Congenital anomalies最新文献

{"title":"Cohort Study of Pregnancy Outcomes After Exposure to Fexofenadine or Olopatadine in the First Trimester.","authors":"Kaori Yamazaki, Mikako Goto, Sachi Koinuma, Kayoko Hishinuma, Shingo Yamazaki, Atsuko Murashima, Itsuko Ishii","doi":"10.1002/cga.70056","DOIUrl":"https://doi.org/10.1002/cga.70056","url":null,"abstract":"<p><p>Medication safety must be carefully considered during pregnancy because of the potential risks to the fetus. Allergic diseases during pregnancy, oral second-generation antihistamines, such as fexofenadine and olopatadine, are often used when topical agents are insufficiently effective. However, there are limited data on their teratogenic risk, particularly in the Japanese population. A cohort study was conducted using data from Japanese teratogenicity information services at two institutions: Toranomon Hospital and the National Center for Child Health and Development. Outcomes in pregnant women exposed to fexofenadine or olopatadine during the first trimester were compared with those in controls exposed to nonteratogenic drugs. The primary endpoint was the incidence of major birth defects defined by the EUROCAT criteria. Secondary outcomes included preterm birth and low birth weight. Logistic regression analyses were performed with adjustment for maternal age, alcohol consumption, smoking, and comorbidities. In total, 1473 eligible pregnancies for the analysis of major birth defects were included. Major birth defects occurred in 1.8% of the fexofenadine group (n = 231) and 3.0% of the olopatadine group (n = 186), showing no significant increase compared with 1.8% of the control group (n = 1056). Logistic regression showed no association between either antihistamine and major birth defects, preterm birth, or low birth weight after adjustment. No consistent pattern of anomalies was identified. This study found no evidence that exposure to fexofenadine or olopatadine in the first trimester increases the risk of major birth defects. These second-generation antihistamines appear to be relatively safe in pregnant women with allergic conditions.</p>","PeriodicalId":93953,"journal":{"name":"Congenital anomalies","volume":"66 1","pages":"e70056"},"PeriodicalIF":1.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147725009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two Cases of Prenatally Suspected Fetal Bartter Syndrome With a Novel Genetic Variant Indicated by Polyhydramnios and Amniotic Fluid Biochemistry.","authors":"Tomomichi Ito, Norikazu Watanabe, Keiko Yamanouchi, Satoru Nagase","doi":"10.1002/cga.70057","DOIUrl":"10.1002/cga.70057","url":null,"abstract":"","PeriodicalId":93953,"journal":{"name":"Congenital anomalies","volume":"66 1","pages":"e70057"},"PeriodicalIF":1.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147725046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Neonatal Manifestation of Geleophysic Dysplasia Type 1: A Case Report Highlighting Phenotypic Overlap With Al-Gazali Skeletal Dysplasia.","authors":"Kazuhiro Shimura, Yuko Tsujioka, Toshihide Kijima, Yosuke Ichihashi, Reiko Kushima, Gen Nishimura, Tomonobu Hasegawa, Satoshi Narumi","doi":"10.1002/cga.70058","DOIUrl":"10.1002/cga.70058","url":null,"abstract":"<p><p>Geleophysic dysplasia type 1 is a rare skeletal dysplasia caused by biallelic pathogenic variants in ADAMTSL2. Affected children typically show a \"happy-natured facial appearance,\" postnatal short stature with acromelic limb shortening, progressive joint contracture, and skin tightness. Most patients are diagnosed in childhood, and very little is known about the neonatal manifestation. We report a Japanese girl with Geleophysic dysplasia type 1, whose neonatal manifestations were enough to raise suspicion of the disorder on retrospective clinical and radiological review. At birth, she presented with joint contractures, short digits, mild pulmonary stenosis, and a normal facial appearance, and later developed severe short stature, camptodactyly, gait disturbance, and a round face with a flat nasal bridge and upslanting palpebral fissures. The clinical constellation led to a suspicion of Geleophysic dysplasia type 1 at age 3 years, and exome sequencing revealed variants in ADAMTSL2, a recurrent pathogenic missense variant (p.Ser635Leu) and a novel nonsense variant (p.Cys666*). On radiological grounds, she manifested with the same skeletal alterations in the neonatal period and at age 3 years, including severe brachydactyly with cone-shaped epiphyses and metaphyseal broadening. The distinctive skeletal phenotype overlapped with that of Al-Gazali skeletal dysplasia, an ADAMTSL2-associated potentially lethal skeletal dysplasia, suggesting a phenotypic continuum between both entities. The present case suggests that a subset of Geleophysic dysplasia type 1 may present with diagnostic physical and radiological manifestations in the neonatal period. Early recognition of neonatal skeletal features can facilitate prompt diagnosis and early clinical management for affected children.