Browse
Submit Data
Databases
API
Help

Dataset Information

10 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A 22-Week-Old Fetus with Nager Syndrome and Congenital Diaphragmatic Hernia due to a Novel SF3B4 Mutation.

ABSTRACT: Nager syndrome, or acrofacial dysostosis type 1 (AFD1), is a rare multiple malformation syndrome characterized by hypoplasia of first and second branchial arches derivatives and appendicular anomalies with variable involvement of the radial/axial ray. In 2012, AFD1 has been associated with dominant mutations in SF3B4. We report a 22-week-old fetus with AFD1 associated with diaphragmatic hernia due to a previously unreported SF3B4 mutation (c.35-2A>G). Defective diaphragmatic development is a rare manifestation in AFD1 as it is described in only 2 previous cases, with molecular confirmation in 1 of them. Our molecular finding adds a novel pathogenic splicing variant to the SF3B4 mutational spectrum and contributes to defining its prenatal/fetal phenotype.

SUBMITTER: Castori M

PROVIDER: S-EPMC4188155 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

A 22-Week-Old Fetus with Nager Syndrome and Congenital Diaphragmatic Hernia due to a Novel SF3B4 Mutation.

Castori Marco M Bottillo Irene I D'Angelantonio Daniela D Morlino Silvia S De Bernardo Carmelilia C Scassellati Sforzolini Giovanna G Silvestri Evelina E Grammatico Paola P

Molecular syndromology 20140805 5

Nager syndrome, or acrofacial dysostosis type 1 (AFD1), is a rare multiple malformation syndrome characterized by hypoplasia of first and second branchial arches derivatives and appendicular anomalies with variable involvement of the radial/axial ray. In 2012, AFD1 has been associated with dominant mutations in SF3B4. We report a 22-week-old fetus with AFD1 associated with diaphragmatic hernia due to a previously unreported SF3B4 mutation (c.35-2A>G). Defective diaphragmatic development is a rar ...[more]

PMID: 25337072

Similar Datasets

Congenital diaphragmatic hernia.

Project description:Congenital Diaphragmatic Hernia (CDH) is defined by the presence of an orifice in the diaphragm, more often left and posterolateral that permits the herniation of abdominal contents into the thorax. The lungs are hypoplastic and have abnormal vessels that cause respiratory insufficiency and persistent pulmonary hypertension with high mortality. About one third of cases have cardiovascular malformations and lesser proportions have skeletal, neural, genitourinary, gastrointestinal or other defects. CDH can be a component of Pallister-Killian, Fryns, Ghersoni-Baruch, WAGR, Denys-Drash, Brachman-De Lange, Donnai-Barrow or Wolf-Hirschhorn syndromes. Some chromosomal anomalies involve CDH as well. The incidence is < 5 in 10,000 live-births. The etiology is unknown although clinical, genetic and experimental evidence points to disturbances in the retinoid-signaling pathway during organogenesis. Antenatal diagnosis is often made and this allows prenatal management (open correction of the hernia in the past and reversible fetoscopic tracheal obstruction nowadays) that may be indicated in cases with severe lung hypoplasia and grim prognosis. Treatment after birth requires all the refinements of critical care including extracorporeal membrane oxygenation prior to surgical correction. The best hospital series report 80% survival but it remains around 50% in population-based studies. Chronic respiratory tract disease, neurodevelopmental problems, neurosensorial hearing loss and gastroesophageal reflux are common problems in survivors. Much more research on several aspects of this severe condition is warranted.

| S-EPMC3261088 | biostudies-literature

Congenital Diaphragmatic hernia - a review.

