www.elsevier.com/locate/jpedsurg

Journal of Pediatric Surgery (2009) 44, 2211–2215

Congenital absence of intestinal smooth muscle: a casereport and review of the literatureDaniel Stephens a,⁎, Robert Arensmanb,Srikumar Pillai b, Victoria Alagiozian-Angelova c

aUniversity of Minnesota, Minneapolis, MN 55405, USAbUniversity of Illinois at Chicago, Chicago, IL 60607, USAcJohn H. Stroger Jr. Hospital of Cook County, Chicago, IL 60612, USA

Received 23 April 2009; revised 3 August 2009; accepted 6 August 2009

0d

Key words:Intestinal perforation;Newborn;Necrotizing enterocolitis;Spontaneous intestinalperforation (SIP);

Congenital absence ofintestinal musculature(CAIM)

Abstract Herein is reported case of an otherwise healthy full-term infant girl who presented withnumerous spontaneous intestinal perforations with congenital absence of intestinal muscularis mucosaeand muscularis propria. Few other cases are reported in the English literature with varying presentations.We review those cases, theories of pathogenesis, embryology, and possible connections to variousclinical presentations.© 2009 Elsevier Inc. All rights reserved.

1. Case report

A 3-week-old full-term 2.7-kg girl was born withoutcomplications by normal spontaneous vaginal delivery to ahealthy 21-year-old primagravid mother. She developedwatery diarrhea and nonbloody, nonbilious emesis at 2 weeksof life. She was admitted 5 days later for dehydration and wasnoted to have occult blood-positive stool. She improvedclinically with intravenous fluids and antibiotics and toleratedoral feeds. Four days later, she developed significantabdominal distension with pneumatosis intestinalis andpneumoperitoneum on abdominal radiographs. At explora-tion, significant intraperitoneal air and fluid from a singleascending colon perforation was noted. This was repaired,and a Brooke loop ileostomy was constructed. Four days

⁎ Corresponding author. Tel.: +1 312 714 5575; fax: +1 312 435 9003.E-mail address: daniel.stephens@gmail.com (D. Stephens).

022-3468/$ – see front matter © 2009 Elsevier Inc. All rights reserved.oi:10.1016/j.jpedsurg.2009.08.008

later, stool was seen in the wound. Reexploration revealedwound dehiscence with additional perforations proximal anddistal to the ileostomy. A small segment of ileum wasresected, which provided the pathologic findings for this case;a new proximal Brooke ileostomy and distal mucous fistulawere created. Five days later, she was again noted to havewound dehiscence, evisceration, and sucus in the abdominalcavity. Reexploration revealed 20 “punched-out” perfora-tions of the small intestines, each located at the junction of themesentery and small bowel wall. All were oversewn.

Further perforations occurred with the development ofmultiple enterocutaneous and enteroenteric fistulae, but wedid not elect to operate at this time. The patient remained inthe pediatric intensive care unit for several months with acourse complicated by DIC and TPN cholestasis. Eventually,all distal small bowel, compromising approximately 70% ofher small intestine, was resected. She was begun on a smallbowel adaptation regimen that was quite successful; her

2212 D. Stephens et al.

proximal small bowel and colon were joined, and she iscurrently stable and growing nearing 2 years of age.

Histologic examination of the specimen submitted fromthe first ileal resection showed focal ulceration, disruption ofbowel wall, and transmural inflammation consistent with theperforation site. There were 3 different foci of prominentedema of the submucosa with distended focally ectaticvessels (Fig. 1A) and multiple microscopic foci of inflam-matory collections (Fig. 1B), composed mainly of smalllymphocytes, with accompanying fibroblastic proliferation.The inflammatory foci were scattered and appeared both insubmucosal and subserosal distribution, some adjacent to thefoci of muscle loss. The myxoinflammatory foci did notinvade into the muscle; for example, no definite morphologicevidence of inflammatory myopathy was present. The borderof remaining muscle and the lack thereof were very sharp andclean of inflammation. Immunostains for smooth muscle anddesmin demonstrated partial or complete loss of the musclefibers adjacent to the myxoinflammatory pockets as seen inthe images (Fig. 1C). Histologic sections show the presenceof ganglion cells in both submucosal and myenteric plexuses;

