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Annals of Epidemiology Jun 2024We assessed the risk of congenital anomalies in children who have a sibling with cancer.
PURPOSE
We assessed the risk of congenital anomalies in children who have a sibling with cancer.
METHODS
We performed a matched cohort study of children born between 2006 and 2022 in Quebec. The exposure was having a sibling with cancer. Exposed children were matched to unexposed children based on sex, number of siblings, birth order, and year. The outcome included heart defects, orofacial clefts, and other anomalies. Using conditional logistic regression, we estimated odds ratios (OR) and 95 % confidence intervals (CI) for the association between having a sibling with cancer and the likelihood of having a congenital anomaly.
RESULTS
A total of 2403 children who had a sibling with cancer were matched to 240,257 unexposed children. Congenital anomalies were more frequent in children who had a sibling with cancer compared with unexposed children (10.3 % vs 8.9 %). Overall, having a sibling with cancer was only weakly associated with congenital anomalies (OR 1.18, 95 % CI 1.04-1.35). Exposed children tended to have greater odds of polydactyly/syndactyly (OR 1.89, 95 % CI 1.11-3.21) and urinary defects (OR 1.50, 95 % CI 1.09-2.08) compared with unexposed children.
CONCLUSIONS
Children who have a sibling with cancer have an only weakly elevated risk of congenital anomalies.
Topics: Humans; Male; Female; Siblings; Congenital Abnormalities; Neoplasms; Quebec; Child; Child, Preschool; Cohort Studies; Infant; Risk Factors; Logistic Models; Infant, Newborn; Case-Control Studies; Odds Ratio; Adolescent
PubMed: 38614217
DOI: 10.1016/j.annepidem.2024.04.005 -
International Journal of Molecular... Apr 2024Canine osteosarcoma (OSA) is an aggressive bone neoplasia with high metastatic potential. Metastasis is the main cause of death associated with OSA, and there is no...
Canine osteosarcoma (OSA) is an aggressive bone neoplasia with high metastatic potential. Metastasis is the main cause of death associated with OSA, and there is no current treatment available for metastatic disease. Proteomic analyses, including matrix-assisted laser desorption/ionisation-time of flight mass spectrometry (MALDI TOF/TOF MS), are widely used to select molecular targets and identify proteins that may play a key role in primary tumours and at various steps of the metastatic cascade. The main aim of this study was to identify proteins differently expressed in canine OSA cell lines with different malignancy phenotypes (OSCA-8 and OSCA-32) compared to canine osteoblasts (CnOb). The intermediate aim of the study was to compare canine OSA cell migration capacity and assess its correlation with the malignancy phenotypes of each cell line. Using MALDI-TOF/TOF MS analyses, we identified eight proteins that were significantly differentially expressed ( ≤ 0.05) in canine OSA cell lines compared to CnOb: cilia- and flagella-associated protein 298 (CFAP298), general transcription factor II-I (GTF2I), mirror-image polydactyly gene 1 protein (MIPOL1), alpha-2 macroglobulin (A2M), phosphoglycerate mutase 1 (PGAM1), ubiquitin (UB2L6), ectodysplasin-A receptor-associated adapter protein (EDARADD), and leucine-rich-repeat-containing protein 72 (LRRC72). Using the Simple Western technique, we confirmed high A2M expression in CnOb compared to OSCA-8 and OSCA-32 cell lines (with intermediate and low A2M expression, respectively). Then, we confirmed the role of A2M in cancer cell migration by demonstrating significantly inhibited OSA cell migration by treatment with A2M (both at 10 and 30 mM concentrations after 12 and 24 h) in a wound-healing assay. This study may be the first report indicating A2M's role in OSA cell metastasis; however, further in vitro and in vivo studies are needed to confirm its possible role as an anti-metastatic agent in this malignancy.
Topics: Animals; Dogs; Proteomics; Transcription Factors; Cell Movement; Leucine-Rich Repeat Proteins; Macroglobulins; Osteosarcoma
PubMed: 38612805
DOI: 10.3390/ijms25073989 -
Animals : An Open Access Journal From... Mar 2024The Taihu Dianzi pigeon is a breed native to China, and its special piebalding, crest, and polydactyly phenotypes are the result of artificial and natural selection....
