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Hirschsprung disease
This condition affects the digestive system, primarily the large bowel, causing blockages due to missing nerve cells. It typically presents in newborns and infants, leading to severe constipation and other gastrointestinal issues.
Overview
Hirschsprung disease is a congenital condition, meaning it is present from birth, affecting the large bowel (colon). It occurs when specific nerve cells, known as ganglion cells, are missing from a segment of the bowel. These cells are crucial for the normal movement of the bowel, which pushes waste material through the digestive system. Without these nerve cells, the affected segment of the bowel remains tightly constricted, leading to a build-up of stools [PMID:33671212].
This condition can vary in severity depending on how long the affected segment of the bowel is. In some cases, only a short section is involved, while in others, a much longer part, or even the entire large bowel, may lack these nerve cells. Hirschsprung disease affects approximately 1 in 5,000 live births.
Symptoms & clinical features
The symptoms of Hirschsprung disease usually appear shortly after birth. A common initial sign is that a newborn does not pass meconium (the first stool) within the first 24 to 48 hours of life. Other symptoms often include a swollen abdomen, vomiting, and severe constipation [PMID:33671212].
Older infants and children with Hirschsprung disease, especially those with less severe forms, may experience ongoing chronic constipation, abdominal discomfort, and poor weight gain. In some instances, a life-threatening complication called enterocolitis can develop, which involves inflammation and infection of the bowel, causing fever, bloody diarrhoea, and severe abdominal swelling.
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Affected organs
Hirschsprung disease primarily affects the large bowel, also known as the colon. The condition involves the absence of ganglion cells, which are part of the enteric nervous system, from a section of this organ. While the main impact is on the large bowel, the abnormal bowel function can secondarily affect the entire digestive system due to blockages and pressure build-up.
Risks & severity
The severity of Hirschsprung disease depends on the length of the bowel segment missing nerve cells. A shorter affected segment generally leads to milder symptoms and potentially later diagnosis, while a longer affected segment often causes more severe symptoms that present very early in life. The most severe form, total colonic aganglionosis, involves the entire large bowel.
Untreated Hirschsprung disease carries significant risks, including severe malnutrition, chronic constipation, and the potentially fatal complication of enterocolitis. With timely diagnosis and appropriate surgical intervention, most individuals with Hirschsprung disease can live healthy lives, though some may experience ongoing bowel issues [PMID:33671212].
Genetic causes
Hirschsprung disease is considered a complex or polygenic condition, meaning it often results from a combination of changes in several genes and environmental factors. Several genes have been associated with an increased risk of developing the condition.
Key genes implicated include RET, EDN3, and EDNRB. The RET gene provides instructions for making a protein that is vital for the development of nerve cells, including those in the bowel [PMID:24606132]. Pathogenic changes in RET can disrupt this crucial process. The EDN3 and EDNRB genes are also involved in the development of nerve cells in the bowel. Variants in these genes can impair the normal migration and development of these cells during embryonic growth, leading to their absence in affected bowel segments [PMID:11523773].
Inheritance pattern
Hirschsprung disease has a complex inheritance pattern, meaning it does not follow a simple dominant or recessive model. Instead, it is thought to result from the combined effect of multiple genetic changes, sometimes alongside environmental factors. This means that while genetic factors play a significant role, the condition does not typically pass down in a straightforward manner within families.
If one child in a family has Hirschsprung disease, the risk for subsequent children to be affected is generally low but higher than in the general population. The exact risk can depend on the specific genetic changes involved and the length of the bowel segment affected in the first child. Genetic counselling can provide families with more precise information regarding recurrence risks.
Diagnosis & testing
Diagnosis of Hirschsprung disease typically begins with clinical observation of symptoms, especially in newborns who fail to pass meconium. Initial investigations may include X-rays of the abdomen. However, a definitive diagnosis usually requires a rectal biopsy, where a small tissue sample is taken from the bowel wall to check for the presence or absence of ganglion cells.
