s00383-019-04580-4

Vol.:(0123456789)
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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fol-
lowing terms “association of Hirschsprung’s disease and anorectal malformation”, “aganglionosis and anorectal malforma-
tion” 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 malforma-
tions 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
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 data-
base for the keywords “association of Hirschsprung’s disease
and anorectal malformation”, “aganglionosis and anorec-
tal malformation” and “congenital megacolon and anorec-
tal malformation” for studies published between 1952 and
2019. There was no restriction regarding the language of
the publications. Reference lists of relevant articles were
* 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

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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, key-
words 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].
Forty-three studies met the defined inclusion crite-
ria, 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. Associ-
ated 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 agan-
glionosis 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 ini-
tial diagnosis of ARM was 8months. The surgical treat-
ment 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.
Fig. 1 This is an information
flow diagram, demonstrating the
process of selection and exclu-
sion of articles from the litera-
ture search for the purposes of
systematic review

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Discussion
Both HSCR and ARM are relatively common congenital
anomalies encountered in pediatric surgery [1]. The asso-
ciation of both anomalies is very rare with an incidence
of2.0–3.4% [1]. This systematic review showed the inci-
dence 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 inci-
dence 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 test-
ing for Pallister–Hall syndrome identified a GLI3 het-
erozygous, apparently de novo novel nonsense mutation
[47]. Gastrointestinal malformations may occur in Pallis-
ter–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 mod-
els 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 symptoma-
tology and radiological findings. Eltayeb etal. [7] reported
that five cases in their series had delayed diagnosis. The
patients had developed abdominal distention and progres-
sive 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 correc-
tion 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 inci-
dence of coexistence of ARM and HSCR with sever associ-
ated syndrome. It is important to have attention for rectal
biopsy for the patient with severe and progressive constipa-
tion after full correction of ARM.
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of
interest.
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