The Taihu Dianzi pigeon is a breed native to China, and its special piebalding, crest, and polydactyly phenotypes are the result of artificial and natural selection. Here, we analyzed the genetic differences among three kinds of pigeons with different phenotypes at the genomic level. A selective sweep was conducted based on the fixation index () and nucleotide diversity () ratio, and the results revealed that was related to the formation of the distinctive piebalding of the Taihu Dianzi pigeon. Combined with the results of genome-wide association studies, we identified candidate genes associated with the crest ( and ) and polydactyly ( and ). The candidate genes identified in this study and their variants may be useful for understanding the genetic mechanism underlying the special phenotypes of the Taihu Dianzi pigeon. This study provides new insights into the genetic factors that may influence the formation of the special piebalding, crest, and polydactyly characteristics in pigeons.
PubMed: 38612286
DOI: 10.3390/ani14071047 -
Plastic and Reconstructive Surgery.... Apr 2024Postaxial polydactyly is a common congenital foot anomaly. However, the severity of the anomaly varies from simple cases with only soft tissue duplication to complex...
BACKGROUND
Postaxial polydactyly is a common congenital foot anomaly. However, the severity of the anomaly varies from simple cases with only soft tissue duplication to complex cases with bone and joint disorders. In our clinical practice, we found a new morphological anomaly of postaxial polydactyly. We encountered several cases of postaxial polydactyly with bone fragments located between the fourth and fifth toes. The bone fragments were independent of the joint cavity. The mechanisms underlying its development remain unknown because it is a novel disorder. In the present study, we investigated the characteristics of the excess bone to formulate an embryological hypothesis.
METHODS
We examined the frequency and trends in the occurrence of excess bone using data from photographs and radiographs of these cases. An example of a disorder similar to excess bone is mosaic-like alignment, as reported by Iba et al. We also compared the characteristics of the mosaic-like alignment with those of the excess bone. Based on these data and existing embryological knowledge, we hypothesized the origin of the excess bone.
RESULTS
Excess bone and mosaic-like alignments showed different characteristics. Therefore, both were considered completely different disorders. We hypothesized that excess bone was caused by damage to the interdigital ectoderm immediately before interdigital programmed cell death.
CONCLUSIONS
We encountered a new form of postaxial polydactyly. This can be a factor influencing the treatment strategy because it can affect alignment and stability.
PubMed: 38596575
DOI: 10.1097/GOX.0000000000005717 -
Hand Surgery & Rehabilitation Jun 2024
Topics: Humans; Polydactyly; Toes; Male; Female
PubMed: 38583708
DOI: 10.1016/j.hansur.2024.101690 -
Heliyon Apr 2024gene mutations can result in various forms of polysyndactyly, such as Greig cephalopolysyndactyly syndrome (GCPS, MIM: #175700), Pallister-Hall syndrome (PHS, MIM:...
BACKGROUND
gene mutations can result in various forms of polysyndactyly, such as Greig cephalopolysyndactyly syndrome (GCPS, MIM: #175700), Pallister-Hall syndrome (PHS, MIM: #146510), and isolated polydactyly (IPD, MIM: #174200, #174700). Reports on IPD-associated mutations are rare. In this study, a novel mutation was identified in a Chinese family with IPD.
RESULTS
We report a family with six members affected by IPD. The family members demonstrated several special phenotypes, including sex differences, abnormal finger joint development, and different polydactyly types. We identified a novel frameshift variant in the gene (NM_000168.6: c.1820_1821del, NP_000159.3: p.Tyr607Cysfs*9) by whole-exome sequencing. Further analysis suggested that this mutation was the cause of polydactyly in this family.
CONCLUSIONS
The discovery of this novel frameshift variant in our study further solidifies the relationship between IPD and and expands the previously established spectrum of mutations and associated phenotypes.
PubMed: 38571622
DOI: 10.1016/j.heliyon.2024.e28638 -
Indian Journal of Otolaryngology and... Apr 2024To study the presentation and plan of treatment of patient with Rosai Dorfman Disease. Rosai-Dorfman disease(RDD), is rare, non-neoplastic, multisystemic histiocytic...
