The disorder may occur by itself or in association with other genetic disorders such as Down syndrome. About half of isolated cases are linked to a specific genetic mutation and about 20% occur within families. Some of these occur in an autosomal dominant manner. The cause of the remaining cases is unclear. If otherwise normal parents have one child with the condition, the next child has a 4% risk of being affected. Genetics Type OMIM Gene Locus<unk> 1 RET 10q11.2<unk> 2 EDNRB 13q22<unk> 3 GDNF 5p13.1-p12<unk> 4 EDN3 20q13.2-q13.3<unk> 5 ? 21q22<unk> 6 ? 3p21<unk> 7 ? 19q12<unk> 8 ? 16q23<unk> 9 ? 4q31-32 — SOX10 22q13 — ECE1 1p36.1 — NRTN 19p13.3 — GEMIN2 (Gem-associated protein 2) 14q13-q21 — NTRK1 1q23.1 — ZEB2 2q22.3 Several genes and specific regions on chromosomes (loci) have been shown or suggested to be associated with<unk> : 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 can cause cancer if it is mutated or overexpressed. RET proto-oncogene RET is a gene that codes for proteins that assist cells of the neural crest in their movement through the digestive tract during the development of the embryo. Those neural crest cells eventually form bundles of nerve cells called ganglions. EDNRB codes for proteins that connect these nerve cells to the digestive tract. Thus, mutations in these two genes could directly lead to the absence of certain nerve fibers in the colon. Research suggests that several genes are associated with<unk> . Also, new research suggests that mutations in genomic sequences involved in regulating EDNRB have a bigger impact on<unk>  than previously thought. RET can mutate in many ways and is associated with Down syndrome. Since Down syndrome is comorbid in 2% of<unk> 's cases, a likelihood exists that RET is involved heavily in both<unk>  and Down syndrome. RET is also associated with medullary thyroid cancer and neuroblastoma, which is a type of cancer common in children. Both of these disorders are more common in<unk> 's patients than in the general population. One function that RET controls is the travel of the neural crest cells through the intestines in the developing fetus. The earlier the RET mutation occurs in<unk> , the more severe the disorder becomes. Other genes Common and rare DNA variations in the neuregulin 1 (NRG1) and NRG3 (NRG3) were first shown to be associated with the<unk>  in Chinese patients through a Genome Wide Association Study by the Hong Kong team in 2009 and 2012, respectively Subsequent studies in both Asian and Caucasian patients confirmed the initial findings by the University of Hong Kong. Both rare and common variants in these two genes have been identified in additional Chinese, Thai, Korean, Indonesian, and Spanish patients. These two genes are known to play a role in the formation of the enteric nervous system; thus, they are likely to be involved in the pathology of<unk> , at least in some cases. Another gene associated with this condition is NADPH oxidase, EF-hand calcium binding domain 5 (NOX5). This gene is located on the long arm of chromosome 15 (15q23).
Hirschsprung's disease
Meconium
Retained antrum syndrome
Intestinal pseudo-obstruction
Hartnup disease
Necrotizing enterocolitis
Meckel's diverticulum
Intestinal malrotation