Assessment of functional outcome following Duhamel retro-rectal pull-through surgery for Hirschsprung's disease: a follow-up study

Context: Hirschsprung's disease (HD) is one of the commonest problems requiring surgery in children. More than 95% of children present during new-born period, when they are treated with leveling colostomy and are followed with pull-through surgery a few months later, once the child has gained adequate weight to withstand a major surgery. The commonest pull through surgery done is the Duhamel retro-rectal pull-through (DRPT) repair. Settings and Design: This is a retrospective study of children who presented to one unit in our institute, a tertiary care referral hospital for children less than 12 years, with HD and underwent DRPT procedure during the period between July 2017 to June 2020. The children were evaluated after three years of follow-up for fecal incontinence and constipation. The study was conducted in children diagnosed with classical segment recto-sigmoid HD who underwent surgery. The children who were diagnosed with HD other than classical segment, who underwent primary pull through surgery and who underwent other repairs for HD were excluded from the study. Results: Thirty-two children underwent DRPT procedure during the study period. Of them, five (15.6%) children were lost on follow-up and one (3.1%) child had expired in the immediate post-operative period. Twenty-six children were included in the study. The bowel function score was calculated. The mean age of definitive surgery was 4.2 years. The follow-up period was a minimum of three years. Only two children had a "good" score of eighteen and above. Nineteen children had a "fair" score of 13-17. Five children had a "poor" score of less than thirteen, and among them, two had a "very poor" score of less than nine. The mean BFS was 13.72. Conclusions: Functional outcomes following Duhamel procedure are satisfactory, with 7.7% of children are in the fringe of requiring another surgery for constipation and pseudo-incontinence. (AU)

Analysis of ZEB2 gene variation in two patients with Mowat-Wilson syndrome / 中华医学遗传学杂志

OBJECTIVE@#To identify pathogenic variants in two patients with suspected for Mowat-Wilson syndrome (MWS).@*METHODS@#Genomic DNA was extracted from peripheral blood samples of the patients and his family members, and gene variants were analysis by Trio-whole exome sequences and copy number variation sequencing.@*RESULTS@#Patient 1 was found to carried a de novo heterozygous c.2769C>A (p.Y923*) nonsense variant of ZEB2 gene. The variant was not found in his healthy parents and sister. Patient 2 carried a de novo heterozygous frameshift variant of the ZEB2 gene, namely c.315delC (p.A105Afs*3), which has not been previously reported. Both variants were predicted to be pathogenic and can lead to premature occurrence of stop codons.@*CONCLUSION@#The heterozygous c.2769C>A (p.Y923*) and c.315delC (p.A105Afs*3) variants of the ZEB2 gene probably underlay the pathogenesis in the two patients. Gene testing has facilitated confirmation of the diagnosis and genetic counselling.

Função Intestinal e qualidade de vida de pacientes operados por anomalias anorretais e doença de Hirschsprung / Intestinal function and quality of life in patients operated for anorectal anomalies and Hirschsprung's disease

RESUMO Introdução: As Anomalias Anorretais (AAR) e a Doença de Hirschsprung (DH) são doenças congênitas que necessitam de tratamento cirúrgico. O qual está associado a complicações na função intestinal. Objetivo: Avaliar a função intestinal e a qualidade de vida de pacientes operados por AAR e DH. Métodos: Um estudo transversal e descritivo foi realizado com crianças operadas por AAR e DH em dois hospitais terciários entre 2008 e 2018. Foram entrevistados apenas pacientes com idade superior a 3 anos. A população final foi de 12 pacientes. A função intestinal foi avaliada por meio da Classificação Internacional de Krickenbeck para resultados pós- -operatórios. Foi aplicado também um questionário para avaliação da qualidade de vida. Resultados: A média de idade dos pacientes no momento da entrevista foi de 7,08 anos ± 2,28. Dentre os 12 pacientes entrevistados, 66,7% tinham o diagnóstico de AAR e 33,3% de DH. 91,7% dos pacientes apresentavam escapes fecais após a cirurgia. 33,3% da amostra tinham constipação. Apenas um paciente tinha história prévia de enterocolite, e este apresentou o pior escore de qualidade de vida. Os resultados do questionário de qualidade de vida mostraram que o único paciente sem escapes fecais tinha o melhore escore. Além disso, observou-se que os pacientes com malformações altas possuíam piores escores de qualidade de vida. Conclusão: A função intestinal, após o tratamento cirúrgico, estava prejudicada. A maioria dos pacientes apresentou escapes fecais. Esse desfecho parece afetar os escores de qualidade de vida. O que enfatiza a necessidade de seguimento clínico e manejo intestinal após o tratamento cirúrgico. PALAVRA-CHAVE: Malformações anorretais, doença de Hirschsprung, anormalidades congênitas, incontinência fecal, constipação intestinal

