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

Pelizzo, Gloria; Calcaterra, Valeria; Villanacci, Vincenzo; Mura, Giovanni Battista; Bassotti, Gabrio

doi:10.5152/tjg.2018.17582

Cited by 7 publications

(5 citation statements)

References 11 publications

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“…Gastrointestinal symptoms were a significant comorbidity in our population. There have been previous descriptions of severe GI symptoms in DM1, including pseudo-obstruction, 19,20 and we found similar findings with three patients experiencing obstruction or pseudoobstruction. In a large cohort of 913 adult patients with DM1, 79% of patients had some GI complaint.…”

Section: Discussionsupporting

confidence: 91%

Clinical and genetic characteristics of childhood‐onset myotonic dystrophy

et al. 2019

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Introduction Myotonic dystrophy type 1 (DM1) is caused by a CTG (cytosine‐thymine‐guanine) trinucleotide repeat expansion. Congenital DM (CDM) presents in the first month of life, whereas individuals with infantile and juvenile DM1 have later onset of symptoms. Methods We performed a retrospective chart review of patients with childhood‐onset DM1 seen at one of three locations in Dallas, Texas between 1990 and 2018. Symptoms, disease course, cognitive features, and family history were reviewed. Results Seventy‐four patients were included; CDM was diagnosed in 52 patients. There was maternal inheritance in 74% of patients. CTG repeat number ranged from 143 to 2300. Neuropsychiatric and cognitive deficits were common. Over half of the patients had GI disturbances, and orthopedic complications were common. Discussion Myotonic dystrophy type 1 in children requires a multidisciplinary approach to management. Presenting symptoms vary, and repeat expansion size does not necessarily directly relate to severity of symptoms. A consensus for outcome measures is required.

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Section: Discussionsupporting

confidence: 91%

Clinical and genetic characteristics of childhood‐onset myotonic dystrophy

et al. 2019

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“…Patients with myotonic dystrophy may have dysphagia, gastroesophageal reflux, cholecystectomy at a young age (154), or megacolon (155); in the autosomal dominant type 1 form, 70% of patients presented with these manifestations as well as malnutrition and fecal incontinence in childhood or adolescence (156). In myotonic dystrophy type 1, there are also reports of chronic intestinal pseudo-obstruction and megacolon associated with smooth muscle α-actin deficiency and inflammation of the myenteric plexus (157).…”

Section: R E V I E W S E R I E S : G U T-b R a I N A X I Smentioning

confidence: 99%

Gastrointestinal motility disorders in neurologic disease

Camilleri¹

2021

Journal of Clinical Investigation

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Conflict of interest: MC owns equity in Enterin Inc., which is developing ENT-01 for Parkinson disease. In the past year, MC has received research grants from Allergan (eluxadoline for bile acid diarrhea), Takeda (TAK-954 for gastroparesis), and ILSI North America (intestinal permeability). MC has submitted patent applications for (a) capsule for colonic transit by scintigraphy (publication number US5827497A); (b) 13C-mannitol for permeability measurements (publication number US20190145953); and (c) obesity-metabolomics to identify different phenotypes (publication number WO2019104146A1).

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“…As previously noted, the non-specific symptoms of severe abdominal pain and distention, nausea and vomiting, constipation and/or diarrhea experienced by DM affected individuals are common and can indicate intestinal involvement in the disease. Often, the combination of these symptoms would suggest an intestinal blockage, however, early case studies of DM-affected individuals experiencing chronic diarrhea found no physical obstructions in the small or large intestine by X-ray examination [ 45 , 52 , 60 , 65 , 76 , 77 , 78 , 79 , 80 , 81 ]. Having signs and symptoms of mechanical obstruction without a physical blockage is known as pseudo-obstruction, which often occurs in the small or large intestine and results from GI dysmotility.…”

Section: Clinical Findingsmentioning

confidence: 99%

“…An intestinal permeability assay using 51CrEDTA identified altered intestinal permeability (> 3% 51CrEDTA) in 52 out of 57 DM1-affected subjects (91.22%) [ 23 ], indicating that the intestinal barrier is impaired. Intestinal dysmotility can lead to inflammation and SIBO that can impact the intestinal barrier, and while detailed descriptions of DM intestinal biopsies are lacking, samples have been remarked as having “mild, chronic inflammatory changes” [ 49 , 52 , 59 , 77 , 81 , 84 ]. Steatosis and nonalcoholic fatty liver disease (NAFLD) may also contribute to altered gut permeability [ 88 , 89 ].…”

Section: Clinical Findingsmentioning

confidence: 99%

“…While the majority of histological evaluations of affected tissues have not shown significant morphological changes other than mild inflammatory changes in GI mucosa [ 52 , 59 , 81 ], a handful of case studies have identified alterations in the myenteric nerve plexus or atrophy of smooth muscle [ 28 , 77 ]. For instance, transmission electron microscopy of a colonic sample from a DM affected male experiencing megacolon showed a >75% loss in neuron number, but with otherwise normal myenteric plexus structure [ 77 ].…”

Section: Clinical Findingsmentioning

confidence: 99%

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Clinical and Molecular Insights into Gastrointestinal Dysfunction in Myotonic Dystrophy Types 1 & 2

Peterson

Cooper

2022

IJMS

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Myotonic dystrophy (DM) is a highly variable, multisystemic disorder that clinically affects one in 8000 individuals. While research has predominantly focused on the symptoms and pathological mechanisms affecting striated muscle and brain, DM patient surveys have identified a high prevalence for gastrointestinal (GI) symptoms amongst affected individuals. Clinical studies have identified chronic and progressive dysfunction of the esophagus, stomach, liver and gallbladder, small and large intestine, and rectum and anal sphincters. Despite the high incidence of GI dysmotility in DM, little is known regarding the pathological mechanisms leading to GI dysfunction. In this review, we summarize results from clinical and molecular analyses of GI dysfunction in both genetic forms of DM, DM type 1 (DM1) and DM type 2 (DM2). Based on current knowledge of DM primary pathological mechanisms in other affected tissues and GI tissue studies, we suggest that misregulation of alternative splicing in smooth muscle resulting from the dysregulation of RNA binding proteins muscleblind-like and CUGBP-elav-like is likely to contribute to GI dysfunction in DM. We propose that a combinatorial approach using clinical and molecular analysis of DM GI tissues and model organisms that recapitulate DM GI manifestations will provide important insight into defects impacting DM GI motility.

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

Abstract: Myotonic dystrophy (MD)

Cited by 7 publications

References 11 publications

Clinical and genetic characteristics of childhood‐onset myotonic dystrophy

Clinical and genetic characteristics of childhood‐onset myotonic dystrophy

Gastrointestinal motility disorders in neurologic disease

Clinical and Molecular Insights into Gastrointestinal Dysfunction in Myotonic Dystrophy Types 1 & 2

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