Pediatric Surgery International https://doi.org/10.1007/s00383-019-04580-4 ORIGINAL ARTICLE Concurrent Hirschsprung’s disease and anorectal malformation: a systematic review Hiroki Nakamura1 · Prem Puri1,2 Accepted: 12 September 2019 © Springer-Verlag GmbH Germany, part of Springer Nature 2019 Abstract Background/purpose Hirschsprung’s disease (HSCR) and anorectal malformation (ARM) are often associated with other congenital malformations, but the association of each other is rare. Some studies have reported the incidence of HSCR associated with ARM ranging from 2.0 to 3.4%. The purpose of this study was to update the current epidemiological and therapeutic features of this rare congenital association. Methods A systematic literature search for relevant articles was performed in four databases using a combination of the following terms “association of Hirschsprung’s disease and anorectal malformation”, “aganglionosis and anorectal malformation” and “congenital megacolon and anorectal malformation” for studies published between 1952 and 2019. Reference lists were screened for additional cases. Results Forty-three studies met the defined inclusion criteria, reporting a total of 126 patients who were diagnosed with HSCR with ARM. Thirty articles reported 42 single case reports of this association. Twelve articles reported 66 cases of HSCR in case series of 3309 ARM patients, resulting in an incidence of 2% of this association. Associated syndrome was found in 25 cases (20%): Currarino syndrome in 11, Down syndrome in 8, Cat eye syndrome in 4 and Pallister–Hall syndrome in 2 patients. Extent of aganglionosis was reported in 62 cases: short or rectosigmoid aganglionosis was reported in 44, long segment aganglionosis in 8, total colonic aganglionosis in 9 and total intestinal aganglionosis in 1 case. Conclusion Although the association of ARM and HSCR is rare, the incidence of HSCR among ARM cases seems to be higher than in the general pediatric population. There was a high incidence of coexistence of ARM and HSCR with severe associated syndromes. Keywords Hirschsprung’s disease · Anorectal malformation · Associated syndromes Introduction Hirschsprung’s disease (HSCR) and anorectal malformation (ARM) are often associated with other congenital malformations encountered in pediatric surgery, with an incidence of 1:5000 live births, but the association of both disease is rare [1–5]. The incidence of HSCR associated with ARM have been reported ranging from 2.0 to 3.4% [6, 7]. The purpose * Prem Puri [email protected] 1 National Children’s Research Centre, Our Lady’s Children’s Hospital, Dublin, Ireland 2 School of Medicine and Medical Science and Conway Institute of Biomolecular and Biomedical Research University College Dublin, Dublin, Ireland of this study was to update the current epidemiological and therapeutic features of this rare congenital association. Materials and methods A systematic review and meta-analysis were conducted based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search of the literature was performed in the Pubmed, Embase, Medline and Cochrane Library electronic database for the keywords “association of Hirschsprung’s disease and anorectal malformation”, “aganglionosis and anorectal malformation” and “congenital megacolon and anorectal malformation” for studies published between 1952 and 2019. There was no restriction regarding the language of the publications. Reference lists of relevant articles were 13 Vol.:(0123456789) Pediatric Surgery International manually searched for further cohorts. Duplicates were deleted. Resulting publications were reviewed in detail for epidemiology, operative treatment, morbidity and clinical outcome. The relevant articles were reviewed by title, keywords and abstract by the authors (H. N. and P. P.) and a full-text assessment of selected articles was performed. Results The initial search yielded a total of 239 publications, of which 236 were identified by electronic database searching and 3 from cross-referencing (Fig. 1). After removal of 85 duplicate listed articles, 154 titles, keywords and abstracts were screened. Of these, 102 non-relevant studies were excluded. The remaining 52 publications were assessed in full-text for eligibility and 9 articles were excluded because they did not address any of the selection criteria. In total, data from 43 studies (published between 1952 and 2019) met defined inclusion criteria and was included in the cumulative