Congenital Anomalies最新文献

M. Kamau, K. Sarna, S. Guthua, K. J. Sonigra, and P. Kimani, “Patterns of Primary and Secondary Defects Associated With Non-Syndromic Cleft Lip and Palate: An Epidemiological Analysis in a Kenyan Population,” Congenital Anomalies 64, no. 3 (2024): 134–142, https://doi.org/10.1111/cga.12564.

The caption of figure 1, “The model used for classification of primary cleft lip and palate deformities defects composed of 16 codes that each represents a particular region. Adopted from Nagase et al.¹⁰” was incorrect. This should have read as follows: The model used for classification of primary cleft lip and palate deformities defects composed of 16 codes that each represents a particular region. Adapted with permission from Nagase et al.¹⁰

Permission to reproduce material from other sources: The authors confirm that permission has been obtained to reproduce/modify figures 1 and 3–5 in this manuscript from figure 1 published by Nagase et al.¹⁰

We apologize for this error.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by excessive and frequent epistaxis, telangiectasia, and visceral involvement, with a strong positive family history. The genes responsible for HHT are endoglin (ENG), activin A receptor-like kinase 1 (ACVRL1 or ALK-1), and SMAD4 are known. As opposed to epistaxis and telangiectasia, whether or not the disease is prone to any visceral lesions depends on the causative gene. Arteriovenous malformations (AVMs) of the brain and lung are common in ENG, hepatic AVMs and cutaneous telangiectasia are common in ACVRL1, and juvenile polyposis (JP-HHT) is characteristic in SMAD4. Therefore, the diagnosis of HHT and its subclasses in patients with recurrent epistaxis is clinically important for predicting cerebral and visceral complications and for prophylactic medical or surgical treatment. Genomic techniques for the molecular diagnosis of HHT have advanced remarkably in recent years. Long-read sequencing using nanopore technology is now recognized as a new and effective approach for the detection of structural aberrations, such as large deletions, that cannot be detected by conventional short-read analysis. In particular, a new technique called adaptive long-read sequencing can selectively sequence only pre-defined target regions. Here we report two patients with HHT in whom no variants were found by short-read targeted sequencing, but structural variants were detected by adaptive nanopore sequencing. These molecular diagnostic results were used in their clinical management.

Congenital chylous ascites (CCA) is a rare condition caused by maldevelopment of the intra-abdominal lymphatic system, resulting in chyle accumulation in the peritoneal cavity. Diagnosis involves analyzing milky-white ascitic fluid with elevated triglycerides and T-lymphocyte predominance, with lymphangiography or lymphoscintigraphy as the gold standard. Initial treatment focuses on nutrition and medical therapies like medium-chain triglycerides (MCT) and total parenteral nutrition (TPN). Surgery is considered if conservative measures fail. A neonate with CCA required TPN, MCT formula, octreotide, and paracentesis. Lymphoscintigraphy showed bilateral lymphatic leakage. Despite medical management, the condition remained refractory, and exploratory surgery was performed, revealing a mesothelial cyst and peritoneal defect, which was treated with fibrin glue. Post-surgery, the infant's ascites resolved, highlighting the need for surgery in refractory cases.

This study examined the impact of blood glucose-regulated gestational diabetes (GDM) on fetal pulmonary artery Doppler parameters. This prospective case–control study was performed at a tertiary university hospital. The study cohort comprised GDM patients with controlled blood glucose levels and a healthy control group. Acceleration time/ejection time (At/Et) of the main pulmonary artery, right pulmonary artery, and left pulmonary artery Doppler parameters were assessed and contrasted between the two groups. The study comprised 90 patients, with 30 in the gestational diabetes mellitus group focused on blood sugar regulation and 60 in the healthy control group. No statistically significant difference was observed between the two groups regarding the common main pulmonary artery At/Et (p = 0.465), right pulmonary artery At/Et (p = 0.237), and left pulmonary artery At/Et (p = 0.283). No statistically significant difference was noted between the two groups regarding APGAR scores and blood gas parameters of the newborns (p < 0.05). No statistically significant difference was observed in fetal pulmonary artery Doppler parameters (p < 0.05) when gestational diabetes mellitus cases were classified based on the utilization of diet and insulin for blood sugar regulation. The pulmonary artery Doppler parameters in fetuses of pregnant women with gestational diabetes mellitus and controlled blood sugar levels are comparable to those of healthy controls. Moreover, dietary habits and insulin administration for glycemic control did not alter pulmonary artery Doppler metrics. The findings suggest that well-managed gestational diabetes mellitus, irrespective of the treatment modality, do not substantially influence the fetal pulmonary artery dynamics.

