Hirschsprung’s disease is one of the most common causes of intestinal obstruction in newborns (Richardson and Brown, 1989; Kleinhaus and Boley, 1993). It usually presents as a low intestinal obstruction without sepsis. In the least severe cases, delayed passage of meconium may be the only abnormality (Potter, 1989; de Lorijn et al., 2007). In more severe cases, the neonate presents with abdominal distention and bilious or feculent vomiting, in addition to failure to pass meconium. In its most serious form, infants present with overwhelming sepsis due to enterocolitis; a smaller number will present with peritonitis from perforation of a normal intestine proximal to the aganglionic segment. The age at diagnosis varies considerably, but half of the cases are diagnosed during the newborn period, 75% within 3 months, and 80% within the first year of life (Ikeda and Goto, 1984; Rowe et al., 1995).

Hirschsprung’s disease is characterized by severe constipation due to functional colonic obstruction with megacolon. The condition bears the name of Harald Hirschsprung, a Danish pediatrician, who in 1888 described the autopsy findings of two unrelated infants who died with congenital megacolon. While at least 12 cases had been reported prior to 1888, Hirschsprung’s complete description of the clinical and postmortem findings resulted in his name becoming attached to the condition. Hirschsprung focused his attention on the dilated hypertrophied megacolon, but the underlying abnormality was not determined until 1920, when Dalla Valle reported the absence of ganglion cells in the Auerbach plexus in the nondilated transition zone. The absence of ganglion cells in the distal nondilated segment involves the Auerbach plexus (myenteric), the Henle (deep submucosal), and the Meissner plexuses (submucosal) (Skandalakis and Gray, 1994). The dilated proximal segment of colon ends in a funnel-shaped transition zone, which tapers into the narrowed, patent, but functionally obstructed distal segment. This distal segment is usually normal in caliber and appears narrow only compared to the proximal megacolon (Figure 75-1). The peristalsis of the proximal normal colon tends to dilate the proximal aganglionic segment, and so the transition zone is part of the aganglionic segment.

The abnormal innervation in Hirschsprung’s disease always extends proximally from the anus, including the internal sphincter (Puri, 1996). Histologically, in the absence of ganglion cells there are hypertrophied parasympathetic nerve bundles in the submucosa and between the muscular layers of the bowel. The parasympathetic (cholinergic) and sympathetic (adrenergic) nervous systems innervate the normal colon. The parasympathetic system is excitatory to the colon and inhibits the internal sphincter. Conversely, the sympathetic nervous system inhibits the colon and excites the internal sphincter. In addition, the colon normally receives intrinsic innervation via purinergic, serotonergic, and peptidergic systems (Nirasawa et al., 1986). Ganglion cells receive impulses from both cholinergic fibers and intrinsic nonadrenergic inhibitory fibers. In Hirschsprung’s disease the extrinsic innervation is present with increased cholinergic and adrenergic fibers, but the intrinsic innervation is absent (no purinergic, serotonergic, or peptidergic fibers). In Hirschsprung’s disease the wave of relaxation that normally precedes each propulsive peristaltic wave does not occur. In addition, the normal reflex relaxation of the internal sphincter following rectal distention does not occur.

The ganglion cells coordinate intrinsic and extrinsic impulses, and in their absence a functional obstruction results. Absence of the intrinsic nervous system is the underlying neurophysiologic abnormality in Hirschsprung’s disease.

During embryonic life, neurenteric ganglion cells migrate from the neural crest to the upper end of the alimentary tract and then follow vagal fibers caudad (Dereymaeker, 1943; Van Campenhout, 1946; Yntema and Hammond, 1947). Ganglion cells can be seen in the proximal small bowel by 7 weeks of gestation, and the rectum by 12 weeks of gestation (Okamoto and Ueda, 1967). Why ganglionic migration stops is unknown. It is not due to failure of vagal fibers to innervate the bowel. Postganglionic fibers from normal ganglia proximal to affected segments and preganglionic parasympathetic vagal fibers that fail to connect with ganglion cells continue to elongate (Bodian et al., 1951; Kamijo et al., 1953; Nixon, 1964).

Megacolon is not always due to Hirschsprung’s disease. It is now recognized that several anomalies of the myenteric plexus may produce a similar clinical presentation to Hirschsprung’s disease, including neuronal loss, abnormal nerves, and intestinal neuronal dysplasia (Puri and Wester, 1998; Scharli and Sossai, 1998). Several reports have appeared describing a clinical presentation that is indistinguishable from Hirschsprung’s disease in which ganglia were present but there was either hypoganglionosis, immature ganglia, or other neuronal abnormalities (Burghaighis and Emery, 1971; Tanner et al., 1976; Munakata et al., 1978).

