Most of the times the disease is diagnosed shortly after birth but in some patients it may be diagnosed later in childhood. The most common presenting features in infants include the following [9].

• Failure to pass meconium shortly after birth
• Difficulty with bowel movements
• Infrequent but explosive stools
• Bloody diarrhea
• Signs of intestinal obstruction.
• Vomiting
• Poor feeding
• Poor weight gain

The clinical features in older children are:

• Chronic constipation
• Fecal impaction
• Malnutrition
• Distended abdomen
• Slow growth

• Trisomy 21

  The aim of this study was to explore the true association of anorectal malformation and Hirschsprung's disease with or without trisomy 21. [ncbi.nlm.nih.gov]

  Children with Down syndrome (Trisomy 21) have a 3-10% risk of also being affected with Hirschsprung disease. Our program has been tracking Hirschsprung disease among live births in select counties since 2005 and are gradually expanding statewide. [health.state.mn.us]

  Despite these advances in our understanding of ENS development, the causal link between trisomy 21 and increased HSCR incidence has remained elusive. [jci.org]

  For example, HSCR may occur as: [1] [2] Part of a syndrome In association with a chromosome anomaly (such as trisomy 21 or Down syndrome) Along with other birth defects but not as a part of a known syndrome As an isolated condition Isolated HSCR can result [rarediseases.info.nih.gov]

• Anemia

  Teenagers with this disease will have experienced severe constipation for most of their lives, and may also have anemia. [chp.edu]

  […] manifesting as fever and explosive diarrhea Dilation causes risk of perforation Later Infancy Alternating obstipation and diarrhea Older Child Constipation alone most likely, see below Foul smelling, ribbon-like stool Intestinal obstruction, hypochromic anemia [pedclerk.bsd.uchicago.edu]

  Common symptoms include: needing to use laxatives to loosen stool or enemas to stimulate bowel movements abdominal swelling a delayed increase in height a delayed increase in weight anemia, which is a condition that causes low energy levels due to a shortage [healthline.com]

  Anemia (a low number of red blood cells). What causes Hirschsprung’s disease? As a baby grows in the womb, his or her nerve cells may not grow from the top of the intestine to the anus. [familydoctor.org]

• Neonatal Intestinal Obstruction

  HSCR (aganglionic megacolon) is a frequent diagnostic and clinical challenge in perinatology and pediatric surgery, and a major cause of neonatal intestinal obstruction. [ncbi.nlm.nih.gov]

  Failure to pass meconium: diagnosing neonatal intestinal obstruction. Am Fam Physician. 1999;60:2043–50. 11. Tomita R, Ikeda T, Fujisaki S, Tanjoh K, Munakata K. [aafp.org]

  Six (5.5%) patients were in the neonatal period. Sixty-four (58.2%) patients had complete intestinal obstruction whereas 42 (38.2%) and 4 (3.6%) patients had chronic intestinal obstruction and intestinal perforation respectively. [bmcresnotes.biomedcentral.com]

  "Failure to Pass Meconium: Diagnosing Neonatal Intestinal Obstruction". American Family Physician. 60 (7): 2043–50. ISSN 0002-838X. PMID 10569507. ^ Martucciello G, Ceccherini I, Lerone M, Jasonni V (2000). "Pathogenesis of Hirschsprung's disease". [en.wikipedia.org]

• Weight Loss

  Other Hirschsprung’s disease symptoms may include excessive vomiting, inability to tolerate feeding and weight loss. Older children may suffer from chronic constipation. If left untreated, Hirschsprung’s disease can be life threatening. [youtube.com]

  loss Failure to thrive Enterocolitis Sepsis Symptoms of Hirschsprung disease in toddlers and older children may include: The inability to have a bowel movement (pass stools) without enemas or suppositories. [medicinenet.com]

  Common presenting signs include anorexia and weight loss and, most commonly, an enlarged abdomen. Abdominal pain, nausea and vomiting, and especially jaundice are less frequently observed. FAP and BWS are associated with an increased risk of HB. [orpha.net]

