RESUMO
PURPOSE: Hirschsprung's disease (HSCR) is the leading cause of neonatal functional intestinal obstruction, which has been identified in many familial cases. HSCR, a multifactorial disorder of enteric nervous system (ENS) development, is associated with at least 24 genes and seven chromosomal loci, with RET and EDNRB as its major genes. We present a genetic investigation of familial HSCR to clarify the genotype-phenotype relationship. METHODS: We performed whole exome sequencing (WES) on Illumina HiSeq X Ten platform to investigate genetic backgrounds of core family members, and identified the possibly harmful mutation genes. Mutation carriers and pedigree relatives were validated by Sanger sequencing for evaluating the gene penetrance. RESULTS: Four familial cases showed potential disease-relative variants in EDNRB and RET gene, accounting for all detection rate of 57.1%. Three familial cases exhibited strong pathogenic variants as frameshift or missense mutations in EDNRB gene. A novel c.367delinsTT mutation of EDNRB was identified in one family member. The other two EDNRB mutations, c.553G>A in family 2 and c.877delinsTT in family 5, have been reported in previous literatures. The penetrance of EDNRB variants was 33-50% according mutation carries. In family 6, the RET c.1858T>C (C620R) point mutation has previously been reported to cause HSCR, with 28.5% penetrance. CONCLUSION: We identified a novel EDNRB (deleted C and inserted TT) mutation in this study using WES. Heterozygote variations in EDNRB gene were significantly enriched in three families and RET mutations were identified in one family. EDNRB variants showed an overall higher incidence and penetrance than RET in southern Chinese families cases.
Assuntos
Doença de Hirschsprung , Obstrução Intestinal , Receptor de Endotelina B , Humanos , Recém-Nascido , China/epidemiologia , Doença de Hirschsprung/genética , Incidência , Mutação , Receptor de Endotelina B/genéticaRESUMO
BACKGROUND: Communicating bronchopulmonary foregut malformation (CBPFM) type IA is extremely rare and is associated with a high mortality rate. This malformation manifests with communication between the lung and the foregut, and this can lead to esophageal atresia and tracheoesophageal fistula (EA-TEF) to the distal pouch. PURPOSE: To detail radiographic findings of CBPFM type IA cases and to summarize an appropriate therapeutic strategy for the management of this disorder. METHODS: Medical data for two patients with CBPFM type IA were retrospectively reviewed with regard to radiographic characteristics, therapy, and outcome. RESULTS: Both cases were initially misdiagnosed due to the presence of EA-TEF. Unusual atelectasis of the lateral lung was observed in chest radiographs, while non-aerated hypoplastic right lung and agenesis of the right main bronchus were detected by computed tomography. A final diagnosis was made by esophagogram. Only one patient survived following surgery. CONCLUSION: CBPFM type IA is a rare condition and is extremely difficult to diagnose. However, CBPFM type IA should be suspected in patients manifesting EA and atelectasis of a unilateral lung on a chest radiograph. The decision to perform a pneumonectomy or bronchoplasty depends on the degree of exiting permitted due to pulmonary damage assessed by computed tomography.
Assuntos
Brônquios/anormalidades , Broncografia , Atresia Esofágica/diagnóstico por imagem , Pulmão/anormalidades , Pulmão/diagnóstico por imagem , Fístula Traqueoesofágica/diagnóstico por imagem , Brônquios/cirurgia , Atresia Esofágica/cirurgia , Evolução Fatal , Humanos , Recém-Nascido , Pulmão/cirurgia , Masculino , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Fístula Traqueoesofágica/cirurgiaRESUMO
BACKGROUND: Enhanced recovery after surgery (ERAS) has been widely used in adult surgery. However, ERAS has not been reported in neonatal surgery. The present prospective study explored the application value of ERAS in treating congenital duodenal obstruction (CDO). METHODS: A total of 68 cases of CDO were collected from October 1, 2017 to July 31, 2019. We divided patients with a prenatal diagnosis of congenital duodenal obstruction into the ERAS group and those who were diagnosed the disease after birth into the control group. The ERAS group adopted ERAS-related measures, and the control group followed the usual measures. The study compared the differences in the gestational age, birth weight, length of hospital stay (LOS), complications, feeding intolerance, and weight one month after surgery between the two groups. RESULTS: A total of 49 patients were included in the analysis, including 23 who were allocated to the ERAS group and 26 to the control group. The LOS was 9.696±1.222 days in the ERAS group and 12.654±1.686 days in the control group, resulting in a significantly shorter LOS in the ERAS group than in the control group (p<0.001). One month after surgery, the neonates in the ERAS group weighted significantly more than those in the control group. No differences were observed in birth weight, gestational age, and the incidence of complications or feeding intolerance between the two groups. CONCLUSION: In this single-center study, the implementation of neonate-specific ERAS for CDO surgery was feasible and safe and led to a shorter LOS without increasing the incidence of complications or feeding intolerance. TYPE OF STUDY: Treatment Study LEVEL OF EVIDENCE: Level III.
Assuntos
Obstrução Duodenal , Recuperação Pós-Cirúrgica Melhorada , Obstrução Duodenal/congênito , Obstrução Duodenal/cirurgia , Feminino , Humanos , Recém-Nascido , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Gravidez , Estudos Prospectivos , Estudos RetrospectivosRESUMO
BACKGROUND: Hirschsprung disease (HD) is a congenital intestinal anomaly resulting from a failure to form enteric ganglia in the lower bowel. Surgery is the main therapeutic strategy, although neural stem cell transplantation has recently shown promise. However, HD remains a challenging disorder to treat. Our aim was to identify drugs that could counteract the dysregulated pathways in HD and could thus be potential novel therapies. METHODS: We used microarray analysis to identify genes differentially expressed in ganglionic and aganglionic bowel samples from eight children with HD. The signature of differentially expressed genes was then used as a search query to explore the Connectivity Map (cMAP), a transcriptional expression database that catalogs gene signatures elicited by chemical perturbagens. RESULTS: We uncovered several dysregulated signaling pathways, and in particular regulation of neuron development, in HD. The cMAP search identified some compounds with the potential to counteract the effects of the dysregulated molecular signature in this disease. One of these, pepstatin A, was recently shown to rescue the migration defects observed in a mouse model of HD, providing strong support for our findings. CONCLUSIONS: This study advances our understanding of the molecular changes in HD and identifies several potential pharmacological interventions. Further testing of the identified compounds is warranted.