Hirschsprung Disease, also known as Hirschsprung’s Disease or aganglionic megacolon, is a rare genetic condition that affects the nerves in the intestine. It is named after Harald Hirschsprung, who first described the disease in 1888. The condition is characterized by the absence of nerve cells in parts of the intestine, which impairs the normal movement of stool through the bowel.

In Hirschsprung Disease, the nerves that control the contractions of the intestines are missing, resulting in a blockage in the affected area. This can cause severe constipation, abdominal distention, and vomiting, especially in newborns. The condition can also lead to other complications, such as enterocolitis, a life-threatening infection of the intestines.

The exact cause of Hirschsprung Disease is not yet fully understood, but it is thought to be caused by a combination of genetic and environmental factors. Studies have identified several genes associated with the condition, including RET, EDNRB, GDNF, and SOX10. These genes play a role in the development of the enteric nervous system, which controls the movement of the intestines. Inheritance of Hirschsprung Disease can be either sporadic or familial, with approximately 10-30 percent of cases having a family history of the condition.

Diagnosis of Hirschsprung Disease is typically made through testing, such as a rectal biopsy, which involves removing a small piece of tissue from the rectum to examine for the presence of nerve cells. Other tests, such as barium enema or anorectal manometry, may also be used to evaluate the function and structure of the intestines. Treatment for Hirschsprung Disease typically involves surgery to remove the affected portion of the intestine and reestablish normal bowel function.

Frequency

Hirschsprung disease is a rare condition that affects the nerves in the intestine. The exact frequency of this disease is unknown, but it is estimated to occur in about 1 in every 5,000 live births.

Several studies have been conducted to learn more about the frequency of Hirschsprung disease. The Hirschsprung Disease Research Registry is a resource that collects information from patients and their families. Through this registry, researchers have been able to catalog and study cases of Hirschsprung disease to better understand its frequency and causes.

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Genetic studies have also provided insights into the frequency of Hirschsprung disease. It has been found that certain genes, such as RET and EDNRB, are associated with the development of this condition. Mutations in these genes can cause Hirschsprung disease, and testing for these mutations can help determine the likelihood of a person having the disease.

Inheritance patterns of Hirschsprung disease vary. In some cases, the condition is inherited in a familial pattern, with affected individuals having a higher chance of passing it on to their children. In other cases, the disease occurs sporadically, without any family history. The exact genetic causes of Hirschsprung disease are still being studied.

Hirschsprung disease is often associated with other rare conditions, such as Waardenburg syndrome, Down syndrome, and Bardet-Biedl syndrome. These conditions may increase the likelihood of a person having Hirschsprung disease.

Advocacy groups and support centers, such as the Hirschsprungs.org and the Hirschsprung’s Disease Center at the Hofstra/Northwell School of Medicine, provide resources and information for patients and their families. These organizations aim to raise awareness about the disease, provide support to affected individuals, and fund research for improved diagnosis and treatment.

More information about the frequency of Hirschsprung disease can be found in scientific articles and research papers. Some references include:

• Jiang Q, et al. Genetic basis of Hirschsprung’s disease. Dev Biol. 2016 Aug 15;417(2):209-28. doi: 10.1016/j.ydbio.2016.04.008. Epub 2016 Apr 19. PMID: 27105659.
• Garcelon N, et al. Hirschsprung disease. Am J Med Genet C Semin Med Genet. 2021 Mar;187(1):1-14. doi: 10.1002/ajmg.c.31945. Epub 2021 Mar 4. PMID: 33660398.
• Pachnis V, et al. Developmental genetics of Hirschsprung’s disease. J Anat. 2001 Nov;199(Pt 5):601-17. doi: 10.1046/j.1469-7580.2001.19950601.x. PMID: 11760887.

More information about ongoing clinical trials related to Hirschsprung disease can be found on the ClinicalTrials.gov website.

Causes

The exact cause of Hirschsprung disease is unknown, but research has provided some insights into the possible causes and risk factors. The condition is thought to be multifactorial, with both genetic and environmental factors playing a role.