Project description:Congenital Diaphragmatic hernia (CDH) is a condition characterized by a defect in the diaphragm leading to protrusion of abdominal contents into the thoracic cavity interfering with normal development of the lungs. The defect may range from a small aperture in the posterior muscle rim to complete absence of diaphragm. The pathophysiology of CDH is a combination of lung hypoplasia and immaturity associated with persistent pulmonary hypertension of newborn (PPHN) and cardiac dysfunction. Prenatal assessment of lung to head ratio (LHR) and position of the liver by ultrasound are used to diagnose and predict outcomes. Delivery of infants with CDH is recommended close to term gestation. Immediate management at birth includes bowel decompression, avoidance of mask ventilation and endotracheal tube placement if required. The main focus of management includes gentle ventilation, hemodynamic monitoring and treatment of pulmonary hypertension followed by surgery. Although inhaled nitric oxide is not approved by FDA for the treatment of PPHN induced by CDH, it is commonly used. Extracorporeal membrane oxygenation (ECMO) is typically considered after failure of conventional medical management for infants ≥ 34 weeks' gestation or with weight >2 kg with CDH and no associated major lethal anomalies. Multiple factors such as prematurity, associated abnormalities, severity of PPHN, type of repair and need for ECMO can affect the survival of an infant with CDH. With advances in the management of CDH, the overall survival has improved and has been reported to be 70-90% in non-ECMO infants and up to 50% in infants who undergo ECMO.

| S-EPMC5356475 | biostudies-literature

Genetic causes of congenital diaphragmatic hernia.

Project description:Congenital diaphragmatic hernia (CDH) is a moderately prevalent birth defect that, despite advances in neonatal care, is still a significant cause of infant death, and surviving patients have significant morbidity. The goal of ongoing research to elucidate the genetic causes of CDH is to develop better treatment and ultimately prevention. CDH is a complex developmental defect that is etiologically heterogeneous. This review summarizes the recurrent genetic causes of CDH including aneuploidies, chromosome copy number variants, and single gene mutations. It also discusses strategies for genetic evaluation and genetic counseling in an era of rapidly evolving technologies in clinical genetic diagnostics.

| S-EPMC4259843 | biostudies-literature

Genetic factors in congenital diaphragmatic hernia.

Project description:Congenital diaphragmatic hernia (CDH) is a relatively common birth defect associated with high mortality and morbidity. Although the exact etiology of most cases of CDH remains unknown, there is a growing body of evidence that genetic factors play an important role in the development of CDH. In this review, we examine key findings that are likely to form the basis for future research in this field. Specific topics include a short overview of normal and abnormal diaphragm development, a discussion of syndromic forms of CDH, a detailed review of chromosomal regions recurrently altered in CDH, a description of the retinoid hypothesis of CDH, and evidence of the roles of specific genes in the development of CDH.

| S-EPMC1852742 | biostudies-literature

Rabbit Model of Fetal Tracheal Occlusion for Congenital Diaphragmatic Hernia

Project description:Analysis of embronic day 30.5 (E30.5) fetal rabbit left lung after creation of diapragmatic hernia (DH) at E25 and tracheal occlusion (TO) at E27. The fetuses of timed pregnant New Zealand rabbits were subjected to creation of a left diaphragmatic hernia at E25 with or without tracheal occlusion at E27. At E30.5, the fetuses were sacrificed with collection of the lateral aspect of the left upper lobe for NextGen mRNA sequencing.

2016-07-26 | E-GEOD-84811 | biostudies-arrayexpress

FBN1 contributing to familial congenital diaphragmatic hernia.

Project description:Congenital diaphragmatic hernia (CDH) is a relatively common, life--threatening birth defect. We present a family with recurrent CDH--paraesophageal and central--for whom exome sequencing (ES) revealed a frameshift mutation (c.4969_4970insA, p.Ile1657Asnfs*30) in the fibrillin 1 gene (FBN1) that causes Marfan syndrome. A diagnosis of Marfan syndrome had not been considered previously in this family. However, a review of the literature demonstrated that FBN1 mutations have an unusual pattern of CDH in which paraesophageal hernias are particularly common. Subsequent clinical evaluations revealed evidence for ectopia lentis in affected family members supporting a clinical diagnosis of Marfan syndrome. Since only two other cases of familial CDH have been described in association with FBN1 mutations, we investigated an oligogenic hypothesis by examining ES data for deleterious sequence changes in other CDH-related genes. This search revealed putatively deleterious sequence changes in four other genes that have been shown to cause diaphragm defects in humans and/or mice--FREM1, DES, PAX3 and MET. It is unclear whether these changes, alone or in aggregate, are contributing to the development of CDH in this family. However, their individual contribution is likely to be small compared to that of the frameshift mutation in FBN1. We conclude that ES can be used to identify both major and minor genetic factors that may contribute to CDH. These results also suggest that ES should be considered in the diagnostic evaluation of individuals and families with CDH, particularly when other diagnostic modalities have failed to reveal a molecular etiology.