  In addition, doctors should consider screening tests for adults with Down syndrome, especially when there is weight loss, poor nutrition or persistant changes in bowel habits. [ndss.org]

  loss 0001824 5%-29% of people have these symptoms Adducted thumb Inward turned thumb 0001181 Diarrhea Watery stool 0002014 Failure to thrive in infancy Faltering weight in infancy Weight faltering in infancy [ more ] 0001531 Intellectual disability Mental [rarediseases.info.nih.gov]

• Pediatric Disease

  […] airway disease (OAD) obstructive airways disease (OAD) obstructive disease occlusive disease (OD) occupational disease old-timers' disease (eggcorn for Alzheimer's disease) organic disease orphan disease paediatric disease,pediatric disease parrot disease [d.definitionfinder.com]

• Constipation

  It includes treatment of constipation, biofeedback, and at times enemas, or more recently, antegrade colonic enemas. Constipation Persistent constipation can be a frustrating problem after a pullthrough. [aboutkidsgi.org]

  In the long term, constipation is more common. Most children toilet train normally. [rileychildrens.org]

  Constipation is common in neonates and children. Most constipation is benign and easily treated. Hirschsprung's disease is an unusual, but well-recognized cause of chronic constipation. [ncbi.nlm.nih.gov]

  Last Updated: Mar 1, 2019 Overview Hirschsprung’s disease (HD) is a congenital disease of the large intestine that causes constipation in infants and young children. [innerbody.com]

• Diarrhea

  Symptoms include abdominal distention, explosive diarrhea, vomiting, fever, lethargy, and rectal bleeding. Non-operative management in a hospital is usually needed. [aboutkidsgi.org]

  This typically presents as abdominal distention or bloating, explosive diarrhea, and vomiting. [surgery.wisc.edu]

  During infancy the child has difficulty gaining weight, constipation, abdominal distension, episodes of diarrhea and vomiting. [childrens.memorialhermann.org]

  Since infectious diarrhea is less common in newborns who are breastfeeding or formula feeding than in older children who eat a wider variety of foods, newborn bloody diarrhea should raise suspicion for Hirschsprung disease. 5. [stlouischildrens.org]

  Instead of constipation, they have loose stool, and a tendency toward diarrhea. [nationwidechildrens.org]

• Abdominal Distension

  During infancy the child has difficulty gaining weight, constipation, abdominal distension, episodes of diarrhea and vomiting. [childrens.memorialhermann.org]

  Signs and symptoms of a bowel obstruction include vomiting, pain and abdominal distension. Your child needs to be treated quickly if these symptoms occur. [chop.edu]

  Clinical features of SV typically present with long-term constipation, severe abdominal pain, and progressive abdominal distension. The "coffee bean sign" could be observed in imaging examinations. [ncbi.nlm.nih.gov]

• Abdominal Pain

  Clinical features of SV typically present with long-term constipation, severe abdominal pain, and progressive abdominal distension. The "coffee bean sign" could be observed in imaging examinations. [ncbi.nlm.nih.gov]

  […] location of abdominal pain can provide information about what may be causing the pain. [en.wikipedia.org]

  In China, a Hirschsprung’s disease patient had 28 pounds of feces surgically removed after complaints of abdominal pain and difficulty breathing. [raredr.com]

  After seeking medical help for abdominal pain and difficulty breathing, he underwent extensive surgery and had a large part of his intestines, containing 12kg of faeces, removed. (For reference, the average human poo weighs about 100g.) [theconversation.com]

• Failure to Thrive

  In some patients, this cuff can extrinsically compress the pull-through, leading to chronic enterocolitis and failure to thrive. We describe a novel technique for managing the Soave cuff as an alternative to a complete redo pull-through. [ncbi.nlm.nih.gov]

  […] to thrive, abdominal distension and often an empty rectal ampulla on rectal examination. [pediatrics.aappublications.org]

  In toddlers and young children, signs include a swollen stomach, persistent constipation, failure to thrive, not eating well and gaining weight at a rapid rate. [raredr.com]

  In older children, the disease may cause chronic constipation, abdominal swelling and failure to thrive. [rileychildrens.org]

