Prevalence, associated disorders and treatment of joint hypermobility syndrome; A systematic review.

Hemophilia A is a congenital bleeding disorder. These patients often require factor VIII replacements predisposing them to the development of antibodies against factor VIII. Such patients require meticulous treatment strategies involving administration of Factor VII, FEIBA (Factor Eight Inhibitor Bypassing Activity) and factor VIII mimics like Emicizumab necessitating a multi-disciplinary team approach, careful titration and follow-up. These agents may also interfere with the coagulation assays rendering false normal values which can be detrimental to the perioperative management with increased risk of acute hemorrhagic episodes. There is scant literature on the management of perioperative bleeding in children with high titer antibodies on Emicizumab. We report the perioperative management of a 13 year old child with severe Hemophilia A with high responding inhibitors posted for robotic nephrectomy. This case highlights the need for a thorough preoperative workup, multi-disciplinary team approach, careful intraoperative titration and postoperative follow-up.

Zika virus (ZIKV) is a mosquito-borne Orthoflavivirus that became a major global health concern following the 2015-2016 outbreaks in South America, where infection was linked to severe neurological outcomes, including microcephaly, congenital Zika syndrome (CZS), and Guillain-Barré syndrome (GBS). Although substantial efforts are underway to develop effective preventive measures, including vaccines and vector-control strategies, ZIKV remains a priority pathogen under the World Health Organization (WHO) R&D Blueprint due to its pandemic potential. This concern is intensified by the expansion of mosquito vectors caused by climate change and the serious outcomes observed in newborns. The severity of ZIKV-related neurological complications highlights the need for research into post-exposure treatments that can reduce long-term effects and improve clinical results. Efforts to identify antiviral molecules, especially strategies like drug repositioning, have highlighted compounds such as nucleoside analogs, which have shown inhibitory effects in preclinical models. Host-targeting approaches have also shown promise, with small-molecule inhibitors and certain organic dyes demonstrating notable antiviral activity in both cell-based and animal models. Furthermore, natural compounds with cytoprotective properties, such as betulinic acid, have emerged as attractive candidates due to their combined antiviral and neuroprotective effects, which may help limit ZIKV-induced pathology. Despite these advances, most evidence remains limited to preclinical research, emphasizing the need for translational and clinical studies that validate the efficacy and safety of these therapeutic strategies, a crucial step toward transforming promising laboratory findings into available, effective treatments.

Cord blood natural killer cell-derived extracellular vesicles inhibit Zika virus infectivity through ITGB2/perforin-mediated envelope disruption in vitro and in vivo.