analysis [1, 6–48]. Fig. 1 This is an information flow diagram, demonstrating the process of selection and exclusion of articles from the literature search for the purposes of systematic review 13 Forty-three studies met the defined inclusion criteria, reporting a total of 126 patients who were diagnosed with HSCR with ARM. Thirty articles reported 42 single case reports of this association. Twelve articles reported 66 cases of HSCR in case series of 3309 ARM patients, resulting in an incidence of 2% of this association. Associated syndrome was reported in 25 cases (20%): Currarino syndrome in 11, Down syndrome in 8, Cat eye syndrome in 4 and Pallister–Hall syndrome in 2 patients (Table 1). Extent of aganglionosis was reported in 62 cases: short or rectosigmoid aganglionosis in 44, long segment aganglionosis in 8, total colonic aganglionosis in 9 and total intestinal aganglionosis in 1 case (Table 2). The mean duration of the diagnosis of HSCR after initial diagnosis of ARM was 8 months. The surgical treatment of HSCR was reported in 45 patients. Different type of pull-through procedures after correction of ARM (36 cases), sphincter myectomies (2 cases) and 7 patients underwent only one pull-through operation for concurrent HSCR and ARM correction. Pediatric Surgery International Table 1 Associated syndrome in patients with HSCR and coexisting ARM Syndrome Number Currarino syndrome Down syndrome Cat-eye syndrome Pallister–Hall syndrome 11 8 4 2 Table 2 Extent of aganglionosis Type Number Short or rectosigmoid Long Total colon Total intestine 44 8 9 1 Discussion Both HSCR and ARM are relatively common congenital anomalies encountered in pediatric surgery [1]. The association of both anomalies is very rare with an incidence of 2.0–3.4% [1]. This systematic review showed the incidence of HSCR associated with ARM cases was 2.0%. This result consisted of 1.26% HSCR cases in 398 patients with ARM in India [46] to 3.4% HSCR cases in 296 cases of ARM in an early survey of pediatric surgeons in the US and Canada [6]. Of the 42 single cases, 23 cases (54.7%) have been reported with the associated syndromes. This high incidence of associated syndromes (e.g. Down syndrome, Cat eye syndrome, Currarino triad and Pallister–Hall syndrome) may be partly explained by the local genetic pool of the patients studied [24, 45]. Teerlink et al. [45] reported 18 ARM cases were diagnosed with HSCR, whose outcomes may indicate some genetic component resulting in both ARM and HSCR. In this review, two cases had Pallister–Hall syndrome. Prenatal genetic testing for Pallister–Hall syndrome identified a GLI3 heterozygous, apparently de novo novel nonsense mutation [47]. Gastrointestinal malformations may occur in Pallister–Hall syndrome because GLI3 affects the SHH pathway, which plays a role in development and signaling pathways between layers of embryonic tissue [47, 49]. Animal models have suggested defects in SHH signaling pathway can lead to genitourinary anomalies such as imperforate anus [50] and dilation of the gastrointestinal tract similar to HSCR [47, 49]. It is not easy to diagnose HSCR with ARM because the underlying ARM may be masking classical HSCR symptoms such as the delayed passage of meconium and abdominal distension. Watanatittan et al. [41] reported a large series and concluded that the diagnosis was delayed after full correction of ARM owing to atypical symptomatology and radiological findings. Eltayeb et al. [7] reported that five cases in their series had delayed diagnosis. The patients had developed abdominal distention and progressive constipation that were masked by the functioning stoma done as a first stage of ARM corrections [7]. Hoffman et al. [1] reported that 88% of the HSCR patients with ARM had continence after ARM and HSCR correction at the end of the followed-up period. Eltayeb et al. [7] reported that 72% of patients showed continence scores were fair or good. However, the limitation of this study is that the mean follow-up period was very short, only 36 months. Conclusion Although the association of ARM and HSCR is rare, the incidence of HSCR among ARM cases seems to be higher than in the general pediatric population. There was high incidence of coexistence of ARM and HSCR with sever associated syndrome. It is important to have attention for rectal biopsy for the patient with severe and progressive constipation after full correction of ARM. 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