ABSTRACT Introduction: Anorectal Anomalies (ARA) and Hirschsprung Disease (DH) are congenital diseases that require surgical treatment, which is associated with complications in intestinal function. Objective: To assess intestinal function and quality of life in patients operated on for ARA and DH. Methods: A crosssectional descriptive study was carried out with children operated on for ARA and DH in two tertiary hospitals between 2008 and 2018. Only patients aged over 3 years were interviewed. The final population consisted of 12 patients. Intestinal function was assessed using the Krickenbeck International Classification for postoperative outcomes. A questionnaire to assess quality of life was also applied. Results: The mean age of patients at the time of the interview was 7.08 years ± 2.28. Among the 12 patients interviewed, 66.7% had a diagnosis of ARA and 33.3% of DH. Fecal leakage after surgery affected 91.7% of the patients, and 33.3% of the sample had constipation. Only one patient had a previous history of enterocolitis, and he had the worst quality of life score. The results of the quality of life questionnaire showed that the only patient without fecal leakage had the best score. Furthermore, it was observed that patients with high malformations had worse quality of life scores. Conclusion: Intestinal function, after surgical treatment, was impaired. Most patients had fecal leakage. This outcome appears to affect quality of life scores. This emphasizes the need for clinical follow-up and intestinal management after surgical treatment. KEYWORDS: Anorectal malformations, Hirschsprung disease, congenital abnormalities, fecal incontinence, constipation

Etiological analysis and surgical method selection of adult megacolon / 中华胃肠外科杂志

Adult megacolon is a rare disease with heterogeneneous etiology. The treatment schemes of megacolon caused by different causes are also different, but surgery is the final and the most effective method. Due to the lack of early understanding of the disease, many patients have not been clearly diagnosed as adult megacolon and have not been properly treated. This article classifies adult megacolon according to the etiology and summarizes its surgical options. For adult Hirschsprung's disease, modified Duhamel, the Jinling procedure, low anterior resection, or pull-through low anterior resection can be used. For patients with idiopathic megacolon, one-stage subtotal colorectal resection can be selected with adequate preoperative preparations. Some patients admitted to the hospital with emergency intestinal obstruction can be treated with conservative treatment or decompression under colonoscopy followed by selective surgery. For patients with aganglionosis, the procedure is subtotal colorectal resection, the same as that of idiopathic megacolon. The procedure is to remove both the dilated proximal intestine and the stenotic distal intestine, then an ileorectal anastomosis or ascending colon rectal anastomosis is performed. For toxic megacolon, colostomy can be done for mild cases, and for severe infections, subtotal colorectal resection is required. Latrogenic megacolon is mostly caused by segmental stenosis or lack of peristalsis, resulting in chronic dilatation of the proximal end and the formation of megacolon. It is necessary to choose a reasonable surgical procedure according to the specific conditions of the patient. The first choice for the treatment of acute colonic pseudo-obstruction syndrome is decompression under colonoscopy. For those with the secondary changes in the intestine, ostomy is still the most effective surgical procedure, but should be performed with caution.

Clinical and genetic analysis of a patient with Mowat-Wilson syndrome / 中华医学遗传学杂志

OBJECTIVE@#To summarize the clinical phenotype and genotype of a Chinese child affected with Mowat-Wilson syndrome (MWS).@*METHODS@#Clinical data of the patient were collected. The patient was analyzed by whole-exome sequencing (WES) as well as Sanger sequencing.@*RESULTS@#The patient was a male infant with recurrent fever and slow growth. He also had characteristic facies, recurrent spasm, and growth retardation. WES revealed that he has carried a heterozygous nonsense c.2609C>G (p.Ser870X) variant of the ZEB2 gene (30% mosaicism). Based on the American College of Medical Genetics and Genomics standards and guidelines, the variant was predicted to be pathogenic (PVS1+PS1+PS2+PM2).@*CONCLUSION@#The c.2609C>G variant of the ZEB2 gene probably underlay the MWS in this child. The mosaicism of the variant may explain his mild symptoms.

Recomendaciones para el diagnóstico y el tratamiento de los síntomas posquirúrgicos persistentes en la enfermedad de Hirschsprung / Recommendations for the diagnosis and treatment of persistent postsurgical symptoms in Hirschsprung disease

La enfermedad de Hirschsprung ocurre en 1 de cada 5000 nacimientos. La falla de migración de las células ganglionares desde la cresta neural en dirección cefalocaudal genera su ausencia en parte o todo el colon. Se manifiesta con falta de eliminación de meconio, distensión abdominal y dificultades en la evacuación. Luego del tratamiento quirúrgico, existen complicaciones a corto y largo plazo. El objetivo de esta publicación es describir las principales causas de síntomas persistentes en los pacientes operados por enfermedad de Hirschsprung y presentar un algoritmo diagnóstico-terapéutico factible de ser realizado en nuestro medio

Hirschsprung disease is characterized by the lack of migration of intrinsic parasympathetic ganglia from neural crest and consequently absence of them at varying length of the bowel, resulting in functional obstruction. The incidence is 1 per 5000 births. After surgery, short term and long term comorbidity commonly occurs. The aim of this article is to revise the main causes of ongoing symptoms after surgery in Hirschsprung disease patients and to show a diagnostic and therapeutic algorithm that can be developed in our community