Epidermodysplasia verruciformis (EV) was described as a congenital skin disease and later as a Mendelian disorder in 1922 and 1946, respectively [1]. For decades, EV was considered a monogenic entity and was also interchangeably referred to as Treeman syndrome (TMS). However, recent advancements in next-generation sequencing (NGS) have revealed that the pathogenesis of EV is distinct from TMS [2]. In fact, a recent study showed that TMS, in some cases, is caused by biallelic loss-of-function CD28 mutations and that TMS warts are driven by α-human papillomavirus (HPV) [2]. Furthermore, at least 21 genes have been implicated in EV pathogenesis. Persistent disseminated flat-like warts in EV patients are derived, for the most part, from weakly virulent, E5- and E8-deficient β-HPVs, which exclusively reside within keratinocytes. However, these β-HPVs, lacking the E5 and E8 genes that are expressed in other genera of more pathogenic HPVs, typically cause only asymptomatic infections in the general population [1]. It is noteworthy that, in addition to β-HPVs, non-β-HPVs (including α- and γ-HPVs) are occasionally associated with the EV phenotype [3]. Mechanistic insights gained from studies of single-gene disorders with EV manifestations suggest dual contributions of keratinocyte-intrinsic immunity and adaptive T-cell immunity to β-HPV clearance. Ultrarare and private mutations in genes governing either keratinocyte-intrinsic immunity or adaptive T-cell immunity, at the priming or effector level, confer predisposition to severe β-HPV infections (Figure 1). These observations led Shen et al., in this issue of the International Journal of Dermatology, and other research groups to categorize EV into classic (TMC6, TMC8, and CIB1), nonclassic (e.g., DOCK8, STK4), and acquired forms [4, 5]. A total of 439 EV patients, comprising 137 classic (typical) EV patients, 46 nonclassic (atypical) EV patients, and 256 acquired EV (AEV) patients, were reviewed. The most commonly reported genes were TMC6, CIB1, TMC8, STK4, and DOCK8. A total of 31 distinct HPVs, belonging to the α-, γ-, and β-HPV genera, were associated with the EV phenotype, with β-HPV-5, -8, and -20 identified as the most common types. Collectively, these genomics-driven advances in EV understanding herald a paradigm shift in the diagnosis, prognosis, and monitoring of EV in the era of precision dermatology. While single-gene EV is a pediatric clinical condition (with an age of onset before 12 years in 89% of cases), most AEV patients are adults, and the disease is prevalent among HIV and transplant populations [5]. The phenocopy in AEV patients underscores the effective suppression of the same surveillance pathways for HPV clearance that are disrupted in hereditary forms [4, 5]. A review of oncologic data in EV patients offers clinically actionable insight into the age of onset and extent of cancer risk. The majority (56%) of monogenic EV patients develop malignancy, occurring decades earlier than in the general population. Moreover, the distinction between isolated and syndromic EV has implications for cancer management: cutaneous malignancies predominate in isolated EV, while extracutaneous malignancies are more common in syndromic forms. These results support genotype-informed cancer surveillance strategies in EV patients. Furthermore, they indicate that EV should be integrated into broader hereditary cancer predisposition frameworks [5]. In sum, EV offers a unique human knockout model for the study of host–virus co-evolution, tissue-specific immunity, and early carcinogenesis. Furthermore, recent genomic advances shift the paradigm of EV from a mere dermatologic curiosity to a prototype for precision dermatology. The authors employed large language models to refine manuscript grammar and phrasing, then reviewed, edited, and accepted full responsibility for the final content. The LEO Foundation (grant LF-OC-22-000965) and the US NIH (grant R01AI143810) supported the authors' studies. The authors declare no conflicts of interest. Clinical and Molecular Perspectives on Epidermodysplasia Verruciformis, https://doi.org/10.1111/ijd.70295. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Truncated N-glycans destabilize POMT1 and POMT2 but do not limit cellular O-mannosylation in HEK293 cells.

Simultaneous detection of PNGase and ENGase activities in tissue lysate or cytosol using a simply designed high-mannose-type glycopeptide probe containing an Asn-leu-leu sequence.

Biochemical genetic testing for congenital disorders of glycosylation after sequencing produces equivocal results.

Zika virus (ZIKV) is a mosquito-borne flavivirus that caused an epidemic in the Americas in 2015-2016, accompanied by severe neurological manifestations, including congenital Zika syndrome and Guillain-Barré syndrome. Our previous data demonstrate that the protein level of karyopherin α6 (KPNA6), a transport factor in nucleocytoplasmic trafficking, increases in ZIKV-infected cells, and that KPNA6 depletion reduces ZIKV replication. Here, we found that ZIKV infection led to the relocation of KPNA6 to the perinuclear region. KPNA6 was observed to partially co-localize with double-stranded RNA, an intermediate in the replication of positive-sense, single-stranded RNA viruses. Further studies revealed that the ZIKV protein NS2B mediates the relocation of KPNA6 and that both proteins interact, as indicated by co-immunoprecipitation. The mutagenesis studies showed that KPNA6 co-precipitated NS2B via its major groove, and that, in turn, NS2B pulled down KPNA6 via its C-terminus. Furthermore, two residues, P115 and G119, in NS2B were identified as critical for interaction with KPNA6, and mutations in either residue abolished virus replication. These results demonstrate that ZIKV induces the relocation of KPNA6 via NS2B, uncovering a novel ZIKV-host interaction to recruit a host proviral factor to facilitate viral proliferation.IMPORTANCELike most other positive-sense RNA viruses, Zika virus (ZIKV) replicates in the cytoplasm; however, the mechanisms by which it recruits host factors for efficient proliferation remain elusive. Our results demonstrate that ZIKV induces the relocation of karyopherin α6 (KPNA6) to the perinuclear region, likely mediated by the viral protein NS2B. Further analysis shows that KPNA6 interacts with NS2B, with two critical residues in NS2B required for the interaction. A mutation in these two residues abolishes virus replication. Despite the absence of a predicted nuclear localization signal sequence in NS2B, this protein was found to bind the major groove of KPNA6. These findings shed light on the interaction between ZIKV and a proviral host factor, providing valuable insights that may inform the development of future antiviral strategies.