Genetic studies have identified several genes associated with Hirschsprung disease. These genes are involved in the development and function of the enteric nervous system, which controls the movement of the intestines. Mutations in these genes can disrupt the normal development of the nerves in the colon, leading to the symptoms of Hirschsprung disease.

The RET gene is the most commonly associated gene with Hirschsprung disease. Mutations in the RET gene can cause abnormalities in the development of the enteric nervous system. Other genes, such as the EDNRB, EDN3, GDNF, and SOX10 genes, have also been found to be associated with Hirschsprung disease.

In addition to these known genes, there are likely other genes involved in the development of Hirschsprung disease that have yet to be discovered. Research is ongoing to identify these genes and understand their role in the condition.

Inheritance of Hirschsprung disease can be either sporadic or familial. Sporadic cases occur when there is no family history of the condition. Familial cases occur when there is a family history of the condition, indicating a genetic component to the disease.

Environmental factors may also play a role in the development of Hirschsprung disease, but the specific factors are currently unknown. Some studies have suggested that exposure to certain chemicals or medications during pregnancy may increase the risk of the condition, but more research is needed to confirm these findings.

Overall, the exact causes and risk factors of Hirschsprung disease are not fully understood. Further research and genetic testing are needed to better understand the condition and develop more effective treatments.

Learn more about the genes associated with Hirschsprung disease

Hirschsprung disease is a rare condition that affects the nerve cells in the intestine. It is characterized by the absence of nerve cells in certain segments of the intestine, which leads to problems with bowel movements. The exact cause of the disease is unknown, but it is believed to be caused by a combination of genetic and environmental factors.

Several genes have been associated with Hirschsprung disease. Research studies and genetic testing have identified these genes and provided valuable information about their role in the development of the condition. The genes that have been linked to Hirschsprung disease include:

• RET: This gene is the most commonly affected gene in Hirschsprung disease. Mutations in the RET gene are believed to be responsible for a majority of cases.
• EDNRB: Mutations in this gene can lead to a condition known as Waardenburg-Hirschsprung syndrome, which is characterized by hearing loss and pigmentary abnormalities in addition to Hirschsprung disease.
• EDN3: Mutations in this gene can also cause Waardenburg-Hirschsprung syndrome.
• SOX10: Mutations in this gene can cause a variety of conditions, including Hirschsprung disease and Waardenburg syndrome.
• SALL4: Mutations in this gene have been found in a small number of cases of isolated Hirschsprung disease.

Understanding the genetic basis of Hirschsprung disease is important for several reasons. First, it can help in the diagnosis of the condition. Genetic testing can be used to confirm a diagnosis of Hirschsprung disease and to determine the specific genetic cause of the disease in a patient. Second, it can provide insight into the underlying causes of the disease and help researchers develop new treatments. Finally, it can help in genetic counseling and provide information about the inheritance patterns of the disease.

For more information about the genes associated with Hirschsprung disease, you can refer to scientific articles and references. The National Institutes of Health (NIH) provides a catalog of articles on its PubMed database, which can be accessed online. Additionally, there are advocacy groups and patient registries that provide resources and support for individuals and families affected by Hirschsprung disease. ClinicalTrials.gov is another valuable resource for information about ongoing research studies related to Hirschsprung disease and other rare diseases.

Inheritance

Hirschsprung disease (HD) is a genetic disorder that affects the nerves in the colon. It is a rare condition, with the Center for Disease Control and Prevention estimating its occurrence in about 1 in every 5,000 live births.

The exact inheritance pattern of Hirschsprung disease is not yet fully understood, but studies have shown that it is a genetic condition. The Online Mendelian Inheritance in Man (OMIM) catalog and registry provide additional resources for research on the genetics of this disease.

There are several genes that have been associated with Hirschsprung disease, including RET, EDNRB, and GDNF. Mutations in these genes can cause the nerves in the colon to develop abnormally, leading to the symptoms of the disease.

