Mowat-Wilson syndrome: neurological and molecular study in seven patients / Síndrome de Mowat-Wilson: estudo neurológico e molecular em sete pacientes

Objective To present a seven-cases serie of Mowat-Wilson syndrome (MWS). Method All patients with positive mutation for the ZEB2 were evaluated by a geneticist and a neurologist, with clinical and laboratorial characterization. Results A peculiar facies and mental retardation were present in all patients. The Denver II scale showed intense delay in all aspects, especially fine motor and adaptive. Acquired microcephaly was observed in five patients. Only one patient did not present epilepsy. Epilepsy was focal and predominating in sleep, with status epilepticus in three patients. The initial seizure was associated with fever in most patients (4/6). The EEG showed epileptic focal activity (5/7). The imaging studies revealed total agenesis (4/7) and partial agenesis of the corpus callosum (1/7). Conclusion Physicians who care for patients with mental retardation and epilepsy should be aware of SMW. .

Objetivo Apresentar uma série de sete casos da síndrome de Mowat-Wilson (SMW). Método Todos os pacientes com estudo positivo para a mutação ZEB2 foram avaliados por um geneticista e um neurologista, com a caracterização clínica e laboratorial. Resultados Todos apresentavam fácies peculiar e retardo mental. A escala de Denver II evidenciou intenso atraso em todos os aspectos, sobretudo motor fino e adaptativo. Microcefalia adquirida foi observada em cinco pacientes. Apenas um paciente não apresentava epilepsia, sendo esta focal e predominando no sono, sendo relatado estado de mal em três pacientes. A crise inicial estava associada à febre na maioria dos pacientes (4/6). O EEG evidenciou atividade epiléptica focal na maioria (5/7). Ao estudo de imagem foi observada agenesia total (4/7) e parcial do corpo caloso (1/7). Conclusão Médicos que lidam com pacientes com retardo mental e epilepsia devem saber distinguir as características peculiares da SMW. .

Resultados a largo plazo en enfermedad de Hirschsprung / Long-term results in Hirschsprung's disease

La Enfermedad de Hirschsprung (EH) es una enfermedad poco frecuente que engloba un sinnúmero de problemáticas tanto para el cirujano infantil como para el paciente y sus familiares. Hay numerosas técnicas quirúrgicas descritas para su resolución y con distintos resultados. Objetivo Analizar el resultado postquirúrgico de nuestra casuística evaluando funcionalidad. Metodología Se realiza estudio retrospectivo de pacientes operados por EH entre el 2000 y 2013 en nuestro centro. Se analizan datos según las distintas técnicas de descenso. Se excluyen, para la evaluación funcional 3 pacientes sin resolución definitiva(pendiente reconstitución y/o descenso) y 3 pacientes sin registro clínico postoperatorio. Resultados y Discusión: se analizan datos de 42 pacientes con biopsias compatibles con EH. La edad al momento del diagnóstico corresponde a una media de 30.5 d y 255 d al momento del descenso. El tipo de descenso utilizado principalmente fue el de Georgeson en 17 pacientes (40.4 por ciento), De La Torre en 9 (21.4 por ciento) y Rehbein en 7 (16.6 por ciento). El 45 por ciento debutaron complicados de los cuales el 63.1 por ciento fue ostomizado previo al descenso. El 35.7 por ciento presenta complicaciones precoces. Los resultados funcionales se evalúan al control con cirujano y por encuesta al cuidador aplicando score PICSS. Los pacientes operados con la técnica de Georgeson según nuestra revisión presentaron menos complicación asociadas a largo plazo, teniendo mejor funcionalidad en un 75 por ciento posterior al año del descenso. Entre las complicaciones tardías 33.3 por ciento presento enterocolitis, 14.3 por ciento soiling y un 28.5 por ciento constipación. 57.1 por ciento de nuestra serie presenta funcionalidad adecuada al último control. Se comparan resultados con encuesta telefónica realizada. Conclusiones El poder aplicar protocolos de evaluación funcional en pacientes operados de EH nos permite objetivar mejor los resultados de nuestras cirugías.