</p>","PeriodicalId":93953,"journal":{"name":"Congenital anomalies","volume":"66 1","pages":"e70058"},"PeriodicalIF":1.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147792329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoplastic Left Heart Syndrome Variant With Unexpected Early Sudden Death in a Newborn Infant With ZTTK Syndrome.","authors":"Kengo Okamoto, Daisuke Nakato, Koichi Kataoka, Naomi Nakagawa, Toshiki Takenouchi","doi":"10.1002/cga.70059","DOIUrl":"10.1002/cga.70059","url":null,"abstract":"","PeriodicalId":93953,"journal":{"name":"Congenital anomalies","volume":"66 1","pages":"e70059"},"PeriodicalIF":1.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147792265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Refining the Neonatal Phenotypic Spectrum of Distal Deletion 14q Syndrome: Early Genomic Diagnosis in Infancy.","authors":"Koji Nakae, Shiori Hamada, Junpei Kawamura, Kentaro Ueno, Toshiki Takenouchi, Yasuhiro Okamoto","doi":"10.1002/cga.70055","DOIUrl":"10.1002/cga.70055","url":null,"abstract":"<p><p>Distal deletion 14q syndrome is a rare chromosomal disorder characterized by variable features, including growth restriction, craniofacial dysmorphism, developmental delay, and congenital anomalies. Diagnosis is often delayed because conventional G-banding may appear normal. Neonatal recognition is rarely reported, and early phenotypic features remain insufficiently defined. We report the case of a male infant born at 37 + 6 weeks of gestation with intrauterine growth restriction, micrognathia, feeding difficulties, hypotonia, and cardiopulmonary instability. Prenatal echocardiography suggested coarctation of the aorta, while postnatal imaging revealed mild bilateral pulmonary artery branch narrowing and distal aortic arch tapering without hemodynamic significance. Research-based trio exome sequencing suggested an approximately 6.5 Mb terminal deletion of chromosome 14q32.2-q32.33, which was subsequently confirmed by chromosomal microarray. Although craniofacial features appeared subtle at birth, a retrospective review following genetic confirmation revealed additional dysmorphic traits. This case underscores the diagnostic utility of genomic testing, which enabled confirmation of distal 14q deletion at 1 month of age. In contrast, previously reported cases were typically diagnosed later in childhood. Our findings refine the neonatal phenotypic spectrum of distal deletion 14q syndrome by documenting subtle but identifiable early craniofacial, vascular, feeding, and auditory features that may prompt earlier suspicion. Early confirmation provided reassurance regarding recurrence risk and allowed for timely planning of nutritional, developmental, and audiological support. This case illustrates how genomic testing can narrow a long-standing diagnostic gap and highlights key neonatal clues that may facilitate earlier recognition of distal deletion 14q syndrome.</p>","PeriodicalId":93953,"journal":{"name":"Congenital anomalies","volume":"66 1","pages":"e70055"},"PeriodicalIF":1.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13092366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694272","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":"Obituary for Dr. Robert L. Brent.","authors":"M. Yasuda","doi":"10.1111/cga.12419","DOIUrl":"https://doi.org/10.1111/cga.12419","url":null,"abstract":"","PeriodicalId":93953,"journal":{"name":"Congenital anomalies","volume":"18 1","pages":"74-75"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79744601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tracheal cartilaginous sleeve in patients with Beare‐Stevenson syndrome","authors":"Eijun Seki, Keisuke Enomoto, K. Tanoue, Mio Tanaka, K. Kurosawa","doi":"10.1111/cga.12352","DOIUrl":"https://doi.org/10.1111/cga.12352","url":null,"abstract":"Tracheal cartilaginous sleeve (TCS), a life-threatening malformation in patients