Familial Hirschsprung’s Disease

Puri, Prem; Nakamura, Hiroki

doi:10.1007/978-3-030-15647-3_6

Cited by 5 publications

(5 citation statements)

References 22 publications

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“…It most commonly presents as sporadic forms (80–90%), which are more often S-HSCR and follow a multifactorial inheritance pattern. The remaining 10–20% of cases are familial and tend to be of L-HSCR/TCA with autosomal dominant inheritance ( 2 , 9 ). HSCR also exhibits significant sex bias with a marked male preponderance.…”

Section: Introductionmentioning

confidence: 99%

The Emerging Genetic Landscape of Hirschsprung Disease and Its Potential Clinical Applications

2021

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Hirschsprung disease (HSCR) is the leading cause of neonatal functional intestinal obstruction. It is a rare congenital disease with an incidence of one in 3,500–5,000 live births. HSCR is characterized by the absence of enteric ganglia in the distal colon, plausibly due to genetic defects perturbing the normal migration, proliferation, differentiation, and/or survival of the enteric neural crest cells as well as impaired interaction with the enteric progenitor cell niche. Early linkage analyses in Mendelian and syndromic forms of HSCR uncovered variants with large effects in major HSCR genes including RET, EDNRB, and their interacting partners in the same biological pathways. With the advances in genome-wide genotyping and next-generation sequencing technologies, there has been a remarkable progress in understanding of the genetic basis of HSCR in the past few years, with common and rare variants with small to moderate effects being uncovered. The discovery of new HSCR genes such as neuregulin and BACE2 as well as the deeper understanding of the roles and mechanisms of known HSCR genes provided solid evidence that many HSCR cases are in the form of complex polygenic/oligogenic disorder where rare variants act in the sensitized background of HSCR-associated common variants. This review summarizes the roadmap of genetic discoveries of HSCR from the earlier family-based linkage analyses to the recent population-based genome-wide analyses coupled with functional genomics, and how these discoveries facilitated our understanding of the genetic architecture of this complex disease and provide the foundation of clinical translation for precision and stratified medicine.

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Section: Introductionmentioning

confidence: 99%

The Emerging Genetic Landscape of Hirschsprung Disease and Its Potential Clinical Applications

2021

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“…The finding that HD is more often present in males is in line with the current literature. [34][35][36] In addition, we found that patients with a syndrome, mainly Down's syndrome, have a higher probability of HD. Indeed, an associated chromosomal abnormality has been reported in 12% of patients with HD.…”

Section: Discussionmentioning

confidence: 66%

Diagnosing Hirschsprung Disease in Children Younger than 6 Months of Age: Insights in Incidence of Complications of Rectal Suction Biopsy and Other Final Diagnoses

et al. 2023

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Background The gold standard for diagnosing Hirschsprung disease (HD) in patients younger than 6 months is pathological examination of rectal suction biopsy (RSB). The aim of this study was to gain insight into the following: (1) complications following RSB, (2) final diagnosis of patients referred for RSB, and (3) factors associated with HD. Methods Patients suspected of HD referred for RSB at our center were analyzed retrospectively. Severity of complications of RSB was assessed using Clavien–Dindo (CD) grading. Factors associated with HD were tested using multivariate logistic regression analysis. Results From 2000 to 2021, 371 patients underwent RSB because of infrequent defecation, at a median age of 44 days. Three patients developed ongoing rectal bleeding (0.8%) graded CD1. Most frequent final diagnoses were: HD (n = 151, 40.7%), functional constipation (n = 113, 31%), idiopathic meconium ileus (n = 11, 3%), and food intolerance (n = 11, 3%). Associated factors for HD were male sex (odds ratio [OR], 3.19; confidence interval [CI], 1.56–6.53), presence of syndrome (OR, 7.18; CI, 1.63–31.69), younger age at time of RSB (OR, 0.98; CI, 0.85–0.98), meconium passage for more than 48 hours (OR, 3.15; CI, 1.51–6.56), distended abdomen (OR, 2.09; CI, 1.07–4.07), bilious vomiting (OR, 6.39; CI, 3.28–12.47), and failure to thrive (OR, 8.46; CI, 2.11–34.02) (model R 2 = 0.566). Conclusion RSB is a safe procedure with few and only minor complications. In the majority of patients referred for RSB under the age of 6 months, HD was found followed by a functional cause for the defecation problems. RSB should be obtained on a low threshold in all patients under the age of 6 months with the suspicion of HD.

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“…Over 90% of HD patients fail to pass the meconium within 24 hours after birth. [15] Total number of paƟents(n= 128) paƟents met the inclusion criteria (n=109) missing data (n=30) number of paƟents analysed (n=79)…”

Section: Discussionmentioning

confidence: 99%

Children with Hirschsprung disease in a developing country: A cohort study of the predictors of a positive rectal biopsy result

et al. 2022

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Chronic constipation, which may be habitually or pathologically caused, is one of the most common complaints in children. One of the important pathological causes is Hirschsprung's disease (HD), which is diagnosed via multiple modalities, mainly rectal biopsy. Our aim was to compare the presentation and different predictive factors for positive rectal biopsy results in a developing country in the Middle East, such as Jordan. This cohort study was conducted at the Jordan University Hospital (JUH). All consecutive children aged <14 years who presented with refractory constipation and underwent rectal biopsies between January 2014 and December 2019 were retrospectively enrolled in the study. In the entire cohort study, 79 patients were enrolled: 45 (57%) were males and 34 (43%) were females. Regarding the biopsy results, 51 (64.6%) cases of refractory constipation without HD and 28 (35.4%) patients with refractory constipation with HD were diagnosed with open rectal biopsies. The male-to-female ratio of HD patients was 3:1. Moreover, 3 (10.7%) children who passed the meconium within the first 24 to 48 hours showed features of HD, while 17 (60.7%) children with delayed passage of the meconium showed features of HD. Abdominal distension was found to be a positive predictor of positive biopsy results (odds ratio [OR] = 4.09, P = .011), and soiling was found to be a negative predictor of positive biopsy results (OR = 0.07, P = .024). In developing countries, children presenting with HD seem to have similar symptoms and signs to those observed with traditional sampling and staining techniques.

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Familial Hirschsprung’s Disease

Cited by 5 publications

References 22 publications

The Emerging Genetic Landscape of Hirschsprung Disease and Its Potential Clinical Applications

The Emerging Genetic Landscape of Hirschsprung Disease and Its Potential Clinical Applications

Diagnosing Hirschsprung Disease in Children Younger than 6 Months of Age: Insights in Incidence of Complications of Rectal Suction Biopsy and Other Final Diagnoses

Children with Hirschsprung disease in a developing country: A cohort study of the predictors of a positive rectal biopsy result

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