Enterocolitis asociada a enfermedad de Hirschsprung / Enterocolitis associated with Hirschsprung's disease

La enterocolitis asociada a enfermedad de Hirschsprung (EAEH) se define como la presencia de diarrea, deposiciones explosivas, distensión abdominal y signos radiológicos de obstrucción intestinal o edema de la mucosa. Es la causa más común de mortalidad en pacientes con enfermedad de Hirschsprung (EH). Puede ocurrir en cualquier etapa de la enfermedad, con una incidencia media del 25 por ciento. La fisiopatología es poco conocida. Etiologías potenciales son la obstrucción mecánica, infecciones, barrera mucosa defectuosa, y un sistema inmunológico deficitario. Microscópicamente la EAEH se caracteriza por criptitis y abscesos en las criptas, seguida de ulceración de la mucosa progresiva conduciendo eventualmente a la necrosis transmural. Los pilares del tratamiento son la reanimación con fluidos, la descompresión del intestino y la terapia antibiótica. A veces se requiere de una estoma cuando estas medidas han fracasado. La mayoría de los pacientes con EAEH siguen teniendo trastornos de la función intestinal muchos años después de la cirugía para la enfermedad de Hirschsprung. Investigaciones en la fisiopatología de la EAEH pueden conducir a medidas preventivas y mejores modalidades de tratamiento.

Hirschsprung’s-associated enterocolitis(HAEC) is defined as the presence of diarrhea, explosive stools, abdominal distension and radiologic evidence of bowel obstruction or mucosal edema. HAEC is the most common cause of mortality in patients with Hirschsprung’s disease. This condition may occur in any stage of the Hirschsprung’s disease, with a mean incidence of 25 percent. The pathophysiology is poorly understood. Potential etiologies are mechanical obstruction, infections, defective mucosal barrier, and impaired immunological system. Microscopically HAEC is characterized by cryptitis and crypt abscesses followed by progressive mucosal ulceration eventually leading to transmural necrosis. The mainstays of treatment are fluid resuscitation, decompression of the bowel and antibiotic therapy. Sometimes a stoma is required when such measures have failed. The majority of patients with HAEC continue to have disturbances of bowel function many years after surgery for Hirschsprung’s disease. Researchs into the pathophysiology of HAEC can lead to better preventative measures and treatment modalities.

Colonic transit study by radio-opaque markers to investigate constipation: validation of a new protocol for a population with rapid gut transit.

BACKGROUND: Constipation is a common problem, which may be due to slow transit or faecal evacuation disorders. Though the screening test of colonic transit study using radio-opaque markers given at 0, 24 and 48 hours followed by abdominal X-ray at 72 hours is a good protocol in the West, it is not suitable for Indians who have a rapid gut transit. METHODS: Nine patients with adult Hirschsprung disease, 11 with chronic intestinal pseudo-obstruction diagnosed using standard investigations and 11 healthy subjects were evaluated by colonic transit study using radio-opaque markers (SGmark), 20 each at O, 12 and 24 hours followed by an abdominal X-ray at 36 and 60 hours. The cut-off was determined by using receiver operating characteristic (ROC) curves, and sensitivity, specificity, positive and negative predictive values and diagnostic accuracy were determined. RESULTS: The total number of markers retained in the abdomen and those in the right segment at 36 hours in patients with Hirschsprung disease and chronic intestinal pseudo-obstruction was higher than that in healthy subjects though the number in the left and rectosigmoid segments were comparable. The abdominal X-ray at 60 hours, total number of markers and number in all segments were higher in patients with Hirschsprung disease and chronic intestinal pseudoobstruction than in healthy subjects. The best cut-off by ROC curves at 36 and 60 hours was 30 and 14 markers, respectively. The sensitivity, specificity, positive and negative predictive values, diagnostic accuracy and area under the ROC curve at 36 hours were 90%, 82%, 90%, 82%, 87% and 0.9, respectively; the corresponding values at 60 hours were 95%, 100%, 100%, 92%, 97% and 0.99, respectively. CONCLUSION: Using the proposed protocol, the colonic transit study is able to distinguish patients with specific motility disorders causing constipation such as Hirschsprung disease and chronic intestinal pseudo-obstruction from healthy subjects with reasonable sensitivity and specificity, and shows that an abdominal X-ray at 60 hours is better than one at 36 hours.

