Hirschsprung's disease (HD or HSCR) is a
birth defect
A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can ...
in which
nerves
A nerve is an enclosed, cable-like bundle of nerve fibers (called axons) in the peripheral nervous system.
A nerve transmits electrical impulses. It is the basic unit of the peripheral nervous system. A nerve provides a common pathway for the e ...
are missing from parts of the
intestine
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans ...
.
The most prominent symptom is constipation
Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...
.[ Other symptoms may include ]vomiting
Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose.
Vomiting can be the result of ailments like Food-poisoning, foo ...
, abdominal pain
Abdominal pain, also known as a stomach ache, is a symptom
Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than ...
, diarrhea
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
and slow growth.[ Symptoms usually become apparent in the first two months of life.][ Complications may include ]enterocolitis
Enterocolitis is an inflammation of the digestive tract, involving enteritis of the small intestine and colitis of the colon. It may be caused by various infections, with bacteria, viruses, fungi, parasites, or other causes. Common clinical manif ...
, megacolon
Megacolon is an abnormal dilation of the colon (also called the large intestine). This leads to hypertrophy of the colon. The dilation is often accompanied by a paralysis of the peristaltic movements of the bowel. In more extreme cases, the feces ...
, bowel obstruction
Bowel obstruction, also known as intestinal obstruction, is a mechanical or Ileus, functional obstruction of the Gastrointestinal tract#Lower gastrointestinal tract, intestines which prevents the normal movement of the products of digestion. Eith ...
and intestinal perforation
Gastrointestinal perforation, also known as ruptured bowel, is a hole in the wall of part of the gastrointestinal tract. The gastrointestinal tract includes the esophagus, stomach, small intestine, and large intestine. Symptoms include severe ab ...
.
The disorder may occur by itself or in association with other genetic disorders
A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...
such as Down syndrome
Down syndrome or Down's syndrome, also known as trisomy 21, is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21. It is usually associated with physical growth delays, mild to moderate intellectual dis ...
or Waardenburg syndrome
Waardenburg syndrome is a group of rare genetic conditions characterised by at least some degree of congenital hearing loss and pigmentation deficiencies, which can include bright blue eyes (or Heterochromia iridum, one blue eye and one brown ey ...
.[ About half of isolated cases are linked to a specific genetic ]mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
, and about 20% occur within families.[ Some of these occur in an ]autosomal dominant
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
manner.[ The cause of the remaining cases is unclear.][ If otherwise normal parents have one child with the condition, the next child has a 4% risk of being affected.][ The condition is divided into two main types, short-segment and long-segment, depending on how much of the bowel is affected.][ Rarely, the ]small bowel
The small intestine or small bowel is an organ in the gastrointestinal tract where most of the absorption of nutrients from food takes place. It lies between the stomach and large intestine, and receives bile and pancreatic juice through the pa ...
may be affected, as well.[ Diagnosis is based on symptoms and confirmed by ]biopsy
A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...
.[
Treatment is generally by surgery to remove the affected section of bowel.][ The surgical procedure most often carried out is known as a "pull through".][ Occasionally, an ]intestinal transplantation
Intestine transplantation (intestinal transplantation, or small bowel transplantation) is the surgical replacement of the small intestine for chronic and acute cases of intestinal failure. While intestinal failure can oftentimes be treated ...
may be recommended.[ Hirschsprung's disease occurs in about one in 5,000 of newborns.] Males are more often affected than females.[ The condition is believed to have first been described in 1691 by Dutch anatomist ]Frederik Ruysch
Frederik Ruysch (; March 28, 1638 – February 22, 1731) was a Dutch botanist and anatomist. He is known for developing techniques for preserving anatomical specimens, which he used to create dioramas or scenes incorporating human parts. His ana ...
and is named after Danish physician Harald Hirschsprung following his description in 1888.
Signs and symptoms
Typically, Hirschsprung disease is diagnosed shortly after birth, although it may develop well into adulthood, because of the presence of megacolon
Megacolon is an abnormal dilation of the colon (also called the large intestine). This leads to hypertrophy of the colon. The dilation is often accompanied by a paralysis of the peristaltic movements of the bowel. In more extreme cases, the feces ...