Enfermedad de Hirschsprung y apendicitis en paciente pediátrico: reporte de caso / Hirschprungs diseases and appendicitis in pediatric patient: case report

La enfermedad de Hirschsprung es una malformación del sistema nervioso entérico, caracterizada por falta de células ganglionares en plexo submucoso y mientérico en pared distal del colon. En el 80% solo existe afectación del recto-sigma, sin embargo, pueden encontrarse casos de aganglionosis total. Reporte de Caso: Se presenta pre-escolar masculino de 4 años de edad, procedente de La Iguala, Lempira, Honduras, con historia de constipación y distensión abdominal de dos años de evolución, que ha empeorado progresivamente, y se atenuaba con el uso de enemas cada dos días para poder defecar. En mayo de 2016 llega al Hospital Mario Catarino Rivas, donde se le realizó una laparotomía exploratoria de emergencia debido a la presencia de deterioro clínico por constipación y distensión abdominal, acompañada de vómitos con restos alimenticios y fiebre alta de una semana de evolución. En dicha operación se realizó colectomía parcial izquierda, además se realizó una colostomía terapéutica y se diagnósticó enfermedad de Hirs-chsprung mediante biopsia, además del hallazgo incidental de apendicitis, se realizó apendicectomía obteniendo en general, una evolución satisfactoria.El estudio histopatológico de la biopsia del recto es el estándar de oro para realizar el diagnóstico. La ausencia de células ganglionares en el plexo submucoso con latinción hematoxilina y eosina establece el diagnóstico. El tratamiento de la enfermedad de Hirschsprung es de tipo quirúrgico y se busca la eliminación del segmento colónico afectado, de manera que se pueda lograr una anastomosis del colon proximal y distal al área agangliónica...(AU)

Oblique vs. circular anastomosis in the children underwent soave's pull-through surgery for the treatment of hirschsprung's disease: which is the best? / Anastomose oblíqua vs. circular em crianças submetidas à soave pull-through para o tratamento da doença de hirschsprung: qual é a melhor?

ABSTRACT Background: Several types of complications including constipation, fecal soiling, perianal excoriation, were reported among different types of surgery for Hirschsprung's disease. Aim: To compare circular and oblique anastomoses following Soave's procedure for the treatment of Hirschsprung's disease. Methods: Children who underwent Saove's pull through procedure with oblique and circular anastomoses were included. Duration of the follow up was two years after surgery. Postoperative complications, such as wound infection, wound dehiscence, peritonitis, fecal soiling, perianal excoriation, were recorded for each patient. Results: Thirty-eight children underwent oblique anastomoses. Circular ones were done for 32 children. Perianal excoriation was seen in 57.89% and 46.87% of children in oblique and circular group, respectively. Enterocolitis was more frequent in circular (40.62%) than oblique (28.94%) group. Anastomotic stricture was more frequent in circular (15.62%) than oblique (7.89%). Conclusion: Perianal excoriation was the most common complication among patient in both groups. Oblique anastomoses had fewer complications than circular, and may be appropriate option for patient who underwent Soave's procedure.

RESUMO Racional: Vários tipos de complicações, incluindo constipação, secreção fecal, escoriação perianal foram relatadas entre diferentes tipos de operações para a doença de Hirschsprung. Objetivo: Comparar as anastomoses circulares e oblíquas realizadas no procedimento de Soave para o tratamento da doença de Hirschsprung. Métodos: Neste estudo, foram incluídas crianças submetidas ao procedimento pull-through de Saove com anastomoses oblíquas e circulares. A duração do acompanhamento foi de dois anos no pós-operatório. Complicações, como infecção da ferida, deiscência da ferida, peritonite, secreção fecal, escoriação perianal foram registradas para cada paciente. Resultados: Trinta e oito crianças foram submetidas à anastomoses oblíquas. As circulares foram realizadas em 32. Escoriação perianal foi observada em 57,89% e 46,87% das crianças nos grupos oblíquo e circular, respectivamente. Enterocolite foi mais frequente no grupo circular (40,62%) do que oblíquo (28,94%). A estenose anastomótica foi mais frequente na circular (15,62%) do que na oblíqua (7,89%). Conclusão: A escoriação perianal foi a complicação mais comum entre os pacientes nos dois grupos. A anastomose oblíqua teve menos complicações do que a anastomose circular e pode ser a opção adequada para o paciente submetido ao procedimento de Soave.

Analysis of a case with Mowat-Wilson syndrome caused by ZEB2 gene variant / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis of a proband with distinctive facial features, global developmental delay, seizures and hypoplasia of corpus callosum through next generation sequencing (NGS).@*METHODS@#Genomic DNA was extracted from peripheral blood samples of the proband and his family members. Whole exome and flanking sequences were screened by NGS. Suspected variants were verified by Sanger sequencing.@*RESULTS@#The proband was found to carry a heterozygous c.2824G>T (p.G942X) variant of the ZEB2 gene, which was verified by Sanger sequencing to be a de novo variant.@*CONCLUSION@#The heterozygous c.2824G>T (p.G942X) variant of the ZEB2 gene probably underlies the Mowat-Wilson syndrome in the proband.

