Infants present with marked abdominal distension and bilious emesis. Distension may be severe enough to cause respiratory compromise. Obstruction may occur on the first day of life, but children may also initially have apparently normal bowel movements or “mild constipation” and then present acutely with abdominal distension and vomiting at an older age. Because HSCR requires a high index of suspicion for diagnosis, some infants are hospitalized repeatedly for episodes of presumed “gastroenteritis ” that were actually a manifestation of HSCR-associated intestinal obstruction. The clinical distinction is that gastroenteritis may cause severe vomiting, but does not typically cause as much abdominal distension as HSCR. Vomiting associated with infectious enteritis is also usually followed by diarrhea, whereas intestinal obstruction should be accompanied by reduced stool passage. A distended abdomen occurs in 57–93 % of infants with Hirschsprung disease and bilious emesis occurs in 19–37 % [12, 14, 22–24]. Abdominal distension and bilious emesis are also a very common presentation in premature infants with HSCR (96 % and 92 %, respectively). Note that since the ENS forms during the first trimester of pregnancy, incidence of HSCR is similar in term and preterm infants [25].

HSCR presents with bowel perforation about 5 % of the time [26, 27] and HSCR causes about 10 % of all neonatal bowel perforations [28]. Symptoms may not be specific and include poor feeding, emesis, abdominal distension, constipation, diarrhea, and lethargy. In two series with 55 cases reported [26, 27], only one child with perforation was more than two months old. Sixty two percent of the perforations were in the cecum or ascending colon and 15 % were in the appendix. Many of the children with bowel perforation had long-segment disease (34 % total colonic aganglionosis, with an additional 23 % having aganglionosis proximal to the splenic flexure). Since long-segment HSCR is less common than short-segment disease (Table 25.2), proximal colon perforation in a young infant should dramatically raise concern for long-segment HSCR. In 55 % of reported cases, the perforation was proximal to the transition zone in ganglion cell containing bowel. In 13 % the perforation was at the transition zone. In 30 %, however, the perforation occurred in aganglionic bowel distal to the transition zone.

Delayed passage of meconium should suggest the diagnosis of HSCR, but defining HSCR risk in infants with delayed passage of meconium is challenging because the timing of meconium passage reported for healthy infants is variable. In a study of 979 infants older than 34 weeks gestational age in the United States, 97 % passed meconium by 24 h of life, and 99.8 % passed meconium by 36 h of life [29]. Breastfeeding or bottle-feeding did not influence the timing of the first bowel movement, and multivariate analysis demonstrated that only prematurity was a significant predictor of delayed passage of meconium. A similar study in Turkey [30] also demonstrated that 724/743 (97 %) passed meconium by 24 h after birth and 740/743 (99.6 %) passed meconium by the time that they were 48 h old. However, a smaller study in the Netherlands, reported only 56/71 (79 %) of term infants passed meconium by 24 h after birth [31] and in a study of 267 healthy infants in Nigeria, only 92 % passed their first bowel movement by 48 h after birth [32]. In the Nigerian study, 5 % of the infants were preterm, but even if the preterm infants are excluded, the data suggest that at most 97 % of the healthy full-term infants studied passed their first bowel movement by the time they were 48 h old. Excluding premature infants from the analysis is important since prematurity predisposes to delayed passage of meconium. A study of 611 infants reported that only 57 % of infants less than 29 weeks EGA, 66 % of infants between 29 and 32 weeks EGA, and 80 % of infants between 32 and 37 weeks EGA [33] passed meconium by the end of their “second calendar day” and 1 % of premature infants did not pass meconium until after day of life 9.

In children with Hirschsprung disease, delayed passage of meconium is much more common than in healthy infants. Nonetheless, up to 50 % of children with HSCR pass meconium by 48 h after birth [22, 34, 35], so passage of meconium within 48 h of birth does not exclude a diagnosis of HSCR.

HSCR causes constipation , but constipation unrelated to HSCR is very common (e.g., 25 % of healthy children) and HSCR is rare, so constipation alone usually does not indicate HSCR. “Severe” constipation and constipation beginning within the first few months of life does increase concern for HSCR and the likelihood of disease. For example, in one study, rectal biopsy was performed on all children over a year of age who were referred to a specialty center for consultation and who had constipation refractory to more than 6 months of medical management. Nineteen out of 395 biopsies demonstrated HSCR (5 %), a 250-fold increased risk compared to the population prevalence of HSCR (1/5000) [36]. Constipation in isolation also appears to be an uncommon presentation of HSCR in infants. In particular, the wide range of normal bowel movement frequency in healthy infants makes it difficult to use constipation as the only indication to evaluate for HSCR. In a study of 911 healthy children in Turkey [30] between 2 and 12 months of age, mean stool frequency was once a day, but at 2 months of age, stool frequency varied from once a week to eight times per day.

