Skip segment Hirschsprung's disease in a patient with Shah ... · Skip segment Hirschsprung’s disease in a patient with Shah-Waardenburg Syndrome Sofía Lizandro Ruiz*, Carolina

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J Ped Surg Case Reports 15 (2016) 44e47

Journal of Pediatric Surgery CASE REPORTS

Skip segment Hirschsprung’s disease in a patient withShah-Waardenburg Syndrome

Sofía Lizandro Ruiz*, Carolina Moreno Hurtado, Rute Cavaco Fernandes,José Ignacio Santamaría Ossorio, Ramón Núñez NúñezDepartment of Pediatric Surgery, Hospital Universitario Materno Infantil, SES, Calle Violeta, 4, 06010, Badajoz, Extremadura, Spain

a r t i c l e i n f o

Article history:Received 18 July 2016Received in revised form29 August 2016Accepted 29 August 2016

Keywords:Skip segment Hirschsprung’s diseaseWaardenburg syndromeIntestinal biopsy

* Corresponding author.E-mail address: [email protected] (S.L

2213-5766/� 2016 The Authors. Published by Elsevierhttp://dx.doi.org/10.1016/j.epsc.2016.08.012

a b s t r a c t

Introduction: We present a new case of Skip segment Hirschsprung’s disease (SSHD) associated toWaardenburg’s syndrome, in a patient with total colonic aganglionosis (TCA). Even though there aremore than 30 cases reported in the literature, SSHD’s existence is controversial, due to the fact that thereis not clear embriological theory to explain this phenomenon.Case report: 20 months-old male patient, that at four days-old had a temporary ileostomy because of anepisode of intestinal obstruction. A microileum and right microcolon was observed at the moment ofsurgery. Biopsies of the ileum and microcolon confirmed the aganglionism. At four months-old definitivesurgery was performed according to Boley’s procedure. Hystopathological study of the surgical pieceshowed absence of ganglion cells in cecum and ascending colon (SSHD). The postoperatory has beenfavorable. A mutation in SOX10 gen was objectified in the molecular study, that confirmed the ShahWaardenburg syndrome.Discussion: Most of cases of SSHD were observed in patients with TCA, as in our case. These patientsusually need a temporary stoma before the definitive surgery. We think that the only way to discoverSSHD cases is to make extended biopsies in left, transverse and right colon, and in ileum, while per-forming the ileostomy or in the definitve surgery.Conclusion: SSHD must be included as a new phenotype in Hirschsprung spectrum. Preservation of theseintestinal segments can improve intestinal function, specially in patients with TCA.� 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND

license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Hirschsprung’s disease (HD) is characterized by the absence ofthe enteric nervous system in the bowel [1]. In most cases, the dis-ease involves the rectum or rectosigmoid, but it can involve (5e10%of the cases) the entire colon or even a significant amount of thesmall intestine [1]. HD results from failure of enteric neural crest-derived cells to complete colonization of the intestine during fetaldevelopment (5th to 12th weeks of gestation) [2,3]. It is postulatedthat the earlier arrest of migration, the longer the resulting agan-glionic segment [3]. Skip segmentHirschsprung’s disease (SSHD) is arare phenomenon, involving a ‘skip area’ in a normally ganglionatedintestine, which is surrounded proximally and distally by aganglio-nosis [3]. The occurrence of SSHD has no clear embryologicalexplanation and its diagnosis may bemissed as it is rarely suspectedat initial surgery. Despite the first case being reported as early as1954 [4] and the 30 cases that have been reported to date, its

. Ruiz).

Inc. This is an open access article u

existence is often questioned on theoretical grounds. Waardenburgsyndrome (WS) is a rare autosomal recessive neurocristopathy withvariable presentation. Four types ofWS are described. Type-IV is theassociation of WS with HD. This type is called Shah-WaardenburgSyndrome (SWS). The classic presentations of SWS include HD,sensorineural deafness, and depigmentation of hairs, skin, and theiris [5]. In patients with SWS, the aganglionic segment may be longandmayhave total colonic or total intestinal aganglionosis [6,7]. Thetreatment of HD is surgical and involves the removal of the agan-glionic segment and anastomosis of the innervated bowel to theanus above the dentate line [1].

The aim of this report is to present a new case of SSHD in apatient with total colonic aganglionosis associated with Waarden-burg syndrome and a systematic review of literature.

1. Case report

A 20-month-old male child is the first child of non-consan-guineous healthy parents, born at term with a birth weight of

nder the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Fig. 1. Abdominal X-ray: dilated loops and no gas in distal colon. Fig. 2. A contrast enema of 4 months old. Left microcolon and normal appearance ofthe right colon was observed.