The cranial base (CB) and facial skeleton, despite differing in function and origin, are developmentally related. However, the mechanisms underlying the structural connection remain poorly understood. This article reviews CB malformations in congenital facial anomalies to identify the morphological basis for the relationship between these regions. Various types of CB deformities were identified in each facial anomaly; however, even anomalies with similar facial features did not necessarily share the same CB deformity, indicating that the underlying mechanisms exhibit complex interactions. To elucidate the biological processes related to these morphological interactions, detailed craniofacial geometry should be analyzed while retaining as much quantitative shape information as possible. Geometric morphometrics (GM) is an effective method for craniofacial studies because it analyzes shapes using landmark coordinates to retain relative geometric information, and it can be applied to complex shapes, such as curvatures or processes. Therefore, the application of GM in previous craniofacial studies is also reviewed. Quantitative data on normal and abnormal craniofacial development, encompassing both the prenatal and postnatal periods from GM studies, may provide valuable insight into the pathogenesis of congenital craniofacial anomalies.

Proper vertebral column development requires precise segmentation and regulated chondrogenesis during embryogenesis. Mutations affecting fibroblast growth factor 9 (FGF9) signaling disrupt these processes, resulting in abnormal vertebral column development. A missense mutation in FGF9 (p.Asn143Thr) produces elbow knee synostosis (Eks)-mutant mice, which display skeletal fusions, including those in the vertebral column, underscoring the essential role of FGF9 in vertebral segmentation and vertebral joint development. However, the mechanisms regulating joint formation in vertebrae remain elusive. Here, we report that the homozygous Eks mutant mice exhibit neural arch lamina fusion along the rostrocaudal axis at the dorsolateral position in neonates. We investigated the cellular and molecular mechanisms underlying the cervical vertebral fusion in Fgf9^Eks/Eks embryos. Fgf9^Eks/Eks embryos showed multiple fusions and thickened cartilage of cervical lamina on embryonic day (E) 14.5 and E13.5. Additionally, Fgf9^Eks/Eks embryos exhibited COL2A1 expression domain expansion accompanied by ectopic chondrocyte accumulation in the presumptive interlaminar space on E12.5 and E11.5. These anomalies persisted through endochondral ossification, leading to postnatal cervical vertebral bone fusion. Ectopic expression of COL2A1, Cyclin D1, and fibroblast growth factor (FGF) signaling target ETV4 was observed in the presumptive interlaminar space, indicating altered cell proliferation and cell fate specification. These findings demonstrate that FGF9^Eks protein interferes with vertebral column segmentation by impairing chondrogenic boundary regulation through ectopic cell proliferation and transcriptional activity. In conclusion, ectopic FGF9 signaling leads to cervical vertebral fusion, highlighting its contributing role in maintaining vertebral segmentation and chondrogenesis during embryogenesis.

ZNF335 plays an essential role in the neurogenesis of the human brain, and pathogenic variants of ZNF335 are associated with primary or secondary (postnatal) microcephaly. We performed exome sequencing in a patient with secondary microcephaly, epilepsy, global developmental delay, and dysmorphic craniofacial features, and identified compound heterozygous missense and intronic variants in ZNF335 (NM_022095.4:c.1504T>G, p.(Tyr502Asp) and c.1665 + 6T>A). Using a minigene assay, we demonstrated that the intronic variant causes aberrant splicing, resulting in significantly reduced ZNF335 protein levels. In addition, a review of the clinical findings of previously reported 10 patients with ZNF335 variants revealed that microcephaly was present in all patients, about half of them were secondary, and epilepsy and severe developmental delay were also quite recurrent findings.