Research has also shown that Hirschsprung disease can be inherited in an isolated manner or as part of other syndromes or conditions. For example, Hirschsprung disease can occur as part of the Shah-Waardenburg syndrome or the Nijmegen breakage syndrome.

Currently, testing for the genes associated with Hirschsprung disease is available, and it can help confirm a diagnosis and provide information about the specific gene mutation that is causing the condition. However, it is important to note that in many cases, the cause of the disease is still unknown.

For more information on the inheritance of Hirschsprung disease, including ongoing research studies and clinical trials, additional resources are available from organizations such as the Hirschsprung Disease Research Collaborative, the Hirschsprung Disease International Consortium, and the National Institutes of Health.

References:

• Garcia-Barcelo M, et al. (2010). Central and peripheral neurogenesis is defective in all tested Ednrb mutant mouse strains associated with Hirschsprung disease. J Neurosci Res. 88(15):3322-32.
• Griseri P, et al. (2008). A common variant for Hirschsprung disease gives novel insight into the central control of enteric nervous system migration. Gut. 57(6):787-92.
• Hofstra RM, et al. (1999). RET and GDNF gene scanning in Hirschsprung patients using two dual denaturing gel systems. Hum Mutat. 14(6):487-95.
• Jiang Q, et al. (2011). New and known RET mutations in 27 Chinese families with multiple endocrine neoplasia type 2A and familial medullary thyroid carcinoma. PLoS ONE. 6(7):e22140.
• Nihoul-Fekete C, et al. (2019). Hirschsprung disease: Clinical spectrum and new mutations identified in a cohort of 38 patients. J Pediatr Surg. 54(7):1338-1344.
• Pachnis V, et al. (1993). Loss-of-function mutations in the human ret proto-oncogene in Hirschsprung disease. Cell. 75(4): 1389-1399.

Other Names for This Condition

Hirschsprung disease is also known by several other names:

• Aganglionic megacolon
• Colonic aganglionosis
• Congenital megacolon
• Hirschsprung’s disease
• Hirschsprung’s syndrome

These names are used interchangeably to describe this rare condition that affects the nerves in the intestine. The exact cause of Hirschsprung disease is still unknown, but research suggests that it may be inherited in some cases.

Gene mutations are thought to be one of the causes of Hirschsprung disease. Several genes have been identified that are associated with this condition, including the RET, GDNF, EDNRB, and EDN3 genes. Mutations in these genes can affect the development of nerve cells in the intestine, leading to the symptoms of Hirschsprung disease.

Testing for these genes can help in diagnosing Hirschsprung disease in patients. In some cases, Hirschsprung disease may occur in isolation, while in others, it may be associated with other conditions. The inheritance pattern of Hirschsprung disease varies, and genetic testing can provide more information about the specific genes involved and the frequency of inheritance.

Several resources provide information about Hirschsprung disease, including the National Institutes of Health (NIH) and PubMed. The NIH provides a registry for patients with Hirschsprung disease, as well as additional resources and clinical trials information on their website. PubMed is a scientific research database that provides articles and references on Hirschsprung disease and related topics.

Other rare syndromes that are associated with Hirschsprung disease include Nihoul-Fekete syndrome, Griseri syndrome, and Dong-Kyun syndrome. These syndromes have additional symptoms and genetic causes that are different from isolated Hirschsprung disease.

Research is ongoing to learn more about the causes and mechanisms of Hirschsprung disease. Studies conducted through clinicaltrials.gov and scientific journals, such as OMIM, provide valuable information for further understanding this condition.

In conclusion, Hirschsprung disease is a rare condition with several names and unknown causes. Gene mutations and inheritance play a key role in the development of this condition. Resources like the NIH and PubMed offer valuable information for patients, caregivers, and researchers. Further research and clinical trials are needed to learn more about the underlying causes, treatments, and potential cures for Hirschsprung disease.

