Materiały źródłowe

• #1 Hirschsprung Disease: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/178493-overview

  Hirschsprung disease is a developmental disorder characterized by the absence of ganglia in the distal colon, resulting in a functional obstruction. […] One possible etiology of Hirschsprung disease is the arrest of aboral neuroblast migration. Alternatively, although normal cell migration may occur, neuroblasts may be subject to apoptosis, failure of proliferation, or improper differentiation within the affected distal intestinal segment. Fibronectin, laminin, neural cell adhesion molecule (NCAM), and neurotrophic factors present in the intestinal stroma are necessary for normal enteric ganglion development, whereas their absence or dysfunction may also have a role in the etiology of Hirschsprung disease. […] Investigators have also identified several genes whose improper expression results in a Hirschsprung disease phenotype. Genome-wide association studies (GWAS) in Europeans and Asians have identified three common disease-susceptibility variants at the RET, SEMA3, and NRG1 loci.

• #2 Hirschsprung’s Disease | Riley Children’s Health

  https://www.rileychildrens.org/health-info/hirschsprungs-disease

  Hirschsprung’s disease causes blockage of the large intestine due to abnormal nerve development in the bowel. It is a congenital condition, which means it is present from birth. […] Hirschsprung’s disease is caused by an abnormality in nerve and muscle function. Muscle contractions in the normal gut help digested materials move through the intestine. This is called peristalsis. Nerves between the muscle layers trigger the contractions. In Hirschsprung’s disease, the nerves (called ganglion cells) are missing from a short or long part of the bowel. Areas without these nerves cannot push material through. This causes a blockage. […] Hirschsprung’s disease causes about 25 percent of all newborn intestinal obstructions. […] Hirschsprung’s disease is a condition from birth in which a person lacks ganglion nerve cells (usually in the colon) and is unable to push out stool in a normal manner.

• #3 Hirschsprung’s Disease | Symptoms, Diagnosis & Treatment

  https://www.cincinnatichildrens.org/health/h/hirschsprung

  Hirschsprungs disease occurs in about 1 out of 5,000 live births. It is three times more common in males than females. About 5% of cases are linked to Trisomy 21 (Down syndrome). About 2% of cases are linked to Mowat-Wilson syndrome. […] The cause of Hirschsprungs disease is unclear. There is nothing a parent can do that causes the disease. In most cases, the disease results from an abnormality in the genes. The cause of those abnormalities is not known. […] Most people with Hirschsprungs disease do not have a family history of the disease. But, if one parent has Hirschsprungs disease, there is about a 1% chance their child will have it too. If a couple has a child with Hirschsprungs disease, there is about a 5% chance that a sibling will be born with it. If a parent or child has long-segment Hirschsprungs disease, the chances a sibling will be born with Hirschsprungs disease are higher than if the parent or child has short-segment Hirschsprungs disease.

• #4 Hirschsprung disease Information | Mount Sinai – New York

  https://www.mountsinai.org/health-library/diseases-conditions/hirschsprung-disease

  Hirschsprung disease causes a blockage of the large intestine. It occurs due to poor muscle movement in the bowel. It is a congenital condition, which means it is present from birth. […] In people with Hirschsprung disease, the nerves are missing from a part of the bowel. Areas without these nerves cannot push material through. This causes a blockage. Intestinal contents build up behind the blockage. The bowel and abdomen swell as a result. […] Hirschsprung disease causes about 25% of all newborn intestinal blockages. It occurs 5 times more often in males than in females. Hirschsprung disease is sometimes linked to other inherited or congenital conditions, such as Down syndrome.

• #5 Congenital aganglionic megacolon (Hirschsprung disease) – UpToDate

  https://www.uptodate.com/contents/congenital-aganglionic-megacolon-hirschsprung-disease

  Hirschsprung disease (HD) is a motor disorder of the colon, which is caused by the failure of neural crest cells (precursors of enteric ganglion cells) to migrate completely during intestinal development during fetal life. The most accepted theory of the cause of HD is that there is a defect in the craniocaudal migration of neuroblasts originating from the neural crest, a process that begins at four weeks of gestation and ends at week 7 with the arrival of neural crest-derived cells at the distal end of the colon. In HD, the cells fail to reach the distal colon, rendering that segment aganglionic and therefore with abnormal motor function, resulting in HD. […] Mutations in several genes have been identified in patients with HD. HD is a genetically complex disorder caused by variants in multiple rare genes with low penetrance and variable expression. Thus, individuals with multiple pathogenic variants have substantially increased risk compared with those with fewer pathogenic variants. For nonsyndromic forms, long-segment disease tends to be transmitted by autosomal dominant inheritance and short-segment disease often reflects autosomal recessive or multifactorial inheritance.

• #6 Hirschsprung’s Disease: Causes, Symptoms, Diagnosis, Treatment

  https://www.webmd.com/children/what-is-hirschsprungs-disease

  Hirschsprung’s disease typically starts in the early months of pregnancy. Usually, as the baby develops, nerve cells are created throughout the entire digestive system, from the esophagus which leads from the mouth to the stomach all the way to the rectum. Normally, a person will have up to 500 million of these types of nerve cells. Among other roles, these cells move food through your digestive system. […] In a baby with Hirschsprung’s, the nerve cells stop growing at the end of the large intestine, just before the rectum and anus. In some children, the cells are also missing from other places in the digestive system. Without these nerve cells, the body can’t sense when poop reaches a certain point in the intestine. The poop gets stuck and forms a blockage. […] Gene changes called mutations sometimes cause Hirschsprung’s disease. Parents who carry the code for Hirschsprung’s disease in their genes, especially mothers, may pass it on to their children. But the genetic factors behind this disease are complicated.

• #7 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Causes-and-Symptoms-of-Hirschsprungs-Disease.aspx

  Hirschsprungs disease (HD) is a congenital disorder that is caused by a loss of nerve cells at the end of the bowel. […] The disease is believed to be caused by a failure of nerve cells derived from the neural crest to continue their migration toward the end of the bowel during embryonic development. […] An alternative etiology to the arrested neuroblasts migration is that they may have completed their journey through the entire bowel, but later undergo apoptosis (i.e., cell death) or dysfunctional proliferation and/ or differentiation within the distal bowel. […] The absence of factors, such as neural cell adhesion molecule (NCAM), laminin, fibronectin and other neurotrophic factors, which are all necessary for the development of enteric ganglia, may have an imperative role in the etiology of HD.