with craniosynostosis syndromes, is a solid cartilaginous tube lacking the pars membranacea, caused by defective C-shaped tracheal rings. Without tracheostomy, it has a 90% mortality by 2 years. Beare-Stevenson syndrome (BSS) is a distinct craniosynostosis syndrome characterized by cutis gyrata. BSS is caused by one of two specific gain-of-function mutations of FGFR2, including p.Y375C and p.S372C (Supporting information Reference S1). Studies attribute the high mortality of BSS to respiratory distress, secondary to TCS, and other unexplained factors. However, in most BSS patients, the mechanism by which TCS causes sudden death remains unknown. To increase knowledge regarding TCS and Chiari malformation for respiratory distress in BSS, we report two cases with BSS and TCS. Patient 1 was the second child of healthy Japanese parents. After birth, she was intubated for severe respiratory failure caused by airway obstruction and choanal stenosis. Chest computed tomography (CT) and bronchoscopy showed dorsal recession of the tracheal internal wall, suggesting TCS (Figure 1A). She underwent ventriculoperitoneal (VP)-shunt placement; tracheostomy owing to choanal stenosis and glossoptosis; conventional cranioplasty with fronto-orbital advancement for anterior part expansion; and decompression for Chiari malformation, which had resulted in hydrocephaly, at 1, 2, 3, and 10 months, respectively. Thereafter, she was followed with oxygen therapy. At 5 years, she developed severe sleep apnea. A polysomnography (PSG) showed severe central sleep apnea with apnea hypoxia index (AHI) 140/h and SpO2 nadir 74%. Although bronchoscopy showed improvements in the tracheal wall abnormality, spinal magnetic resonance imaging revealed a hyper-intense signal at the C2 level (Figure 1B). She underwent additional decompression and required mechanical ventilation during sleep. Genetic analysis revealed a pathogenic FGFR2 variant c.1124A>G (p.Tyr375Cys). Currently, at 6 years of age, she can shuffle and requires mechanical ventilation during sleep. Patient 2 was the third child of healthy parents. His detailed clinical course in early childhood has been described previously. He underwent tracheostomy, owing to severe respiratory distress caused by choanal stenosis and epiglottis thickening; VP-shunt placement; conventional cranioplasty with fronto-orbital advancement for anterior part expansion; and decompression for Chiari malformation, which had resulted in hydrocephaly, at 16 days and at 2, 8, and 18 months, respectively. The tracheostomy tube was custom-made and designed to elongate and get over the portion of TCS. At age 10, he developed obstructive respiratory distress. Chest CT showed tracheostomy tube obstruction by a TCS-related dented deformity (Figure 1C). At 12 years of age, he died suddenly after respiratory distress caused by tracheostomy tube obstruction. The tip of the tracheostomy","PeriodicalId":93953,"journal":{"name":"Congenital anomalies","volume":"68 1","pages":"97 - 99"},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90963777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered neuronal activity in the auditory brainstem following sound stimulation in thalidomide‐induced autism model rats","authors":"L. E. Tsugiyama, Michiru Ida-Eto, Takeshi Ohkawara, Y. Noro, M. Narita","doi":"10.1111/cga.12353","DOIUrl":"https://doi.org/10.1111/cga.12353","url":null,"abstract":"Auditory hypersensitivity in autism is frequently observed in clinics. Dysfunction in the auditory brainstem has been suspected. We have established autism model rats using prenatal thalidomide exposure. Here we investigated whether abnormal response occurs in the brainstem following sound stimulus in autism model rats. Autism model rats were prepared by prenatal exposure to thalidomide on embryonic days 9 and 10 in pregnant rats. Then, the animals were exposed to 16‐kHz pure tone auditory stimulus and c‐Fos immunostaining was performed to examine the neuronal activity on postnatal day 49 to 51. Following sound stimulus, increased number of c‐Fos‐positive neurons was observed in the medial nucleus of the trapezoid body of autism model rats compared with the control rats. These results suggest that prenatal thalidomide might cause altered processing of auditory stimulus, leading to the characteristics of auditory hypersensitivity in autism.","PeriodicalId":93953,"journal":{"name":"Congenital anomalies","volume":"4 1","pages":"82 - 