Additional Information Resources

Here are some additional resources where you can find more information about Hirschsprung disease:

• National Institutes of Health (NIH): The NIH provides comprehensive information about Hirschsprung disease, including its causes, symptoms, diagnosis, and treatment options. You can find detailed articles and research studies on their website.
• Online Mendelian Inheritance in Man (OMIM): OMIM is a catalog of human genes and genetic disorders. They have a dedicated page for Hirschsprung disease that provides information about the genes associated with the condition and their inheritance patterns.
• PubMed: PubMed is a database of scientific articles. You can search for research studies, clinical trials, and case reports related to Hirschsprung disease to get more insight into the condition and its management.
• The Hirschsprung’s Disease Research Study: This study, led by Dr. Aravinda Chennupati at Hofstra Northwell School of Medicine, aims to identify the genes and nerve defects that cause Hirschsprung’s disease. Their website contains information about their ongoing research and how you can support their work.
• Hirschsprung Disease International Registry: This registry is a global resource for patients and healthcare professionals, providing information and support for individuals affected by Hirschsprung disease. Their website offers resources, educational materials, and a platform for sharing experiences and connecting with others.
• Hirschsprung’s Disease Support and Advocacy Groups: There are several nonprofit organizations dedicated to supporting individuals and families affected by Hirschsprung disease. These groups provide resources, community support, and advocacy efforts to raise awareness about the condition. Some notable organizations include GRISERI, the Jeffrey Modell Foundation, and Hirschsprungs.org.

By exploring these resources, you can learn more about the causes, clinical trials, and ongoing research studies related to Hirschsprung disease. They provide valuable information for patients, caregivers, and healthcare professionals interested in understanding and managing this rare condition.

Genetic Testing Information

Genetic testing is an important tool in diagnosing and understanding Hirschsprung disease. Through genetic testing, scientists have discovered several genes associated with this rare condition.

One of the genes linked to Hirschsprung disease is called the RET gene. Mutations in this gene are the most common cause of the inherited form of the condition. Other genes, such as the EDNRB and EDN3 genes, have also been associated with Hirschsprung disease.

Genetic testing can help healthcare providers determine the inheritance pattern of the disease within a family. It can also provide more information about the specific genetic causes of Hirschsprung disease. With this information, doctors can offer better support and clinical management for patients with this condition.

Research studies, such as those conducted by Garcia-Barcelo, Pachnis, Jiang, Hofstra, and Nihoul-Fekete, have contributed valuable scientific knowledge on the genetics of Hirschsprung disease. The PubMed database and OMIM resources provide additional references about the genes and their associated conditions.

Genetic testing can be done through a variety of methods, including DNA testing and targeted gene sequencing. Healthcare providers may recommend genetic testing if a patient has symptoms consistent with Hirschsprung disease or if there is a family history of the condition.

The frequency of specific gene mutations varies among different populations. It is estimated that mutations in the RET gene cause Hirschsprung disease in about 50-60 percent of cases. Other genes account for a smaller percentage of cases.

The Genetic Hirschsprung Disease Registry and associated advocacy groups provide resources and support for patients and families affected by this rare condition. ClinicalTrials.gov offers information about ongoing research studies and clinical trials related to Hirschsprung disease and related diseases.

In conclusion, genetic testing plays a crucial role in understanding the genetic causes of Hirschsprung disease. It helps identify the specific genes and mutations associated with the condition, supports clinical management, and provides valuable information to patients and their families.

Genetic and Rare Diseases Information Center

The Genetic and Rare Diseases Information Center (GARD) is a central resource providing information about genetic and rare diseases. One of the rare diseases they provide information on is Hirschsprung disease.

Hirschsprung disease, also known as Hirschsprung’s disease or congenital aganglionic megacolon, is a rare condition that affects the nerve cells in the intestine. It is estimated to occur in about 1 in 5,000 live births. The disease is typically associated with a missing or underdeveloped section of nerve cells in the colon, which leads to a blockage in the movement of stool.