, or because the baby fails to pass the first stool (meconium
Meconium is the earliest stool of a mammalian infant resulting from defecation. Unlike later feces, meconium is composed of materials ingested during the time the infant spends in the uterus: intestinal epithelial cells, lanugo, mucus, amniotic ...
) within 48 hours of delivery. Normally, 90% of babies pass their first meconium within 24 hours, and 99% within 48 hours.
Other symptoms include symptoms of bowel perforation such as vomiting, constipation, poor feeding, lethargy, and diarrhea. Symptoms of bowel obstruction would include vomiting of bile and abdominal distension. Those who pass stools after 36 to 48 hours after birth should raise suspicion of Hirschsprung disease. Such suspicion can also be risen if there is only passage of stools after suppository, rectal exam, or enema. Children who do not respond to constipation treatment for six months should also raise suspicion of such disease. Enterocolitis
Enterocolitis is an inflammation of the digestive tract, involving enteritis of the small intestine and colitis of the colon. It may be caused by various infections, with bacteria, viruses, fungi, parasites, or other causes. Common clinical manif ...
, an acute complication of Hirschsprung disease, is characterised by sudden onset of fever, abdominal distension, vomiting, passage of bloody stools or release of explosive gas or stools after rectal examination.
Some cases are diagnosed later, into childhood, but usually before age 10. The child may experience fecal retention, constipation, or abdominal distention.
Associated syndromes
Hirschsprung's disease can also present as part of multi system disorders, such as:
* Bardet–Biedl syndrome
Bardet–Biedl syndrome (BBS) is a ciliopathic human genetic disorder that produces many effects and affects many body systems. It is characterized by rod/cone dystrophy, polydactyly, central obesity, hypogonadism, and kidney dysfunction in so ...
* Cartilage–hair hypoplasia
Cartilage–hair hypoplasia (CHH) is a rare genetic disorder. Symptoms may include short-limbed dwarfism due to skeletal dysplasia, variable level of immunodeficiency, and predisposition to cancer. It was first reported by Victor McKusick in 196 ...
* Congenital central hypoventilation syndrome
Central hypoventilation syndrome (CHS) is a sleep-related breathing disorder that causes ineffective breathing, apnea, or respiratory arrest during sleep (and during wakefulness in severe cases). CHS can either be congenital (CCHS) or acquired ( ...
* MEN2
Multiple endocrine neoplasia type 2 (also known as "Pheochromocytoma and amyloid producing medullary thyroid carcinoma", "PTC syndrome," and "Sipple syndrome") is a group of medical disorders associated with tumors of the endocrine system. The tu ...
* Mowat–Wilson syndrome
Mowat–Wilson syndrome is a rare genetic disorder that was clinically delineated by David R. Mowat and Meredith J. Wilson in 1998. The condition affects both males and females, has been described in various countries and ethnic groups around the w ...
* Smith–Lemli–Opitz syndrome
Smith–Lemli–Opitz syndrome is an inborn error of cholesterol synthesis. It is an autosomal recessive, multiple malformation syndrome caused by a mutation in the enzyme 7-Dehydrocholesterol reductase encoded by the DHCR7 gene. It causes a bro ...
* Trisomy 21
A trisomy is a type of polysomy in which there are three instances of a particular chromosome, instead of the normal two. A trisomy is a type of aneuploidy (an abnormal number of chromosomes).
Description and causes
Most organisms that reprodu ...
(Down syndrome
Down syndrome or Down's syndrome, also known as trisomy 21, is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21. It is usually associated with physical growth delays, mild to moderate intellectual dis ...
)
* Some forms of Waardenburg syndrome
Waardenburg syndrome is a group of rare genetic conditions characterised by at least some degree of congenital hearing loss and pigmentation deficiencies, which can include bright blue eyes (or Heterochromia iridum, one blue eye and one brown ey ...
Cause
The disorder may occur by itself or in association with other genetic disorders
A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...
such as Down syndrome
Down syndrome or Down's syndrome, also known as trisomy 21, is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21. It is usually associated with physical growth delays, mild to moderate intellectual dis ...
