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X-linked chronic idiopathic intestinal pseudo-obstruction

MIM.300048 Xq28

Friday 30 November 2007

Definition: X-linked intestinal pseudo-obstruction is a rare disorder caused by mutations in FLNA, the gene encoding the cytoskeletal protein filamin A. It has been regarded as a hereditary enteric neuropathy largely on the basis of sparse and incomplete pathologic studies.

Synopsis

Diffuse abnormal layering of small intestinal smooth muscle (DAL) is a rare malformation, which has only been described in rare male patients with intestinal pseudo-obstruction. (#20871226#)

Light microscopic, ultrastructural, and immunohistochemical studies showed abnormal lamination of the small intestinal muscularis propria with associated absent or severely reduced FLNA immunoreactivity.

Intestinal samples show multinucleate myocytes in small and large intestine, along the submucosal surface of the muscularis propria.

Neither diffuse abnormal layering of small intestinal smooth muscle (DAL), nor the pattern of myocyte multinucleation observed in patients have been described outside the context of X-linked intestinal pseudo-obstruction. (#20871226#)

These histopathologic features may be specific for this hereditary disorder and suggest an underlying myopathic basis for dysmotility in affected patients.

Etiology

- germline mutation in the gene encoding filamin A (FLNA) (MIM.300017)

Idiopathic chronic intestinal pseudoobstruction (ICIPO)

Idiopathic chronic intestinal pseudoobstruction (ICIPO) is caused by severe abnormality of gastrointestinal motility.

The patients have recurrent symptoms and signs of intestinal obstruction without any mechanical lesion.

CIPO can be secondary to several disorders such as Chagas disease, myxedema, or Duchenne muscular dystrophy (MIM.310200).

Among primary forms of CIPO are those associated with defects of enteric neuronal cells. One genetic form of CIPO results, not from lack of migration of enteric ganglion cells, but from qualitative abnormalities of the enteric ganglia and nerve fibers, suggesting the presence of a differentiation defect.

References

- Diffuse abnormal layering of small intestinal smooth muscle is present in patients with FLNA mutations and x-linked intestinal pseudo-obstruction. Kapur RP, Robertson SP, Hannibal MC, Finn LS, Morgan T, van Kogelenberg M, Loren DJ. Am J Surg Pathol. 2010 Oct;34(10):1528-43. PMID: #20871226#

- Gargiulo A, Auricchio R, Barone MV, Cotugno G, Reardon W, Milla PJ, Ballabio A, Ciccodicola A, Auricchio A. Filamin A is mutated in X-linked chronic idiopathic intestinal pseudo-obstruction with central nervous system involvement. Am J Hum Genet. 2007 Apr;80(4):751-8. PMID: #17357080#