Fig. 1 A, Low power magnification cross section of the small bowesubmucosal and subserosal location (asterisk). Loss of smooth muscle fidistribution is appreciated (original magnification: ×200, H&E stain). B, Hmuscularis mucosae (arrow) and partial prolapse of the mucosa in the loopower magnification of loss of muscularis mucosae (arrow; original magniSome areas of the myenteric (Auerbach's) plexus had increased numbe(comparative histomorphologic observation; original magnification: ×40

some areas of the myenteric (Auerbach) plexus had increasednumber of ganglion cells in bigger clusters with continuousdistribution (based on pure comparative histomorphologicobservation; Fig. 1D).

Definitive histologic evidence of findings previouslyreported in Ehlers-Danlos syndrome (EDS) [1] were not seen,but early manifestations could not be ruled out. Collagenelectrophoresis studies showed no abnormalities and eliminatedsome of the more common forms of EDS. Immunologicevaluation including normal immunoglobulin levels, negativehuman immunodeficiency virus, and normal complete bloodcount including differential with adequate lymphocytic re-sponse made immunodeficiency syndromes unlikely. Noevidence for primary connective tissue disease or vasculitiswas discovered.

2. Discussion

Congenital absence of intestinal musculature (CAIM) is arare but documented entity, although its true incidence is

l wall, demonstrating intact mucosa with loose edematous foci inbers in both submucosal (thin arrow) and subserosal (thick arrow)igher power of the image in Fig. 1, showing focal complete loss of

se submucosa (original magnification: ×400, H&E stain). C, Higherfication: ×400, desmin immunostain). D, Presence of ganglion cells.r of ganglion cells in bigger clusters with continuous distribution0, S-100 immunostain).

2213Congenital absence of intestinal smooth muscle

unknown. First described in the 1960s [2], these congenitaldefects have been documented and confirmed by primarysources in the English literature only 24 times, our caserepresents the 25th [2-17]. Few other cases may exist; however,because of lack of ability or detail, they are not discussed [18].

Multiple theories regarding the etiology have beenproposed from embryologic, pathologic, and clinical obser-vations. One theory proposes focal intrauterine ischemia of

Table 1 Details of cases reviewed

GA Age atpresentation(d)

Sex Risk forhypoxia

Clinicalfeatures

Alawadhi et al 33 1 F + Dist

Carroll FT 1 M + Dist

Dhall et al FT 2 M − Dist

Emanuel et al 37 1 M − DistHuang et al 27 5 F + Dist

32 3 M + DistHuang et al 37 3 M − Dist

Husain et al 26 11 F + Disc36 3 M + Dist

35 ND ND − DistIzraeli et al 27 1 ND + Dist

26 2 ND + Dist29 9 ND + Dist, disc28 2 ND + Apnea28 2 F + Dist

Litwin et al 27 3 M + Dist

26 2 M + Dist29 9 F + Dist

Miyagawa et al 38 1 F − DistMorikawa et al 31 1 F + DistSkov et al 28 7 M + Dist, discSolowiejczyk et al 62 ND − Incarcerated

inguinal herniaSteiner et al FT 2 M − Dist

Stephens FT 14 F − Dist

Timmermans andDonnay

FT 2 M − Dist

Moore et al ND ND ND ND ND

Risk factors for hypoxia include cardiopulmonary disease/anomalies, indomethacatheter, and prematurity. Dist indicates abdominal distension; Disc, abdominalterminal ileum; GA, gestational age; F, female; M, male; ND, not determined.

the developing gastrointestinal tract [4]. Occurrence in thewatershed area of the terminal ileum and the commonlydescribed “punched out,” antimesenteric lesions as well asthe correlation with hypoxia, ischemia, and respiratorydistress syndrome support this claim, but these features arenot universal. Interestingly, the lesions in our case werelocated at the junction of the mesentery and the bowel wall;others cases were circumferential.

