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Genetic and Rare Diseases Information Center (GARD)

Down syndrome


* Not a rare disease
Información en español

Other Names for this Disease
  • Trisomy 21
  • Down's syndrome
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.

Your Question

I lost a daughter in the late 70's due to complications from long segment Hirschsprung disease. I also lost a little sister when she was 6 months-old. She had Down syndrome, a heart defect, cleft lip and cleft palate, and a single kidney. Are these conditions related? My children are thinking about starting a family of their own. They would like to learn more about risks to their future offspring.

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

What causes Hirschsprung disease?

There are a number of different causes of Hirschsprung disease (HSCR). For example, HSCR may occur as:[1]

  • A part of a syndrome
  • In association with a chromosome anomaly (such as trisomy 21 or Down syndrome) 
  • Along with other birth defects but not as a part of a known syndrome
  • As an isolated condition
Last updated: 6/8/2012

How is Down syndrome and Hirschsprung disease related?

While not all children with Down syndrome have HSCR, they are at an increased risk for this condition. Approximately 12% of people with Down syndrome have HSCR (and 2-10% of people with HSCR have Down syndrome).[1] The underlying cause for this increased risk for HSCR is not well understood.

Down syndrome is usually not inherited, but occurs due to a random event during the formation of reproductive cells (egg or sperm) when an extra copy of chromosome 21 is passed on through the egg or sperm. You may be interested in learning more about general risk factors for this type of Down syndrome at the MayoClinic Web site. To visit the page click here.

Less commonly, a parent may carry a rearrangement of their chromosomes that increases their chance of having a child with Down syndrome as well as fertility problems and miscarriages. Click here to read more about this type of Down syndrome, called translocation Down syndrome.

A genetic professional can review your son and daughter-in-law's family history to help assess their specific chances of having a child with Down syndrome.

Last updated: 6/8/2012

Is isolated Hirschsprung disease inherited?

Isolated HSCR occurs in around 70% of individuals with HSCR. Isolated HSCR is thought to be caused by a combination of gene changes and environmental factors. Isolated HSCR has been associated with changes (mutations) in at least six genes.[1] Carrying one or more of these gene changes increases a person’s risk for HSCR, but most people who carry the gene changes never develop the condition. Recurrence risk can be estimated based upon a number of factors, including:[1]
  • The relationship of the relative to the affected individual (e.g., sibling, parent...)
  • The affected individual's gender 
  • The relative's gender 
  • The severity of HSCR (e.g., long segment vs. short segment disease)
  • Also the family's medical and testing history

Once again a genetic professional can help assess your children's, and their future offspring’s, risk for HSCR. Family history information (and where possible medical records) can be very important in assessing this risk. 

Last updated: 6/8/2012

What syndromes are associated with Hirschsprung disease?

Examples of syndromes associated with HSCR, include:[1]
  • Bardet-Biedl syndrome
  • Cartilage-hair hypoplasia
  • Familial dysautonomia
  • Fryns syndrome
  • Goldberg-Shprintzen syndrome
  • Intestinal neuronal dysplasia
  • L1 syndrome
  • Multiple endocrine neoplasia type 2A & 2B
  • Mowat-Wilson syndrome
  • Neurofibromatosis type 1
  • Smith-Lemli-Opitz syndrome
  • Waardenburg syndrome type 4
  • Congenital central hypoventilation syndrome

These syndromes have many other signs and symptoms. When HSCR occurs as part of a syndrome, inheritance risk will depend on the parent syndrome's mode of inheritance.

Last updated: 6/8/2012

How can I find a genetics professional in my area?

Genetics clinics are a source of information for individuals and families regarding genetic conditions, treatment, inheritance, and genetic risks to other family members. More information about genetic consultations is available from Genetics Home Reference. To find a genetics clinic, we recommend that you contact your primary healthcare provider for a referral.

The following online resources can help you find a genetics professional in your community:
Last updated: 6/5/2014

Other Names for this Disease
  • Trisomy 21
  • Down's syndrome
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.