Project description:Cerebral arteriovenous malformations (AVMs) are the most common vascular malformations worldwide and the leading cause of hemorrhagic strokes that result in crippling neurological deficits. Here, using newly generated mouse model, we discovered that genome-wide ocuppancy of H4K8ac and H3K27me3 decreased in mouse cerebral AVMs.
Project description:Congenital muscular dystrophy type 1A (MDC1A) is caused by recessive variants in laminin α2 (LAMA2). Patients have been found to have white matter signal abnormalities on magnetic resonance imaging (MRI) but rarely structural brain abnormalities. We describe the autopsy neuropathology in a 17-year-old with white matter signal abnormalities on brain MRI. Dystrophic pathology was observed in skeletal muscle, and the sural nerve manifested a mild degree of segmental demyelination and remyelination. A diffuse, bilateral cobblestone appearance, and numerous points of fusion between adjacent gyri were apparent on gross examination of the cerebrum. Brain histopathology included focal disruptions of the glia limitans associated with abnormal cerebral cortical lamination or arrested cerebellar granule cell migration. Subcortical nodular heterotopia was present within the cerebellar hemispheres. Sampling of the centrum semiovale revealed no light microscopic evidence of leukoencephalopathy. Three additional MDC1A patients were diagnosed with cobblestone malformation on brain MRI. Unlike the autopsied patient whose brain had a symmetric distribution of cobblestone pathology, the latter patients had asymmetric involvement, most severe in the occipital lobes. These cases demonstrate that cobblestone malformation may be an important manifestation of the brain pathology in MDC1A and can be present even when patients have a structurally normal brain MRI.
Project description:Congenital lung malformations (CLM) are most commonly treated with a pulmonary lobectomy. However, due to technological advancement, video-assisted thoracoscopic surgery (VATS) segmentectomy is becoming an attractive alternative to VATS lobectomy. This study aimed to evaluate the safety, feasibility, and efficacy of VATS segmentectomy as a lung parenchyma-saving strategy in children with CLM. A retrospective analysis was performed on 85 children, for whom VATS segmentectomy was tried for CLM between January 2010 and July 2020. We compared the surgical outcomes of VATS segmentectomy with the outcomes of 465 patients who underwent VATS lobectomy. Eighty-four patients received VATS segmentectomy and thoracotomy conversion was necessary for one patient for CLM. The mean age was 3.2 ± 2.5 (range 1.2-11.6) years. The mean operative time was 91.4 ± 35.6 (range 40-200) minutes. The median duration of chest tube drainage was 1 (range 1-21) day, and the median length of postoperative hospital stay was 4 (range 3-23) days. There were no postoperative mortality and postoperative complications developed in 7 patients (8.2%), including persistent air leakage in 6 patients (7.1%) and postoperative pneumonia in 1 patient (1.2%). The median follow-up period was 33.5 (interquartile range 31-57) months and there were no patients requiring re-intervention or reoperation during the follow-up period. In the VATS segmentectomy group, the persistent air leakage rate was higher than in the VATS lobectomy group (7.1 vs. 1.1%, p = 0.003). Otherwise, postoperative outcomes were comparable between the two groups. VATS segmentectomy in children with CLM is a technically feasible alternative to VATS lobectomy with acceptable early and mid-term outcomes. However, the persistent air-leakage rate was higher in VATS segmentectomy.
Project description:Congenital renal tract malformations (RTMs) are the major cause of severe kidney failure in children. Studies to date have identified defined genetic causes for only a minority of human RTMs. While some RTMs may be caused by poorly defined environmental perturbations affecting organogenesis, it is likely that numerous causative genetic variants have yet to be identified. Unfortunately, the speed of discovering further genetic causes for RTMs is limited by challenges in prioritising candidate genes harbouring sequence variants. Here, we exploited the computer-based artificial intelligence methodology of supervised machine learning to identify genes with a high probability of being involved in renal development. These genes, when mutated, are promising candidates for causing RTMs. With this methodology, the machine learning classifier determines which attributes are common to renal development genes and identifies genes possessing these attributes. Here we report the validation of an RTM gene classifier and provide predictions of the RTM association status for all protein-coding genes in the mouse genome. Overall, our predictions, whilst not definitive, can inform the prioritisation of genes when evaluating patient sequence data for genetic diagnosis. This knowledge of renal developmental genes will accelerate the processes of reaching a genetic diagnosis for patients born with RTMs.