Involvement Grossfindings

Histopathologicfindings

Outcome

TI Perforation Absent muscularispropria

S

TI Volvulus Absent submucosaand muscularis

D—4mo

I Intussesception Absent/thinning ofmuscularis

S

SB Perforation Absent muscularis D—10 hPI Dilated bowel Absent/thinning of

muscularis, acuteinflammation

S

SB Perforation Absent inner muscularis SI Perforation Absent inner muscularis,

no inflammationD—5 d

TI Volvulus Absent muscularis D—17 dSB Perforation Absent muscularis,

congestion, ischemiaS

SB Dilated bowel Absent muscularis SMI Perforation ND STI Perforation ND STI Perforation ND STI Perforation ND STI Perforation Absent muscularis

propriaS

MI Perforation Absent/thinning ofmucosa, submucosa,and muscularis

S

TI Perforation ND STI Perforation ND SJ Dilated bowel Absent muscularis D—72 dJ, I Volvulus Absent muscularis SSB Perforation Absent muscularis D—20 dJ, I Dilated bowel Absent submucosa,

congestionS

TI Intussesception Absent submucosaand muscularis

D—40 d

SB Perforation Absent muscularis,congestion, chronicinflammation

S

I Perforation ND D—17 d

ND ND Absent muscularis ND

cin use, low apgars, complicated delivery, meconium, umbilical arterydiscoloration; J, jejunum; I, ileum; MI, mid-ileum; SB, small bowel; TI,

2214 D. Stephens et al.

Another theory suggests that remnants of developmen-tal diverticula present in embryos 7 to 40 mm in sizeregress to create this lesion [3]. However, another theoryrelates regression of the omphalomesenteric remnant withresorption of the muscle of adjacent ileum [3]. Althoughthere seems to be a preponderance of cases withperforations in the terminal ileum, there are reports ofcases ranging in location from the stomach to the colon(Table 1). The relation to concurrent intussusception mayrepresent either a cause or a result, as a weakenedsegment of intestine may predispose to intussusception;however, intrauterine intussusception is a known cause ofintestinal atresia and may also be attributed to degener-ation of muscle layers [19]. Some authors suggestprimary agenesis as a cause. There is no convincingevidence for or against this proposed etiology.

Some cases of spontaneous intestinal perforation (SIP)could be explained by CAIM, but the few cases of SIP thathave been pathologically evaluated show thinning of themuscular layers, but this has been attributed to focalischemia and compression by intraluminal meconium [20].Recently, another author proposed that some cases may infact be acquired rather than congenital in origin, citinghistologic evidence of muscle necrosis in 2 clinically andpathologically similar cases, findings which may have beenneglected in previous reports [7]. An infrequent vascularform of EDS may present similarly clinically but isdistinguishable by genetic testing, as was done in thiscase, and results in the development of other pathogno-monic features of EDS.

Clinically, patients present with a variety of signs andsymptoms including abdominal distension, discoloration,pneumoperitoneum, and also as accidental and postmor-tem findings. Congenital absence of intestinal musculaturemay cause intestinal obstruction, necrotizing enterocolitis,volvulus, intussusception, or predispose for SIP [9].Pathologically, these cases encompass a breadth offindings ranging from thinning to absence of some orall layers of the small intestines, with and withoutpresence of inflammation, congestion, and edema, assummarized in Table 1.

This case is unusual in its presentation at such a late date.In addition, most cases reported underwent only 1 reparativeprocedure with relative success, particularly since advancesin care in the 1980s; however, this patient underwent severalreparative procedures for numerous perforations, apparentlychronologically distinct. She also had numerous complica-tions, not present in most cases that generally recoveredquickly after surgery.

3. Conclusion

Congenital absence of intestinal musculature representsa distinct entity, which may present in a variety of ways.

Although both necrotizing enterocolitis and SIP have beenstudied extensively, there is no clear etiology for either,and CAIM may be an overlapping etiology in bothdiseases. Congenital absence of intestinal musculature mayalso account for significantly more cases than what isthought. Although the true etiology of CAIM remainsunclear, whether it is truly congenital, or perhaps acquired,it certainly deserves further studies. These studies areindicated to more clearly delineate the causes and riskfactors for intestinal perforation in the newborn. Consid-eration should be given to biopsy and pathologicevaluation at the time of surgery and, in appropriatecases, follow up later in life with possible biopsy toevaluate the extent of disease and to better understand thenatural history of the disease.

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