Enfermedad de Hirschsprung en recién nacidos: propósito de un caso clínico / Hirschsprung disease in newborns: a clinical case

La enfermedad de Hirschsprung es la causa más común de obstrucción intestinal inferior en el primer mes de vida. El objetivo de esta publicación es comunicar una forma de presentación frecuente de esta enfermedad y reforzar la importancia de la sospecha y acciones oportunas por parte del pediatra. Caso clínico: recién nacido varón 36hs de vida. Término, adecuado a la edad gestacional, vigoroso, sin dismorfias externas. A las 36 hs de vida instala vómitos, distensión abdominal progresiva, sin expulsión de meconio desde el nacimiento. Al examen abdomen distendido, dolor difuso a la palpación. Tacto rectal: ampolla vacía. Radiografía simple de abdomen compatible con oclusión intestinal. Radiografía de colon con contraste sugestiva de Enfermedad de Hirschsprung (EH) de segmento corto que se confirma con biopsia rectal. Se realizan lavados colónicos hasta resolución quirúrgica a los 6 meses de vida. Requirió plan de dilatación anal con buena evolución posterior sin complicaciones. Conclusiones: El pediatra cumple un rol fundamental en la sospecha diagnóstica de la EH y debe conocer sus diferentes formas de presentación. Es de suma importancia sospechar esta enfermedad en recién nacidos que presenten oclusión intestinal en las primeras horas de vida.

Hirschsprung's disease is the most common cause of lower intestinal obstruction in the first month of life. The objective of this publication is to communicate a frequent form of presentation of this disease and to reinforce the importance of timely diagnosis by pediatricians. Clinical case: male newborn 36hs of life. Term, Appropiate for gestational age, vigorous, without external dysmorphism. After 36 hours of life, he started vomiting, progressive abdominal distension, no meconium was observed. At the distended abdomen examination, diffuse pain on palpation. Rectal touch: empty blister. Simple abdominal radiography compatible with intestinal occlusion. Colon radiograph with contrast suggestive of Hirschsprung's disease (HD) of short segment that was confirmed with rectal biopsy. Colonic irrigations were performed until surgical resolution at 6 months of age. It required an anal dilatation plan with good posterior evolution without complications. Conclusions: The pediatrician has a fundamental role in the diagnostic suspicion of HD and must know its different forms of presentation. It is very important to suspect this disease in newborns who have intestinal occlusion in the first hours of life.

Vivencias de los padres o cuidadores de niños con enfermedad de Hirschsprung o con malformaciones anorrectales, bajo seguimiento después de la cirugía / Experiences of parents and/or caretakers of children with Hirschsprung's disease or anorectal malformations during follow-up after pediatric surgery

Resumen Introducción. La enfermedad de Hirschsprung y las malformaciones anorrectales son enfermedades que afectan a los niños y comprometen su vida desde el nacimiento, por lo que su diagnóstico y tratamiento temprano son esenciales. Las comorbilidades que implican a largo plazo llevan a los padres y cuidadores a situaciones que pueden generar graves complicaciones para el niño si no se cuenta con el acompañamiento adecuado. Objetivo. Describir y analizar las vivencias de los padres de niños con enfermedad de Hirschsprung o malformaciones anorrectales bajo seguimiento tras haber sido sometidos a cirugía. Materiales y métodos. Se hizo un estudio cualitativo con un enfoque fenomenológico mediante entrevistas a cinco padres de niños con enfermedad de Hirschsprung y a otros cinco de niños con malformaciones anorrectales. Resultados. Se encontraron experiencias comunes, de las cuales surgieron los siguientes temas: a) el diagnóstico difícil, debido a los sentimientos y al impacto generados por la noticia, situación que no siempre es detectada tempranamente por el personal de salud; b) el tratamiento, el cual provoca aislamiento social por las hospitalizaciones y la presencia de una ostomía, además de que los recursos se concentran en el niño en detrimento del hogar; se requiere capacidad de afrontamiento para lograr la reparación quirúrgica definitiva, y c) el contexto, ya que las instituciones de salud pueden convertirse en barreras; además, el personal de salud debe disponer de mayor educación al respecto y son necesarias las redes de apoyo social. Conclusión. Las vivencias reflejan que el diagnóstico, el tratamiento y el contexto generan un gran impacto en las vidas de los padres o cuidadores de niños con estas condiciones.

