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J Ped Surg Case Reports 1 (2013) 340e342

Journal of Pediatric Surgery CASE REPORTS

journal homepage: www.jpscasereports.com

Colonic stenosis in infant with connective tissue disorder

Irene Isabel P. Lim a, Joan Durbin b, Sandra Tomita a,*

aDivision of Pediatric Surgery, Department of Surgery, New York University Langone Medical Center, 530 First Ave., Suite 10W, New York, NY 10016, USAbDepartment of Pathology, New York University Langone Medical Center, USA

a r t i c l e i n f o

Article history:Received 11 July 2013Received in revised form19 September 2013Accepted 20 September 2013Available online xxx

Key words:Colonic stenosisColonic atresiaLoeyseDietz syndrome

* Corresponding author. þ1 212 263 7391.E-mail address: sandra.tomita@nyumc.org (S. Tom

2213-5766 � 2013 The Authors. Published by Elsevierhttp://dx.doi.org/10.1016/j.epsc.2013.09.004

a b s t r a c t

Congenital colonic stenosis is an exceptionally rare condition, with less than 15 cases in the literature.Although it has some similarities to small intestinal atresia and small intestinal stenosis, colonic atresiaand colonic stenosis has been found in association with other anomalies such as Hirschsprung’s disease,craniofacial abnormalities, and musculoskeletal anomalies. In this case report, we present a 6 month oldmale with suspected LoeyseDietz syndrome (a connective tissue disorder), who presented with colonicstenosis.

� 2013 The Authors. Published by Elsevier Inc. Open access under CC BY-NC-ND license.

Colonic stenosis is an extremely rare condition. Like colonicatresia, and unlike small intestinal atresia and stenosis, it can beassociated with other unusual anomalies. We present a case ofcolonic stenosis associated with a connective tissue disorder.

1. Case report

A 6 month old male infant with probable LoeyseDietz syn-drome, a connective tissue disorder related to Marfan’s syndrome,was brought to the emergency room after several episodes ofvomiting that began the night prior to presentation. He was notedto be more lethargic with decreased appetite and decreased urineoutput. Although his abdomen is chronically distended, which wasfelt to be part of his skin hyperelasticity, the parents noted that hisabdomen appeared more distended than usual. Prior to presenta-tion, the patient had one bowel movement a day but was noted togrunt and appear to strain with each bowel movement. Otherwise,there were no significant gastrointestinal symptoms noted. Feedswere slowly being transitioned from liquid to solid foods beginning2 weeks prior to presentation.

An abdominal radiograph showed multiple dilated loops ofbowel with air fluid levels, as well as a paucity of air in rectum

ita).

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(Fig. 1). An ultrasound was significant for a prominent dilated loopof bowel, unclear if small or large, in the right abdomen andcollapsed loops in the left abdomen, but no intussusception.Computed tomography again revealed marked bowel distention,but locating the transition point was difficult due to the degree ofdistention. Exploratory laparotomywas performed, with findings ofcolonic stenosis at the mid-transverse colon with an extremelydilated, non-fixated right colon that was primarily filled with airand liquid stool. This severe stenosis was resected, measuringapproximately 2 cm in length. An area of narrowing was notedabout two centimeters distal to this stenosis; a red rubber catheterwas easily passed through this area. Another stenotic area wasfound in the descending colon, through which the catheter couldnot be passed and as such, a coloplasty was performed (Fig. 2). Acolostomy was performed with mucous fistula. Primary anasto-mosis was not performed due to the significant size discrepancybetween the proximal and distal ends of the colon and concern for afunctional obstruction with primary anastomosis. The patienttolerated the procedure well and was discharged home on post-operative day 5. The pathology of the resected specimen showedmarkedly increased submucosal collagen deposition and normalganglion cells (Figs. 3 and 4). A suction rectal biopsy was also doneto rule out Hirschsprung’s disease; this showed normal ganglioncells.

A genetic abnormality was suspected in this patient while in-utero when a fetal ultrasound showed bilateral clubfeet, bilateralknee dislocations, and unilateral renal agenesis. At birth, he wasnoted to have a constellation of findings concerning for a connec-tive tissue disorder; in addition to the prenatal findings, he was

se.

Fig. 1. Abdominal radiograph showing dilated bowel loops.

Fig. 3. H and E stain showing collagen deposition in colon.