• #8 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Causes-and-Symptoms-of-Hirschsprungs-Disease.aspx

  Hirschsprungs disease (HD) is a congenital disorder that is caused by a loss of nerve cells at the end of the bowel. […] The disease is believed to be caused by a failure of nerve cells derived from the neural crest to continue their migration toward the end of the bowel during embryonic development. […] An alternative etiology to the arrested neuroblasts migration is that they may have completed their journey through the entire bowel, but later undergo apoptosis (i.e., cell death) or dysfunctional proliferation and/ or differentiation within the distal bowel. […] The absence of factors, such as neural cell adhesion molecule (NCAM), laminin, fibronectin and other neurotrophic factors, which are all necessary for the development of enteric ganglia, may have an imperative role in the etiology of HD.

• #9 Hirschsprung Disease: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/178493-overview

  Hirschsprung disease is a developmental disorder characterized by the absence of ganglia in the distal colon, resulting in a functional obstruction. […] One possible etiology of Hirschsprung disease is the arrest of aboral neuroblast migration. Alternatively, although normal cell migration may occur, neuroblasts may be subject to apoptosis, failure of proliferation, or improper differentiation within the affected distal intestinal segment. Fibronectin, laminin, neural cell adhesion molecule (NCAM), and neurotrophic factors present in the intestinal stroma are necessary for normal enteric ganglion development, whereas their absence or dysfunction may also have a role in the etiology of Hirschsprung disease. […] Investigators have also identified several genes whose improper expression results in a Hirschsprung disease phenotype. Genome-wide association studies (GWAS) in Europeans and Asians have identified three common disease-susceptibility variants at the RET, SEMA3, and NRG1 loci.

• #10 Hirschsprung Disease: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/178493-overview

  Hirschsprung disease is a developmental disorder characterized by the absence of ganglia in the distal colon, resulting in a functional obstruction. […] One possible etiology of Hirschsprung disease is the arrest of aboral neuroblast migration. Alternatively, although normal cell migration may occur, neuroblasts may be subject to apoptosis, failure of proliferation, or improper differentiation within the affected distal intestinal segment. Fibronectin, laminin, neural cell adhesion molecule (NCAM), and neurotrophic factors present in the intestinal stroma are necessary for normal enteric ganglion development, whereas their absence or dysfunction may also have a role in the etiology of Hirschsprung disease. […] Investigators have also identified several genes whose improper expression results in a Hirschsprung disease phenotype. Genome-wide association studies (GWAS) in Europeans and Asians have identified three common disease-susceptibility variants at the RET, SEMA3, and NRG1 loci.

• #11 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Causes-and-Symptoms-of-Hirschsprungs-Disease.aspx

  Hirschsprungs disease (HD) is a congenital disorder that is caused by a loss of nerve cells at the end of the bowel. […] The disease is believed to be caused by a failure of nerve cells derived from the neural crest to continue their migration toward the end of the bowel during embryonic development. […] An alternative etiology to the arrested neuroblasts migration is that they may have completed their journey through the entire bowel, but later undergo apoptosis (i.e., cell death) or dysfunctional proliferation and/ or differentiation within the distal bowel. […] The absence of factors, such as neural cell adhesion molecule (NCAM), laminin, fibronectin and other neurotrophic factors, which are all necessary for the development of enteric ganglia, may have an imperative role in the etiology of HD.

• #12 Hirschsprung Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562142/

  In Hirschsprung disease, there is a disruption of the migration process and differentiation of neural crest cells at the level of the enteric nervous system, which is under the control of the RET gene and its ligands. This disturbance causes a total absence of GC in the nerve plexuses. […] HD transmission is complex, involving multigenic inheritance. Its penetrance is weak, variable, and sex-dependent. The main gene involved is the proto-oncogene RET found in about 35% of sporadic cases and 49% of familial cases. […] The other genes involved in the etiopathogenesis of HD are implicated in only 5 to 10% of cases. It includes the ligands of the RET receptor: glial cell-derived neurotrophic factor (GDNF), endothelin-3, endothelin receptor B (EDNRB), SOX10 transcription factor, and the PHOX2B gene.

• #13 Hirschsprung’s disease – Wikipedia

  https://en.wikipedia.org/wiki/Hirschsprung%27s_disease

  The disorder may occur by itself or in association with other genetic disorders such as Down syndrome.[2] […] About half of isolated cases are linked to a specific genetic mutation and about 20% occur within families.[1] […] Some of these occur in an autosomal dominant manner.[1] […] The cause of the remaining cases is unclear.[1] […] If otherwise normal parents have one child with the condition, the next child has a 4% risk of being affected.[2] […] Several genes 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.[20] […] Mutations in these two genes could directly lead to the absence of certain nerve fibers in the colon.

• #14 Hirschsprung disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/hirschsprung-disease/

  Hirschsprung disease can occur in combination with other conditions, such as Waardenburg syndrome, type IV; Mowat-Wilson syndrome; or congenital central hypoventilation syndrome. These cases are described as syndromic. Hirschsprung disease can also occur without other conditions, and these cases are referred to as isolated or nonsyndromic. […] Isolated Hirschsprung disease can result from mutations in one of several genes, including the RET, EDNRB, and EDN3 genes. However, the genetics of this condition appear complex and are not completely understood. While a mutation in a single gene sometimes causes the condition, mutations in multiple genes may be required in some cases. The genetic cause of the condition is unknown in approximately half of affected individuals. […] Mutations in the RET gene are the most common known genetic cause of Hirschsprung disease. The RET gene provides instructions for producing a protein that is involved in signaling within cells. This protein appears to be essential for the normal development of several kinds of nerve cells, including nerves in the intestine. Mutations in the RET gene that cause Hirschsprung disease result in a nonfunctional version of the RET protein that cannot transmit signals within cells. Without RET protein signaling, enteric nerves do not develop properly. Absence of these nerves leads to the intestinal problems characteristic of Hirschsprung disease.

• #15 Hirschsprung Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562142/

  In Hirschsprung disease, there is a disruption of the migration process and differentiation of neural crest cells at the level of the enteric nervous system, which is under the control of the RET gene and its ligands. This disturbance causes a total absence of GC in the nerve plexuses. […] HD transmission is complex, involving multigenic inheritance. Its penetrance is weak, variable, and sex-dependent. The main gene involved is the proto-oncogene RET found in about 35% of sporadic cases and 49% of familial cases. […] The other genes involved in the etiopathogenesis of HD are implicated in only 5 to 10% of cases. It includes the ligands of the RET receptor: glial cell-derived neurotrophic factor (GDNF), endothelin-3, endothelin receptor B (EDNRB), SOX10 transcription factor, and the PHOX2B gene.

