Purpose: The diagnosis of Hirschsprung's disease (HSCR) should take place early in the neonatal period, because without an effective diagnosis and appropriate treatment, a considerable proportion of infants will go on to develop serious complications such as acute enterocolitis or toxic megacolon. Because no more than 10 % of HSCR cases have a late presentation with classical chronic constipation and megacolon, the clinician has to make a difficult, early diagnosis, which is the crux of the clinical problem. The aim of this review paper is to present all tools currently available to make a clear HSCR diagnosis and to discuss the problems facing the clinician and the pediatric surgeon in the correct identification of HSCR and of other intestinal dysganglionoses.
Methods: Based on the current state of knowledge and 24 years' personal experience in clinical practice and basic research in this field, I describe an algorithmic approach that enables clinicians and surgeons to rationalize and maximize the clarity of diagnosis through a complementary set of procedures and enzyme-histochemical reactions.
Results: Two innovative techniques, added to the protocol in the last four years, are described: the lyophilized HSCR diagnostic kit, and the one-trocar transumbilical laparoscopic intestinal full-thickness biopsy technique (OTTLB).
Conclusion: The rational, algorithmic diagnostic pathway proposed in this review paper aims to optimize every diagnosis by the stepwise application of a complementary set of procedures and enzyme-histochemical reactions as they become appropriate. In the interests of simplifying genetic molecular diagnosis, I suggest the following guidelines: 1) only in cases of total colonic aganglionosis (TCA) is it advisable to carry out full RET mutation screening (the mutation rate is up to 70 %); and 2) all HSCR patients should be tested only for standard MEN2A and MTC mutations. If these are present, the patients should be followed up carefully with proper surveillance and biochemical testing of other susceptible family members as they are at risk of developing neuroendocrine tumors.