Motility disorders of the gastrointestinal tract.

Over the past decades our knowledge of normal and abnormal gastrointestinal motility has increased tremendously. The availability of manometry to study bowel contraction patterns, laparoscopy to perform full thickness bowel biopsies for histological examination, have added to the investigative armamentarium and helped better diagnose motility disorders. However, the development of newer therapies for bowel motility disorders has been disappointingly slow. Newer modalities such as gastric and bowel pacing provides some hope for the future. In this article we have provided an overview of some of the common motility disorders in children and discussed their management.

Clinicopathological features in 102 cases of Hirschsprung disease

Hirschsprung disease [HD] is a predominantly childhood disorder of intestinal motility with a multifactorial and polygenic etiology. The objective of this study was to document the clinical and pathological features of HD in Kuwait, which has an estimated consanguinity rate of 54%.We analyzed all rectal and colonic biopsies [n=268] for suspected HD identified from the records in the Pathology Department of Al-Sabah Hospital for the period between 1994 and 2004. One hundred and two patients [87 males and 15 females] had historically confirmed HD. Fifty-eight [57%] were neonates [<1 month of age], while 21% were more than 4 months old. The diagnosis was based on open biopsy in 11 cases and rectal biopsies in 91 cases. Nine patients with open biopsies presented as intestinal obstruction, necrotizing enterocolitis, or perforation. The extent of the disease was unknown in 13 patients. There were 67 males and 3 females with short segment HD. Nine had long segment, two ultra-short segment and eight total colonic aganglionosis [TCA]. Five TCA cases involved the small intestine. A skip area was observed in two cases. Six patients had other anomalies. A positive family history for HD was established in three patients. Two of these were male siblings from a consanguineous marriage and had Waardenburg syndrome. This study has highlighted an exceptionally strong male predominance of short segment and a relatively high frequency [5.6%] of small intestinal involvement in HD in Kuwait. These data call for a more detailed epidemiological study with special emphasis on genetics

Aganglionose total do cólon: aspectos radiológicos / Total aganglionosis of the colon: radiological findings

A partir da observação de três pacientes com aganglionose total do cólon e de revisão da literatura, os autores salientam as particularidades diagnósticas desta entidade que justificam uma análise separada da forma típica da doença de Hirschsprung. Não há sinais radiológicos patognomônicos e o diagnóstico definitivo somente pode ser obtido pelo estudo histopatológico. Considerando sua alta incidência de complicações e mortalidade, a aganglionose total do cólon deve ser considerada em todo recém-nascido ou criança maior com evidências radiológicas de obstrução intestinal, quaisquer que sejam os achados de enema opaco.

Megacólon parte 1: Doença de Hirschsprung / Megacolon part 1: Hirschsprung`s disease

A doença de Hirschsprung é uma anomalia congênita que tem como característica intrínseca a ausência dos neurônios intramurais dos plexos nervosos parassimpáticos (Meissner e Auerbach), afetando o intestino grosso, em geral, nos seus segmentos mais distais, como o reto e o cólon sigmóide. Os principais sinais e sintomas da doença são a distensão abdominal que ocorre logo após o nascimento, com presença de vômitos e retardo de mais de 48 horas na passagem do mecônio, sem que haja um fator mecânico obstrutivo reconhecido de imediato. A doença compromete quatro vezes mais os meninos que as meninas e é considerada como devido à falha de migração crânio-caudal da crista neural do vago, tratando-se, pois, de uma neurocristopatia, hoje considerada associada à "deleção" do braço longo do cromossomo 10. Um dos mais intrigantes fatores relativos ao megacólon congênito, além da incidência familiar, é sua alta associação com outras anomalias congênitas que chegam a estar presentes em 28por cento ou mais, dos casos. Deixada evoluir sem o tratamento precoce, em geral, ela provoca retardo do desenvolvimento que, não raramente, culmina com a morte, quase sempre associada a enterocolites graves. O tratamento é cirúrgico e se resume na retirada do segmento denervado, com reconstrução imediata do trânsito intestinal. O envolvimento do médico geneticista na avaliação desses pacientes é obrigatório já que, com a sua participação, o número total de anomalias adicionais reconhecidas triplica.