Project description:ImportanceChemotherapy during the first trimester of pregnancy should be avoided owing to the risk of congenital malformations. However, the precise gestational age at which chemotherapy can be initiated safely remains unclear.ObjectiveTo assess congenital malformation rates associated with gestational age at initiation of chemotherapy among pregnant women with cancer.Design, setting, and participantsThis multicenter cohort study evaluated all pregnant women who received chemotherapy between 1977 and 2019 registered in the International Network on Cancer, Infertility and Pregnancy (INCIP) database. Data were analyzed from February 15 to June 2, 2020.ExposuresCancer treatment with chemotherapy during pregnancy.Main outcomes and measuresAnalysis was focused on major and minor structural malformations in offspring, defined by EUROCAT, detected during pregnancy or at birth.ResultsA total of 755 women in the INCIP database who underwent cancer treatment with chemotherapy during pregnancy were included in analysis. The median (range) age at cancer diagnosis was 33 (14-48) years. Among offspring, the major congenital malformation rate was 3.6% (95% CI, 2.4%-5.2%), and the minor congenital malformation rate was 1.9% (95% CI, 1.0%-3.1%). Chemotherapy exposure prior to 12 weeks gestational age was associated with a high rate of major congenital malformations, at 21.7% (95% CI, 7.5%-43.7%; odds ratio, 9.24 [95% CI, 3.13-27.30]). When chemotherapy was initiated after gestational age 12 weeks, the frequency of major congenital malformations was 3.0% (95% CI, 1.9%-4.6%), which was similar to the expected rates in the general population. Minor malformations were comparable when exposure occurred before or after gestational age 12 weeks (4.3% [95% CI, 0.1%-21.9%] vs 1.8% [95% CI, 1.0-3.0]; odds ratio, 3.13 [95% CI, 0.39-25.28]). Of 29 women who received chemotherapy prior to 12 weeks gestation, 17 (58.6%) were not aware of pregnancy, and 6 (20.7%) experienced a miscarriage (3 women [10.3%]) or decided to terminate their pregnancy (3 women [10.3%]).Conclusions and relevanceThis cohort study found that chemotherapy was associated with an increased risk of major congenital malformations only in the first 12 weeks of pregnancy. The risk of congenital malformations when chemotherapy was administered during the first trimester and the high number of incidental pregnancies during cancer treatment in the INCIP registry underscore the importance of contraceptive advice and pregnancy testing at the start of chemotherapeutic treatment in young women with cancer.
Project description:BackgroundCongenital bronchopulmonary foregut malformation (CBPFM) is a rare congenital malformation involving both the digestive and respiratory system. Early diagnosis is difficult, and delayed recognition may result in considerable complications. The aim of the study was to identify and analyze the clinical characteristics and radiological features of CBPFMs.MethodsA systematic review was conducted in accordance with PRISMA guidelines. PubMed, Ovid database, EMBASE were searched for relevant publications to identify all published case-reports of CBPFM since 1992. Data about the demography, clinical presentation, pathology, imaging features, treatment and prognosis were collected.ResultsSixty-one cases were included in our study. Cases were aged from 1 day to 59 years with the majority aged 3 years or younger. The most common type was group III (37.7%), followed by group II (29.5%)group I (27.9%) and group IV (4.9%). The presentations included respiratory distress (32.8%), cough/choking following food intake and other presentations associated respiratory infection. Thirty-eight cases (62.3%) were diagnosed by upper gastrointestinal series (UGI). Misdiagnosis was common. Eight cases (13.1%) of the included cases died.ConclusionsEarly recognition and extensive delineation of the anatomy of CBPFM are important to correct these anomalies successfully. UGI is the first choice to confirm the abnormal bronchus communicating with the esophagus. Resection of abnormal pulmonary tissue, lobe or even unilateral lung is preferred. Reconstruction procedures are feasible in selected patients.