Abstract Introduction: Hirschsprung's disease and anorectal malformations are pathologies that affect the pediatric population and compromise life from birth, making diagnosis and early treatment essential. The comorbidities they lead to in the long-term take parents and caretakers to situations that, without proper accompaniment, can generate serious complications in the child. Objective: To describe the meaning of the experiences of parents of children with Hirschsprung's disease or anorectal malformations who have had surgical treatment and are being followed-up. Materials and methods: This was a phenomenological qualitative research carried out through interviews with five parents of children with Hirschsprung's disease and five parents of children with anorectal malformations. Results: We found common experiences from which the following topics emerged: a) Difficult diagnosis, which involves the feelings and the impact generated by receiving this news; for health personnel it is not always a situation that is identified early; b) treatment: Social isolation due to hospitalizations and the presence of an ostomy, in addition to the channeling of resources for the child at the expense of those of the home; coping skills are required to achieve definitive surgical repair; and c) context: Health institutions may become barriers and health personnel must have more education in this regard; social support networks are necessary. Conclusion: The experiences reflected that diagnosis, treatment, and context generated great impact on the lives of parents and/or caretakers of children with these pathologies.

Descenso transanal endorrectal De la Torre como tratamiento de enfermedad de hirschsprung, Hospital Escuela, 2013-2015 / Transanal endorectal pull-through de la torre as treatment for Hirschsprung ́s disease, University Hospital, 2013-2015

. Antecedentes: La enfermedad de Hirschsprung (EH) es causa de obstrucción intestinal baja en neonatos. En 1998, De la Torre y Ortega publicaron una importante modificación a la técnica de Soave, realizando un descenso transanal endorrectal. Objetivo:Describir la experiencia en el tratamiento de la Enfermedad de Hirschsprung mediante la técnica descrita por De la Torre, Hospital Escuela, Tegucigalpa, 2013-2015. Metodología: Estudio descriptivo transversal. Se revisaron expedientes clínicos y se registró información sobre características sociodemográficas y clínicas de los pacientes. Los resultados se presentan como frecuencias y porcentajes de las variables estudiadas. La información personal de los pacientes se manejó confidencialmente. Resultados: Se identificó un total de26 casos intervenidos en el periodo del estudio. El 73.1% (19) pertenecía al sexo masculino, 46.2% (12) se diagnosticó antes de 12 meses de vida; sin enfermedades asociadas. La biopsia diagnosticó la enfermedad en el 100% de los casos. La longitud del colon resecado fue de 10-20 cm en 88.5% (23), con un tiempo quirúrgico de 4-5 horas 69.2% (18). El 19.2% (5) presentó complicaciones. Se inició alimentos en menos de 5 días en 96.1% (25), la estancia hospitalaria fue menor a 7 días en 88.5% (23). Discusión: El descenso endorrectal transanal es una operación segura con pocas complicaciones operatorias y postoperatorias. En este estudio, la estancia hospitalaria y el tiempo hasta la alimentación oral completa fueron más cortos que los procedimientos convencionales lo que generó menores costes hospitalarios. Consideramos que ésta es la técnica de elección para enfermos con la Enfermedad de Hirschsprung...(AU)

Complications after transabdominal soave's procedure in children with hirschsprung's disease / Complicações após o procedimento de soave transabdominal em crianças com doença de hirschsprung

ABSTRACT Background: Hirschsprung's disease is a congenital disorder that causes functional obstruction of large bowel. Aim: To evaluate complication and bowel function score of children with Hirschsprung's disease who underwent transabdominal Soave's procedure. Methods: In this study all the children with Hirschsprung's disease who underwent transabdominal Soave procedure were evaluated regarding bowel function and complication of trans-abdominal Soave's procedure. Results: Were enrolled 160 children. Enterocolitis and constipation were seen in 15% of the cases. Fecal incontinency was the least frequent study which was seen in 1% of the children. Conclusion: Constipation and enterocolitis was the most frequent complication following transabdominal Soave technique.

RESUMO Racional: A doença de Hirschsprung é um distúrbio congênito que causa obstrução funcional do intestino grosso. Objetivo: Avaliar as complicações e o escore de função intestinal de crianças com a doença submetidas ao procedimento transabdominal de Soave. Métodos: Neste estudo, todas as crianças com doença de Hirschsprung submetidas ao procedimento transabdominal de Soave foram avaliadas quanto à função intestinal e complicação do procedimento. Resultados: Foram incluídas 160 crianças. Enterocolite e constipação foram observadas em 15% dos casos. A incontinência fecal foi menos frequente e observada em 1% das crianças. Conclusão: Obstipação e enterocolite foram as complicações mais frequentes após a técnica de Soave transabdominal em crianças.

