Skip to content
How It Works
Explore
Resources Ask a Question
Who It's For
Patients Caregivers Providers
Log In Ask a Question
PubMed This is a summary of 24 peer-reviewed journal articles Updated
Pediatric Surgery

Subtypes, Genetics, and Family Risks

At a Glance

Hirschsprung disease is classified into subtypes based on how much of the intestine is missing nerve cells. The condition is strongly linked to genetics, especially mutations in the RET gene, and the risk of having another child with the disease varies depending on the specific subtype.

Hirschsprung disease is not a “one-size-fits-all” condition. It is classified into several subtypes based on how much of the intestine is affected. Understanding your child’s specific subtype can help you and your medical team anticipate the complexity of surgery and the long-term management needs [1][2].

Subtypes by Segment Length

The disease is named based on where the nerve cells (ganglia) stop.

  • Short-Segment (S-HSCR): This is the most common form, affecting about 80% to 84% of cases [2][3]. The missing nerve cells are limited to the rectum and the sigmoid colon [4][5].
  • Long-Segment (L-HSCR): This type affects a larger portion of the colon and can sometimes extend into the small intestine [6][7]. It accounts for approximately 9% of cases [2].
  • Total Colonic Aganglionosis (TCA): A rarer and more severe form where the entire large intestine lacks nerve cells [8][9]. This occurs in about 7.5% to 10% of children [2][8].
  • Total Intestinal Aganglionosis (TIA): The rarest and most severe form, where the entire large intestine and most or all of the small intestine are affected [9][7].
  • Ultra-Short Segment (USHD): A variant where only a very tiny area at the very end of the rectum is affected [4].
  • Skip-Segment: An extremely rare situation where a section with nerve cells is “skipped” and followed by another section without them [10].

The Role of Genetics

Hirschsprung disease is considered a neurocristopathy, meaning it stems from a “hiccup” in how neural crest cells move during development [11][12].

  • The RET Gene: The RET gene is the most important gene linked to the condition [13][14]. Mutations in RET are found in about 50% of familial cases (where it runs in the family) and 15-20% of sporadic cases (where it happens for the first time) [13]. RET mutations are often linked to more severe forms, like long-segment or total colonic disease [13][15].
  • Other Genes: Many other genes, such as NRG1, EDNRB, and PHOX2B, can also play a role [16][17].

Associated Syndromes

In about 30% of cases, Hirschsprung disease occurs alongside other conditions [14].

  • Down Syndrome (Trisomy 21): This is the most common association [1][18]. Approximately 5% of children with Down syndrome also have Hirschsprung disease [18].
  • Haddad Syndrome: A combination of Hirschsprung disease and Congenital Central Hypoventilation Syndrome (CCHS), where children have trouble breathing while asleep [1][19].
  • Mowat-Wilson Syndrome: Linked to specific facial features, heart defects, and developmental delays [20][21].

Risks for Future Children

If you have one child with Hirschsprung disease, the risk for future siblings is generally around 7.6% [22]. However, this risk changes significantly based on the subtype:

  • In families with Total Colonic Aganglionosis (TCA), the recurrence risk jumps to 20% [22].
  • The risk is also higher if a parent was affected by the disease [22][23].

Because of these complexities, many families choose to meet with a genetic counselor to better understand their specific situation and plan for the future [24][23].

For more details on how these subtypes dictate the surgical approach, see Surgical Treatment and the Pull-Through Procedure.

Common questions in this guide

What are the different subtypes of Hirschsprung disease?
Hirschsprung disease is classified by how much of the intestine lacks nerve cells. The most common type is short-segment, affecting only the lower part of the colon, while rarer forms like total colonic aganglionosis affect the entire large intestine.
Is Hirschsprung disease genetic?
Yes, genetics play a significant role in Hirschsprung disease. Mutations in the RET gene are the most common cause, especially in cases where the condition runs in the family or involves a larger portion of the intestine.
What are the chances of having another child with Hirschsprung disease?
If you have one child with Hirschsprung disease, the general risk for future siblings is around 7.6%. However, this risk can jump to 20% or higher depending on the specific subtype, such as total colonic aganglionosis, and your family history.
Can Hirschsprung disease happen with other conditions?
Yes, in about 30% of cases, it occurs alongside other syndromes. The most commonly associated condition is Down syndrome, but it can also be linked to Haddad syndrome and Mowat-Wilson syndrome.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Based on the contrast enema and biopsy, which subtype does my child have: short-segment, long-segment, or total colonic?
  2. 2.What is the specific 'RET' gene status for my child, and does this change the expected outcome or risk for future children?
  3. 3.Should we consider testing for associated conditions like Down syndrome or Congenital Central Hypoventilation Syndrome (Haddad syndrome)?
  4. 4.What is the recurrence risk for our family specifically, given the length of my child's affected segment?
  5. 5.How does the length of the aganglionic segment affect the type of surgery my child will need?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (24)
  1. 1