To study the presentation and plan of treatment of patient with Rosai Dorfman Disease. Rosai-Dorfman disease(RDD), is rare, non-neoplastic, multisystemic histiocytic disorder. Nodal form is more common. It's self-limiting disorder of unknown etiology. Symptomatic treatment is mainstay. Bardet-Biedl syndrome (BBS) is rare ciliopathic, autosomal-recessive disorder, affecting multiple organs. Characterized by marked central obesity, retinal dystrophy, polydactyly, mental retardation, hypogonadism and renal dysfunction. Treatment is symptomatic with hormone supplementation & regular follow-ups. 10 year male presented with swelling over left side of neck and intermittent fever since 2 years, diminished vision in night since 5 years. History of similar complaints on right side 5 years back. Fine needle aspiration cytology(FNAC)-features consistent with Rosai Dorfman Disease. Examination showed short stature, squint eyes, polydactyly. Multiple palpable neck nodes of variable sizes. Ophthalmic evaluation showed Retinitis Pigmentosa. Paediatric consultation for syndromic evaluation, features were consistent with Bardet Biedel syndrome. Since the presentation is same as that of opposite side in past, because of recurrence of symptoms even with regular antibiotic and steroid therapy, and no local recurrence of disease on right side, surgical excision is planned for the patient. Rosai-Dorfman disease and Bardet-Biedl syndrome are rare disorders presenting many diagnostic and therapeutic challenges. High degree of clinical suspicion (RDD & BBS) with typical histopathological features (RDD) are diagnostic. Symptomatic treatment is useful and surgical excision can be done for recurrent/ complicated cases of RDD while symptomatic treatment with regular follow-up for BBS.
PubMed: 38566667
DOI: 10.1007/s12070-023-04374-0 -
Bone Research Apr 2024Syndactyly type V (SDTY5) is an autosomal dominant extremity malformation characterized by fusion of the fourth and fifth metacarpals. In the previous publication, we...
Syndactyly type V (SDTY5) is an autosomal dominant extremity malformation characterized by fusion of the fourth and fifth metacarpals. In the previous publication, we first identified a heterozygous missense mutation Q50R in homeobox domain (HD) of HOXD13 in a large Chinese family with SDTY5. In order to substantiate the pathogenicity of the variant and elucidate the underlying pathogenic mechanism causing limb malformation, transcription-activator-like effector nucleases (TALEN) was employed to generate a Hoxd13Q50R mutant mouse. The mutant mice exhibited obvious limb malformations including slight brachydactyly and partial syndactyly between digits 2-4 in the heterozygotes, and severe syndactyly, brachydactyly and polydactyly in homozygotes. Focusing on BMP2 and SHH/GREM1/AER-FGF epithelial mesenchymal (e-m) feedback, a crucial signal pathway for limb development, we found the ectopically expressed Shh, Grem1 and Fgf8 and down-regulated Bmp2 in the embryonic limb bud at E10.5 to E12.5. A transcriptome sequencing analysis was conducted on limb buds (LBs) at E11.5, revealing 31 genes that exhibited notable disparities in mRNA level between the Hoxd13Q50R homozygotes and the wild-type. These genes are known to be involved in various processes such as limb development, cell proliferation, migration, and apoptosis. Our findings indicate that the ectopic expression of Shh and Fgf8, in conjunction with the down-regulation of Bmp2, results in a failure of patterning along both the anterior-posterior and proximal-distal axes, as well as a decrease in interdigital programmed cell death (PCD). This cascade ultimately leads to the development of syndactyly and brachydactyly in heterozygous mice, and severe limb malformations in homozygous mice. These findings suggest that abnormal expression of SHH, FGF8, and BMP2 induced by HOXD13Q50R may be responsible for the manifestation of human SDTY5.
Topics: Mice; Humans; Animals; Brachydactyly; Hedgehog Proteins; Transcription Factors; Syndactyly; Limb Deformities, Congenital
PubMed: 38561387
DOI: 10.1038/s41413-024-00322-y -
International Medical Case Reports... 2024Jeune syndrome, or asphyxiating thoracic dystrophy (JATD), is a rare autosomal recessive skeletal dysplasia with heterogeneous genetic and clinical phenotypes, which...