Fig. 3. Ileocoloplasty according to Boley’s procedure.

S.L. Ruiz et al. / J Ped Surg Case Reports 15 (2016) 44e47 45

2550 g. Family history (second degree) of HD was present. Therewas history of failure of meconium passage within the first48 hours. Twelve hours later, the patient began to displayfeeding intolerance, abdominal distention and bilious vomiting.On admission he was noted to be in poor general condition withsigns of dehydration and jaundice, while also displaying painfulabdominal distention. There was no explosive stool after digitalrectal exam, but narrow rectal ampulla was observed. Thepatient had blonde hair and blue eyes, with rotatory nystagmus.A plain abdominal X-ray (Fig. 1) showed dilated loops (probablyof the small intestine), and no gas was observed in the distalcolon, suggesting intestinal obstruction. A left microcolon wasidentified through an enema study with gastrografin. Thelaparatomy performed at four days old identified a microcolonand microileon (80 cm), with proximal dilatation; therefore, atemporary ileostomy was made. Also, intestinal biopsies(microileun and microcolon) were performed, which confirmedthe aganglionism.

The patient remained hospitalized for a few months due toseveral episodes of enterocolitis, and as result of the malabsortionrelated to short bowel syndrome. A contrast enema (Fig. 2) madein the fourth month revealed a left microcolon and normalappearance of the right colon.

Afterward, a Boley type ileocoloplasty (Fig. 3), with mechanicalsuture, was performed. In it, a segment (10 cm) of the right colonwas anastomosed to a normal ileon. Next, the cecum, with a partof the ascending colon, left microcolon and microileon wereresected (Fig. 4). The intervention was completed by ileorectalanastomosis (Rehbein procedure). The patient had a favorableevolution during the postoperative period, needing daily rectalirrigations with saline, in the first months of his life. Nowadays thepatient has good weight for height development. A hystopatho-logical study of the resected intestine (Fig. 4) revealed the

presence of ganglion cells in a 10 cm segment of the right colon(cecum and ascending colon) and aganglionism in the rectum,rectosigmoid, descending colon and microileum (Fig. 5AeD) (skipsegment Hirschprung’s disease). Stunted psychomotor develop-ment was observed, associated with deep bilateral deafness. Car-yotype and metabolic studies came back normal. Aberrantmyelination was found through magnetic resonance imaging. Amolecular genetic study showed a novo mutation in SOX10 genthat confirmed the SWS syndrome.

Fig. 4. Surgical piece: Left microcolon and 80 cm of microileum. Normal appearing ofthe right colon. A 10 cm segment of ascending colon and initial segment of transversecolon (used in the ileocoloplasty) is not shown.

S.L. Ruiz et al. / J Ped Surg Case Reports 15 (2016) 44e4746

2. Discussion

Skip segment Hirschsprung’s disease (SSHD) is a term used torefer a normally ganglionated intestine, surrounded proximally

Fig. 5. Hystopathological study of surgical piece (calretinin immunohistochemistry). A: Aganglion cells in the submucosal plexus of the cecum. C. Presence of ganglion cell in the submfibers in the mienteric plexus of the left colon.

and distally by aganglionosis. It cannot be confused with ‘zonalaganglionosis’, that referes to an aganglionic intestinal segmentbetween two normally innervated segments [8]. ‘Double zonalaganglionosis’ refers to an aganglionic segment that contains anarea of normal innervation; it differs from SSHD in that, in thelater, the rectum is always aganglionic whereas in ‘double zonal’aganglionosis, it can be ganglionic [9]. HD is the most commonneurocristopathy in humans (1/5000 new borns) and is char-acterized by the absence of ganglion cells along an intestinalsegment that in 70e80% is the distal segment, i.e. the rec-tosigmoid [2]. This condition causes the affected segment todisfunction and episodes of intestinal obstruction, especially innewborns [10]. The lower limit of HD is always constant(internal anal sphincter) while the upper limit is variable. Thisallows us to classify HD into various phenotypes: Short segment(S-HD: aganglionosis up to the upper sigmoid colon), longsegment (L-HD: aganglionosis up to the splenic flexure andbeyond), and the total colonic aganglionosis (TCA) forms [11].According to our review of the English literature (Table 1), thereare more than 30 described cases of SSHD [3,9,12e17] therefore,this phenotype should be included in the HD’s spectrum. Of allthose cases, approximately 90% were observed in the TCA withthe remaining cases being the rectosigmoid type of HD. Thelength of the SSHD segment, according to the cases described,has oscillated from a few centimeters (9 cm) in some children, tothe entire ganglionated transverse colon in others [3,12]. TheSSHD in our patient, according to the hystopathological study,affected the cecum and ascending colon (10 cm). HD’setiology has no clear explanation, but the participation of themain genes (RET, EDNRB, EDN3, SOX10) is known; they areresponsible for the migration, proliferation, differentiation andsurvival of the neural crest-derived cells during the embryonicenteric nervous system (ENS) development (5th to 12th weeks

bsence of ganglion cells in the submucosal plexus of the microileum. B. Presence ofucosal plexus of ascending colon. D. Absence of ganglion cells and hypertrophy of nerve

Table 1Cases of SSHD reported in the literature from 1954 to 2016.

