Myotonic Dystrophy Type 1 Complicated by Colonic Obstruction Due to a Bezoar.

INTRODUCTION

Myotonic dystrophy type 1 (DM1) is the most frequent adult muscular dystrophy and results from a trinucleotide repeat expansion (CTG)n in the DM1 protein kinase gene located on chromosome 19q13.3.[1] This amplification is correlated with the severity of the disease and is the main factor determining the age of onset. Along with prominent distal weakness and myotonia, multisystem involvement is common in DM1. The prominent variations in systemic involvement in a given individual are poorly understood, and the effects of modifier genes or epigenetic factors are a matter of debate.[2]

Involvement of the gastrointestinal (GI) tract is frequent and may occur at any level. Upper GI symptoms include dysphagia, heartburn, emesis, regurgitation, coughing while eating and dyspepsia, while abdominal pain and bloating, changes in bowel habits, and dyschezia are common signs of lower GI dysfunction.[345] While the diagnosis of DM1 is usually obvious from its neuromuscular manifestations, it becomes more difficult when these are overshadowed by involvement of other organ systems. We present a woman who came to medical attention due to severe and persistent GI symptoms and cardiac complaints, culminating in surgery to relieve bezoar-induced colonic obstruction. Retrospective analysis of her medical history and electrophysiological testing subsequently revealed her underlying DM1.

CASE REPORT

A 43-year-old woman presented in June 2016 with abdominal pain and left iliac fossa tenderness. Abdominal computed tomography (CT) scan showed colonic inflammation with intraluminal whorled, hyperdense matter – thought to be a bezoar – without high-grade large bowel obstruction [Figure 1a]. Although symptoms settled with laxative treatment, she continued to have abdominal pain. This worsened in May 2018, and a repeat CT scan showed a bezoar apparently impacted at the junction of the descending colon and sigmoid, with distal sigmoid collapse, upstream colonic dilatation, and probable inflammation secondary to subacute obstruction [Figure 1b]. Failure to dislodge the impacted mass at open surgery led to sigmoid resection and anastomosis. Visual inspection confirmed the radiological impression of a bezoar.

Figure 1

Computed tomography scan of the abdomen in June 2016 (a) and May 2018 (b) showing a large bolus of hyperdense, whorled matter in the colon (white arrows) persisting over 2 years. The descending colon and cecum in (b) are dilated with mural thickening consistent with localized colonic inflammation (white asterisks), whereas the sigmoid is collapsed distally

Her past medical history was extremely complex, with chronic bowel symptoms: early satiety, constipation alternating with diarrhea, bloating, and nausea initially diagnosed as irritable bowel syndrome (IBS). Severe constipation with fecal impaction necessitated hospital admission in 1997. Frequent nocturnal palpitations, chest pain, and dizziness led to normal extended cardiac rhythm monitoring, echocardiograms, cardiac magnetic resonance imaging, and stress myocardial perfusion scanning.

The postoperative course was marked by severe nausea, anorexia, weight loss, and cognitive dullness. Psychiatric evaluation did not detect any evidence of mental illness, and she denied voluntarily ingesting hair. She did, however, admit to possible exposure to animal fur from her pets.

At neurological review, walking difficulties were noted since adolescence, with toe walking and contractures of the Achilles tendons. Subsequently, neck weakness and proximal weakness in the lower limbs developed particularly over the 2 years before presentation. On examination, she had ptosis, wasted temporalis muscles producing a “hatchet facies,” and a weak, thin “swan neck” with wasted sternocleidomastoids. Eye movements were normal with no nystagmus. Myotonia was evident in the handgrip and on percussion of the thenar eminence and the forearm extensor muscles. The distal upper and lower limbs were weak. Reflexes were absent in the lower limbs, whereas the sensory examination was normal.

Serum creatine kinase was elevated at 370 IU/L. Electromyography confirmed the presence of myotonia with myopathic motor unit potentials without evidence of muscle fiber irritability. Left quadriceps muscle biopsy was consistent with myopathic changes.

DISCUSSION

This case illustrates the multisystem nature of DM1. Although the patient did have muscle weakness from adolescence, her abdominal and cardiac complaints overshadowed the underlying neuromuscular disorder for many years, leading to a delay in diagnosis. The factors determining the phenotypic expression of the genetic mutation in organs other than skeletal muscle are unclear. Somatic instability of the CTG repeat expansion may be age- or tissue-dependent, contributing to tissue-specific involvement in a given patient.