Jeune syndrome, or asphyxiating thoracic dystrophy (JATD), is a rare autosomal recessive skeletal dysplasia with heterogeneous genetic and clinical phenotypes, which primarily affects cartilage and bone development. Herein, we report a patient with a lethal form of SRTD3 without polydactyly (JATD), which led to severe restrictive lung disease and fatal respiratory failure. A full-term boy was born to a 30-year-old mother who was known to have hypothyroidism and was on thyroxine. The parents were first-degree cousins and had one healthy older son. Fetal ultrasound showed a cephalic fetus, normal amniotic fluid and a fundal placenta. All long bones and ribs were below the 1% percentile. The femur was bowed with no fractures or signs of significant demineralization at time of imaging. Head and abdominal circumference were within normal range. An echocardiogram on the 2nd day of life showed severe pulmonary hypertension (PHTN). Nitric oxide was started due to the presence of persistent hypoxia and severe PHTN. The patient continued to require high cardiorespiratory support, but the medical condition worsened, and respiratory failure persisted. The patient died of severe respiratory failure at 16 days of life due to respiratory insufficiency secondary to a severely restricted thoracic cage. Whole-exome sequencing (WES) revealed a homozygous mutation in the DYNC2H1 (NM_001377.3) gene, namely, the c.9041G>T NP_001368.2: p.(Arg3014Ile) missense variant, which results in the substitution of the arginine codon at amino acid position 3014 with an isoleucine codon. The phenotyping of the patient's JATD and the detection of a homozygous variant in the DYNC2H1 gene confirmed the diagnosis of short-rib thoracic dysplasia-3 without polydactyly. In summary, the patient had isolated skeletal anomalies without polydactyly or other organ involvement. Additionally, the infant had severe PHTN on top of the respiratory failure, which eventually caused death. Considerably more work will need to be done to determine the clinical spectrum of JATD and understand its genetic heterogeneity.
PubMed: 38550721
DOI: 10.2147/IMCRJ.S447466 -
Ultrasound in Obstetrics & Gynecology :... Mar 2024To assess diagnostic accuracy of 2D ultrasound at 11-14 weeks gestation as a screening test for individual fetal anomalies and identify screening factors impacting... (Review)
Review
OBJECTIVES
To assess diagnostic accuracy of 2D ultrasound at 11-14 weeks gestation as a screening test for individual fetal anomalies and identify screening factors impacting detection.
METHODS
Systematic review and meta-analysis, developed and registered with PROSPERO (CRD42018111781). MEDLINE, EMBASE, Web of Science Core Collection and The Cochrane Library) were searched for studies evaluating the diagnostic accuracy of screening for 16 pre-specified, non-cardiac, congenital anomalies considered to be of interest to the early anomaly scan. We included prospective and retrospective studies from any healthcare setting and low risk, mixed risk and unselected populations. The reference standard was the detection of an anomaly on postnatal or post-mortem examination. Data were extracted to populate 2 x 2 tables and meta-analysis (random-effects model) undertaken to determine the diagnostic accuracy of screening for the pre-specified anomalies (individually and as a composite). Secondary analyses were performed to determine the impact of (1) imaging protocol (2) ultrasound modality (3) publication year and (4) index of sonographer suspicion at time of scan. Post-hoc secondary analysis was conducted to assess performance for studies from 2010. Risk of bias and quality assessment was undertaken for included studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2).
RESULTS
From 5684 citations, 202 papers were identified as eligible and reviewed, resulting in the inclusion of 526,322 fetuses (52 studies) of which 2,399 were affected by one or more of the 16 anomalies. Individual anomalies were not equally amenable to detection on first trimester ultrasound ranging from high (>80%) detection rates for severe conditions including acrania (98%), gastroschisis (96%) and exomphalos (95%) and holoprosencephaly (88%); they were lower for open spina bifida (69%), lower urinary tract obstruction (66%) lethal skeletal dysplasias (57%) and limb reduction defects (50%) and below 50% for facial clefts (43%), polydactyly (40%) and congenital diaphragmatic hernia (38). Conditions with low (<30%) detection rates included bilateral renal agenesis (25%), closed spina bifida (21%), isolated cleft lip only (14%) and talipes (11%). Specificity was >99% for all anomalies. Secondary analysis showed improvement of detection with publication year, and that the use of imaging protocols had a statistically significant impact on screening performance (p<0.0001).
CONCLUSIONS
Accurate detection of congenital anomalies using first trimester ultrasound is feasible. In this study we have determined screening characteristics for individual anomalies and have shown that detection rates and false positive rates are dependent on the type of anomaly. The use of a standardised protocol allows diagnostic performance to be maximised, and this particularly enhances screening performance for the detection of spina bifida, facial clefts and limb reduction defects. Highlighting the types of anomalies amenable to diagnosis and determining favourable screening test factors can support the development of first-trimester anomaly screening programs. This article is protected by copyright. All rights reserved.
PubMed: 38547384
DOI: 10.1002/uog.27649