Hirschsprung disease (HSCR, aganglionic megacolon) represents the main genetic cause of functional intestinal obstruction with an incidence of 1/5000 live births. This developmental disorder is a neurocristopathy and is characterised by the absence of the enteric ganglia along a variable length of the intestine. In the last decades, the development of surgical approaches has importantly decreased mortality and morbidity which allowed the emergence of familial cases. Isolated HSCR appears to be a non-Mendelian malformation with low, sex-dependent penetrance, and variable expression according to the length of the aganglionic segment. While all Mendelian modes of inheritance have been described in syndromic HSCR, isolated HSCR stands as a model for genetic disorders with complex patterns of inheritance. The tyrosine kinase receptor RET is the major gene with both rare coding sequence mutations and/or a frequent variant located in an enhancer element predisposing to the disease. Hitherto, 10 genes and five loci have been found to be involved in HSCR development.

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Hirschsprung disease, associated syndromes and genetics: a review

The developmental etiology and pathogenesis of Hirschsprung disease.

Hirschsprung disease is defined by the absence of enteric neurons at the end of the bowel. The enteric nervous system (ENS) is the intrinsic nervous system of the bowel and regulates most aspects of bowel function. When the ENS is missing, there are no neurally mediated propulsive motility patterns, and the bowel remains contracted, causing functional obstruction. Symptoms of Hirschsprung disease include constipation, vomiting, abdominal distension and growth failure. Untreated disease usually causes death in childhood because bloodstream bacterial infections occur in the context of bowel inflammation (enterocolitis) or bowel perforation. Current treatment is surgical resection of the bowel to remove or bypass regions where the ENS is missing, but many children have problems after surgery. Although the anatomy of Hirschsprung disease is simple, many clinical features remain enigmatic, and diagnosis and management remain challenging. For example, the age of presentation and the type of symptoms that occur vary dramatically among patients, even though every affected child has missing neurons in the distal bowel at birth. In this Review, basic science discoveries are linked to clinical manifestations of Hirschsprung disease, including partial penetrance, enterocolitis and genetics. Insights into disease mechanisms that might lead to new prevention, diagnostic and treatment strategies are described.

Hirschsprung disease — integrating basic science and clinical medicine to improve outcomes

Appendicitis is a condition characterized by inflammation of the appendix. All cases require removal of the inflamed appendix, either by laparotomy or laparoscopy. Untreated, mortality is high, mainly because of peritonitis and shock.[1] Reginald Fitz first described acute and chronic appendicitis in 1886,[2] and it has been recognized as one of the most common causes of severe acute abdominal pain worldwide.

Appendicitis

The genetics of Hirschsprung disease.

Colonic volvulus: A rare presentation of Hirschsprung's disease

Between 1976-1993, 302 patients were diagnosed to have Hirschsprung's disease (HD) in Hacettepe University Children's Hospital. All patients have been searched for the occurrence of associated anomalies and other parameters including 1) sex, 2) gestational age, 3) birth weight, 4) length of aganglionic segment, 5) familial occurrence, 6) consanguinity. Forty-nine of 302 patients were proved to have 83 associated congenital anomalies together with HD. Distribution of anomalies was as follows; central nervous system and special senses 28.92%, genitourinary system 26.51%, skeletal 24.09%, gastrointestinal 12.05%, cardiovascular 8.43%. In eleven patients more than one anomaly involving different systems were detected; only one of these patients was female and six of them have shown short segment disease. Down's syndrome was present in 5 patients. Female: male ratio was 1:4.2 for the whole series and 1:6 for the patients with Hirschsprung associated congenital anomalies (HACA). In the HACA group the percentage increased in favor of long-segment and extensive aganglionosis without statistical significance (p>0.05). The majority of patients were term babies and their birth weights were between 2500g < 3500g. Consanguinity was present in 36 families. No affected parents were detected but two sisters and four brothers were proved to have HD. Three pairs of twins, one of which was monozygotic, and all showing discordance were detected. There was no difference between HACA group and HD without HACA in terms of sex, birth weight, length of aganglionic segment and consanguinity. Although HD seemed to be genetically heterogeneous HACA did not have a genetically different origin from that of HD.

Hirschsprung-associated congenital anomalies

Appendiceal perforation: A potentially lethal initial mode of presentation of Hirschsprung's disease

Enterocolitis is still the main source of mortality and morbidity in Hirschsprung's disease (HD). Between 1976 and 1993, 79 (26%) of 302 Hirschsprung patients proved to have Hirschsprung-associated enterocolitis (HAEC). Mortality was 7.6 percent (6 patients). HAEC patients, those who died of HAEC and those without HAEC were analyzed for differences in 34 parameters. The length of the aganglionic segment was found not to be a risk factor for HAEC, but early diagnosis and prompt treatment were found to decrease the occurrence of preoperative HAEC. Although we defined HAEC as foul-smelling, explosive diarrhea, some other symptoms and signs, such as abdominal distention on physical examination, vomiting, dehydration, and a history of nonspecific diarrhea were encountered with significant frequency. None of the patients had Down's syndrome. Sepsis was detected in all of the patients who died of HAEC. The severity of HAEC did not increase with the number of attacks of HAEC, and mortality was greater in the first three attacks. Differences in results between some series seemed to be related to differing definitions of HAEC.

Clinical risk factors of hirschsprung-associated enterocolitis. II: Postoperative enterocolitis.

Les auteurs decrivent le cas d'un enfant porteur d'une fistule arterio-veineuse post-traumatique de la rate. Le diagnostic non invasif et le traitement conservateur des plaies de la rate devient de plus en plus frequent et fait supposer une augmentation de la frequence de cette complication actuellement assez rare.

Aneurysmatic arteriovenous fistula complicating splenic injury

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