Project description:A rare case of an adult male with malformation of the skull, face, hands and feet called acrocephalosyndactly or Apert syndrome is presented. Its probable cause, features and treatment is discussed. It is a unique case who survived upto the age of 32 years without any operative intervention and adjusted in the society though he has all the stigmas of the above syndrome. We have concluded and made a point that in the adult sufferer, facial deformity is not so important and urgent for the treatment than syndactyly, which handicaps the sufferer in performing the daily routine work.
Project description:Vestibular paroxysmia (VP) is an uncommon paroxysmal disease, characterized by vertigo, tinnitus, and postural unsteadiness. The main reason of VP is neurovascular cross compression, while few cases of VP accompanied with congenital vascular malformation were reported. Here, we describe a 22-year-old patient with VP caused by congenital anterior inferior cerebellar artery (AICA) malformation who completely recovered after taking oral medicine. This report shows that VP caused by congenital vascular malformation can occur in adults and that oral medication is effective.
Project description:BackgroundCongenital lung malformations (CLM) are a gamut of lesions that originate throughout the embryonic period and manifest in the neonatal or sporadically in the prenatal period, characteristically might stay well for some time, to be found inadvertently or to present with complications. In the 13 years from Jan. 2003 to Dec. 2015, this prospective cohort study included consecutive pediatric patients under 12 years old, who presented either emergently or electively with any variety of CLM. The lesions encompassed in this assortment were congenital lobar emphysema (CLE), congenital pulmonary airway malformation (CPAM), bronchogenic cysts (BC), and bronchopulmonary sequestration (BPS).ResultsSixty-eight pediatric patients with CLM were operated at our institution; 18 CPAMs, 22 CLEs, 19 BPSs (17 intralobar and 2 extralobar), and 9 patients with BCs. The patients' age ranged from 1 to 54 months (mean age of 10.73 ± 9.73 months), with overall male gender predominance (61.76%). Both CLE and CPAM had a male predominance, while BC and BPS had equivocal gender distribution. CLE patients had the earliest presentation at 2.89 ± 1.5 months and congenital cystic adenomatoid malformations (CCAM) had the latest presentation at 21.78 ± 15.6 months (F = 15.27, p < 0.0001). Lobectomy was the commonest procedure performed. Fifty-nine lobectomies were performed (21 LUL, 15 RLL, 14 LLL, 8 RUL, and 1 middle lobectomy). Six cystectomies were performed for BC. Twenty-three cases (33.8%) had postoperative complications that were mainly significant or prolonged air leak (13.24%), pneumonia (5.88%), 3 cases of hemothorax (4.4%), pulmonary atelectasis in 2 patients (2.94%), 1 patient developed effusion (1.47%), and there were 2 mortalities.ConclusionsCLM must be in mind in the differential diagnoses of any case with repeated infection, respiratory distress, or radiological abnormalities. Surgery in the form of lobectomy or lesser resection is generally safe.
Project description:Congenital pancreatic cysts (CPCs) are rare developmental anomalies that arise in-utero from the pancreas. They are exceedingly rare in the literature, and most are discovered postnatally. Prenatal diagnosis is uncommon with only 21 published reports of prenatally diagnosed CPCs in the literature. CPCs may form unilocular or multilocular macrocysts which can distort normal anatomy. There is considerable overlap of imaging features with other macrocystic lesions of the neonatal abdomen. Ultrasound-guided biopsy and analysis of cyst aspirate for pancreatic enzymes may assist with obtaining an accurate preoperative diagnosis. We report a case of a 37-week gestational age female infant born with a known prenatal 9.5 cm macrocystic intrabdominal mass. An intrabdominal lymphatic malformation was initially diagnosed based on clinical and imaging features. Since conservative therapy with with cyst drainage and serial sclerotherapy was not effective, an ultrasound-guided biopsy was performed to rule out malignancy. Pancreatic tissue was identified on pathology. An exploratory laparotomy and total cystectomy was performed which confirmed the diagnosis of congenital pancreatic cyst originating from the pancreatic tail. This case highlights the diagnostic challenge of congenital pancreatic cysts and the importance of a multimodal and multidisciplinary diagnostic approach.