.[ About half of isolated cases are linked to a specific genetic ]mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
and about 20% occur within families.[ Some of these occur in an ]autosomal dominant
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
manner.[ The cause of the remaining cases is unclear.][ If otherwise normal parents have one child with the condition, the next child has a 4% risk of being affected.][
]
Genetics
Several genes
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
and specific regions on chromosomes ( loci) have been shown or suggested to be associated with Hirschsprung's disease:
The ''RET'' proto-oncogene accounts for the highest proportion of both familial and sporadic cases, with a wide range of mutations scattered along its entire coding region. A proto-oncogene
An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels. can cause cancer if it is mutated or overexpressed.
''RET'' proto-oncogene
''RET'' is a gene that codes for proteins that assist cells of the neural crest in their movement through the digestive tract during the development of the embryo. Those neural crest cells eventually form bundles of nerve cells called ganglions. ''EDNRB'' codes for proteins that connect these nerve cells to the digestive tract. Thus, mutations in these two genes could directly lead to the absence of certain nerve fibers in the colon. Research suggests that several genes are associated with Hirschsprung's disease. Also, new research suggests that mutations in genomic sequences involved in regulating'' EDNRB'' have a bigger impact on Hirschsprung's disease than previously thought.
''RET'' can mutate in many ways and is associated with Down syndrome. Since Down syndrome is comorbid in 2% of Hirschsprung's cases, a likelihood exists that ''RET'' is involved heavily in both Hirschsprung's disease and Down syndrome. ''RET'' is also associated with medullary thyroid cancer
Medullary thyroid cancer is a form of thyroid carcinoma which originates from the parafollicular cells (C cells), which produce the hormone calcitonin.Hu MI, Vassilopoulou-Sellin R, Lustig R, Lamont JP"Thyroid and Parathyroid Cancers"in Pazdur R, ...
and neuroblastoma
Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the neck, chest, abdomen, or spine. Symptoms may include bone pain, a lump in th ...
, which is a type of cancer common in children. Both of these disorders are more common in Hirschsprung's patients than in the general population. One function that ''RE''T controls is the travel of the neural crest cell
Neural crest cells are a temporary group of cells unique to vertebrates that arise from the embryonic ectoderm germ layer, and in turn give rise to a diverse cell lineage—including melanocytes, craniofacial cartilage and bone, smooth muscle, ...
s through the intestines in the developing fetus
A fetus or foetus (; plural fetuses, feti, foetuses, or foeti) is the unborn offspring that develops from an animal embryo. Following embryonic development the fetal stage of development takes place. In human prenatal development, fetal deve ...
. The earlier the ''RET'' mutation occurs in Hirschsprung's disease, the more severe the disorder becomes.
Other genes
Common and rare DNA variations in the neuregulin 1 (''NRG1'') and NRG3 (''NRG3'') were first shown to be associated with the disease in Chinese patients through a Genome Wide Association Study by the Hong Kong team in 2009 and 2012, respectively Subsequent studies in both Asian and Caucasian patients confirmed the initial findings by the University of Hong Kong. Both rare and common variants in these two genes have been identified in additional Chinese, Thai, Korean, Indonesian, and Spanish patients. These two genes are known to play a role in the formation of the enteric nervous system; thus, they are likely to be involved in the pathology of Hirschsprung's disease, at least in some cases.
Another gene associated with this condition is NADPH oxidase, EF-hand calcium binding domain 5 ( NOX5).[Shin JG, Seo JY, Seo JM, Kim DY, Oh JT, Park KW, Kim HY, Kim JH, Shin HD (2019) Association analysis of NOX5 polymorphisms with Hirschsprung disease. J Pediatr Surg] This gene is located on the long arm of chromosome 15
Chromosome 15 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 15 spans about 102 million base pairs (the building material of DNA) and represents between 3% and 3.5% of the total DN ...
(15q23).
Pathophysiology
During normal prenatal development
Prenatal development () includes the development of the embryo and of the fetus during a viviparous animal's gestation. Prenatal development starts with fertilization, in the germinal stage of embryonic development, and continues in fetal devel ...