• Otalgia

  Involvement of facial nerve leads to otalgia, lower motor neuron homolateral facial paralysis, and vesicular eruptions in auricle. [ncbi.nlm.nih.gov]

  • HZ oticus manifests as severe otalgia and associated cutaneous vesicular eruption, usually of the external canal and pinna.• When associated with facial paralysis, the infection is called Ramsay Hunt syndrome. 2. • Ramsay Hunt syndrome accounts for [slideshare.net]

• Irritability

  This demonstrates that perianal pseudoverrucous papules and nodules can be severe but are entirely reversible upon removal of the source of skin irritation. [ncbi.nlm.nih.gov]

  Use this cream at all times to protect the skin from the irritating effects of diarrhea. [surgery.ucsf.edu]

  It is important to protect the skin around the anus at all times to prevent irritation, using a cream called "butt balm." Your child's nurse will teach you how to mix and apply the cream. [ucsfbenioffchildrens.org]

  Common causes of pain in the abdomen include gastroenteritis and irritable bowel syndrome.[2] About 15% of people have a more serious underlying condition such as appendicitis, leaking or ruptured abdominal aortic aneurysm, diverticulitis, or ectopic [en.wikipedia.org]

The general physical examination of a child with Hirschsprung’s disease will show distended abdomen. Loops of bowel may be felt in the abdomen. There will be loss of muscle tone in the rectal muscles on rectal examination.
The investigations carried out to confirm the diagnosis include:

• Plain abdominal X-ray: show distended bowel loops.
• Barium enema: classic finding is narrowed distal colon with proximal dilatation.
• Anorectal manometry: detects the absence of normal inhibitory reflexes in the rectum and anus.
• Full thickness rectal biopsy: performed under general anesthesia and shows the absence of ganglion cells in the affected part.
• Suction rectal biopsy: it is currently the gold standard test in the diagnosis of hirschsprung’s disease. It involves the immunohistochemical staining for acetylcholinesterase and calretinin.

• X-Ray Abnormal

  X-ray abnormalities are present. Treatment involves nasogastric drainage, antibiotics, intravenous fluids and decompression of the colon and rectum, usually by irrigations. Enterocolitis can be minimized by the routine use of irrigations. [eapsa.org]

• Hypoalbuminemia

  She had hypocalcemia and hypoalbuminemia with high PT and INR. Because of loss of conscious, she admitted at PICU. Laboratory findings showed hyperammonemia in this case, but other criteria were normal. [ncbi.nlm.nih.gov]

The management of patients with Hirschsprung’s disease consists of supportive care and definitive treatment. Supportive or medical treatment is to treat general manifestations of the disease before definitive surgical treatment is performed and also to manage postoperative bowel function. It consists of:

• Intravenous fluids to maintain fluid and electrolyte balance.
• Nasogastric decompression.
• Intravenous antibiotics both preoperatively and postoperatively.
• Rectal and colonic lavage with a large caliber rectal tube [10].

Post operatively, antibiotics are given to prevent enterocolitis. If enterocolitis develops, then resuscitation along with antibiotics and mast cell stabilizer drugs are helpful. Injection of botulinum toxin within the contracted internal sphincter may help in inducing normal bowel movements in postoperative patients.

The definitive treatment for Hirschsprung’s disease is surgery. The affected part of the colon is resected and an end to end anastomosis is made between the normal bowel loops. There are a number of procedures to repair the aganglionic colon.

• Swenson procedure: The affected segment is resected up to the sigmoid colon and an anastomosis is created between the normal colon and low rectum.
• Duhamel procedure: The whole of the aganglionic bowel is resected and anastomosis is performed by bringing the proximal colon to the remaining rectum through the retro rectal space.
• Soave (endorectal) procedure: In this technique, rectal mucosa and submucosa are resected and the normal bowel is pulled through the affected muscular cut off of the rectum.
• Anorectal myomectomy: It is performed in case of extremely short segment disease.
• Laproscopic approach: The unaffected bowel is joined with the rectal cut off after delivering the rectum and aganglionic bowel through the anus.
• Transanal pull through procedures: This procedure in carried out through the anus without any intra-abdominal dissection.