Association of rs2435357 and rs1800858 polymorphisms in ret proto-oncogene with hirschsprung disease: systematic review and meta-analysis / Associação dos polimorfismos rs2435357 e rs1800858 no proto-oncogene ret com doença de hirschsprung: revisão sistemática e metanálise

ABSTRACT Introduction: Many published studies have estimated the association of rs2435357 and rs1800858 polymorphisms in the proto-oncogene rearranged during transfection (RET) gene with Hirschsprung disease (HSCR) risk. However, the results remain inconsistent and controversial. Aim: To perform a meta-analysis get a more accurate estimation of the association of rs2435357 and rs1800858 polymorphisms in the RET proto-oncogene with HSCR risk. Methods: The eligible literatures were searched by PubMed, Google Scholar, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) up to June 30, 2018. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the susceptibility to HSCR. Results: A total of 20 studies, including ten (1,136 cases 2,420 controls) for rs2435357 and ten (917 cases 1,159 controls) for rs1800858 were included. The overall results indicated that the rs2435357 (allele model: OR=0.230, 95% CI 0.178-0.298, p=0.001; homozygote model: OR=0.079, 95% CI 0.048-0.130, p=0.001; heterozygote model: OR=0.149, 95% CI 0.048-0.130, p=0.001; dominant model: OR=0.132, 95% CI 0.098-0.179, p=0.001; and recessive model: OR=0.239, 95% CI 0.161-0.353, p=0.001) and rs1800858 (allele model: OR=5.594, 95% CI 3.653-8.877, p=0.001; homozygote model: OR=8.453, 95% CI 3.783-18.890, p=0.001; dominant model: OR=3.469, 95% CI 1.881-6.396, p=0.001; and recessive model: OR=6.120, 95% CI 3.608-10.381, p=0.001) polymorphisms were associated with the increased risk of HSCR in overall. Conclusions: The results suggest that the rs2435357 and rs1800858 polymorphisms in the RET proto-oncogene might be associated with HSCR risk.

RESUMO Introdução: Muitos estudos publicados estimaram a associação dos polimorfismos rs2435357 e rs1800858 do proto-oncogene rearranjado durante a transfecção (RET) com o risco de doença por Hirschsprung (HSCR). No entanto, os resultados permanecem inconsistentes e controversos. Objetivo: Realizar metanálise para obter estimativa mais precisa da associação dos polimorfismos rs2435357 e rs1800858 no proto-oncogene RET com risco de HSCR. Método: A literatura elegível foi pesquisada pelo PubMed, Google Scholar, EMBASE e CNKI até 30 de junho de 2018. Resultados: Um total de 20 estudos, incluindo dez (1.136 casos 2.420 controles) para rs2435357 e dez (917 casos 1.159 controles) para rs1800858 foram incluídos. Os resultados globais indicaram que o rs2435357 (modelo alelo: OR=0,230, IC 95% 0,178-0,298, p=0,001; modelo homozigoto: OR=0,079, IC 95% 0,048-0,130, p=0,001; modelo heterozigoto: OR=0,149 , IC 95% 0,048-0,130, p=0,001, modelo dominante: OR=0,132, IC 95% 0,098-0,179, p=0,001 e modelo recessivo: OR=0,239, IC 95% 0,161-0,353, p=0,001) e rs1800858 (modelo alelo: OR=5,594, IC 95% 3,653-8,877, p=0,001; modelo homozigoto: OR=8,453, IC 95% 3,783-18,890, p=0,001; modelo dominante: OR=3,469, IC 95% 1,881- 6,396, p=0,001 e modelo recessivo: OR=6,120, 95% CI 3,608-10,381, p=0,001) polimorfismos foram associados com o aumento do risco de HSCR em geral. Conclusões: Os resultados sugerem que os polimorfismos rs2435357 e rs1800858 no proto-oncogene RET podem estar associados ao HSCR.

Prenatal diagnosis of a fetus with Mowat-Wilson syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a fetus featuring increased nuchal thickness.@*METHODS@#Routine G-banding karyotyping and single nucleotide polymrophism array were carried out to detect genomic copy number variations (CNVs) in the fetus.@*RESULTS@#The fetus was found to harbor a heterozygous 3.8 Mb deletion in the 2q22.2-q22.3 region encompassing the ZEB2 gene, which is closely associated with Mowat-Wilson syndrome (MWS).@*CONCLUSION@#Haploinsufficiency of the ZEB2 gene may predispose to MWS. Lack of knowledge regarding to the ultrasonographic features of MWS may lead to misdiagnosis of the syndrome.

Effect of enhancer of zeste homolog 2 on the expression of glial cell line-derived neurotrophic factor family receptor α-1 in the colon tissue of children with Hirschsprung's disease / 中国当代儿科杂志