, cells from the neural crest migrate into the large intestine (colon) to form the networks of nerves called the myenteric plexus (Auerbach plexus) (between the smooth muscle
Smooth muscle is an involuntary non-striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit mus ...
layers of the gastrointestinal tract wall) and the submucosal plexus
The submucosal plexus (Meissner's plexus, plexus of the submucosa, plexus submucosus) lies in the submucosa of the intestinal wall. The nerves of this plexus are derived from the myenteric plexus which itself is derived from the plexuses of parasy ...
(Meissner plexus) (within the submucosa of the gastrointestinal tract wall). In Hirschsprung disease, the migration is not complete and part of the colon lacks these nerve bodies that regulate the activity of the colon. The affected segment of the colon cannot relax and pass stool through the colon, creating an obstruction.
The most accepted theory of the cause of Hirschsprung is a defect in the craniocaudal migration of neuroblasts originating from the neural crest that occurs during the first 12 weeks of gestation
Gestation is the period of development during the carrying of an embryo, and later fetus, inside viviparous animals (the embryo develops within the parent). It is typical for mammals, but also occurs for some non-mammals. Mammals during pregna ...
. Defects in the differentiation of neuroblasts
In vertebrates, a neuroblast or primitive nerve cell is a postmitotic cell that does not divide further, and which will develop into a neuron after a migration phase. In invertebrates such as ''Drosophila,'' neuroblasts are neural progenitor cells ...
into ganglion cells and accelerated ganglion cell destruction within the intestine may also contribute to the disorder.
This lack of ganglion cells in the myenteric and submucosal plexus is well documented in Hirschsprung's disease. With Hirschsprung's disease, the segment lacking neurons (aganglionic) becomes constricted, causing the normal, proximal section of bowel to become distended with feces. This narrowing of the distal colon and the failure of relaxation in the aganglionic segment are thought to be caused by the lack of neurons containing nitric oxide synthase.
The most cited feature is absence of ganglion cells: notably in males, 75% have none in the end of the colon (rectosigmoid) and 8% lack ganglion cells in the entire colon. The enlarged section of the bowel
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
is found proximally, while the narrowed, aganglionic section is found distally, closer to the end of the bowel. The absence of ganglion cells results in a persistent overstimulation of nerves in the affected region, resulting in contraction.
The equivalent disease in horses is lethal white syndrome
Lethal white syndrome (LWS), also called overo lethal white syndrome (OLWS), lethal white overo (LWO), and overo lethal white foal syndrome (OLWFS), is an autosomal genetic disorder most prevalent in the American Paint Horse. Affected foals are bo ...
.
Diagnosis
Definitive diagnosis is made by suction biopsy of the distally narrowed segment. A histologic examination of the tissue would show a lack of ganglionic nerve cells. Diagnostic techniques involve anorectal manometry
Anorectal manometry (ARM) is a medical test used to measure pressures in the anus and rectum and to assess their function. The test is performed by inserting a catheter, that contains a probe embedded with pressure sensors, through the anus and in ...
, barium enema
A lower gastrointestinal series is a medical procedure used to examine and diagnose problems with the human colon of the large intestine. Radiographs (X-ray pictures) are taken while barium sulfate, a radiocontrast agent, fills the colon via an ...
, and rectal biopsy
A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...
.
The suction rectal biopsy is considered the current international gold standard
A gold standard is a monetary system in which the standard economic unit of account is based on a fixed quantity of gold. The gold standard was the basis for the international monetary system from the 1870s to the early 1920s, and from the la ...
in the diagnosis of Hirschsprung's disease.
Radiologic findings may also assist with diagnosis. Cineanography (fluoroscopy
Fluoroscopy () is an imaging technique that uses X-rays to obtain real-time moving images of the interior of an object. In its primary application of medical imaging, a fluoroscope () allows a physician to see the internal structure and functio ...
of contrast medium
A contrast agent (or contrast medium) is a substance used to increase the contrast of structures or fluids within the body in medical imaging. Contrast agents absorb or alter external electromagnetism or ultrasound, which is different from radiop ...
passing anorectal region) assists in determining the level of the affected intestines.