Mortality rates in untreated Hirschsprung’s disease are approximately 80%. The prognosis of Hirschsprung’s disease is generally good after surgery. Some of the patients may develop complications like constipation, fecal incontinence or enterocolitis which may lead to mortality rates as high as 30%. Patients who suffer from an associated syndrome or have long-segment disease have a much poorer prognosis [7] [8].

Hirschsprung’s disease is known to be caused by mutations in the RET-proto oncogene on chromosome 10q11.2. Family history of the disease is positive in about 30% of cases. In addition, there are several syndromes associated with the occurrence of Hirschsprung’s disease - the most common of which is Down syndrome. Other less common syndromes are Waardenburg-Shah syndrome, Goldburg-Shpritzen megacolon syndrome and congenital central hypoventilation syndrome.

Hirschsprung’s disease is a congenital disorder that may be familial or acquired. The condition is more common among white males. The male to female ratio is 4.32:1. The disease affects 1 in 5400 to 7200 newborns in the United States annually. It is more common in Asian-Americans. According to international data, the annual incidence rate of the disease is estimated to be 1 case in around 1500 to 7000 newborns [1] [2]. The condition is found to be present in about 9% of patients with Down syndrome [3].

The enteric nervous system supplying the intestines consists of submucosal (Meissner’s) plexus, myenteric (Auerbach’s) plexus and the smaller mucosal plexus. The absorption, secretion, motility and blood flow of the gut is under the control of enteric nervous system. The normal intestinal motility is under the control of the enteric ganglia. The intrinsic neurons cause relaxation of the intestinal smooth muscles while extrinsic neurons containing cholinergic and adrenergic fibers cause contraction and inhibition respectively.

In Hirschsprung’s disease, the myenteric and submucosal plexuses are absent and the control of intestinal smooth muscles is predominantly extrinsic. This leads to increased smooth muscle tone in the intestine which in turn causes uncoordinated peristalsis and functional obstruction.

The ganglions in the enteric nervous system are derived from the neural crest cells which migrate to the intestine during the twelfth week of development. One of the most accepted causes of aganglionosis in Hirschsprung’s disease is the failure of migration of the neural crest cells. In other cases, there might be apoptosis, failure of proliferation or improper differentiation of the neuroblasts despite their normal migration to the colon. Alternatively, there may be some dysfunction or absence of the factors like laminin, fibronectin, neural cell adhesion molecule and neurotropic factors, which are responsible for normal enteric ganglion development.

Genetic studies suggest that the most common gene mutation associated with Hirschsprung’s disease is the RET proto-oncogene [4] [5]. Overexpression of DVL1 and DVL3 gene has also been found to be present in Hirschsprung’s disease. In addition to mutation in the RET proto-oncogene, about 50% of the patients with this disorder have got mutations in several other genes; GDNF, GFR alpha1, NRTN, EDNRB, ET3, ZFHX1B, PHOX2b, SOX10 and SHH [6].

There is no preventive measure against Hirschsprung disease as it is a developmental disorder.

Hirschsprung’s disease, also known as congenital aganglionic megacolon, is a developmental disorder characterized by inability of the distal colon to relax due to the failure of migration of neural crest cells into the colon to form the enteric nerve plexuses. There is absence of ganglion cells in the affected segment due to which the affected part of the colon remains contracted and the proximal segment becomes dilated. This results in functional intestinal obstruction.

About 90% of the patients are diagnosed in the new born period. Hirschsprung’s disease is suspected in any neonate who does not pass meconium within 24 to 48 hours of birth. The condition is diagnosed with barium enema and rectal biopsy and is treated by surgically removing the affected portion of intestine.

Hirschsprung’s disease is a congenital anomaly of the colon in which the normal peristaltic movements in a portion of gut are absent leading to functional obstruction of the intestine. The infants with this disease are unable to pass meconium after birth. Some patients may present in childhood with symptoms of chronic constipation, distended abdomen and malnutrition etc. if diagnosed timely, it is not a life threatening condition and is treated successfully by surgery.

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