    Hirschsprung disease.

    Montalva L, Cheng LS, Kapur R, et al.

    Nature reviews. Disease primers 2023; (9(1)):54 doi:10.1038/s41572-023-00465-y.

    PMID: 37828049
  2. 2

    Functional Outcomes After Surgery for Total Colonic, Long-Segment, Versus Rectosigmoid Segment Hirschsprung Disease.

    Verkuijl SJ, Meinds RJ, van der Steeg AFW, et al.

    Journal of pediatric gastroenterology and nutrition 2022; (74(3)):348-354 doi:10.1097/MPG.0000000000003355.

    PMID: 34775429
  3. 3

    Surgical management of short-segment Hirschsprung disease.

    Etskovitz H, Kim RS, Wang SZ, Nandivada P

    World journal of pediatric surgery 2024; (7(4)):e000916 doi:10.1136/wjps-2024-000916.

    PMID: 39845183
  4. 4

    Ultrashort-segment Hirschsprung disease in a 4-year-old female.

    Rodas A, Barillas S, Ardebol J

    Journal of surgical case reports 2020; (2020(9)):rjaa320 doi:10.1093/jscr/rjaa320.

    PMID: 33024529
  5. 5

    Association Analysis of SLC6A20 Polymorphisms With Hirschsprung Disease.

    Lee JS, Oh JT, Kim JH, et al.

    Journal of pediatric gastroenterology and nutrition 2016; (62(1)):64-70 doi:10.1097/MPG.0000000000000880.

    PMID: 26049783
  6. 6

    Spectrum of Clinicopathological Deviations in Long-Segment Hirschsprung Disease Compared With Short-Segment Hirschsprung Disease: A Single-Institution Study.

    Alnajar H, Murro D, Alsadi A, Jakate S

    International journal of surgical pathology 2017; (25(3)):216-221 doi:10.1177/1066896916675729.

    PMID: 27784831
  7. 7

    Unexpected gap between intraoperative caliber change of the intestine and normoganglia in patients with intestinal aganglionosis.

    Sekioka A, Fukumoto K, Miyake H, et al.

    Pediatric surgery international 2019; (35(10)):1115-1121 doi:10.1007/s00383-019-04534-w.

    PMID: 31392504
  8. 8

    Ernica Clinical Consensus Statements on Total Colonic and Intestinal Aganglionosis.

    Granström AL, Irvine W, Hoel AT, et al.

    Journal of pediatric surgery 2024; (59(10)):161565 doi:10.1016/j.jpedsurg.2024.04.019.

    PMID: 38763854
  9. 9

    Concurrent Hirschsprung's disease and anorectal malformation: a systematic review.

    Nakamura H, Puri P

    Pediatric surgery international 2020; (36(1)):21-24 doi:10.1007/s00383-019-04580-4.

    PMID: 31552492
  10. 10

    Distal Rectal Skip-Segment Hirschsprung Disease and the Potential for False-Negative Diagnosis.

    Coe A, Avansino JR, Kapur RP

    Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 2016; (19(2)):123-31 doi:10.2350/15-08-1686-OA.1.

    PMID: 26372258
  11. 11

    PHOX2B: a diagnostic cornerstone in neurocristopathies and neuroblastomas.

    Windels ML, Cordier F, Van Dorpe J, et al.

    Journal of clinical pathology 2024; (77(6)):378-382 doi:10.1136/jcp-2023-209047.

    PMID: 38458747
  12. 12

    Identification of New Potential LncRNA Biomarkers in Hirschsprung Disease.