• #16 Hirschsprung’s Disease: Diagnosis and Management | AAFP

  https://www.aafp.org/pubs/afp/issues/2006/1015/p1319.html

  Hirschsprungs disease (congenital megacolon) is caused by the failed migration of colonic ganglion cells during gestation. […] The disease is caused by the failure of ganglion cells to migrate cephalocaudally through the neural crest during weeks four to 12 of gestation, causing an absence of ganglion cells in all or part of the colon. […] The cause of Hirschsprungs disease is multifactorial, and the disease can be familial or develop spontaneously. […] Eight genomes have been associated with Hirschsprungs disease; however, most cases are not considered familial. […] Current research is focusing on the RET proto-oncogene on chromosome 10q11.2. […] Hirschsprungs disease associated with this gene has been linked to multiple endocrine neoplasia, type IIA (i.e., medullary carcinoma of the thyroid and adrenal tumors).

• #17 Hirschsprung disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/hirschsprung-disease/

  Hirschsprung disease can occur in combination with other conditions, such as Waardenburg syndrome, type IV; Mowat-Wilson syndrome; or congenital central hypoventilation syndrome. These cases are described as syndromic. Hirschsprung disease can also occur without other conditions, and these cases are referred to as isolated or nonsyndromic. […] Isolated Hirschsprung disease can result from mutations in one of several genes, including the RET, EDNRB, and EDN3 genes. However, the genetics of this condition appear complex and are not completely understood. While a mutation in a single gene sometimes causes the condition, mutations in multiple genes may be required in some cases. The genetic cause of the condition is unknown in approximately half of affected individuals. […] Mutations in the RET gene are the most common known genetic cause of Hirschsprung disease. The RET gene provides instructions for producing a protein that is involved in signaling within cells. This protein appears to be essential for the normal development of several kinds of nerve cells, including nerves in the intestine. Mutations in the RET gene that cause Hirschsprung disease result in a nonfunctional version of the RET protein that cannot transmit signals within cells. Without RET protein signaling, enteric nerves do not develop properly. Absence of these nerves leads to the intestinal problems characteristic of Hirschsprung disease.

• #18 Hirschsprung Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562142/

  In Hirschsprung disease, there is a disruption of the migration process and differentiation of neural crest cells at the level of the enteric nervous system, which is under the control of the RET gene and its ligands. This disturbance causes a total absence of GC in the nerve plexuses. […] HD transmission is complex, involving multigenic inheritance. Its penetrance is weak, variable, and sex-dependent. The main gene involved is the proto-oncogene RET found in about 35% of sporadic cases and 49% of familial cases. […] The other genes involved in the etiopathogenesis of HD are implicated in only 5 to 10% of cases. It includes the ligands of the RET receptor: glial cell-derived neurotrophic factor (GDNF), endothelin-3, endothelin receptor B (EDNRB), SOX10 transcription factor, and the PHOX2B gene.

• #19 Pediatric Hirschsprung Disease: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/929733-overview

  Hirschsprung disease is generally sporadic, although the incidence of familial disease has been increasing (overall incidence: 7.6%). Hirschsprung disease is also reported to occur in two thirds of twins, primarily males. […] Multiple loci appear to be involved, including chromosomes 13q22, 21q22, and 10q. […] Mutations in the Ret proto-oncogene have been associated with multiple endocrine neoplasia (MEN) 2A or MEN 2B and familial Hirschsprung disease. […] Other genes associated with Hirschsprung disease include the glial cell-derived neurotrophic factor gene, the endothelin-B receptor gene, and the endothelin-3 gene. […] Hirschsprung disease is strongly associated with Down syndrome; 5-15% of patients with Hirschsprung disease also have trisomy 21. […] Other associations include Waardenburg syndrome, congenital deafness, malrotation, gastric diverticulum, and intestinal atresia.

• #20 Hirschsprung Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562142/

  In Hirschsprung disease, there is a disruption of the migration process and differentiation of neural crest cells at the level of the enteric nervous system, which is under the control of the RET gene and its ligands. This disturbance causes a total absence of GC in the nerve plexuses. […] HD transmission is complex, involving multigenic inheritance. Its penetrance is weak, variable, and sex-dependent. The main gene involved is the proto-oncogene RET found in about 35% of sporadic cases and 49% of familial cases. […] The other genes involved in the etiopathogenesis of HD are implicated in only 5 to 10% of cases. It includes the ligands of the RET receptor: glial cell-derived neurotrophic factor (GDNF), endothelin-3, endothelin receptor B (EDNRB), SOX10 transcription factor, and the PHOX2B gene.

• #21 Hirschsprung disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/hirschsprung-disease/

  Hirschsprung disease can occur in combination with other conditions, such as Waardenburg syndrome, type IV; Mowat-Wilson syndrome; or congenital central hypoventilation syndrome. These cases are described as syndromic. Hirschsprung disease can also occur without other conditions, and these cases are referred to as isolated or nonsyndromic. […] Isolated Hirschsprung disease can result from mutations in one of several genes, including the RET, EDNRB, and EDN3 genes. However, the genetics of this condition appear complex and are not completely understood. While a mutation in a single gene sometimes causes the condition, mutations in multiple genes may be required in some cases. The genetic cause of the condition is unknown in approximately half of affected individuals. […] Mutations in the RET gene are the most common known genetic cause of Hirschsprung disease. The RET gene provides instructions for producing a protein that is involved in signaling within cells. This protein appears to be essential for the normal development of several kinds of nerve cells, including nerves in the intestine. Mutations in the RET gene that cause Hirschsprung disease result in a nonfunctional version of the RET protein that cannot transmit signals within cells. Without RET protein signaling, enteric nerves do not develop properly. Absence of these nerves leads to the intestinal problems characteristic of Hirschsprung disease.

• #22 Hirschsprung disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/hirschsprung-disease/

  The EDNRB gene provides instructions for making a protein called endothelin receptor type B. When this protein interacts with other proteins called endothelins, it transmits information from outside the cell to inside the cell, signaling for many important cellular processes. The EDN3 gene provides instructions for a protein called endothelin 3, one of the endothelins that interacts with endothelin receptor type B. Together, endothelin 3 and endothelin receptor type B play an important role in the normal formation of enteric nerves. Changes in either the EDNRB gene or the EDN3 gene disrupt the normal functioning of the endothelin receptor type B or the endothelin 3 protein, preventing them from transmitting signals important for the development of enteric nerves. As a result, these nerves do not form normally during embryonic development. A lack of enteric nerves prevents stool from being moved through the intestine, leading to severe constipation and intestinal blockage.

• #23 Hirschsprung Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562142/

  In Hirschsprung disease, there is a disruption of the migration process and differentiation of neural crest cells at the level of the enteric nervous system, which is under the control of the RET gene and its ligands. This disturbance causes a total absence of GC in the nerve plexuses. […] HD transmission is complex, involving multigenic inheritance. Its penetrance is weak, variable, and sex-dependent. The main gene involved is the proto-oncogene RET found in about 35% of sporadic cases and 49% of familial cases. […] The other genes involved in the etiopathogenesis of HD are implicated in only 5 to 10% of cases. It includes the ligands of the RET receptor: glial cell-derived neurotrophic factor (GDNF), endothelin-3, endothelin receptor B (EDNRB), SOX10 transcription factor, and the PHOX2B gene.

