Genetic Basis
Several genes and specific regions on chromosomes (loci) have been shown or suggested to be associated with Hirschsprung's disease:
| Type | OMIM | Gene | Locus |
|---|---|---|---|
| HSCR1 | 142623 | RET | 10q11.2 |
| HSCR2 | 600155 | EDNRB | 13q22 |
| HSCR3 | 600837 | GDNF | 5p13.1-p12 |
| HSCR4 | 131242 | EDN3 | 20q13.2-q13.3 |
| HSCR5 | 600156 | ? | 21q22 |
| HSCR6 | 606874 | ? | 3p21 |
| HSCR7 | 606875 | ? | 19q12 |
| HSCR8 | 608462 | ? | 16q23 |
| HSCR9 | 611644 | ? | 4q31-32 |
| – | 602229 | SOX10 | 22q13 |
| – | 600423 | ECE1 | 1p36.1 |
| – | 602018 | NRTN | 19p13.3 |
| – | 602595 | SIP1 | 14q13-q21 |
Hirschsprung's disease can also present as part of a syndrome in Waardenburg-Shah syndrome, Mowat-Wilson syndrome, Goldberg-Shpritzen megacolon syndrome, and congenital central hypoventilation syndrome.
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. A proto-oncogene is a gene that can cause cancer if it is mutated or over-expressed.
Research published in 2002 suggested that Hirschsprung's may be caused by the interaction between two proteins encoded by two variant genes. The RET proto-oncogene on chromosome 10 was identified as one of the two genes involved. The other protein that RET must interact with in order to cause Hirschsprung’s disease is termed EDNRB, and is encoded by the gene EDNRB located on chromosome 13.
Hirschsprung's disease, hypoganglionosis, gut dysmotility, gut transit disorders and intussusception have been recorded with the dominantly inherited neurovisceral porphyrias (acute intermittent porphyria, hereditary coproporphyria, variegate porphyria). Children may require enzyme or DNA testing for these disorders as they may not produce or excrete porphyrins prepuberty.
Read more about this topic: Hirschsprung's Disease
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