Genetic testing, often facilitated through the NHS Genomic Medicine Service, can be carried out to identify variants in genes such as RET, EDN3, and EDNRB. This testing can help confirm a diagnosis, inform prognosis, and provide information for family planning. Referrals for genetic testing and counselling are typically made by paediatricians or specialist gastrointestinal teams using relevant R-codes, such as those listed on PanelApp for rare developmental disorders.
Management & lifestyle
The primary treatment for Hirschsprung disease is surgery to remove the section of the bowel that lacks nerve cells and to reconnect the healthy parts of the bowel. This procedure is typically performed in early infancy. Following surgery, most children experience improved bowel function.
Ongoing management may involve dietary advice, laxatives, or enemas in some cases to help regulate bowel movements and prevent constipation. Regular follow-up with a paediatric gastroenterologist or a specialist surgeon is important to monitor for potential complications like enterocolitis or persistent bowel dysfunction. Support from specialist nurses and dietitians within the NHS framework helps manage the condition effectively.
UK care pathway
In the UK, individuals suspected of having Hirschsprung disease are typically referred to paediatric specialists, often within the NHS Genomic Medicine Service (GMS) pathways. Diagnosis involves clinical assessment and usually a bowel biopsy. Genetic testing, if deemed appropriate by a clinical geneticist, can be accessed through the GMS, which uses R-codes for specific diagnostic pathways. Genetic counsellors are available to provide support and information to families regarding inheritance patterns and future family planning.
Frequently asked questions
Is Hirschsprung disease inherited?
Hirschsprung disease typically has a complex inheritance pattern, meaning it can be influenced by multiple genetic changes and sometimes environmental factors. While genetic factors play a role, it does not usually pass down in a simple, predictable way. Genetic counselling can help families understand their specific risks.
What is the long-term outlook for someone with Hirschsprung disease?
With timely diagnosis and surgical treatment, most individuals with Hirschsprung disease can live full and healthy lives. Some may experience ongoing bowel issues, such as constipation or occasional enterocolitis, which require continued medical management and monitoring.
Can Hirschsprung disease be diagnosed before birth?
Diagnosing Hirschsprung disease before birth is challenging and uncommon. It is usually diagnosed after birth when a newborn shows symptoms like not passing meconium. In some rare cases, severe bowel dilation might be seen on prenatal scans, prompting further investigation.
What is enterocolitis and why is it serious?
Enterocolitis is a serious inflammation and infection of the bowel, which can be a complication of Hirschsprung disease. It causes symptoms like fever, vomiting, abdominal swelling, and bloody diarrhoea. If not treated quickly, it can be life-threatening, making prompt medical attention crucial.
How is Hirschsprung disease treated?
The main treatment for Hirschsprung disease is surgery to remove the section of the bowel that is missing nerve cells and reconnect the healthy parts. This restores normal bowel function. After surgery, some individuals may need ongoing support for bowel management.
References
- Ambartsumyan L, Smith C, Kapur RP. Diagnosis of Hirschsprung Disease. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society. 2020. PMID: 31791203
- Hirschsprung disease. Nature reviews. Disease primers. 2023. PMID: 37828120
- King SK, Karpelowsky J. Hirschsprung disease. ANZ journal of surgery. 2017. PMID: 28975740
- Dasgupta R, Langer JC. Hirschsprung disease. Current problems in surgery. 2004. PMID: 15614238
- Ehrenpreis T. Hirschsprung's disease. The American journal of digestive diseases. 1971. PMID: 4942817
- Pemmada V, Bhat G, Bhat BK. Adult Hirschsprung's Disease. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract. 2023. PMID: 36717467
- Wetherill C, Sutcliffe J. Hirschsprung disease and anorectal malformation. Early human development. 2014. PMID: 25448783
- Hei Ha JL, Hang Lui VC, Hang Tam PK. Embryology and anatomy of Hirschsprung disease. Seminars in pediatric surgery. 2022. PMID: 36417785