• #24 Hirschsprung Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562142/

  In Hirschsprung disease, there is a disruption of the migration process and differentiation of neural crest cells at the level of the enteric nervous system, which is under the control of the RET gene and its ligands. This disturbance causes a total absence of GC in the nerve plexuses. […] HD transmission is complex, involving multigenic inheritance. Its penetrance is weak, variable, and sex-dependent. The main gene involved is the proto-oncogene RET found in about 35% of sporadic cases and 49% of familial cases. […] The other genes involved in the etiopathogenesis of HD are implicated in only 5 to 10% of cases. It includes the ligands of the RET receptor: glial cell-derived neurotrophic factor (GDNF), endothelin-3, endothelin receptor B (EDNRB), SOX10 transcription factor, and the PHOX2B gene.

• #25 Hirschsprung disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/hirschsprung-disease/

  The EDNRB gene provides instructions for making a protein called endothelin receptor type B. When this protein interacts with other proteins called endothelins, it transmits information from outside the cell to inside the cell, signaling for many important cellular processes. The EDN3 gene provides instructions for a protein called endothelin 3, one of the endothelins that interacts with endothelin receptor type B. Together, endothelin 3 and endothelin receptor type B play an important role in the normal formation of enteric nerves. Changes in either the EDNRB gene or the EDN3 gene disrupt the normal functioning of the endothelin receptor type B or the endothelin 3 protein, preventing them from transmitting signals important for the development of enteric nerves. As a result, these nerves do not form normally during embryonic development. A lack of enteric nerves prevents stool from being moved through the intestine, leading to severe constipation and intestinal blockage.

• #26 Hirschsprung Disease: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/178493-overview

  Hirschsprung disease is a developmental disorder characterized by the absence of ganglia in the distal colon, resulting in a functional obstruction. […] One possible etiology of Hirschsprung disease is the arrest of aboral neuroblast migration. Alternatively, although normal cell migration may occur, neuroblasts may be subject to apoptosis, failure of proliferation, or improper differentiation within the affected distal intestinal segment. Fibronectin, laminin, neural cell adhesion molecule (NCAM), and neurotrophic factors present in the intestinal stroma are necessary for normal enteric ganglion development, whereas their absence or dysfunction may also have a role in the etiology of Hirschsprung disease. […] Investigators have also identified several genes whose improper expression results in a Hirschsprung disease phenotype. Genome-wide association studies (GWAS) in Europeans and Asians have identified three common disease-susceptibility variants at the RET, SEMA3, and NRG1 loci.

• #27 Hirschsprung’s disease – Wikipedia

  https://en.wikipedia.org/wiki/Hirschsprung%27s_disease

  Research suggests that several genes are associated with Hirschsprung’s disease.[22] […] 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. […] Another gene associated with this condition is NADPH oxidase, EF-hand calcium binding domain 5 (NOX5).[26] […] 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. […] Defects in the differentiation of neuroblasts into ganglion cells and accelerated ganglion cell destruction within the intestine may also contribute to the disorder.[28] […] The absence of ganglion cells results in a persistent overstimulation of nerves in the affected region, resulting in contraction.

• #28 Causes and consequences: development and pathophysiology of Hirschsprung disease | World Journal of Pediatric Surgery

  https://wjps.bmj.com/content/7/4/e000903

  The remaining 10%-20% of cases are familial, usually have autosomal dominant inheritance, and are often associated with long segment or total colonic HSCR. […] Along with EDNRB, the RET gene has been shown to be the main gene associated with HSCR, with coding and splice site mutations in RET having been identified in up to 50% of familial cases and 15%-35% of sporadic cases. […] In addition to EDNRB and RET, recent advances in genome-wide association analysis and next-generation sequencing have identified 30 HSCR candidate genes including genes in the RET-GDNF and EDNRB-ET3 signaling pathways, transcription factors such as SOX10, PHOX2B and ZEB2, and genes associated with a number of other signaling pathways involved in enteric neural development, such as the neuregulin, semaphorin, hedgehog and notch signaling pathways.

• #29 Hirschsprung disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/hirschsprung-disease/

  Hirschsprung disease can occur in combination with other conditions, such as Waardenburg syndrome, type IV; Mowat-Wilson syndrome; or congenital central hypoventilation syndrome. These cases are described as syndromic. Hirschsprung disease can also occur without other conditions, and these cases are referred to as isolated or nonsyndromic. […] Isolated Hirschsprung disease can result from mutations in one of several genes, including the RET, EDNRB, and EDN3 genes. However, the genetics of this condition appear complex and are not completely understood. While a mutation in a single gene sometimes causes the condition, mutations in multiple genes may be required in some cases. The genetic cause of the condition is unknown in approximately half of affected individuals. […] Mutations in the RET gene are the most common known genetic cause of Hirschsprung disease. The RET gene provides instructions for producing a protein that is involved in signaling within cells. This protein appears to be essential for the normal development of several kinds of nerve cells, including nerves in the intestine. Mutations in the RET gene that cause Hirschsprung disease result in a nonfunctional version of the RET protein that cannot transmit signals within cells. Without RET protein signaling, enteric nerves do not develop properly. Absence of these nerves leads to the intestinal problems characteristic of Hirschsprung disease.

• #30 Hirschsprung’s Disease: Diagnosis and Management | AAFP

  https://www.aafp.org/pubs/afp/issues/2006/1015/p1319.html

  Hirschsprungs disease also can be associated with neurologic, cardiovascular, urologic, and gastrointestinal abnormalities. […] Down syndrome (trisomy 21) is the most common chromosomal abnormality associated with the disease, accounting for approximately 10 percent of patients. […] Other conditions that have been linked to Hirschsprungs disease include congenital deafness, hydrocephalus, diverticulum of the bladder, Meckels diverticulum, imperforate anus, ventricular septal defect, renal agenesis, cryptorchidism, Waardenburgs syndrome (pigment defects associated with deafness), neuroblastomas, and Ondines curse (primary alveolar hypoventilation).

• #31 Pediatric Hirschsprung Disease: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/929733-overview

  Hirschsprung disease is generally sporadic, although the incidence of familial disease has been increasing (overall incidence: 7.6%). Hirschsprung disease is also reported to occur in two thirds of twins, primarily males. […] Multiple loci appear to be involved, including chromosomes 13q22, 21q22, and 10q. […] Mutations in the Ret proto-oncogene have been associated with multiple endocrine neoplasia (MEN) 2A or MEN 2B and familial Hirschsprung disease. […] Other genes associated with Hirschsprung disease include the glial cell-derived neurotrophic factor gene, the endothelin-B receptor gene, and the endothelin-3 gene. […] Hirschsprung disease is strongly associated with Down syndrome; 5-15% of patients with Hirschsprung disease also have trisomy 21. […] Other associations include Waardenburg syndrome, congenital deafness, malrotation, gastric diverticulum, and intestinal atresia.

