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1 in every 5,000 children is born with Hirschsprung's disease (HD). Total colonic aganglionosis is an extended form of HD and is present in 2-13% of all patients with the disease.Paediatricians from a general hospital referred a 12-day-old male neonate on account of suspected abdominal obstruction and sepsis. An ileostomy was created and biopsies were taken during a laparotomy. Examination of the biopsies indicated total colonic aganglionosis. This diagnosis was unexpected because the symptoms of obstruction had occurred late and the radiological findings were not characteristic of Hirschsprung's disease.Persistent passage problems after delayed meconium passage are important alarm symptoms of Hirschsprung's disease. This diagnosis must be considered and ruled out in these patients in order to avoid an acute presentation of this disease.

The receptor tyrosine kinase RET is expressed in cell lineages derived from the neural crest and has a key role in regulating cell proliferation, migration, differentiation and survival during embryogenesis. Germline and somatic mutations in RET that produce constitutively activated receptors cause the cancer syndrome multiple endocrine neoplasia type 2 and several endocrine and neural-crest-derived tumors, whereas mutations resulting in nonfunctional RET or lower expression of RET are found in individuals affected with Hirschsprung disease. This review focuses on the genetics and molecular mechanisms underlying the different inherited human neural-crest-related disorders in which RET dysfunction has a crucial role and discusses RET as a potential therapeutic target.

In a male neonate 'blowing bubbles', three diagnoses were seen on a combined thoracic and abdominal X-ray: esophageal atresia with tracheoesophageal fistula, Hirschsprung's disease, and suspected Down's syndrome (because of the presence of II pairs of ribs).

The RET gene encodes a receptor tyrosine kinase involved in normal and neoplastic development of neural crest cell lineages. Activating RET mutations are present in patients with multiple endocrine neoplasia types 2A and 2B (MEN2A, 2B) and in familial medullary thyroid carcinoma (FMTC) patients, whereas inactivating RET mutations are found in patients with Hirschsprung (HSCR) disease. In particular for MEN2A and FMTC, the clinical management largely depends on the specific mutation found.

To evaluate the results of proctocolectomy with creation of an ileac pouch anal anastomosis (IPAA).Retrospective.Of the 100 patients in whom an IPAA procedure was performed in the period 1994/'99 in the Department of Surgery of the Academic Medical Centre, Amsterdam, the Netherlands, data were collected on the complications: in the patients with a follow-up of over 12 months the functional results were studied.The group comprised 48 males and 52 females with a mean age of 36.3 years (range: 15-62). Preoperative diagnoses were ulcerative colitis (n = 84), familial polyposis coli (12), slow transit obstipation (2), Hirschsprung's disease (1) and Muir-Torre syndrome (1). Median operating time was 2.3 h, peroperative blood and fluid loss 500 ml and median hospital stay 15 days. There was no mortality. Ten patients had a loop ileostomy formation, in 6 because of postoperative complications. A total of 30 patients developed postoperative complications, peroperatively or during follow-up 10 of those patients needed a relaparotomy. After 12 months 1 pouch had to be excised and 2 patients still had a loop ileostomy due to postoperative complications. In 56 patients with at least 12 months follow-up, median 24-hour stool frequency was 6. Eighty-nine per cent of these patients were satisfied or highly satisfied with the overall outcome.A proctocolectomy with IPAA formation is a safe procedure with good functional results.

Hirschsprung's disease (HSCR) is a congenital disorder characterized by intestinal obstruction due to the absence of intramural ganglia along variable lengths of the colon. Occurrence among family members and recurrence risks among siblings are indications for involvement of genetic predispositions. Mutations have been discovered in five different susceptibility genes. One of the most important findings is the detection of specific mutations in the so-called RET gene, which can also be responsible for the multiple endocrine neoplasia type 2A (MEN2A) syndrome. HSCR patients with such specific mutations run an increased risk of developing MEN type 2A related tumours.