Treatment
Treatment of Hirschsprung's disease consists of surgical removal (resection) of the abnormal section of the colon, followed by reanastomosis.
Colostomy
The first stage of treatment used to be a reversible colostomy
A colostomy is an opening ( stoma) in the large intestine (colon), or the surgical procedure that creates one. The opening is formed by drawing the healthy end of the colon through an incision in the anterior abdominal wall and suturing it int ...
. In this approach, the healthy end of the large intestine is cut and attached to an opening created on the front of the abdomen. The contents of the bowel are discharged through the hole in the abdomen and into a bag. Later, when the patient's weight, age, and condition are right, the "new" functional end of the bowel is connected with the anus. The first surgical treatment involving surgical resection followed by reanastomosis without a colostomy occurred as early as 1933 by Doctor Baird in Birmingham
Birmingham ( ) is a city and metropolitan borough in the metropolitan county of West Midlands in England. It is the second-largest city in the United Kingdom with a population of 1.145 million in the city proper, 2.92 million in the West ...
on a one-year-old boy.
Other procedures
The Swedish-American surgeon Orvar Swenson
Orvar Swenson (7 February 1909 – 13 April 2012) was a Swedish-born American pediatric surgeon. He discovered the cause of Hirschsprung's disease and in 1948, with Alexander Bill, performed the first pull-through operation in a child with megacolo ...
(1909–2012), who discovered the cause of Hirschsprung's, first performed its surgical treatment, the pull-through surgery, in 1948. The pull-through procedure repairs the colon by connecting the functioning portion of the bowel to the anus. The pull-through procedure is the typical method for treating Hirschsprung's in younger patients. Swenson devised the original procedure, and the pull-through surgery has been modified many times.'
Currently, several different surgical approaches are used, which include the Swenson, Soave, Duhamel, and Boley procedures.[ The Swenson procedure leaves a small portion of the diseased bowel. The Soave procedure, named after the Italian pediatric surgeon, (1917–1984), leaves the outer wall of the colon unaltered. The Boley procedure, pioneered by the American surgeon, ]Scott Boley
Scott may refer to:
Places Canada
* Scott, Quebec, municipality in the Nouvelle-Beauce regional municipality in Quebec
* Scott, Saskatchewan, a town in the Rural Municipality of Tramping Lake No. 380
* Rural Municipality of Scott No. 98, Sask ...
(b. 1941), is a small modification of the Soave procedure, so the term "Soave-Boley" procedure is sometimes used. The Duhamel procedure, named for the French pediatric surgeon Bernard Duhamel (1917–1996), uses a surgical stapler to connect the good and bad bowel.
For the 15% of children who do not obtain full bowel control, other treatments are available. Constipation may be remedied by laxatives or a high-fiber diet. In those patients, serious dehydration can play a major factor in their lifestyles. A lack of bowel control may be addressed by an ileostomy
Ileostomy is a stoma (surgical opening) constructed by bringing the end or loop of small intestine (the ileum) out onto the surface of the skin, or the surgical procedure which creates this opening. Intestinal waste passes out of the ileostomy an ...
– similar to a colostomy, but uses the end of the small intestine rather than the colon. The Malone antegrade colonic enema (ACE) is also an option. In a Malone ACE, a tube goes through the abdominal wall to the appendix, or if available, to the colon. The bowel is then flushed daily. Children as young as 6 years of age may administer this daily flush on their own.
If the affected portion of the lower intestine is restricted to the lower portion of the rectum, other surgical procedures may be performed, such as a posterior rectal myectomy. The prognosis is good in 70% of cases. Chronic postoperative constipation is present in 7 to 8% of the operated cases. Postoperative enterocolitis
Enterocolitis is an inflammation of the digestive tract, involving enteritis of the small intestine and colitis of the colon. It may be caused by various infections, with bacteria, viruses, fungi, parasites, or other causes. Common clinical manif ...
, a severe manifestation, is present in the 10–20% of operated patients.
Epidemiology
According to a 1984 study conducted in Maryland
Maryland ( ) is a state in the Mid-Atlantic region of the United States. It shares borders with Virginia, West Virginia, and the District of Columbia to its south and west; Pennsylvania to its north; and Delaware and the Atlantic Ocean to ...