OBJECTIVE@#To study the expression levels of glial cell line-derived neurotrophic factor family receptor α-1 (GFRα1) and enhancer of zeste homolog 2 (EZH2) in the intestinal tissue of children with Hirschsprung's disease (HSCR), as well as the role of EZH2 in the regulation of GFRα1 gene expression and the pathogenesis of HSCR.@*METHODS@#The samples of colon tissue with spasm from 24 children with HSCR after radical treatment of HSCR were selected as the experimental group, and the samples of necrotized colon tissue from 18 children with neonatal necrotizing enterocolitis after surgical resection were selected as the control group. Real-time PCR and Western blot were used to measure the expression levels of GFRα1 and EZH2 in colon tissue in both groups. Human neuroblastoma SH-SY5Y cells were divided into an EZH2 over-expression group and a negative control group. The cells in the EZH2 over-expression group were transfected with pCMV6-EZH2 plasmid, and those in the negative control group were transfected with pCMV6 plasmid. The expression levels of EZH2 and GFRα1 were measured after transfection.@*RESULTS@#Compared with the control group, the experimental group had significant reductions in the mRNA and protein expression levels of GFRα1 and EZH2 in colon tissue (P<0.05), and the protein expression of EZH2 was positively correlated with that of GFRα1 (r=0.606, P=0.002). Compared with the negative control group, the EZH2 over-expression group had significant increases in the expression levels of EZH2 and GFRα1 after SH-SY5Y cells were transfected with EZH2 over-expression plasmid (P<0.05).@*CONCLUSIONS@#Low expression of EZH2 in the colon tissue of children with HSCR may be one of the causes of inadequate expression of GFRα1 and onset of HSCR.

Clinical and genetic features of Mowat-Wilson syndrome: an analysis of 3 cases / 中国当代儿科杂志

Mowat-Wilson syndrome (MWS) is a rare autosomal dominant genetic disease caused by zinc finger E-box-binding homeobox 2 (ZEB2) gene mutation and has various clinical manifestations including intellectual disability/global developmental delay, unusual facies and multiple congenital malformations. This article reports the clinical features and gene mutations of three children diagnosed with MWS by ZEB2 gene analysis. All three children had Hirschsprung disease and unusual facies. One child died of severe heart failure and pneumonia at the age of 4 months. Global developmental delay was not discovered by her parents due to her young age. The other two children had severe global developmental delay. All three children carried a de novo heterozygous nonsense mutation in the ZEB2 gene, among which c.756C>A (p.Y252X) had not been reported before. Such mutations produced truncated proteins and were highly pathogenic. MWS is presented with strong clinical and genetic heterogeneity. Clinicians should consider the possibility of MWS when a child has unusual facies of MWS, intellectual disability/global developmental delay and multiple congenital malformations. Gene detection helps to make a confirmed diagnosis.

An ANKRD11 exonic deletion accompanied by a congenital megacolon in an infant with KBG syndrome

KBG syndrome is an autosomal dominant syndrome presenting with macrodontia, distinctive facial features, skeletal anomalies, and neurological problems caused by mutations in the ankyrin repeat domain 11 (ANKRD11) gene. The diagnosis of KBG is difficult in very young infants as the characteristic macrodontia and typical facial features are not obvious. The youngest patient diagnosed to date was almost one year of age. We here describe a 2-month-old Korean boy with distinctive craniofacial features but without any evidence of macrodontia due to his very early age. He also had a congenital megacolon without ganglion cells in the rectum. A de novo deletion of exons 5–9 of the ANKRD11 gene was identified in this patient by exome sequencing and real-time genomic polymerase chain reaction. As ANKRD11 is involved in the development of myenteric plexus, a bowel movement disorder including a congenital megacolon is not surprising in a patient with KBG syndrome and has possibly been overlooked in past cases.

Waardenburg Syndrome Type IV De Novo SOX10 Variant Causing Chronic Intestinal Pseudo-Obstruction / 대한소아소화기영양학회지

Waardenburg syndrome (WS) type IV is characterized by pigmentary abnormalities, deafness and Hirschsprung's disease. This syndrome can be triggered by dysregulation of the SOX10 gene, which belongs to the SOX (SRY-related high-mobility group-box) family of genes. We discuss the first known case of a SOX10 frameshift mutation variant defined as c.895delC causing WS type IV without Hirschsprung's disease. This female patient of unrelated Kuwaiti parents, who tested negative for cystic fibrosis and Hirschsprung's disease, was born with meconium ileus and malrotation and had multiple surgical complications likely due to chronic intestinal pseudo-obstruction. These complications included small intestinal necrosis requiring resection, development of a spontaneous fistula between the duodenum and jejunum after being left in discontinuity, and short gut syndrome. This case and previously reported cases demonstrate that SOX10 gene sequencing is a consideration in WS patients without aganglionosis but with intestinal dysfunction.

Enfermedad de Hirschsprung: resultados del tratamiento quirúrgico en el Hospital Pediátrico Pereira Rossell / Hirschsprung disease: results of surgical treatment performed at the Pereira Rossell Pediatric Hospital / Doença de Hirschsprung: resultados do tratamento cirúrgico no Hospital Pediátrico Pereira Rossell

