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Myotonic dystrophy type 1 and pseudo-obstruction in a child with smooth muscle a-actin deficiency and eosinophilic myenteric plexitis.


Myotonic dystrophy (MD) type 1 is a neuromuscular disorder having several clinical phenotypes (congenital, childhood-onset, adult-onset, and late-onset forms) and a broad clinical spectrum (1). The gastrointestinal tract is often involved in patients with MD, and digestive symptoms may be the first sign of dystrophic disease and may precede the musculo-skeletal features (2).

Lower gut involvement may cause chronic intestinal pseudo-obstruction (CIPO). Most cases of CIPO in MD have been described in adults and in only three instances in children, but histological abnormalities were not reported in two of these latter cases. However, in adults, either no or subtle histologic alterations in the smooth muscle in patients with MD type 1 have been documented (3).

We report the unique case of a child with MD type 1 having CIPO associated with eosinophilic myenteric plexitis and smooth muscle a-actin deficiency.


A 12-year-old boy with a previous diagnosis of congenital MD type 1 (cytosine-thymine-guanine triplet expansion in the 3'-nontranslated region of the dystrophia myotonica protein kinase gene) was admitted in November 2016 because of symptoms of bowel obstruction after complaining of abdominal pain, vomiting, and diarrhea for 2 days. His past medical history revealed three previous hospital admissions elsewhere (April and December 2013 and January 2014) where surgery was performed for intestinal obstruction, but no surgical or histological documentation was available. The patient was irritable and presented with vomiting, abdominal distention, abdominal tenderness, and absence of bowel sounds. Blood chemistry analysis revealed increased C-reactive protein levels and mild elevation in liver enzyme and hemoglobin level. The white blood cell count (including eosinophils), red blood cell count, and platelet number were within normal limits. A plain abdominal X-ray revealed severe small and large bowel distention without pneumoperitoneum (Figure 1). Explorative laparoscopy showed distention of the terminal ileum and colonic volvulus of the ascending colon. Immediately after volvulus detorsion and suction of a liter of chylous effusion, multiple full-thickness ileal and ascending colon biopsies were obtained. One week later, the appearance of toxic megacolon required venting ileostomy to be performed. The subsequent period was uneventful.

The patient's histological assessment revealed mild inflammatory changes in the mucosa, normal aspects of the myenteric plexus in the ileum (Figure 2a and b), and the presence of eosinophils in the muscularis propria and myenteric plexus (myenteric plexitis) within the large bowel (Figure 2c and d). Plexitis was graded as mild (presence of <4 eosinophils penetrating, apportioned to, or within an enteric ganglion) according to previously published criteria (4). No additional feature of plexitis (lymphocytic infiltration) and of smooth muscle degeneration, such as fibrosis or vacuolization, was present. Immunohistochemical staining for elements of the enteric nervous system (neuron-specific enolase, S100, and c-Kit; Leica Biosystem, Milan, Italy) was normal in both intestinal segments, whereas staining for a-smooth muscle actin revealed no expression in the circular layer of the small bowel (Figure 2e and f) and normal expression in the muscular layers of the colon.

Written informed consent to publish this case was obtained from the child's parents.


Although MD is characterized by myotonic phenomena and progressive muscular weakness, multisystem involvement (endocrine, cardiovascular, and ocular abnormalities; cognitive impairment; and mental retardation) is frequent (1). The gastrointestinal tract is also commonly involved, particularly having motility abnormalities occurring from the esophagus to the anus (2). Of interest, there is scarce correlation between skeletal muscle damage and gastrointestinal disturbances, whereas the severity of gut involvement and the duration of disease duration are usually correlated (1-3).

Histologic smooth muscle abnormalities are poorly documented in MD, and it has been hypothesized that such an involvement might precede changes in striated muscles. Some studies have suggested that neurological abnormalities or visceral neuropathy involving substance P and enkephalin-immunoreactive fibers of the smooth muscle play a role (2,5-6).

While combinations of neuropathic, mesenchymopathic, and myopathic changes in cases of CIPO are not uncommon and the loss of a-actin may be observed in normal tissues, particularly in the terminal ileum, such an association in a patient with MD is a novel observation (7). Although CIPO may be independently due to MD and/or to an abnormal expression of a-actin and/or to eosinophilic plexitis, these features have never been simultaneously described in the same patient.

The functional significance of a-smooth muscle actin staining abnormalities in gastrointestinal disease is still unclear. The different levels of a-isoactin expression in different viscera observed in experimental animal models suggest a functional effect of such changes (7). Alterations in contractile proteins might influence motility, although the effects of a change in smooth muscle a-actin alone should be less profound than that of other significant cytoskeletal or structural abnormalities. Of interest, as shown in experimental animal models, low-grade inflammation limited to the mucosa may modulate actin expression, and this immunomodulation can persist after the initial stimulus is removed; this condition may thus impair intestinal motor activity (8). Impaired smooth muscle a-actin expression has been reported to be a valuable biomarker of CIPO in clinical practice.

