Congenital Pouch Colon: Role of Genetics or Environmental Influence?

Abstract

Background: Congenital pouch colon (CPC), a high type of anorectal malformation, is a sporadic disease and several environmental factors are known to be involved in its pathology. To the best of our knowledge, no familial incidence of CPC has been reported anywhere in the literature so far. Aim: In the present study, which is first of its kind, we have reported the familial incidences of CPC and also tried to elucidate the role of genetics in this pathology. Methods: We have reported 1 familial pedigree of CPC and 2 incidences of dizygotic twins (DZ), out of them one is affected and another one is normal. Highly comprehensive microarray CytoScan HD from Affymetrix was employed to understand the defects underlying submicroscopic genomic imbalance like segment duplication and deletion of the twin patients vis-à-vis their parents and unaffected siblings in these DZ twins. Results: A total of 21 copy number variations (CNVs) were reported in the patient samples that did not overlap with the CNVs in normal parents and healthy sibling, including 5 loss, 3 LOH and 13 gain with size varied from 95 bp to 77 kbp. Genetic analysis revealed involvement of 12 potential genetic loci on Chr 1, 2, 3, 4, 6, 11, and 16. Conclusion: Genetic study found that CPC could be a developmental disorder. These findings are important for further elucidating genetic causes of CPC pathogenesis.

Is Pouch Specific to Colon and Not Ileum?

“…We observed several missense as well as frameshift variants to be in concordance with colorectal cancer exome datasets [38] besides a few non-coding RNAs especially lnc-EPB41-1-1 shown to be promiscuously interacting with KIF13A, a gene causal to CPC [39]. Furthermore, our microarray findings also show that few noncoding RNAs are differentially expressed in CPC samples [40]. On the other hand, the situation is notably different in ulcerative colitis in adults when compared to the Crohn's disease where there is recurrence [41].…”

“…The crux of the treatment lies on timely diagnosis and planned management. Hence, it is important for gastroenterologists and pediatric clinicians to be aware of the CNVs in form of 5 Loss, 3 LOH and 13 gain wew observed with size 95 bp to 77kbp [40] Discovered rare variants associated with CPC Stop gain and stop lost mutation were identified [32] Identified Inc-EPB41-1 from WES Inferred Inc-EPB41 interaction with KIF13Aprotein causal to CPC [ pathological perspective for proper diagnostic, evaluation and surgical management. The overall mortality of CPC was previously as high as 30-40%, but has now come down to 10-20% due to growing awareness of this condition and improvements in surgical and neonatal care management.…”

Congenital pouch colon in Duhok, outcome and complications: Case series

“…Many other factors have been found to be associated with the development of this condition such as environmental factors, genetic and dietary factors like iodine and vitamin B12 deficiency. About 90% of the cases are reported from India but recently there is increasing awareness about this rare anomaly and some cases are now reported from other parts of the world [4,[11], [12], [13]].…”

Pouch colon in children

“…Патология наиболее распространена на западе и севере Индии (2,5-9 % от всех аноректальных пороков), а также в Пакистане и Непале. Индийскими коллегами при анализе лечения 152 пациентов в период с 1992 по 2005 год было установлено, что у мальчиков врожденный порок развития встречался в семь раз чаще, чем у девочек [8,11,12].…”