I.I.P. Lim et al. / J Ped Surg Case Reports 1 (2013) 340e342 341

noted to have hypertelorism, blue sclera, mandibular hypoplasia,broad palate, abnormalities in finger position (ulnar deviation andoverlapping of digits with contractures), hyperelastic skin. Exten-sive workup included echocardiogram, which revealed a normalaorta, and a chest x-ray that showed anterior herniation of lungacross the midline. He was noted to have poor weight gain despitetolerating liquid, then recently, solid feeds (3rd percentile forweight and 7th percentile for height). Genetic tests revealed amutation in the transforming growth factor beta receptor 2(TGFBR2) exon, consistent with LoeyseDietz syndrome.

2. Discussion

Colonic atresia is the rarest atresia of the gastrointestinal tract,comprising only 1.8e15% of intestinal atresias, occurring inapproximately 1 in 1498 to 1 in 40,000 births [1]. Even rarer iscongenital colonic stenosis which is exceedingly unusual, with lessthan 15 cases reported in the literature [2e5]. Similar to small in-testinal atresias, vascular insult is often cited as the cause of colonicatresia and stenosis; the frequent association of colonic atresia with

Fig. 2. Intraoperative photograph showing nonfixed colon with dilated transversecolon with most proximal stenosis (thin arrow) and most distal stenosis (thick arrow).

gastroschisis and small intestinal atresias (15e20%) would seem tosuggest this as a likely etiology [6]. Most present at birth and lateonset presentations, such as this case, are atypical. This patient’s

Fig. 4. Trichrome stain showing collagen deposition in colon.

I.I.P. Lim et al. / J Ped Surg Case Reports 1 (2013) 340e342342

later presentation may be related to his recent transition to solidfood.

Unlike small intestinal atresias, there are well-documentedassociations of colonic atresia with other significant anomalies.Hirschsprung’s disease is seen in at least 2% of patients with colonicatresia [1,7]. Imperforate anus has also been described in a numberof patients with colonic atresia [8]. Colonic atresia has been asso-ciated with abnormalities of the musculoskeletal system (syndac-tyly, polydactyly, clubfoot, absent radius, absent hand, heart), aswell as craniofacial anomalies (facial hemiaplasia, anophthalmia)[9e12]. This has led to the speculation that although a vascularinsult may explain many cases of colonic atresia, another mecha-nism such as an early embryonal disruption may lead to thephenotype with a variety of anomalies [11e13].

The present case may also support this theory of a commongenetic origin as responsible for this constellation of anomalies. Ourpatient has been diagnosedwith probable LoeyseDietz syndrome, aconnective tissue disorder, related to but distinct from Marfan’ssyndrome, associated with clubfeet, joint hypermobility, hyper-telorism, and cleft palate. Characterized by mutations in thetransforming growth factor (TGF) beta receptor pathway,LoeyseDietz syndrome is an autosomal dominant syndrome inwhich patients have abnormal collagen, placing them at risk ofaortic aneurysms and arterial dissections [14]. It is noteworthy thatanother connective tissue disorder, Stickler syndrome, has alsobeen seen in a patient with colonic atresia [15]. Stickler syndrome isa chondrodystrophywith congenital alteration of type II and type VIcollagen; characteristics include eye abnormalities such as myopia,hearing loss, and hypermobile joints [16]. Interestingly, the pa-thology of our resected colon specimen showedmarkedly increasedsubmucosal collagen deposition, further suggesting that there is acommon link between the colonic stenosis and the primary disease.Little is known about the significance of these pathologic findingsas colonic stenoses in the presence of collagen disorders are rare.Mutations involved in LoeyseDietz syndrome, particularly the TGF-Beta pathway, may have a key role. Studies have implicated theoverexpression of TGF-beta in localized collagen deposition inmouse colon, leading to the development of severe fibrosis andintestinal obstruction [17]. Moreover, increased expression of TGF-Beta was observed in patients with collagenous colitis, marked bytypical thickening of the submucosal collagen layer [18], similar to

this patient’s colon specimen. This patient’s presentation mayactually signify two events that are direct results of the primarydiseaseda vascular insult in-utero which precipitated scar forma-tion and excessive collagen deposition due to mutations in the TGF-beta pathway, ultimately leading to the clinical presentation ofcolonic stenosis.

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