Disease of Hirschsprung

disease of Hirschsprung is a faulty operation of the final part of the intestine resulting in a constipation or an obstruction of the bowels. This anomaly is the result of the absence of congenital development of the cells neuroganglionnaires ensuring the transmission of information necessary to the intestinal regulation.

This disease is regarded as a neurochristopathy or disease deriving from peaks neurales.

This disease can be isolated or to fall under a syndrome.

In the nonsyndromic forms, several genes were found responsible for this disease

Other names of the disease

Total digestive Aganglionose
Standard disease of Hirschsprung 1 dominant form
Standard disease of Hirschsprung 2 recessive form
Standard disease of Hirschsprung 3
mégacolon congenital

Incidence

1 out of 4000 births in 80 % of the cases a boy in the nonsyndromic forms.

Description

The majority of the children have delays of emission of méconium occurring only after more than 48 hours of life. The clinical signs are digestive: constipation, abdominal distension or vomiting or entérocolite. But 10 % HS will be made only after the age of 1 year (In the nonsyndromic forms)

Clinical forms

According to the extent of the attack of the disease at the intestinal level, one distinguishes:

Hirschsprung runs segment located to sigmoid in 80 % of the cases.
Hirschsprung long segment extended to the colonist in 15 % of the cases.
Localised total Hirschsprung with all the intestine in 5 % of the cases.

Diagnosis

Rest primarily on the intestinal biopsy of rectum who shows the hypertrophy of parasympathetic nervous fibres and the ganglionic absence of cell of the plexuses of Meissner.

Differential diagnosis

Etiology

Nonsyndromic forms

6 genes were identified like persons in charge for disease of Hirschsprung:

RET located on the locus q11.2 of chromosome 10. Gene generally implied in the family forms of disease of Hirschsprung.OMIM 164761 (rearranged during transfection protooncogene)
GDNF located on the locus p13.1-p12 of chromosome 5
NRTN located on the locus p13.3 of chromosome 19
EDNRB located on the locus q22 of chromosome 13
EDN3 located on the locus q13.2-q13.3 of chromosome 20
ECE1 located on the locus p36.1 of chromosome 1

Syndromic genetic forms

**GENETIC DISEASES COMPRISING A DISEASE OF HIRSCHSPRUNG**
Syndromes	Clinical signs	Transmission	Chromosome locus	Gene	Frequency	Number MIM
Syndrome of Bardet-Biedl	Backwardness Obesity Polydactyly Pigmentary retinite Renal and genital anomalies	Recessive		7 loci known	2-10%	209900
Recessive Chondrodysplasy métaphysaire autosomic	Nanism Hair rare Immunizing deficit	Recessive	9 p13	RMRP	7-9%	250250
Syndrome of Ondine	Hypoventilation Neuroblastome			PHOX2B/RET, GDNF, EDN3, BDNF	16%	209880
Family Dysautonomy		Recessive	9 q31	IKBKAP	?	[ 1 ]
Syndrome of Mowat-Wilson	Microcephalus Backwardness Sterility of the callous body Congenital Cardiopathy Epilepsy Small size	Dominant	2q22	ZFHX1B	62-70%	235730
idiopathic chronic intestinal Pseudo-obstruction		Dominant and Recessive	?	?	Until 20 %	243180
Syndrome of Goldberg		Recessive	10 q21.1	KIAA1279		609460
Neoplasy endocrinienne multiple type 2		Dominant		RET	Rare	171400
Standard Neurofibromatose 1		Dominant			Unknown	162200
Syndrome of Smith-Lemli-Opitz	Backwardness Syndactylie Cardiopathy Sexual anomalies	Recessive	11 q12-q13	DHCR7	Unknown	270400
Syndrome of Waardenburg-Shah		Dominant and Recessive			Almost 100%	[ 2 ]
L1 syndrome	Backwardness Sterility of the callous body Hydrocéphalie Inch in adduction	Recessive with X	X	L1CAM	Unknown	[ 3 ]

Chromosomal

Trisomy 21
Délétion 10q
Délétion 13q
Délétion 2q22

Cause unknown

Count for 10 to 15 % of the cases of disease of Hirschsprung.

Surgical treatment

Sources

(in) Online Mendelian Inheritance in Man, OMIM (TM). Johns Hopkins University, Baltimore, MANDELEVIUM. MIM Number: 142623 [ 4 ]
(in) Melissa A Parisi, Hirschsprung Disease Overview In: GeneReviews At GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2005. [ 5 ].