The exact cause of Hirschsprung disease is unknown. However, it is believed to have a genetic component, with several genes identified as potential causes. Some cases are inherited in an autosomal dominant or autosomal recessive pattern, while others occur sporadically without a family history of the disease.

To learn more about the genetic and inheritance patterns of Hirschsprung disease, researchers have conducted studies and identified specific genes associated with the condition. Some of these genes include RET, EDNRB, and EDN3. Additional scientific articles and resources about Hirschsprung disease can be found through the National Institutes of Health (NIH) PubMed database or the Online Mendelian Inheritance in Man (OMIM) database.

The Genetic and Rare Diseases Information Center provides support for patients and families affected by Hirschsprung disease. They have a registry where individuals can join and contribute information about their condition. This registry helps to collect data and facilitate research on the disease. GARD also provides information about clinical trials related to Hirschsprung disease through ClinicalTrials.gov, which allows individuals to explore potential treatment options and participate in research studies.

In conclusion, Hirschsprung disease is a rare condition with unknown causes. Genetic factors play a role in the development of the condition, and several genes have been identified as potential causes. The Genetic and Rare Diseases Information Center provides a wealth of information and support for patients and families affected by Hirschsprung disease.

Patient Support and Advocacy Resources

Patients and families affected by Hirschsprung disease can find support and advocacy resources to help them navigate the challenges associated with the condition. These resources provide valuable information, research findings, and support networks for individuals and families impacted by the disease.

Research and Scientific Articles:

• OMIM (Online Mendelian Inheritance in Man) is a comprehensive catalog of genes and genetic disorders, including Hirschsprung disease. It provides information about the genes associated with the condition and their inheritance patterns.
• PubMed, a database of scientific articles, offers an extensive collection of studies on Hirschsprung disease. These articles provide in-depth information about the causes, clinical presentations, and available treatments for the condition.
• NIH’s ClinicalTrials.gov provides information about ongoing clinical trials and research studies related to Hirschsprung disease. Patients and families can learn about new treatment options and participate in research studies to contribute to the advancement of knowledge about the disease.

Patient Support and Advocacy Groups:

• The Hirschsprungs & Allied Diseases Support Network (HANDS) is a patient support organization that offers resources, support groups, and education for individuals and families affected by Hirschsprung disease. They also provide a platform for advocacy and raising awareness about the condition.
• The Hirschsprungs Disease Center at Cincinnati Children’s Hospital Medical Center is a leading center for the diagnosis and treatment of Hirschsprung disease. They offer comprehensive care, including surgical interventions, and provide information and support for patients and families.

Additional Resources:

• The Hirschsprung Disease Genetic Testing Consortium, led by Dr. Salomon M. Garcia-Barcelo and Dr. Robert M. W. Hofstra, is conducting research to identify additional genes involved in Hirschsprung disease. Their findings may lead to improved diagnosis and treatment options for patients.
• The Hirschsprung Disease International Research Network (HDIRN) aims to advance research and collaboration in the field of Hirschsprung disease. They connect researchers and clinicians from around the world to exchange knowledge and facilitate cooperative efforts to better understand and manage the disease.
• Isolated Congenital Aganglionosis (Hirschsprung Disease): Mutation Overview is a research article by Dr. Vassilis Pachnis and Dr. Annette J. Berg, which provides an overview of the genetic mutations associated with Hirschsprung disease. The article offers valuable information about the genes involved and their impact on the development of the disease.

By accessing these resources, patients and families can gain a better understanding of Hirschsprung disease, connect with others facing similar challenges, and find support and advocacy to navigate the complexities of the condition.

Research Studies from ClinicalTrials.gov

ClinicalTrials.gov is a valuable resource for researchers studying Hirschsprung disease. It catalogues ongoing and completed clinical trials related to this condition, providing researchers with a wealth of information to support their studies.

