Hirschsprung’s disease (HSCR) is characterized by paralysis in the terminal part of the large intestine.

This pathology appears from birth and is the consequence of an absence of nerve ganglia (cells forming a bulge on the path of the nerve) in the wall of the intestine.

The swallowing of food through the digestive tract until it is excreted is, in large part, possible thanks to intestinal peristalsis. This peristalsis is a set of contractions of the intestinal muscles allowing the advance of the food bolus along the digestive tract.

In this situation where there is an absence of nerve ganglia in the large intestine, peristalsis is no longer provided by the body. In this sense, a dilation of the intestine and an increase in its volume is created.

The associated symptoms are all the more important if the area of ​​the nerve ganglia is large. (1)

This disease is therefore defined by atypical intestinal symptoms: intestinal obstruction. It is a blockage of transit and gas leading to abdominal pain, colic (intestinal cramps), nausea, bloating, etc.

HSCR affects approximately 1 in 5 births per year. The form affecting the terminal part of the colon (large intestine) mainly affects boys. (000) Girls are more subject to the development of this disease in a more widespread form. (2)

This pathology predominantly affects babies and young children. (3)

Several forms of the disease have been demonstrated (2):

– the “classic” shape, or also called “short-segment shape”. This form is most common in patients with this pathology, up to 80%. This form of the disease affects the terminal part of the colon to the rectal segment;

 – the “long-segment” form, which extends to the sigmoid colon, affects nearly 15% of patients;

– the “total colic” form, affecting the colon as a whole, concerns 5% of patients.

Intestinal transit is controlled by the nervous system. Nerve ganglia are therefore located in the intestine allowing the transfer of information from the brain for the control of intestinal peristalsis and thus the progression of food along the digestive tract.

An absence of these nodes, in the case of Hirschsprung’s disease, prevents any transmission of information and thus blocks intestinal peristalsis. Food can no longer pass through the intestines and ends up blocked in the digestive tract.

Symptoms of this disease are usually noticeable very early at birth. However, in some cases, they can appear after one or two years. (3)

Symptoms affecting newborns and children are mainly:

– transit difficulties;

– an inability to expel meconium (first excrements of the newborn) during the first 48 hours;

– constipation;

– jaundice;

– vomitings ;

– diarrhea;

– abdominal pain;

– undernourishment.

Symptoms affecting older children are:

– severe constipation with complications (failure to thrive in height and weight);

– poor nutrition;

– abdominal distension;

– a fever.

The child may also develop intestinal infections, such as enterocolitis.

Additional abnormalities may also be visible: sensorineural hearing loss (Waardenburg-Shah syndrome), intellectual disability (Mowat-Wilson syndrome), central alveolar hypoventilation (Haddad syndrome), limb abnormalities (Bardet-syndrome) Biedl), medullary thyroid cancer (multiple endocrine neoplasia type 2B) or chromosomal abnormalities (Down syndrome). (2)

Hirschsprung’s disease is caused by an abnormality in the development of the enteric nervous system. It is an aganglionosis, ie an absence of nerve ganglia (also called “Cajal cells”) in the intestines. This lymph node deficit is more particularly located in the terminal part of the large intestine (colon).

In the subject affected by this pathology, this part of the intestine therefore remains in a state of tonic and permanent contraction. This situation leads to intestinal obstruction. (2)

Both genetic and environmental factors have been implicated in the development of Hirschsprung’s disease. (2)

Indeed, certain genes have been demonstrated in the development of this pathogenesis. It is a polygenetic disease which concerns in particular the genes:

– Proco-oncogene ret (RET);

– the glial cell-derived neutrotrophic factor gene (GDNF);

– the type B endothelin receptor gene (EDNRB);

– the endothelin 3 gene (EDN3);

– the gene for endothelin 1 converting enzyme 1 (ECE1);

– the gene for the cell adhesion molecule L1 (L1CAM).

As stated previously, Hirschsprung’s disease is the consequence of the absence of nerve ganglia in the large intestine up to the anus, preventing intestinal peristalsis and therefore the ascending of food to this level.

This deficit of Cajal cells (nerve ganglia) is the consequence of a deficit in the growth of these cells during fetal development. The causes of this lack of cell growth before birth are not yet known. Nevertheless, the possibility of a relationship between the general health of the mother during her pregnancy period and the absence of this type of cells in the fetus has been put forward.

Many genes have been shown in the development of the disease. The presence of these genes can be frequent within the same family. A part of heredity would then be at the origin of the development of this disease.

In addition, certain pathologies can also be an additional risk factor in terms of the development of Hirschsprung’s disease. This is particularly the case with Down’s syndrome. (3)

The differential diagnosis is made according to the characteristic symptoms of the disease presented by the subject: intestinal obstruction, anorectal stenosis, pelvic tumors, etc. (2)

The diagnosis most often associated with the disease is made through a rectal biopsy. This biopsy shows the presence or absence of nerve ganglia in the large intestine. In addition, an overexpression of acetylcholine esterase (enzyme allowing acetylcholine to be hydrolyzed into acetic acid and choline). (2)

A barium enema (X-ray examination to visualize the large intestine) can also be performed in the diagnosis of this pathology. This method makes it possible to visualize a transient area of ​​absence of nerve cells, indicating the development of Hischsprung’s disease. However, this diagnostic technique is not 100% reliable. Indeed, 10 to 15% of cases of Hirschsprung disease would not be diagnosed after this diagnostic attempt. (4)

The most important treatment for the disease is surgery. It allows the ablation of the part of the intestine deficient of nerve cells. (4)

In the case of total damage to the colon, a colon transplant may be necessary. (2)

Following this, an ostomy (surgical technique allowing to make the connection between two organs) can be carried out in order to connect the operated part of the intestine with the anus or with the upper part of the intestine. This stoma can be either permanent or temporary depending on the case. (4)

Surgery helps reduce the symptoms associated with the disease. However, the prognosis is not complete and inflammatory complications can appear and be lethal.