• #32 Hirschsprung’s Disease: Diagnosis and Management | AAFP

  https://www.aafp.org/pubs/afp/issues/2006/1015/p1319.html

  Hirschsprungs disease also can be associated with neurologic, cardiovascular, urologic, and gastrointestinal abnormalities. […] Down syndrome (trisomy 21) is the most common chromosomal abnormality associated with the disease, accounting for approximately 10 percent of patients. […] Other conditions that have been linked to Hirschsprungs disease include congenital deafness, hydrocephalus, diverticulum of the bladder, Meckels diverticulum, imperforate anus, ventricular septal defect, renal agenesis, cryptorchidism, Waardenburgs syndrome (pigment defects associated with deafness), neuroblastomas, and Ondines curse (primary alveolar hypoventilation).

• #33 Hirschsprung disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/hirschsprung-disease/

  Hirschsprung disease can occur in combination with other conditions, such as Waardenburg syndrome, type IV; Mowat-Wilson syndrome; or congenital central hypoventilation syndrome. These cases are described as syndromic. Hirschsprung disease can also occur without other conditions, and these cases are referred to as isolated or nonsyndromic. […] Isolated Hirschsprung disease can result from mutations in one of several genes, including the RET, EDNRB, and EDN3 genes. However, the genetics of this condition appear complex and are not completely understood. While a mutation in a single gene sometimes causes the condition, mutations in multiple genes may be required in some cases. The genetic cause of the condition is unknown in approximately half of affected individuals. […] Mutations in the RET gene are the most common known genetic cause of Hirschsprung disease. The RET gene provides instructions for producing a protein that is involved in signaling within cells. This protein appears to be essential for the normal development of several kinds of nerve cells, including nerves in the intestine. Mutations in the RET gene that cause Hirschsprung disease result in a nonfunctional version of the RET protein that cannot transmit signals within cells. Without RET protein signaling, enteric nerves do not develop properly. Absence of these nerves leads to the intestinal problems characteristic of Hirschsprung disease.

• #34 Hirschsprung’s Disease: Diagnosis and Management | AAFP

  https://www.aafp.org/pubs/afp/issues/2006/1015/p1319.html

  Hirschsprungs disease also can be associated with neurologic, cardiovascular, urologic, and gastrointestinal abnormalities. […] Down syndrome (trisomy 21) is the most common chromosomal abnormality associated with the disease, accounting for approximately 10 percent of patients. […] Other conditions that have been linked to Hirschsprungs disease include congenital deafness, hydrocephalus, diverticulum of the bladder, Meckels diverticulum, imperforate anus, ventricular septal defect, renal agenesis, cryptorchidism, Waardenburgs syndrome (pigment defects associated with deafness), neuroblastomas, and Ondines curse (primary alveolar hypoventilation).

• #35 Hirschsprung disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/hirschsprung-disease/

  Hirschsprung disease can occur in combination with other conditions, such as Waardenburg syndrome, type IV; Mowat-Wilson syndrome; or congenital central hypoventilation syndrome. These cases are described as syndromic. Hirschsprung disease can also occur without other conditions, and these cases are referred to as isolated or nonsyndromic. […] Isolated Hirschsprung disease can result from mutations in one of several genes, including the RET, EDNRB, and EDN3 genes. However, the genetics of this condition appear complex and are not completely understood. While a mutation in a single gene sometimes causes the condition, mutations in multiple genes may be required in some cases. The genetic cause of the condition is unknown in approximately half of affected individuals. […] Mutations in the RET gene are the most common known genetic cause of Hirschsprung disease. The RET gene provides instructions for producing a protein that is involved in signaling within cells. This protein appears to be essential for the normal development of several kinds of nerve cells, including nerves in the intestine. Mutations in the RET gene that cause Hirschsprung disease result in a nonfunctional version of the RET protein that cannot transmit signals within cells. Without RET protein signaling, enteric nerves do not develop properly. Absence of these nerves leads to the intestinal problems characteristic of Hirschsprung disease.

• #36 Hirschsprung’s Disease: Diagnosis and Management | AAFP

  https://www.aafp.org/pubs/afp/issues/2006/1015/p1319.html

  Hirschsprungs disease also can be associated with neurologic, cardiovascular, urologic, and gastrointestinal abnormalities. […] Down syndrome (trisomy 21) is the most common chromosomal abnormality associated with the disease, accounting for approximately 10 percent of patients. […] Other conditions that have been linked to Hirschsprungs disease include congenital deafness, hydrocephalus, diverticulum of the bladder, Meckels diverticulum, imperforate anus, ventricular septal defect, renal agenesis, cryptorchidism, Waardenburgs syndrome (pigment defects associated with deafness), neuroblastomas, and Ondines curse (primary alveolar hypoventilation).

• #37 Hirschsprung’s Disease: Diagnosis and Management | AAFP

  https://www.aafp.org/pubs/afp/issues/2006/1015/p1319.html

  Hirschsprungs disease also can be associated with neurologic, cardiovascular, urologic, and gastrointestinal abnormalities. […] Down syndrome (trisomy 21) is the most common chromosomal abnormality associated with the disease, accounting for approximately 10 percent of patients. […] Other conditions that have been linked to Hirschsprungs disease include congenital deafness, hydrocephalus, diverticulum of the bladder, Meckels diverticulum, imperforate anus, ventricular septal defect, renal agenesis, cryptorchidism, Waardenburgs syndrome (pigment defects associated with deafness), neuroblastomas, and Ondines curse (primary alveolar hypoventilation).

• #38 Hirschsprung’s Disease: Diagnosis and Management | AAFP

  https://www.aafp.org/pubs/afp/issues/2006/1015/p1319.html

  Hirschsprungs disease also can be associated with neurologic, cardiovascular, urologic, and gastrointestinal abnormalities. […] Down syndrome (trisomy 21) is the most common chromosomal abnormality associated with the disease, accounting for approximately 10 percent of patients. […] Other conditions that have been linked to Hirschsprungs disease include congenital deafness, hydrocephalus, diverticulum of the bladder, Meckels diverticulum, imperforate anus, ventricular septal defect, renal agenesis, cryptorchidism, Waardenburgs syndrome (pigment defects associated with deafness), neuroblastomas, and Ondines curse (primary alveolar hypoventilation).