    Torroglosa A, Villalba-Benito L, Fernández RM, et al.

    International journal of molecular sciences 2020; (21(15)) doi:10.3390/ijms21155534.

    PMID: 32748823
  13. 13

    RET gene is a major risk factor for Hirschsprung's disease: a meta-analysis.

    Tomuschat C, Puri P

    Pediatric surgery international 2015; (31(8)):701-10 doi:10.1007/s00383-015-3731-y.

    PMID: 26164711
  14. 14

    A genome-wide association analysis of chromosomal aberrations and Hirschsprung disease.

    Bae JS, Koh I, Cheong HS, et al.

    Translational research : the journal of laboratory and clinical medicine 2016; (177()):31-40.e6 doi:10.1016/j.trsl.2016.06.001.

    PMID: 27370899
  15. 15

    A Scoring System to Predict the Severity of Hirschsprung Disease at Diagnosis and Its Correlation With Molecular Genetics.

    Núñez-Ramos R, Fernández RM, González-Velasco M, et al.

    Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 2017; (20(1)):28-37 doi:10.1177/1093526616683883.

    PMID: 28276298
  16. 16

    Effects of RET, NRG1 and NRG3 Polymorphisms in a Chinese Population with Hirschsprung Disease.

    Yang D, Yang J, Li S, et al.

    Scientific reports 2017; (7()):43222 doi:10.1038/srep43222.

    PMID: 28256518
  17. 17

    Correction of Hirschsprung-Associated Mutations in Human Induced Pluripotent Stem Cells Via Clustered Regularly Interspaced Short Palindromic Repeats/Cas9, Restores Neural Crest Cell Function.

    Lai FP, Lau ST, Wong JK, et al.

    Gastroenterology 2017; (153(1)):139-153.e8 doi:10.1053/j.gastro.2017.03.014.

    PMID: 28342760
  18. 18

    Advances in understanding the association between Down syndrome and Hirschsprung disease (DS-HSCR).

    Moore SW

    Pediatric surgery international 2018; (34(11)):1127-1137 doi:10.1007/s00383-018-4344-z.

    PMID: 30218169
  19. 19

    Sonographic findings of total colonic aganglionosis in a neonate with Haddad syndrome: A case report.

    Lim YJ, Jung HK

    Journal of clinical ultrasound : JCU 2022; (50(6)):810-813 doi:10.1002/jcu.23147.

    PMID: 35080777
  20. 20

    Polymicrogyria in a 10-month-old boy with Mowat-Wilson syndrome.

    Murray SB, Spangler BB, Helm BM, Vergano SS

    American journal of medical genetics. Part A 2015; (167A(10)):2402-5 doi:10.1002/ajmg.a.37171.

    PMID: 26012591
  21. 21

    A Case Report of a Prenatally Missed Mowat-Wilson Syndrome With Isolated Corpus Callosum Agenesis.

    Şenbil N, Arslan Z, Sayın Kocakap DB, Bilgili Y

    Child neurology open 2021; (8()):2329048X211006511 doi:10.1177/2329048X211006511.

    PMID: 33997095
  22. 22

    Familial Hirschsprung's disease: a systematic review.

    Mc Laughlin D, Puri P

    Pediatric surgery international 2015; (31(8)):695-700 doi:10.1007/s00383-015-3730-z.

    PMID: 26179259
  23. 23

    Hirschsprung disease: Insights on genes, penetrance, and prenatal diagnosis.

    Wang XJ, Camilleri M

    Neurogastroenterology and motility 2019; (31(11)):e13732 doi:10.1111/nmo.13732.

    PMID: 31609069
  24. 24

    High Levels of Interest in Reproductive Genetic Information in Parents of Children and Adults With Hirschsprung Disease.

    Berrios CD, Chakravarti A, Biesecker BB

    Journal of pediatric gastroenterology and nutrition 2019; (69(3)):299-305 doi:10.1097/MPG.0000000000002392.

    PMID: 31107799

This page provides educational information about Hirschsprung disease subtypes and genetics. Always consult a pediatric gastroenterologist or genetic counselor for advice specific to your child and family's unique situation.

Get notified when new evidence is published on Hirschsprung disease.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.