A large French study[2] demonstrated a significant role of gender in influencing the clinical profile and severity of this disease: men frequently had the “typical” clinical syndrome with muscle weakness and myotonia with cardiac and respiratory involvement, developmental and cognitive abnormalities, and dysmorphism, whereas women tended to have a later onset of symptoms with a high incidence of extramuscular manifestations including cataracts, dysphagia, digestive tract dysfunction (defined as either constipation or diarrhea), incontinence, thyroid disorders, and obesity. Women were less disabled by DM1, were less frequently hospitalized, and had lower mortality. Variations in gene expression and metabolism of skeletal muscle, increased oxidative stress, and hormonal effects on myotonia may explain these findings.[2]

GI symptoms including stomach pain, bloating, early satiety, and fluctuations between diarrhea and constipation – similar to IBS – are common in DM1.[34] Dysphagia (79.9%), gastrooesophageal reflux (54.7%), gastric ulcers (25.2%), and constipation (45.6%) were prevalent among 418 DM1 patients followed over 5 years.[6] Women in this study were more likely to have constipation and gallbladder problems. Similarly, the French DM-Scope registry (n = 1409) showed a significantly higher risk of dysphagia in women (52.1% compared to 44.1% of men).[2] Diarrhea, steatorrhea, crampy, and poorly localized abdominal pain are also frequent: episodic diarrhea has been reported in up to a third of all patients with DM1.[34] Intestinal pseudo-obstruction may become especially troublesome during pregnancy and bouts of gastroenteritis, leading to vomiting, cramps, distension, and constipation.[7]

Gastroduodenal manometry and radiological studies have demonstrated reduced or absent intestinal peristaltic activity with delayed intestinal transit in patients with DM1.[8] Gastric emptying as measured by the 13C-acetate breath test was impaired in DM1, even in patients asymptomatic for upper GI dysfunction. It was significantly worse in symptomatic patients, particularly if the duration of DM1 was >5 years.[59] Although the degree of skeletal muscle damage as measured by the muscular disability rating scale does not correlate with GI symptoms, the duration of the disease does appear to be important.[3910] This may indicate that the GI dysfunction evolves over time, and that the extents of skeletal and smooth muscle damage do not correlate with each other.[359]

Skeletal muscle damage and gastric motor disturbances can progress independently of each other.[10] Smooth muscle damage in the upper GI tract is not common, but when it does happen, it tends to occur earlier and be more severe than that occurring in the skeletal muscle. On histology, smooth muscle cells are swollen, fragmented, atrophic, or replaced by fatty tissue.[311] Alterations in GI hormone levels including postprandial motilin and glucagon-like peptide-1 levels may also play a significant role.[912] Myenteric plexus degeneration with loss of neurons, axonal fragmentation, glial cell proliferation, loss of nitric oxide synthase activity, and poor reactivity to substance P and enkephalin may lead to abnormal peristalsis and recurrent intestinal pseudo-obstruction. As in our patient, this may precede significant skeletal muscle weakness by as much as 15 years.[3]

As a consequence of abnormal GI function in DM1, visceral dilatation, gastroparesis, and gastric bezoars have been reported. Bezoars are retained concretions of undigested matter that under conditions of altered GI anatomy or disordered motility accumulate within the stomach and may subsequently migrate to distal parts of the GI tract. The only other report of bezoar formation in DM1 to date was in a patient with known DM1 prescribed procainamide as a treatment for myotonia.[13] Polypoid antral masses with reduced gastric and esophageal peristalsis were noted on endoscopy, and cytologic washings showed food concretions. To our knowledge, bezoar-induced intestinal obstruction has never been reported as a presenting feature of DM1.

CONCLUSION

This is the first report of bezoar-related GI dysfunction as the presenting symptom of DM1. Prominent GI and cardiac complaints overshadowed her muscle weakness for a significant period. This underlines that DM1 is a multisystem disorder with protean manifestations, and diagnosis may require a high degree of suspicion. Clinical features are not directly related to the genotype and are influenced by gender. GI symptoms are common, particularly in women, and do not correlate with the severity of skeletal muscle involvement.

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The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.