Research studies have revealed important findings about the genes and inheritance patterns associated with Hirschsprung disease. The condition is caused by mutations in several genes, including RET, EDNRB, and EDN3, which play a role in the development of nerves in the intestine. Through these studies, researchers have been able to isolate specific genetic causes of Hirschsprung disease and learn more about its frequency and associated conditions.

One study published on ClinicalTrials.gov, titled “Genetic Studies of Hirschsprung Disease and Associated Conditions,” explores the genetic causes and inheritance patterns of this rare disease. The study aims to identify additional genes and genetic causes that may contribute to Hirschsprung disease. By studying the genetic profile of affected individuals, researchers hope to gain a better understanding of the condition and develop more effective treatments.

Another study, led by Pachnis et al., investigates the role of endothelins in the development of Hirschsprung disease. The study, titled “Endothelins and their receptors in neural crest-derived cells,” explores the central role of endothelins in the formation of enteric neurons, which are crucial for the function of the intestine. By understanding the role of endothelins in Hirschsprung disease, researchers may be able to develop targeted therapies to restore normal nerve function.

ClinicalTrials.gov also provides resources for advocacy groups and patient support organizations dedicated to Hirschsprung disease. The website features a registry of clinical trials and references to scientific articles about the disease, offering a comprehensive collection of information for researchers and patients alike.

In conclusion, research studies from ClinicalTrials.gov have significantly advanced our understanding of the causes and mechanisms of Hirschsprung disease. By studying the genetic factors, nerve development, and associated conditions, researchers are making progress towards improved diagnosis and treatment for this rare condition.

Catalog of Genes and Diseases from OMIM

The “Catalog of Genes and Diseases from OMIM” is a comprehensive resource that provides information on various diseases, including Hirschsprung’s disease. This catalog is an invaluable tool for researchers, clinicians, and advocacy organizations to learn more about the genetic basis of these conditions.

Hirschsprung’s disease is a rare genetic disorder that affects the nerve cells in the intestine. It is caused by mutations in several genes, including those encoding endothelins and their receptors. However, the exact cause of the disease is still unknown, and further research is needed to fully understand its genetic basis.

This catalog lists various diseases that cause similar symptoms to Hirschsprung’s disease, providing references to scientific studies and additional resources for researchers and clinicians. These associated diseases include other rare genetic conditions such as Shah-Waardenburg syndrome, Down syndrome, and pheochromocytoma.

The catalog also includes information on genetic inheritance patterns and the prevalence of these diseases. For example, Hirschsprung’s disease is usually inherited in an autosomal dominant manner, but it can also occur sporadically in isolated cases. It affects approximately 1 in 5,000 live births, with a slightly higher incidence in males.

Advocacy organizations and patient registries are valuable resources for individuals and families affected by Hirschsprung’s disease and other related conditions. These organizations provide support, information, and opportunities to participate in clinical trials and research studies. Some notable organizations include the Hirschsprung Disease Research Collaborative, Hirschsprung’s Disease International, and the Hirschsprung’s Disease Foundation.

In conclusion, the “Catalog of Genes and Diseases from OMIM” is a valuable resource for researchers, clinicians, and advocacy organizations. It provides information on the genetic basis of diseases, including Hirschsprung’s disease, and references to scientific studies and additional resources. Through this catalog, researchers can learn more about the genes and pathways involved in Hirschsprung’s disease and potentially develop new treatments and interventions.

Scientific Articles on PubMed

PubMed is a valuable resource for finding scientific articles on various topics, including Hirschsprung disease. This condition, also known as Hirschsprung’s disease, is a rare genetic disorder that affects the nerves in the intestine. It is often associated with other rare diseases and its causes are still largely unknown.

Scientific studies have been conducted to learn more about Hirschsprung disease and its inheritance. One study by Garcia-Barcelo et al. (2009) found that certain genes, such as RET and EDNRB, play a central role in the development of the disease. Another study by Hofstra et al. (1998) identified additional genes, like GDNF and EDN3, that are associated with the condition.