Introducción: la enfermedad de Hirschsprung es una patología que puede ser de diagnóstico y tratamiento complejo. Requiere un manejo multidisciplinario y una importante experiencia para minimizar la morbilidad aguda y a largo plazo. Objetivos: Estudiar las características de los pacientes operados por enfermedad de Hirschsprung en el Hospital Pediátrico del Hospital Pereira Rossell en los últimos 10 años (2006-2016), identificar sus complicaciones y su resultado a largo plazo. Material y método: se revisaron las historias clínicas entre enero de 2006 y julio de 2016. Se estudiaron distintas variables y se comparó la evolución según las diferentes técnicas quirúrgicas. Se utilizaron como métodos estadísticos el test exacto de Fisher y test de Chi cuadrado. Resultados: se analizaron las historias de 30 pacientes en el período comprendido, de los cuales 22 eran de sexo masculino y 8 femenino. En 16 pacientes se realizó el diagnóstico mediante biopsia por aspiración, en 11 se realizó por medio de una biopsia quirúrgica y en 1 caso se llegó al diagnóstico mediante manometría anorrectal. 24 pacientes se diagnosticaron antes del primer año de vida, y 19 se operaron antes del 1er año. En 23 pacientes la enfermedad era de extensión rectosigmoidea. Se realizó la técnica De La Torre Mondragón en 14 casos y en 9 la técnica de Soave o su variante Soave/Boley. Conclusión: la técnica endoanal es la más utilizada para la patología de extensión rectosigmoidea, se evidencia una clara predilección por este abordaje en los últimos años. Si bien no hemos podido evaluar en su totalidad los pacientes intervenidos por la técnica de De La Torre creemos que posee grandes ventajas al evitar el abordaje abdominal. Hemos identificado claros puntos a mejorar como la importancia en el diagnóstico y tratamiento precoz, la necesidad de redes bien establecidas y el control a largo plazo en este tipo de patología. Valoramos la versatilidad de equipo quirúrgico en cuanto a la utilización de diferentes técnicas adecuadas a las necesidades de cada paciente.

Introduction: Hirschsprung's disease could involve a complex diagnosis and treatment. It requires long-term multidisciplinary management practices and vast experience in order to minimize acute morbidity. Goals: Study the epidemiology of patients with Hirschsprung's disease at the Pereira Rossell Pediatric Hospital during 10 years (2006-2016) and identify their complications and long-term outcomes. Materials and methods: we reviewed the medical records between January 2006 and July 2016. We studied different variables and compared the evolution after performing the different surgical techniques. We used Fisher's exact test and Chi square test as statistical methods. Results: we analyzed 30 medical records in this period, 22 males and 8 females. 16 patients had been diagnosed through aspiration biopsy, 11 through surgical biopsy and in one case the diagnosis was reached through anorectal manometry. 24 patients were diagnosed before the first year of life, and 19 received surgery before the first year of life. In the case of 23 patients, the disease involved rectosigmoid extension. The La Torre Mondragón technique was performed in 14 cases and the Soave technique or its Soave/Boley variant was performed in 9 cases. Conclusion: endoanal is the most used technique for the rectosigmoid extension pathology and it seems to be the technique of choice in the last years. Although we have not been able to fully assess patients operated using the De La Torre technique, we believe that it has many advantages in avoiding the abdominal approach. We have identified clear areas for improvement, such as the importance of diagnosis and early treatment, the need for well-established networks and long-term control for this type of pathology. We value the surgical team's versatility when using different techniques customized to the patients' needs.

Introdução: a doença de Hirschsprung é uma patologia que pode exigir um diagnóstico e tratamento complexos. Requer manejo multidisciplinar de longo prazo e vasta experiência para minimizar a morbidade aguda. Objetivos: estudar as características dos pacientes operados pela doença de Hirschsprung no Hospital Pediátrico Pereira Rossell durante 10 anos (2006-2016), e poder identificar suas complicações e os resultados no longo prazo. Material e métodos: Estudamos diferentes variáveis nas histórias clínicas entre janeiro de 2006 e julho de 2016 e comparamos a evolução de acordo com as diferentes técnicas cirúrgicas utilizadas. Utilizamos o teste exato de Fisher e o teste qui-quadrado como métodos estatísticos. Resultados: analisamos as histórias clínicas de 30 pacientes no período mencionado, 22 do sexo feminino e 8 do sexo masculino. Em 16 pacientes o diagnóstico foi feito através duma biópsia aspirativa, em 11 através duma biópsia cirúrgica e em um caso o diagnóstico foi realizado através duma manometria anorretal. 24 pacientes foram diagnosticados antes do primeiro ano de vida, e 19 foram operados antes do primeiro ano. Em 23 pacientes, a doença foi do tipo extensão retossigmóide. Utilizamos a técnica da Torre de Mondragón em 14 casos e a técnica Soave ou sua variante Soave/Boley em 9 casos. Conclusão: a técnica endoanal tem sido a mais utilizada e a preferida para o tratamento da patologia da extensão retossigmóide nos últimos anos. Embora não tenhamos conseguido avaliar totalmente os pacientes submetidos à técnica de De La Torre, acreditamos que ela tenha grandes vantagens na hora de evitar a abordagem abdominal. Identificamos áreas para o melhoramento no diagnóstico e tratamento precoce, a necessidade de redes bem estabelecidas e o controle de longo prazo nesse tipo de patologia. Valorizamos a versatilidade da equipe cirúrgica no uso das diferentes técnicas adaptadas às necessidades de cada paciente.