In addition, as the enteric nervous system is not altered, the muscular component is likely to have played an important role, together with eosinophilic plexitis (a well-known cause of CIPO that might affect neuroenteric functions) and further muscular impairment by eosinophilic infiltration (9). These abnormalities may have caused volvulus, which is an infrequent complication of CIPO, even though eosinophilic plexitis, which occasionally occurs in Hirschsprung's disease, might have been a secondary phenomenon to the obstruction caused by volvulus (10, 11).

In the present peculiar case, the clinical aspects of CIPO might have been due to several possible causes associated with neuromuscular dysfunction. The relationship between MD, gastrointestinal motility, and symptoms must be always carefully investigated. Histologic aspects and immunohistochemical assessment should be included in the diagnostic work-up of each case to improve the knowledge of basal mechanisms underlying gastrointestinal involvement in MD and possible associations with other pathological conditions and to propose new therapeutic perspectives to manage this difficult condition in a more targeted manner.

Informed Consent: Informed consent was obtained from patient's parents who participated in this study.

Peer-review: Externally peer-reviewed.

Author Contributions: Concept - G.P., V.C., V.V., G.B.; Design - G.P., V.C., V.V., G.B; Supervision - G.P., V.V., G.B.; Resource - G.P., V.V., G.B.B., G.B.; Materials - G.P., V.V., G.B.; Data Collection and/or Processing - G.P., V.V., G.B.B., G.B.; Analysis and/or Interpretation - G.P., V.V., G.B.; Literature Search - V.C., G.B.; Writing - G.P., V.C., G.B.; Critical Reviews - G.P., V.V., G.B.

Conflict of Interest: No conflict of interest was declared by the authors

Financial Disclosure: The authors declared that this study has received no financial support.


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(6.) Yoshida MM, Krishnamurthy S, Wattchow DA, Furness JB, Schuffler MD. Megacolon in myotonic dystrophy caused by a degenerative neuropathy of the myenteric plexus. Gastroenterology 1988; 95: 820-7. [CrossRef]

(7.) Gamba E, Carr NJ, Bateman AC. Deficient alpha smooth muscle actin expression as a cause of intestinal pseudo-obstruction: fact or fiction? J Clin Pathol 2004; 57: 1168-71. [CrossRef]

(8.) Knowles CH, Silk DB, Darzi A, et al. Deranged smooth muscle alpha-actin as a biomarker of intestinal pseudo-obstruction: a controlled multinational case series. Gut 2004; 53: 1583-9. [CrossRef]

(9.) Schappi MG, Smith VV, Milla PJ, Lindley KJ. Eosinophilic myenteric ganglionitis is associated with functional intestinal obstruction. Gut 2003; 52: 752-5. [CrossRef]

(10.) de Betue CT, Boersma D, Oomen MW, Benninga MA, de Jong JR. Volvulus as a complication of chronic intestinal pseudo-obstruction syndrome. Eur J Pediatr 2011; 170: 1591-5. [CrossRef]

(11.) Lowichik A, Weinberg AG. Eosinophilic infiltration of the enteric neural plexuses in Hirschsprung's disease. Pediatr Pathol Lab Med 1997; 17: 885-91. [CrossRef]

Gloria Pelizzo (1), Valeria Calcaterra (2), Vincenzo Villanacci (3), Giovanni Battista Mura (4), Gabrio Bassotti (5)

(1) Department of Pediatric Surgery, Children's Hospital, Mediterranean Institute for Pediatric Excellence, Palermo, Italy

(2) Department of Pediatry, University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

(3) Department of Pathology, Spedali Civili di Brescia, Brescia, Italy

(4) Department of Pediatric Surgery, Santa Maria della Misericordia Hospital, Perugia, Italy

(5) Division of Gastroenterology, Department of Medicine, University of Perugia Medical School, Perugia, Italy

Address for Correspondence: Gloria Pelizzo E-mail:

Received: October 25, 2017 Accepted: November 11, 2017

DOI: 10.5152/tjg.2018.17582
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2018 Gale, Cengage Learning. All rights reserved.

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Title Annotation:CASE REPORT
Author:Pelizzo, Gloria; Calcaterra, Valeria; Villanacci, Vincenzo; Mura, Giovanni Battista; Bassotti, Gabri
Publication:The Turkish Journal of Gastroenterology
Date:Mar 1, 2018
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