86"},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82474692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A female patient with X‐linked Ohdo syndrome of the Maat‐Kievit‐Brunner phenotype caused by a novel variant of MED12","authors":"Hiroaki Murakami, Yumi Enomoto, Y. Tsurusaki, Y. Sugio, K. Kurosawa","doi":"10.1111/cga.12350","DOIUrl":"https://doi.org/10.1111/cga.12350","url":null,"abstract":"MED12 is a component of the large multiprotein Mediator complex. MED12 variants have been linked to three different X-linked intellectual disability (ID) syndromes, including Ohdo syndrome of the Maat-Kievit-Brunner phenotype (OSMKB), Opitz-Kaveggia (FG) syndrome, and Lujan-Fryns syndrome (LFS). This article is protected by copyright. All rights reserved.","PeriodicalId":93953,"journal":{"name":"Congenital anomalies","volume":"4 1","pages":"91 - 93"},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87328664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low‐prevalence mosaicism of chromosome 18q distal deletion identified by exome‐based copy number profiling in a child with cerebral hypomyelination","authors":"T. Shiohama, M. Nakashima, Hajime Ikehara, Mitsuhiro Kato, H. Saitsu","doi":"10.1111/cga.12351","DOIUrl":"https://doi.org/10.1111/cga.12351","url":null,"abstract":"Partial deletions of chromosome 18q distal lead to diverse congenital dysmorphic features such as hypomyelination short stature cleft lip and palate foot deformity and aural atresia. In contrast mosaicism of 18q distal deletion is a rarer situation with a highly variable phenotype, leading to clinical diagnostic challenges A Japanese female was born at term with no asphyxia. Her family history was unremarkable. At 5 months of age, the patient was admitted due to no head control. Physical examination revealed general muscle hypotonus, course face with hypertelorism, microcephaly (37.5 cm, −2.7SD), curly hair, lymphedema foot, short fifth fingers, and malposition of the first and the fifth foot digits. Gastrointestinal and urological examination revealed tubular anal duplication, right hydronephrosis, and vesicoureteral reflux. She subsequently presented focal epilepsy with the dominancy in the left upper limb and bilateral sensorineural hearing loss. Brain magnetic resonance imaging at 5 years of age showed complete agenesis of the corpus callosum (ACC) (Figure 1A) and diffuse cerebral hypomyelination (Figure 1B). At 10 years, she could sit supported, but say no words. G-banded analysis at 2 years of age showed a normal female karyotype (46,XX). We performed whole exome sequencing (WES) at 11 years of age. We could not find any possible pathogenic single nucleotide variants but found about 20 Mb deletion at 18q21.31-qter (chr18:56585841-77513763) by two copy number variants (CNVs) detection tools (Figure 1C,D). The quantitative polymerase chain reaction showed 0.8 of relative copy number ratio to a control sample. The FISH analysis using 18q unique probe showed two copy signal patterns in all the 10 lymphocytes prepared at 2 and 7 years. Finally, we evaluated the WES data by H3M2 program, a detection program of runs of homozygosity. In the normal two copy region, B allele frequency (BAF), the ratio between B-allele read counts and the total number of reads mapped to that position (A + B allele), showed three lines. Value of zero and 1.0 means homoor hemizygous for A and B alleles, respectively, and about 0.5 means heterozygous allele. However, in the deletion interval, BAF showed four lines, suggesting that two types of heterozygous alleles (mosaic A or B allele deletion in the A/B heterozygous allele) were present in this region (Figure 1D). Chromosomal microarray analysis (CytoScan HD Array, Affymetrix) showed arr[hg19] 18q21.2q23(51392374-78 014 123)x1-2 (Figure S1). Therefore, we concluded that this patient has the low-prevalence mosaic deletion of 18q21.2qter. The partial deletion on the chromosome 18q23 including myelin basic protein (MBP) and a galanin receptor (GALR1) is critically related to cerebral hypomyelination. Prior cohort studies reported that partial chromosome 18q deletion was identified in three of 26 patients with hypomyelination leukodystrophy, and none of 162 patients with ACC. Although the combination of cerebral hypomyelin","PeriodicalId":93953,"journal":{"name":"Congenital anomalies","volume":"34 1","pages":"94 - 96"},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90894938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}