, Hirschsprung's disease appears in 18.6 per 100,000 live births. In Japan, it occurs at a similar rate of about one in 5,000 births (20 per 100,000). It is more common in male than female (4.32:1) and in white rather than nonwhite. Nine percent of the Hirschsprung cases were also diagnosed as having Down syndrome. Most cases are diagnosed before the patient is 10 years of age.
History
The first report of Hirschsprung's disease dates to 1691, when it was described by Dutch
Dutch commonly refers to:
* Something of, from, or related to the Netherlands
* Dutch people ()
* Dutch language ()
Dutch may also refer to:
Places
* Dutch, West Virginia, a community in the United States
* Pennsylvania Dutch Country
People E ...
anatomist
Anatomy () is the branch of biology concerned with the study of the structure of organisms and their parts. Anatomy is a branch of natural science that deals with the structural organization of living things. It is an old science, having its ...
Frederik Ruysch
Frederik Ruysch (; March 28, 1638 – February 22, 1731) was a Dutch botanist and anatomist. He is known for developing techniques for preserving anatomical specimens, which he used to create dioramas or scenes incorporating human parts. His ana ...
. However, the disease is named after Harald Hirschsprung, the Danish
Danish may refer to:
* Something of, from, or related to the country of Denmark
People
* A national or citizen of Denmark, also called a "Dane," see Demographics of Denmark
* Culture of Denmark
* Danish people or Danes, people with a Danish a ...
physician who first described two infants who died of this disorder in 1888.[
Hirschsprung's disease is a ]congenital
A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can ...
disorder of the colon in which certain nerve cells, known as ganglion cells
{{stack,
A ganglion cell is a cell found in a ganglion. Examples of ganglion cells include:
* Retinal ganglion cell (RGC) found in the ganglion cell layer of the retina
* Cells that reside in the adrenal medulla, where they are involved in th ...
, are absent, causing chronic constipation
Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...
. In patients with Hirschsprung disease, both myenteric and submucosal plexuses are absent. A barium enema is the mainstay of diagnosis of Hirschsprung's, though a rectal biopsy showing the lack of ganglion cells is the only certain method of diagnosis.
The first publication on an important genetic discovery of the disease was from Martucciello Giuseppe ''et al.'' in 1992. The authors described a case of a patient with total colonic aganglionosis associated with a 46, XX, del 10 (q11.21 q21.2) karyotype. The major gene of Hirschsprung disease was identified in this chromosomal 10 region, it was the RET proto-oncogene.
The usual treatment is "pull-through" surgery where the portion of the colon that does have nerve cells is pulled through and sewn over the part that lacks nerve cells.[(National Digestive Diseases Information Clearinghouse).] For a long time, Hirschsprung's was considered a multifactorial disorder, where a combination of nature and nurture was considered to be the cause. However, in August 1993, two articles by independent groups in ''Nature Genetics'' said that Hirschsprung's disease could be mapped to a stretch of chromosome 10
Chromosome 10 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 10 spans about 133 million base pairs (the building material of DNA) and represents between 4 and 4.5 percent of the tot ...
.
This research also suggested that a single gene was responsible for the disorder. However, the researchers were unable to isolate it.
See also
* Achalasia
Esophageal achalasia, often referred to simply as achalasia, is a failure of smooth muscle fibers to relax, which can cause the lower esophageal sphincter to remain closed. Without a modifier, "achalasia" usually refers to achalasia of the esoph ...
* Ileus
Ileus is a disruption of the normal propulsive ability of the intestine. It can be caused by lack of peristalsis or by mechanical obstruction.
The word 'ileus' is from Ancient Greek ''eileós'' (, "intestinal obstruction"). The term 'subileus' re ...
, failure of peristaltic muscle activity in the gut
* Intestinal neuronal dysplasia
* Hirschsprung's disease-type D brachydactyly syndrome
References
External links
*
{{DEFAULTSORT:Hirschsprung's Disease
Gastrointestinal tract disorders
Congenital disorders of digestive system
Rare diseases
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