Cenani-Lenz syndactyly syndrome (CLSS, OMIM 212780) is a rare autosomal recessive disorder characterized by syndactyly and oligodactyly of the digits, fusion of carpal and tarsal bones, and radioulnar synostosis. Craniofacial anomalies and renal malformations have been reported in approximately half of cases, with variable expression. The condition results from homozygous or compound heterozygous mutations in the LRP4 gene. We identified a consanguineous family with four individuals affected by CLSS, comprising two brothers and their two maternal male cousins. All patients presented with bilateral complex syndactyly, characterized by absent phalanges, reduced and disorganized metacarpals, and cutaneous toe syndactyly. The 2-year-old proband had a horseshoe kidney, whereas his 6-year-old cousin presented with right renal agenesis. None of the patients exhibited growth and developmental delay, cardiac anomalies, or intellectual disability. Based on the clinical suspicion of CLSS, targeted next-generation sequencing of the LRP4 gene was performed. This analysis revealed a biallelic variant, c.3830G>T (NM_002334.3), resulting in the protein change p.Arg1277Leu, which has not been previously described. CLSS is a rare congenital disorder affecting distal limb development and is frequently associated with renal malformations and variable dysmorphic features. In this report, we describe four affected individuals carrying a novel homozygous missense variant in the LRP4 gene, thereby broadening the clinical and genetic spectrum of CLSS and highlighting the pathogenic significance of this newly identified variant.

Cystic fibrosis (CF) is a genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and is classically associated with male infertility due to obstructive azoospermia secondary to congenital bilateral absence of the vas deferens. Increasing evidence suggests that CFTR dysfunction may also contribute to nonobstructive forms of male infertility. Accordingly, CFTR is widely expressed throughout the male reproductive tract, including Sertoli cells, germ cells, and mature spermatozoa. This review summarizes current evidence linking CFTR mutations and variants to hypogonadism, impaired spermatogenesis, altered sperm function, and reduced reproductive outcomes. Clinical studies indicate a high prevalence of testosterone deficiency in men with CF or CBAVD, often occurring in the presence of normal gonadotropin levels. Genetic and meta-analytic data support an association between CFTR variants, particularly the IVS8-5T polymorphism, and nonobstructive azoospermia. Experimental studies further demonstrate that CFTR plays a critical role in spermatogenesis via regulation of the cAMP-CREB signaling pathway in Sertoli cells and through modulation of microRNA expression affecting germ cell proliferation. CFTR expression in spermatozoa is also implicated in capacitation, motility, and fertilizing capacity through coordinated chloride and bicarbonate transport and interactions with SLC26 family members. Emerging evidence additionally suggests a role for CFTR in early embryonic development, with potential implications for assisted reproductive technology outcomes. Collectively, these findings challenge the traditional view of CF-related male infertility as purely obstructive and highlight CFTR mutations as a potential contributor to nonobstructive infertility. Further studies are required to clarify pathogenic mechanisms and explore targeted therapeutic strategies.

The C-terminal region of KIF26B is indispensable for nephron progenitor condensation and kidney formation in mice.

PHOX2B defects alter protein folding, cell-cycle, and mitochondrial pathways in an in vitro model of CCHS.