In children with HSCR, rectal exam or other forms of rectal stimulation may cause a sudden “explosive” release of intraluminal contents and relieve abdominal distension. This is uncommon in other conditions and should raise concern about HSCR. Rectal exam is, however, not otherwise useful in identifying children with HSCR. In particular, “anal tone” is not a reliable indicator of disease.

Defining when children have enterocolitis presents its’ own challenges (see below for symptoms), but enterocolitis is a dangerous and common presentation for HSCR. When enterocolitis occurs, children with HSCR have diarrhea instead of constipation.

Given the diverse presenting symptoms of HSCR, it remains difficult to decide who to evaluate. The more “classic” features of HSCR that are present, the more likely the child has HSCR. Given the high morbidity and mortality in untreated HSCR, evaluation for HSCR should be performed in many children who do not end up having this disease to avoid missing this potentially life-threatening medical problem.

This is a simple procedure taking only a few minutes using an instrument designed to take small pieces of the rectal mucosa (e.g., Noblett or rbi2 instrument) to reduce the risk of bowel perforation or hemorrhage [43]. Because there are no sensory nerve endings that respond to cutting in the area of the rectum where the biopsies are obtained, sedation and pain medicines are not required, but sedation is sometimes used in older children. Biopsies should be obtained at 2–3 cm from the dentate line (i.e., the transition between rectal and squamous mucosa) because there is a physiological submucosal aganglionosis in the terminal rectum. From a practical standpoint, however, some authors advocate obtaining biopsies at multiple levels (e.g., 1–3 cm from the dentate line) because precise positioning of the biopsy can be difficult. Biopsy tissues obtained is sectioned, stained, and examined by a pathologist to identify ganglion cells. There is some controversy about the optimal staining method, but hematoxylin and eosin and acetylcholinesterase are commonly used techniques [42, 43]. Calretinin staining might improve diagnostic accuracy [44, 45], but data are still limited. A meta-analysis analyzing data from 993 patients indicated that the mean sensitivity of rectal suction biopsy for HSCR is 93 %, and the mean specificity is 98 % [46]. A more recent manuscript documents 935 cases of HSCR diagnosed by rectal mucosal biopsy (a total of 19,365 biopsies in 6615 children) with no false-positive or false-negative diagnoses (i.e., 100 % sensitivity and specificity) [47]. Serious bleeding and bowel perforation are uncommon with rectal suction biopsy, but can occur. One series of 1340 biopsies [48] reported three bowel perforations (0.2 %), one death (0.07 %), and three rectal hemorrhage (0.2 %) requiring blood transfusion. More recent studies also document low but nonzero rates of serious bleeding or bowel perforation (0 complication in 297 children [49], 0 complication in 88 infants [50], and two episodes of bleeding requiring transfusion (0.7 %) plus one episode of rectal perforation and sepsis (0.035 %) in 272 children) [51]. The most common problem with rectal suction biopsies, however, is that they are so small that they are “inadequate” 6–26 % of the time, requiring repeat biopsy to make a diagnosis [49, 51, 52]. The more recently introduced rbi2 biopsy instrument appears to give a lower frequency of “inadequate specimens” [50] and may give larger biopsies. It is not yet clear if there are also more complications (bleeding or bowel perforation) using the new instrument since large cohort studies have not been published.

This method tests for the rectoanal inhibition reflex using a small balloon attached to a tube inserted into the rectum [46]. This reflex is absent in children with HSCR. Sensitivity and specificity of anorectal manometry are 91 % and 94 %, respectively, but this test is not required to diagnose HSCR [46]. The equipment needed to do th is test is also expensive, and significant experience is needed to evaluate results in infants less than a year of age, so the test is not widely available. Recently developed high-resolution anorectal manometry does not appear to provide increased sensitivity or specificity for HSCR diagnosis (89 % and 83 %, respectively, compared to rectal suction biopsy) [53].

This is an X-ray test where images are obtained as contrast is infused into the colon via the anal canal to look for evidence of the distal bowel contraction that occurs in areas of aganglionosis. The change in bowel caliper between contracted distal aganglionic bowel and more dilated ganglion cell containing bowel is called the “transition zone” and suggests HSCR. Although contrast enema may have value in planning the surgical approach to HSCR, the radiographic and anatomic transition from aganglionic to ganglion cell containing bowel may not be in the same location. Note too that in total colonic HSCR, there is no colon transition zone. Furthermore, the sensitivity (70 %) and specificity (50–80 %) are considerably lower using contrast enema for HSCR diagnosis than other methods [24, 46]. The role of contrast enema in HSCR diagnosis therefore remains a matter of debate.

Deeper biopsies can be performed by a surgeon under general anesthesia if the diagnosis remains uncertain after rectal suction biopsy. This method should unambiguously identify enteric neurons if they are present.