Ileo meconial familiar complicado no asociado a fibrosis quística: presentación de casos clínicos / Complicated familiar meconium ileus non associated with cyst fibrosis: Clinical cases

Se reportan los casos de tres pacientes pediátricos, hermanos consanguíneos, que presentaron al nacimiento una de las tres formas clínicas de íleo meconial. Aun cuando es un caso de presentación familiar, se realizaron estudios genéticos en los que fue posible descartar alteración genética asociada con fibrosis quística o enfermedad de Hirschsprung, considerándose a estos pacientes portadores de una enfermedad meconial familiar, poco descrita en la literatura internacional

Análise das alteraçöes do óxido nítrico em pacientes com megacólon chagásico / Analysis of the alterations of nitric oxide in the patient with megacolon in Chaga's disease

A fisiopatologia da Doença de Chagas ainda näo está completamente esclarecida. O óxido nítrico (NO) tem sido citado como neurotransmissor responsável pelo relaxamento do esfíncter interno do ânus no indivíduo normal. Neuronal nicotinamida adenina dinucleotídeo fosfato (NADPH) diaforase pode ser usado como marcador neuronal do NO. Objetivos: Examinar as alteraçöes nos neurônios produtores de NO do cólon de pacientes submetidos à ressecçäo por megacólon avançado e comparar com o intestino delgado dos mesmos pacientes e com controles. Métodos: Espécimes obtidos da ressecçäo do reto e biópsias extramucosas do intestino delgado de 11 pacientes chagásicos foram comparadas a 10 pacientes controles com câncer de cólon. Os tecidos foram fixados em soluçäo de Zamboni e submetidos à histoquímica para neurônios contendo NADPH diaforase. A reatividade foi avaliada utilizando-se uma escala de 0 a 4 nas diversas camadas da parede intestinal: musculatura lisa longitudinal (ML), plexo mioentérico (PM), musculatura lisa circular (MC), plexo submucoso (PSM), e mucosa (M). Resultados: Os casos controles mostraram os plexos mioentérico e submucoso bem corados e uma rica rede de terminaçöes nervosas nas camadas musculares. Os espécimes provenientes de doentes chagásicos revelaram uma diminuiçäo da reatividade e da coloraçäo em todas as camadas do intestino. De maneira geral, houve uma diminuiçäo estatisticamente significante nos neurônios contendo NADPH diaforase. O intestino delgado clinicamente näo envolvido também demonstrou diminuiçäo da reatividade, porém em menor grau. Conclusöes: A atividade da NADPH diaforase está diminuída em pacientes com megacólon avançado, especialmente no plexo mioentérico e na camada muscular lisa; 2. Houve também uma diminuiçäo da atividade neuronal do NO no jejuno clinicamente näo envolvido pela doença, mas em menor grau

Neuronal intestinal dysplasia: a role for surgery?

Neuronal intestinal dysplasia (NID) is a poorly understood colonic motility disorder with characteristic histopathological findings and clinical presentation. It is often associated with Hirschsprung's disease (HD) and can constitute a cause of failure of clinical improvement after adequate resectional pull-through surgery. Other conditions associated with NID are: Chronic Intestinal Pseudo-obstruction (CIPO), anorectal malformations and Multiple Endocrine Neoplasia (MEN) II syndrome patients. To increase the diagnostic yield of NID the pathologist should be aware and use histochemistry evaluation of the rectal biopsy specimen in patients with history of constipation or unexplained bouts of diarrhea. Adequate sampling of the temporary proximal colostomy done to HD patients should be examined for NID pathological changes. Treatment has centered around the clinical picture with most cases managed medically with prokinetic agents, colonic irrigations, and bowel cathartics until improvement and normalization of histology occur. There is evidence of progressive maturation of the enteric nervous system with time. Surgery is indicated for patients with severe clinical deterioration after failed medical management

Doença de Hirschsprung / Hirschsprung's disease

Os autores fazem uma revisäo da literatura a respeito da doença de Hirschsprung com o objetivo de discutir os aspectos mais importantes atuais relacionados a fisiopatologia, diagnóstico e tratamento