizabeth Slear, Claire Thompson, Virginia Ruas","doi":"10.1155/crig/4169170","DOIUrl":"10.1155/crig/4169170","url":null,"abstract":"<p><p>We present a unique case of an infant born with both a microduplication of 22q11.2 and SNRPB gene mutations suggestive of cerebro-costo-mandibular syndrome (CCMS). Microduplications of 22q11 are known to present with a variety of phenotypes ranging from asymptomatic to significant physical and mental health challenges. CCMS is a rare autosomal dominant condition caused by a mutation in the SNRPB gene and typically presents with posterior rib malformations and branchial arch deformities. There have been less than 100 reported cases of CCMS in the literature, and this may be the first documented case of a patient with both CCMS and a 22q11 microduplication.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2026 ","pages":"4169170"},"PeriodicalIF":0.0,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12917849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147272062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}