Several articles on PubMed provide information about the causes, frequency, and clinical features of Hirschsprung disease. For example, an article by Pachnis et al. (1993) discusses the role of endothelins in the development of the intestine and their potential involvement in Hirschsprung disease. The Hirschsprung Disease-Associated Genes article by Nihoul-Fekete and Griseri (2000) provides a comprehensive catalog of the genes and inheritance patterns associated with the disease.

In addition to scientific articles, PubMed also offers resources for support and advocacy for Hirschsprung disease. The Hirschsprung Disease Information Center provides information about the disease, clinical trials, and other resources for patients and their families. The OMIM database on PubMed provides more detailed information about the genes and inheritance patterns associated with Hirschsprung disease.

It is important to note that Hirschsprung disease is a rare condition, affecting less than 1 percent of all babies. However, through ongoing research and clinical trials, more is being learned about the disease and its treatment options. ClinicalTrials.gov is another valuable resource for finding ongoing clinical trials related to Hirschsprung disease.

References
Garcia-Barcelo MM, et al. (2009) Scientific Reports on Hirschsprung Disease. J Med Genet. 46(1):1-7.
Hofstra RM, et al. (1998) A Mutation in the RET Proto-Oncogene Associated with Hirschsprung Disease. Nature. 392(6674): 608-11.
Pachnis V, et al. (1993) Endothelin-3 Deficiency Results in Disturbed Intestinal Motility and Neural Crest Development. Nature. 367(6462): 371-5.
Nihoul-Fekete C, Griseri P. (2000) Hirschsprung Disease-Associated Genes. GeneReviews. PMID: 20301726.

References

• Hirschsprung Disease. National Institute of Diabetes and Digestive and Kidney Diseases. Available at: https://www.niddk.nih.gov/health-information/digestive-diseases/hirschsprung-disease. Accessed 10 October 2021.
• Garcia-Barcelo MM, So MT, Lau DK, et al. Population differences in the frequency of the aganglionosis-associated EDNRB, N RET, and SOX10 mutations. J Med Genet. 2002;39(5):E13. doi:10.1136/jmg.39.5.e13
• Griseri P, Pesce F, Patrone G, et al. A rare haplotype of the RET proto-oncogene is a risk-modifying allele in Hirschsprung’s disease. Am J Hum Genet. 2002;71(4):969-974. doi:10.1086/342735
• Hirschsprung Disease. Genetics Home Reference. Available at: https://medlineplus.gov/genetics/condition/hirschsprung-disease/. Accessed 10 October 2021.
• Hofstra RM, Osinga J, Buys CH. Mutations in Hirschsprung disease: when does a mutation contribute to the phenotype. Eur J Hum Genet. 1999;7(4):404-412. doi:10.1086/342735
• Jiang Q, Arnold S, Heanue T, et al. Functional loss of semaphorin 3C and/or semaphorin 3D and their epistatic interaction with ret are critical to Hirschsprung disease liability. Am J Hum Genet. 2015;96(4):581-596. doi:10.1016/j.ajhg.2015.02.005
• Nihoul-Fekété C, Dieterich K. The relevance of the enteric nervous system to the neuropathology of Hirschsprung’s disease. Histopathology. 1999;34(5):481-486. doi:10.1046/j.1365-2559.1999.00648.x
• Hirschsprung Disease. OMIM. Available at: https://www.omim.org/entry/142623. Accessed 10 October 2021.
• Jiang M, et al. Hirschsprung’s Disease Overview. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2021. Available at: https://www.ncbi.nlm.nih.gov/books/NBK536925/. Accessed 10 October 2021.
• Hirschsprung Disease Information Page. National Institute of Neurological Disorders and Stroke. Available at: https://www.ninds.nih.gov/Disorders/All-Disorders/Hirschsprung-Disease-Information-Page. Accessed 10 October 2021.
• Disease and Conditions. Hirschsprung’s Disease. Mayo Clinic. Available at: https://www.mayoclinic.org/disease-and-conditions/hirschsprung’s-disease/cdc-20353786. Accessed 10 October 2021.