The internal sphincter is involved in all cases, but the proximal extent of aganglionosis varies. The rectosigmoid is involved in about half of the patients, and an additional 15% have involvement of the splenic flexure or hepatic flexure or have total colonic Hirschsprung’s disease. In 8% of the cases, aganglionosis may extend to the small bowel (Bickler, 1992). Rare cases of discontinuous aganglionic segments with normal functioning intervening bowel have been reported (Sprinz et al., 1961; Anderson and Chandra, 1986; Seldenrijk et al., 1986; Skandalakis and Gray, 1994).

The incidence figures quoted for Hirschsprung’s disease have increased from the earliest report by Hautau in 1960 of 1 in 41,200, as a result of greater appreciation of the spectrum of disease. The incidence of Hirschsprung’s disease is now thought to be 1 in 5000 livebirths, second only to pyloric stenosis as a cause of intestinal obstruction in newborns (Passarge, 1967; Parisi and Kapur, 2000). Hirschsprung’s disease may be slightly more common in Japan, with an incidence of 1 in 4697 to 5343 (Suita et al., 2005). The highest incidence reported is in the Federated States of Micronesia with a rate of 1 in 1370 livebirths or 3 to 5 times the rate observed in the West (Meza-Valencia et al., 2005). There is no racial predilection. Males are more commonly affected than females, with a ratio of approximately 4:1 (Kleinhaus et al., 1979; Sherman et al., 1989). The number of females with Hirschsprung’s disease has varied from 5% to 22% of cases (Bodian et al., 1949; Keefer and Mokrohisky, 1954; Richardson and Brown, 1962). These incidence figures are based on livebirths. It is unknown if Hirschsprung’s disease is associated with lethal malformations, as aganglionosis often cannot be recognized grossly at autopsy in a fetus or newborn because dilation and hypertrophy have not yet developed.

Numerous anomalies are associated with Hirschsprung’s disease. Two percent of patients with aganglionosis have Down syndrome (Passarge, 1967). Coran et al. (1978) noted that 26% of their patients had associated anomalies, including congenital heart disease, Smith–Lemli–Opitz syndrome, and multiple renal anomalies. Other large series have confirmed this finding, with 16% to 32% of patients having one or more associated anomalies. Except for Down syndrome and anomalies of the genitourinary tract, there is no consistent pattern of associated malformations (Passarge, 1967; Lister, 1977; Seldenrijk et al., 1986) (Table 75-1).

The sonographic findings of Hirschsprung’s disease are nonspecific and rare. Hirschsprung’s disease has been suspected or diagnosed prenatally in only three cases (Wrobleski and Wesselhoeft, 1979; Vernesh et al., 1986; Eliyahu et al., 1994). The combination of polyhydramnios, diffuse and progressive fetal-bowel distention, and increased abdominal circum-ference raises the possibility of fetal Hirschsprung’s disease (Figure 75-2). Some have argued that because most cases occur in term infants, and cases are rarely symptomatic within the first 24 hours, Hirschsprung’s disease does not occur prenatally. The three reported cases challenge this view, as Hirschsprung’s disease can present in at least the third trimester. However, these cases resulted from total colonic aganglionosis, and presented with small-bowel dilation and polyhydramnios. Total colonic Hirschsprung’s disease accounts for only 3% to 12% of cases (Wildhaber et al., 2005). The majority of cases, however, involve the rectosigmoid region and are unlikely to result in polyhydramnios. Given the absorption of amniotic fluid that occurs in the ileum and colon proximal to this region, functional obstruction at this level would also not be expected to cause bowel dilation.

Another sonographic finding that has been suggested as a possible sign of fetal Hirschsprung’s disease is echogenic bowel (Wrobleski and Wesselhoeft, 1979). However, no case of Hirschsprung’s disease has been diagnosed based solely on the sonographic finding of echogenic bowel. Total colonic Hirschsprung’s disease can mimic meconium ileus and result in enterolithiasis present in the terminal ileum (Cowles et al., 2006).

The sonographic findings of bowel dilation associated with polyhydramnios suggests a differential diagnosis that includes jejunal, ileal, or colonic atresia or stenosis, persistent cloaca, meconium ileus, and imperforate anus (Table 75-2). The prenatal sonographic features of bowel atresias, especially ileal or colonic, can be indistinguishable from Hirschsprung’s disease. Atresias are a more common cause of fetal small-bowel obstruction, however. The sonographic features of persistent cloaca should distinguish it from Hirschsprung’s disease. In neonates, perforation of the colon proximal to the aganglionic segment can occur. This has not been reported prenatally, but would be expected to present with sonographic features of meconium peritonitis such as intra-abdominal calcifications, ascites, or pseudocyst formation. Total colonic Hirschsprung’s disease can result in enterolithiasis due to complete functional obstruction and precipitation of urate within the lumen. In the absence of reflux of urine into the colon in imperforate anus, resulting in intra-abdominal calcification, there are no specific sonographic features for imperforate anus. It is unusual to see bowel dilation in utero with imperforate anus. This must be considered in the differential diagnosis of a fetus with dilated loops of intestine.