• #39 Hirschsprung’s Disease: Diagnosis and Management | AAFP

  https://www.aafp.org/pubs/afp/issues/2006/1015/p1319.html

  Hirschsprungs disease also can be associated with neurologic, cardiovascular, urologic, and gastrointestinal abnormalities. […] Down syndrome (trisomy 21) is the most common chromosomal abnormality associated with the disease, accounting for approximately 10 percent of patients. […] Other conditions that have been linked to Hirschsprungs disease include congenital deafness, hydrocephalus, diverticulum of the bladder, Meckels diverticulum, imperforate anus, ventricular septal defect, renal agenesis, cryptorchidism, Waardenburgs syndrome (pigment defects associated with deafness), neuroblastomas, and Ondines curse (primary alveolar hypoventilation).

• #40 Hirschsprung’s Disease: Diagnosis and Management | AAFP

  https://www.aafp.org/pubs/afp/issues/2006/1015/p1319.html

  Hirschsprungs disease also can be associated with neurologic, cardiovascular, urologic, and gastrointestinal abnormalities. […] Down syndrome (trisomy 21) is the most common chromosomal abnormality associated with the disease, accounting for approximately 10 percent of patients. […] Other conditions that have been linked to Hirschsprungs disease include congenital deafness, hydrocephalus, diverticulum of the bladder, Meckels diverticulum, imperforate anus, ventricular septal defect, renal agenesis, cryptorchidism, Waardenburgs syndrome (pigment defects associated with deafness), neuroblastomas, and Ondines curse (primary alveolar hypoventilation).

• #41 Hirschsprung’s Disease: Diagnosis and Management | AAFP

  https://www.aafp.org/pubs/afp/issues/2006/1015/p1319.html

  Hirschsprungs disease (congenital megacolon) is caused by the failed migration of colonic ganglion cells during gestation. […] The disease is caused by the failure of ganglion cells to migrate cephalocaudally through the neural crest during weeks four to 12 of gestation, causing an absence of ganglion cells in all or part of the colon. […] The cause of Hirschsprungs disease is multifactorial, and the disease can be familial or develop spontaneously. […] Eight genomes have been associated with Hirschsprungs disease; however, most cases are not considered familial. […] Current research is focusing on the RET proto-oncogene on chromosome 10q11.2. […] Hirschsprungs disease associated with this gene has been linked to multiple endocrine neoplasia, type IIA (i.e., medullary carcinoma of the thyroid and adrenal tumors).

• #42 Causes and consequences: development and pathophysiology of Hirschsprung disease | World Journal of Pediatric Surgery

  https://wjps.bmj.com/content/7/4/e000903

  The remaining 10%-20% of cases are familial, usually have autosomal dominant inheritance, and are often associated with long segment or total colonic HSCR. […] Along with EDNRB, the RET gene has been shown to be the main gene associated with HSCR, with coding and splice site mutations in RET having been identified in up to 50% of familial cases and 15%-35% of sporadic cases. […] In addition to EDNRB and RET, recent advances in genome-wide association analysis and next-generation sequencing have identified 30 HSCR candidate genes including genes in the RET-GDNF and EDNRB-ET3 signaling pathways, transcription factors such as SOX10, PHOX2B and ZEB2, and genes associated with a number of other signaling pathways involved in enteric neural development, such as the neuregulin, semaphorin, hedgehog and notch signaling pathways.

• #43 Congenital aganglionic megacolon (Hirschsprung disease) – UpToDate

  https://www.uptodate.com/contents/congenital-aganglionic-megacolon-hirschsprung-disease

  Hirschsprung disease (HD) is a motor disorder of the colon, which is caused by the failure of neural crest cells (precursors of enteric ganglion cells) to migrate completely during intestinal development during fetal life. The most accepted theory of the cause of HD is that there is a defect in the craniocaudal migration of neuroblasts originating from the neural crest, a process that begins at four weeks of gestation and ends at week 7 with the arrival of neural crest-derived cells at the distal end of the colon. In HD, the cells fail to reach the distal colon, rendering that segment aganglionic and therefore with abnormal motor function, resulting in HD. […] Mutations in several genes have been identified in patients with HD. HD is a genetically complex disorder caused by variants in multiple rare genes with low penetrance and variable expression. Thus, individuals with multiple pathogenic variants have substantially increased risk compared with those with fewer pathogenic variants. For nonsyndromic forms, long-segment disease tends to be transmitted by autosomal dominant inheritance and short-segment disease often reflects autosomal recessive or multifactorial inheritance.

• #44 Hirschsprung disease — Knowledge Hub

  https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/hirschsprung-disease/

  Hirschsprung disease is believed to have an oligogenic mechanism of inheritance and can be associated with single-gene variants, variants in non-coding regions, copy number variants (CNVs) and chromosomal anomalies. […] Around 40%50% of familial cases and 10%20% of sporadic cases will be found to have a loss-of-function variant in the RET pathway. […] Inheritance of causative variants in L1CAM (X-linked hydrocephalus) is X-linked recessive, and in KIFBP (Goldberg-Shprintzen megacolon syndrome) is autosomal recessive. […] In non-syndromic Hirschsprung disease where a RET pathogenic variant is identified, inheritance is autosomal dominant with incomplete penetrance (50%70%).

• #45 Hirschsprung’s Disease | Symptoms, Diagnosis & Treatment

  https://www.cincinnatichildrens.org/health/h/hirschsprung

  Hirschsprungs disease occurs in about 1 out of 5,000 live births. It is three times more common in males than females. About 5% of cases are linked to Trisomy 21 (Down syndrome). About 2% of cases are linked to Mowat-Wilson syndrome. […] The cause of Hirschsprungs disease is unclear. There is nothing a parent can do that causes the disease. In most cases, the disease results from an abnormality in the genes. The cause of those abnormalities is not known. […] Most people with Hirschsprungs disease do not have a family history of the disease. But, if one parent has Hirschsprungs disease, there is about a 1% chance their child will have it too. If a couple has a child with Hirschsprungs disease, there is about a 5% chance that a sibling will be born with it. If a parent or child has long-segment Hirschsprungs disease, the chances a sibling will be born with Hirschsprungs disease are higher than if the parent or child has short-segment Hirschsprungs disease.

• #46 Hirschsprung’s Disease | Symptoms, Diagnosis & Treatment

  https://www.cincinnatichildrens.org/health/h/hirschsprung

  Hirschsprungs disease occurs in about 1 out of 5,000 live births. It is three times more common in males than females. About 5% of cases are linked to Trisomy 21 (Down syndrome). About 2% of cases are linked to Mowat-Wilson syndrome. […] The cause of Hirschsprungs disease is unclear. There is nothing a parent can do that causes the disease. In most cases, the disease results from an abnormality in the genes. The cause of those abnormalities is not known. […] Most people with Hirschsprungs disease do not have a family history of the disease. But, if one parent has Hirschsprungs disease, there is about a 1% chance their child will have it too. If a couple has a child with Hirschsprungs disease, there is about a 5% chance that a sibling will be born with it. If a parent or child has long-segment Hirschsprungs disease, the chances a sibling will be born with Hirschsprungs disease are higher than if the parent or child has short-segment Hirschsprungs disease.