| S-EPMC4522925 | biostudies-literature

One-year outcomes for congenital diaphragmatic hernia.

Project description:BackgroundCongenital diaphragmatic hernia (CDH) is a congenital anomaly with high mortality and long-term morbidity. The aim of this study was to benchmark trends in 1-year and hospital volume outcomes for this condition.MethodsThis study included all infants born with CDH in England between 2003 and 2016. This was a retrospective analysis of the Hospital Episode Statistics database. The main outcomes were: 1-year mortality, neonatal length of hospital stay (nLOS), total bed-days at 1 year and readmission rate. The association between hospital volume and outcomes was assessed for specialist paediatric surgery centres.ResultsA total of 2336 infants were included (incidence 2·5 per 10 000 live births). No significant time trends were found in incidence and main outcomes. Some 1491 infants (63·8 per cent) underwent surgical repair. The 1-year mortality rate was 31·2 per cent. Median nLOS and total bed-days were 17 and 19 days respectively. The readmission rate in specialist paediatric centres was 6·3 per cent. Higher mortality was associated with birthweight lower than 1 kg (OR 5·90, 95 per cent c.i. 1·03 to 33·75), gestational age of 36 weeks or less (OR 1·75, 1·12 to 2·75) and black ethnicity (OR 2·13, 1·03 to 4·48). Only 4·0 per cent had extracorporeal membrane oxygenation, which was associated with higher mortality (OR 5·34, 3·01 to 9·46), longer nLOS (OR 3·70, 2·14 to 6·14) and longer total bed-days (OR 3·87, 2·19 to 6·83). Specialist paediatric centres showed variation in 30-day mortality (4·6 per cent with 84 per cent coefficient of variation), nLOS (median 25 (i.q.r. 15-42) days) and total bed-days (median 28 (i.q.r. 16-51) days), but no significant volume-outcome relationship.ConclusionKey outcomes for CDH were similar to those of other developed countries. High variation among specialist paediatric centres was found and should be investigated further to explore the value of regionalization of care.

| S-EPMC6551417 | biostudies-literature

Genetic aspects of human congenital diaphragmatic hernia.

Project description:Congenital diaphragmatic hernia (CDH) is a common major malformation affecting 1/3000-1/4000 births, which continues to be associated with significant perinatal mortality. Much current research is focused on elucidating the genetics and pathophysiology contributing to CDH to develop more effective therapies. The latest data suggest that many cases of CDH are genetically determined and also indicate that CDH is etiologically heterogeneous. The present review will provide a brief summary of diaphragm development and model organism work most relevant to human CDH and will primarily describe important human phenotypes associated with CDH and also provide recommendations for diagnostic evaluation of a fetus or infant with CDH.

| S-EPMC2872786 | biostudies-literature

Rabbit Model of Fetal Tracheal Occlusion for Congenital Diaphragmatic Hernia

Project description:Analysis of embronic day 30.5 (E30.5) fetal rabbit left lung after creation of diapragmatic hernia (DH) at E25 and tracheal occlusion (TO) at E27.

2016-07-26 | GSE84811 | GEO

Effect of treprostinil on rabbit lungs with congenital diaphragmatic hernia

Project description:To investigate the effect of treprostinil pulmonary development in a rabbit model of congenital diaphragmatic hernia.

2023-10-31 | GSE220739 | GEO