Tongue diseases are highly diverse and difficult to differentiate due to their varied etiologies. This clinical review summarizes various tongue diseases based on clinical experience and proposes appropriate treatment strategies, emphasizing the tongue's multifunctional role and its impact on quality of life. This clinical review analyzes a broad spectrum of tongue diseases encountered in clinical practice. Lesions were categorized according to etiology, including infectious, inflammatory, benign and malignant neoplastic, precancerous, congenital, autoimmune, and systemic disease-related manifestations. Relevant literature was reviewed in conjunction with the authors' clinical experience. A total of 36 tongue diseases were classified, and the characteristic clinical features and treatment approaches for each condition were presented. In this clinical review, various tongue diseases are reviewed and treatments were suggested.

BackgroundCongenital anomalies involving the meniscus and anterior cruciate ligament (ACL) are rare and often discovered incidentally. Discoid meniscus is the most frequently reported congenital variant, whereas medial meniscal hypoplasia and ACL agenesis remain exceptionally uncommon.Case PresentationA 16‐year‐old male presented with right knee pain, swelling, and instability following a noncontact basketball injury. He reported a similar episode weeks earlier. Clinical examination revealed anterior laxity, and magnetic resonance imaging (MRI) demonstrated a nonvisualized ACL consistent with a tear and absent tissue suggestive of a subacute injury. The medial meniscus appeared diminutive without evidence of a tear or displaced fragment. Arthroscopy confirmed a hypoplastic medial meniscus without reparable tissue and complete absence of ACL fibers. The patient underwent ACL reconstruction with internal brace augmentation and anterolateral ligament (ALL) reconstruction. A lateral meniscal tear was also repaired. Postoperative recovery demonstrated progressive improvement in range of motion and quadriceps activation.ConclusionThis case highlights a rare presentation of concurrent medial meniscal hypoplasia and congenital absence of the ACL in an otherwise healthy adolescent male. Notably, the patient sustained a pivoting sports‐related injury accompanied by an instability episode, in the absence of any syndromic or systemic congenital anomalies. Recognition of congenital intra‐articular anomalies is essential for accurately interpreting preoperative imaging and understanding that structures such as the ACL and meniscus may not develop in tandem, which can influence surgical planning and clinical decision making.

Kallmann syndrome (KS) is a rare congenital disorder characterized by hypogonadotropic hypogonadism secondary to deficient gonadotropin-releasing hormone (GnRH) secretion, often accompanied by partial or complete anosmia. Deficient GnRH secretion results in decreased levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), causing impaired sexual development and absent secondary sexual characteristics. Against the backdrop of global expansion in rare disease research, KS has become a core research focus, and a comprehensive bibliometric analysis is required to chart the trajectory, trends, hotspots, and future paths in KS research over the last 15 years. A systematic search of the Web of Science Core Collection (WOSCC) retrieved KS publications from January 1, 2009, to August 18, 2025, employing the search term "Kallmann syndrome" with the language restricted to English and no restrictions imposed on publication types. Data analyses were performed using VOSviewer for visualizing collaborative networks, CiteSpace for bursts and clusters, and R for statistics, to evaluate publication trends, countries, institutions, authors, journals, citations, and keywords. KS publications exhibited steady double-digit annual growth, reaching 508 studies. The U.S. ranked first in publication volume, followed by Switzerland and France. Nelly Pitteloud (Switzerland) and Jacques Young (Paris Public Hospitals) were the most prolific and influential authors. The Journal of Clinical Endocrinology and Metabolism published the largest number of KS-related articles; Harvard University was the leading contributing institution. The most highly cited article, "Expert Consensus: European Consensus Statement on Congenital Hypogonadotropic Hypogonadism-Pathogenesis, Diagnosis and Treatment," was cited 575 times in total. Keywords identified hotspots like GnRH deficiency, hypogonadotropic hypogonadism, anosmia, and genetic mutations (> 30 genes), current research frontiers focusing on molecular pathogenesis and personalized therapies. Our study provided a comprehensive overview of Kallmann syndrome research and showed the development status and scientific trend of Kallmann syndrome through bibliometric analysis from 2009 to 2025. The global volume of publications related to Kallmann syndrome has demonstrated a steady year-on-year increase. Research in this field is predominantly led by European and American countries, and cross-regional collaboration serves as a key driver for further advancement. In summary, these findings provide new perspectives for future relevant research and serve as a valuable reference to guide researchers in subsequent studies.