• #47 Hirschsprung’s Disease | Dr Beelke Dhondt

  https://www.atchi.co.za/hirschsprungs-disease/

  Hirschsprungs disease occurs when some of your babys intestinal nerve cells (ganglion cells) dont develop properly, delaying the progression of stool through the intestines. […] Scientists arent sure why the ganglion cells dont migrate down to the end of the rectum completely. However, genetic factors may be involved, especially when longer lengths of intestine are involved or when someone else in the family also has the condition. […] For instance, there is an increased chance that a couple will have a child with Hirschsprungs disease if one of the parents has the disease. (The chances are higher if the mother is the one with Hirschsprungs disease). […] Hirschsprungs disease occurs five times more frequently in boys than in girls. Children with Down syndrome have a higher risk as well.

• #48 Hirschsprung disease Information | Mount Sinai – New York

  https://www.mountsinai.org/health-library/diseases-conditions/hirschsprung-disease

  Hirschsprung disease causes a blockage of the large intestine. It occurs due to poor muscle movement in the bowel. It is a congenital condition, which means it is present from birth. […] In people with Hirschsprung disease, the nerves are missing from a part of the bowel. Areas without these nerves cannot push material through. This causes a blockage. Intestinal contents build up behind the blockage. The bowel and abdomen swell as a result. […] Hirschsprung disease causes about 25% of all newborn intestinal blockages. It occurs 5 times more often in males than in females. Hirschsprung disease is sometimes linked to other inherited or congenital conditions, such as Down syndrome.

• #49 Hirschsprung’s Disease | Dr Beelke Dhondt

  https://www.atchi.co.za/hirschsprungs-disease/

  Hirschsprungs disease occurs when some of your babys intestinal nerve cells (ganglion cells) dont develop properly, delaying the progression of stool through the intestines. […] Scientists arent sure why the ganglion cells dont migrate down to the end of the rectum completely. However, genetic factors may be involved, especially when longer lengths of intestine are involved or when someone else in the family also has the condition. […] For instance, there is an increased chance that a couple will have a child with Hirschsprungs disease if one of the parents has the disease. (The chances are higher if the mother is the one with Hirschsprungs disease). […] Hirschsprungs disease occurs five times more frequently in boys than in girls. Children with Down syndrome have a higher risk as well.

• #50 Hirschsprung’s Disease: Symptoms & Causes Explained

  https://www.bajajallianz.com/blog/wellness/hirschsprungs-disease-causes-and-symptoms.html

  Hirschsprung’s disease is a rare congenital condition that affects the large intestine and can cause varying degrees of digestive issues. […] The exact cause of Hirschsprung’s disease is still unknown, but it is believed to be related to genetic mutations. […] In children with this condition, these nerve cells stop developing partway through the intestines, leading to the symptoms described above. […] Some risk factors for Hirschsprung’s disease include: Genetics: The disease may be passed down in families, particularly if a close relative also has the condition. […] Down syndrome: Children with Down syndrome have an increased risk of developing Hirschsprung’s disease. […] Male gender: Boys are more likely to develop the disease than girls, although the reason for this is not entirely apparent.

• #51 Hirschsprung Disease (for Parents) | Nemours KidsHealth

  https://kidshealth.org/en/parents/hirschsprung.html

  Hirschsprung disease prevents bowel movements (stool) from passing through the intestines due to missing nerve cells in the intestine. Most commonly, it involves the part of the colon close to the anus (where poop leaves the body). But it can involve the entire intestine. It’s caused by a birth defect. […] Doctors aren’t sure why some children get Hirschsprung disease. But they do know it can run in families. It also affects boys more often than girls. Children with Down syndrome and genetic heart conditions also have an increased risk of Hirschsprung disease.

• #52 Hirschsprung Disease | Cigna

  https://www.cigna.com/knowledge-center/hw/medical-topics/hirschsprung-disease-hw183346

  Hirschsprung disease is a birth defect that affects the nerve cells in the large intestine (colon). […] Doctors don’t know what causes Hirschsprung disease, but it tends to run in families. It may also be linked to other medical problems, such as Down syndrome and congenital heart disease.

• #53 Hirschsprung disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/hirschsprung-disease/

  Hirschsprung disease can occur in combination with other conditions, such as Waardenburg syndrome, type IV; Mowat-Wilson syndrome; or congenital central hypoventilation syndrome. These cases are described as syndromic. Hirschsprung disease can also occur without other conditions, and these cases are referred to as isolated or nonsyndromic. […] Isolated Hirschsprung disease can result from mutations in one of several genes, including the RET, EDNRB, and EDN3 genes. However, the genetics of this condition appear complex and are not completely understood. While a mutation in a single gene sometimes causes the condition, mutations in multiple genes may be required in some cases. The genetic cause of the condition is unknown in approximately half of affected individuals. […] Mutations in the RET gene are the most common known genetic cause of Hirschsprung disease. The RET gene provides instructions for producing a protein that is involved in signaling within cells. This protein appears to be essential for the normal development of several kinds of nerve cells, including nerves in the intestine. Mutations in the RET gene that cause Hirschsprung disease result in a nonfunctional version of the RET protein that cannot transmit signals within cells. Without RET protein signaling, enteric nerves do not develop properly. Absence of these nerves leads to the intestinal problems characteristic of Hirschsprung disease.

• #54 About hirschsprungs disease | Children’s Wisconsin

  https://childrenswi.org/medical-care/gastroenterology-liver-and-nutrition-program/conditions/hirschsprungs-disease

  Hirschsprung’s disease occurs when some of the nerve cells that are normally present in the intestine do not form properly while a baby is developing during pregnancy. […] For unknown reasons, the nerve cells do not grow past a certain point in the intestine in babies with Hirschsprung’s disease. […] Scientists are not sure why the intestinal nerve cells do not form completely. Nothing has been shown to cause this problem, including medications a mother takes while pregnant or what a mother eats during pregnancy. […] There is possibly a genetic, or inherited, cause for Hirschsprung’s disease. If a family has a child with Hirschsprung’s disease, there is a 3 to 12 percent chance that another baby they have will also have the disease. Also, there is an increased chance that a couple will have a child with Hirschsprung’s disease if one of the parents has the disease. The chances are higher if the mother is the parent with Hirschsprung’s disease.