Reference Year Sex Numberpatients

Location of skip segment

Keefer 1954 M 1 Rectosigmoid with skip in sigmoidSprinz 1961 F 1 TCA except skip in transverse colonMac Iver 1972 M 1 Rectosigmoid with skip in sigmoidMartin 1979 M 1 TCA except skip in transverse colonDe Chadarevian 1982 M 1 TCA except skip in transverse colonYunis 1983 M 5 TCA except skip in transverse colon

TCA except skip in transverse colonTCA except skip in transverse colonTCA except skip in transverse colonTCA except skip in ascending colon

Taguchi 1983 M 1 TCA except skip in ascending colonSeldenrijk 1986 M 2 TCA with multiple skips

F TCA with multiple skipsAnderson 1986 M 1 TCA except skip in ascending colonKapur 1995 F 2 TCA except skip in ascending colon

F TCA except skip in cecumYang 2005 M 3 TCA with multiple skips

TCA with multiple skipsTCA with multiple skips

Ziad 2006 M 2 TCA except skip in transverse colonF TCA except skip in cecum

Oshio 2008 M 1 TCA except skip in ascending colonPuri 2010 M 1 TCA except skip in trasnverse colonDoi 2011 F 1 TCA except skip in trasnverse colonBurjonrappa 2012 M 1 TCA except skip in ascending colonMoore 2013 M 2 Skip in right and descending colon

F Skip in ascending colon and appendixErten 2014 M 1 TCA except skip in hepatic flexureRagunath 2014 M 1 TCA with skip in ascending colon andHepatic flexureGross 2015 M 1 Skip in transverse and descending colonCurrent case 2016 M 1 TCA except skip in cecum and

ascending colon

S.L. Ruiz et al. / J Ped Surg Case Reports 15 (2016) 44e47 47

of gestation) [18]. The consequence of these genes mutations isthe absence of the enteric nervous system (ENS), that is, agan-glionosis in an intestinal segment. However, the occurrence ofSSHD currently has no clear embryological explanation. Themost convincing theory, according to studies in murine mice, isthat SSHD comes from an anormal pattern of extramuralmigration of the neural crest cells, during embryologicaldevelopment [14]. In 70% of HD’s cases the condition appearsclinically isolated, with the remaining cases being associatedwith other neurocristopathies, like Waardenburg syndrome (1/50.000 newborns), chromosomopathies (Down syndrome in2e10% of cases) or other congenital diseases (18% of patients).In our case, as in the one described by Gross et al. [14], SSHD isassociated with Waardenburg syndrome, confirmed in bothcases by molecular study [19]. A family history of HD canexist (our patient had a second degrade family member). Theheredity can be dominant or recessive, with reduced penetrance,and is mostly found in males. The risk of recurrence betweenbrothers is 200 times more than in the general population [11].A rectal suction biopsy, showing aganglionosis in the submu-cosa, is the golden standard for HD’s diagnosis [20] and acontrast enema is useful to gauge the transitional segment andknow the extension of the aganglionism, but neither allow fordetection of SSHD.

Most patients with TCA need a temporary ileostomy beforethe definitive surgery. That’s why we agree with Burjonrappaand Rankin [15] that, apart from searching for more thanone transitional segment, extended segment intestinal biopsiesin the left and the right colon, the cecum and the small

intestine should be included in the diagnosis of SSHD in L-HDand TCA. If we had proceeded like this, we probably would havechanged the surgical technique, using Kimura’s procedure, asRaguhunath et al. describe [9]. The small intestinal segment inour case was quite long (80 cm), which could have avoided theresection of the right colon. Although Boley’s procedure (Fig. 4)had a favorable functional result, the patient needed daily rectalirrigations with saline during the first postoperative months inorder to prevent enterocolitis.

3. Conclusions

To conclude, SSHD has enough identifying features tobe included in the HD’s classification as a new phenotype. Inpatients with TCA we should investigate the possibility ofSSHD, because preservation of these segments can have a positiveinfluence on the postoperative functional results.

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