Hirschsprung, disease

[MIM 142 623600 155600 156606 874606875606 462611 474613 711613 712]

(Congenital megacolon, digestive aganglionosis )

Prevalence: 1/5000 births, 80% of boys. Mutation of the RET gene on locus 10q11.2 in half of the cases. Other possible gene mutations are: EDNRB (13q22), GDNF, EDN3, SOX10.

Neurocristopathy affecting the development of the neuroblasts of vagal origin and leading to the absence of the cell bodies of the intrinsic nervous system of the distal gut (aganglionosis), at the level of the Meissner and Auerbach plexus.

The failure of relaxation of the affected segment causes a functional occlusion with upstream dilation of the gut (the dilated part is healthy). Presentation : delay of meconium elimination, enterocolitis in a term newborn, intestinal occlusion.

Depending on the extent of aganglionosis from the internal anal sphincter, there are 3 forms:

-        short: aganglionosis extending up to the rectosigmoid (75 %);

-        long: aganglionosis concerning the whole colon (10 %);

-        ultra-short: aganglionosis limited to the lower part of the rectum (5 %).

In general, the short non-syndromic and non-familial forms are transmitted in a non-mendelian mode fashion with variable expression and penetrance depending on sex, while the syndromic and familial forms are transmitted either on a dominant (extended forms) or recessive (short forms) mode.

Frequent associations (30 % of cases): 

-         trisomy 21: there is then often also an esophageal dysfunction due to a deficiency in ganglion cells in the esophagus

-         deletion 13q22 ( EDNRB gene)

-         deletion 10q11.2 (RET gene)

-         deletion 2q 22 (ZFHX1B gene)

-         Haddad syndrome (congenital central alveolar hypoventilation or Ondine 'curse') (PHOX2B gene)

-         Shah-Waardenburg syndrome (Waardenburg type 4): deafness and pigmentary abnormalities of skin and iris (SOX 10 gene), often  very long aganglionosis form

-         Multiple Endocrine Neoplasia (MEN2A)

-         cartilage-hair hypoplasia syndrome (TMR gene on 9p13 mutation): skeletal dysplasia (spondylo-meta-epiphyseal dysplasia), anemia, immune deficit and 10% of these patients present Hirschprung disease

-         neuroblastoma, pheochromocytoma

Rare associations:  

-         Smith-Lemli-Opitz syndrome, 

-         Mowat-Wilson syndrome (ZEB2 /ZFHX1B genes on 2q22) 

-         Bardet-biedl syndrome

-         Goldberg-Shprintzen syndrome ( KIAA1279 gene on 10q22.1 )

-         KID syndrome (form of Ichthyosis Congenita)

-         monosomy 18 p

-         trisomy 18q

-         deletion 20 p

-         mosaicism XO/XX/XXX


Anesthetic implications: 

according to the mode of presentation and associated abnormalities.


References:


Updated: March 2019