• #55 Hirschsprung’s disease – Wikipedia

  https://en.wikipedia.org/wiki/Hirschsprung%27s_disease

  Research suggests that several genes are associated with Hirschsprung’s disease.[22] […] 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. […] Another gene associated with this condition is NADPH oxidase, EF-hand calcium binding domain 5 (NOX5).[26] […] 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. […] Defects in the differentiation of neuroblasts into ganglion cells and accelerated ganglion cell destruction within the intestine may also contribute to the disorder.[28] […] The absence of ganglion cells results in a persistent overstimulation of nerves in the affected region, resulting in contraction.

• #56 Hirschsprung’s disease: what is it, symptoms and treatment | Top Doctors

  https://www.topdoctors.co.uk/medical-dictionary/hirschsprungs-disease

  Hirschsprung’s disease is a congenital condition that affects the large intestine (colon) and causes problems with passing stool. The disease is characterised by the absence of ganglion cells (nerve cells) in segments of the colon, which results in a lack of peristalsis (coordinated muscle contractions that move contents through the intestines) in the affected parts of the colon, causing stool to build up and form a blockage. […] During foetal development, neural crest cells (stem cells) migrate from the neural tube to form various tissues. These neural crest cells are precursors to the ganglion cells in the colon, which are critical for the functioning of the enteric nervous system responsible for peristalsis. […] In Hirschsprung’s disease, the migration of the neural crest cells is incomplete, causing a segment of the colon to lack the ganglion cells necessary for peristalsis. The lack of peristalsis in the affected parts of the colon can lead to the build-up of stool, resulting in severe constipation and abdominal distension. […] The exact cause behind the incomplete migration is still unclear, but several genes have been associated. The most notable ones include mutations in the RET proto-oncogene, mutations in the EDNRB (endothelin receptor B) gene, and mutations in the EDN3 (endothelin 3) gene.

• #57 Hirschsprung’s Disease | Riley Children’s Health

  https://www.rileychildrens.org/health-info/hirschsprungs-disease

  Hirschsprung’s disease causes blockage of the large intestine due to abnormal nerve development in the bowel. It is a congenital condition, which means it is present from birth. […] Hirschsprung’s disease is caused by an abnormality in nerve and muscle function. Muscle contractions in the normal gut help digested materials move through the intestine. This is called peristalsis. Nerves between the muscle layers trigger the contractions. In Hirschsprung’s disease, the nerves (called ganglion cells) are missing from a short or long part of the bowel. Areas without these nerves cannot push material through. This causes a blockage. […] Hirschsprung’s disease causes about 25 percent of all newborn intestinal obstructions. […] Hirschsprung’s disease is a condition from birth in which a person lacks ganglion nerve cells (usually in the colon) and is unable to push out stool in a normal manner.

• #58 Hirschsprung disease Information | Mount Sinai – New York

  https://www.mountsinai.org/health-library/diseases-conditions/hirschsprung-disease

  Hirschsprung disease causes a blockage of the large intestine. It occurs due to poor muscle movement in the bowel. It is a congenital condition, which means it is present from birth. […] In people with Hirschsprung disease, the nerves are missing from a part of the bowel. Areas without these nerves cannot push material through. This causes a blockage. Intestinal contents build up behind the blockage. The bowel and abdomen swell as a result. […] Hirschsprung disease causes about 25% of all newborn intestinal blockages. It occurs 5 times more often in males than in females. Hirschsprung disease is sometimes linked to other inherited or congenital conditions, such as Down syndrome.

• #59 Hirschsprung Disease (HD): Symptoms, Diagnosis and Treatment Options | Nationwide Children’s Hospital

  https://www.nationwidechildrens.org/conditions/hirschsprung-disease

  Hirschsprung disease is a condition you are born with, which causes blockage of the intestine. […] The reason for this is a lack of nerves in the affected segment of the colon and sometimes the small intestine also. […] Hirschsprung disease, also known as megacolon, is a congenital (happening before birth) condition in which nerve cells in the wall of the intestine do not develop properly. […] Hirschsprung disease occurs in one out of every 5,000 live births. […] The disease occurs more often in males than in females, and sometimes can be associated with inherited conditions, one common example being Down syndrome. […] The possible pathology explanations are that the segment at the bottom either has no nerves, or has a section of bowel that was the transition between normal and abnormal nerves (transition zone).

• #60 Hirschsprung Disease (HD): Symptoms, Diagnosis and Treatment Options | Nationwide Children’s Hospital

  https://www.nationwidechildrens.org/conditions/hirschsprung-disease

  Just like with a newborn with Hirschsprung disease, if there is bowel without adequate or normal nerves, that segment of bowel will not function and the bowel above this area will therefore not be able to empty leading to abdominal distension. […] Problems with the pull-through anatomy can result in enterocolitis and can be related to the initial operation. […] Causes for this can include a narrowing of the end of the pull-through (stricture), a twist or kink of the pull-through, a cuff related to the Soave procedure which compresses the end of the pull-through, a large pouch related to a Duhamel procedure, rarely a segment of bowel with normal ganglion cells that doesnt function well due to abnormal motility.

• #61 Hirschsprung Disease: Exploring Its Causes, Consequences, and Novel Treatments

  https://robbreport.com/lifestyle/health-wellness/hirschsprung-disease-exploring-its-causes-consequences-and-novel-treatments-236628/

  Perhaps the most important gene in Hirschsprung disease is Ret, a receptor tyrosine kinase that is mutated in the majority of patients with the disease. […] This multifactorial role of the Gdnf-Ret pathway explains its essential function during ENS formation and the high prevalence of Ret mutations identified in human Hirschsprung disease. […] We believe that restoring normal goblet cell function and mucus layer properties in the colonic epithelium of children with Hirschsprung disease may be a viable therapeutic strategy for preventing HAEC. […] The experiments described above will continue to further our understanding of ENS development, give us new insights into the etiology and pathophysiology of Hirschsprung disease and its complications, and lead to an improved understanding of the embryologic causes and clinical manifestations of other enteric neuropathies.

• #62 Hirschsprung’s Disease: Causes, Symptoms, Diagnosis, Treatment

  https://www.webmd.com/children/what-is-hirschsprungs-disease

  Hirschsprung’s disease typically starts in the early months of pregnancy. Usually, as the baby develops, nerve cells are created throughout the entire digestive system, from the esophagus which leads from the mouth to the stomach all the way to the rectum. Normally, a person will have up to 500 million of these types of nerve cells. Among other roles, these cells move food through your digestive system. […] In a baby with Hirschsprung’s, the nerve cells stop growing at the end of the large intestine, just before the rectum and anus. In some children, the cells are also missing from other places in the digestive system. Without these nerve cells, the body can’t sense when poop reaches a certain point in the intestine. The poop gets stuck and forms a blockage. […] Gene changes called mutations sometimes cause Hirschsprung’s disease. Parents who carry the code for Hirschsprung’s disease in their genes, especially mothers, may pass it on to their children. But the genetic factors behind this disease are complicated.

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