Management of Liver Transplantation in a Pediatric Patient With Heterotaxy Syndrome and Bradyarrhythmia: A Case Report.

BackgroundSome symptoms of orofacial dysfunction, such as dysphagia and dysarthria, are commonly encountered in congenital or childhood-onset neuromuscular diseases (NMD), while others, such as reduced saliva control and difficulties using facial expressions, are not as well researched. Overall, there is a lack of knowledge regarding the extents to which different orofacial functions are affected in persons with NMD.ObjectiveTo identify orofacial dysfunction profiles at group level for congenital or childhood-onset NMD.MethodsThis database study included 206 individuals in the age range of 3-48 years with 21 different congenital or childhood-onset NMD, categorized as anterior horn cell diseases, neuropathies and myopathies. Orofacial dysfunction profiles from the Nordic Orofacial Test - Screening were extracted from a national database of oral health and orofacial functions in rare health conditions.ResultsIn the study population, 70% presented with signs of orofacial dysfunction. Neuropathies had the lowest rate of orofacial dysfunctions (25%), followed by myopathies (72%). Anterior horn cell diseases had the highest rate of orofacial dysfunctions (82%). In all the groups, there were individuals without orofacial dysfunction, except for the subgroups of Spinal Muscular Atrophy type 1 and Duchenne Muscular Dystrophy with age range of 19-49 years in which all the participants (100%) demonstrated orofacial dysfunction according to NOT-S.ConclusionsThis study identifies a considerable proportion of individuals with congenital and childhood-onset NMD exhibiting signs of orofacial dysfunction, indicating the need for further investigation. It also shows to what extents different orofacial functions are affected in subgroups of NMD.

Total colonic aganglionosis (TCA) is a rare but severe congenital disorder that impacts the colon's ability to function properly due to the absence of ganglion cells. Investigating research trends in the diagnosis and treatment of TCA can offer valuable insights into advancements in clinical practices, surgical techniques, and future directions in pediatric gastroenterology. Literatures related TCA were explored through a search in the Web of Science Core Collection (WoSCC) database, spanning the period from 1978 to 2024. Bibliometric analysis and data visualization were conducted using VOSviewer, CiteSpace, and the R package "bibliometrix." A total of 281 articles were analyzed, accumulating over 4,010 citations. The USA led in productivity, with Paris City University as the top institution, and Journal of Pediatric Surgery emerged as the leading journal. Prem, Puri was identified as the most influential author. Current hotspots included genetic mutations, management, clinical guidelines, diagnosis, and pull-through for TCA. Keywords burst analysis showed emerging interests in "diagnosis" (2020-2024), "management" (2022-2024), and "pull-through" (2022-2024). This study presents a bibliometric analysis of TCA, focusing on emerging research trends, influential publications, and global collaborations. The findings identify key advancements in the understanding and treatment of TCA, providing valuable insights for both clinical and basic research in pediatric gastroenterology. Not applicable.

Cleidocranial dysplasia (CCD) is a rare congenital condition characterized by patients presenting with craniofacial anomalies, multiple supernumerary and impacted teeth, retained primary teeth, and delayed eruption, necessitating multi-stage and innovative treatment mechanics to facilitate tooth eruption. This case report highlights the orthodontic management of a 21-year-old female with CCD using a sequential, interdisciplinary approach including the extraction of retained primary and supernumerary teeth, and exposure, bonding, and forced eruption of impacted teeth. The latter was achieved with a custom-fabricated lower appliance and a modified transpalatal arch designed to reinforce anchorage and facilitate simultaneous traction of multiple impacted teeth via a closed surgical technique, achieving their successful retrieval and good orthodontic outcomes.