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At a glance

Inherited syndrome characterized by microcolon, intestinal hypoperistalsis, dilated small bowel loops and constipation, urinary retention, extremely distended bladder (megacystis), and hydronephrosis.

Synonyms

Megacystis-Microcolon-Intestinal Hypoperistalsis Syndrome (MMIHS); MMIH Syndrome; Infantile Visceral Myopathy; Idiopathic Intestinal Pseudoobstruction.

History

First described in five newborn girls by the American pediatric radiologist Walter Evan Berdon and colleagues in 1976.

Incidence

Around 250 patients with various ethnic backgrounds have been described worldwide. A female predominance of up to 4:1 has been reported.

Genetic inheritance

Most cases appear to be sporadic. The mode of transmission, initially thought to be autosomal recessive as parental consanguinity and recurrence in siblings is frequently seen, has been linked to the MYH11 (Myosin, Smooth Muscle, Heavy Chain 11) gene on chromosome 16p13.11. However, several other genes have been implicated in the pathogenesis of MMIHS and more recent research suggests now that autosomal dominant inheritance is also possible. The ACTG2 (Enteric Smooth Muscle Actin Gamma-2) gene is involved in the biosynthesis of Gamma-2 actin filaments, which play a crucial role in the contraction of urinary and intestinal smooth muscles cells. The mutations have been mapped to chromosome 2p13.1 and result in faulty Gamma-2 actin protein that hinders the formation and stabilization of normal actin filaments. Heterozygous mutations in ACTG2 can lead to MMIHS. Mutations of other genes involved in smooth muscle contraction may also cause MMIHS and in approximately 10% of patients, no mutations can be identified.

Pathophysiology

This is still a matter of debate and various hypotheses are mentioned. Some researchers found a lack of interstitial cells of Cajal (ICCs) in the bowel and bladder of these patients. ICCs act as pacemaker cells in the action potential generation of smooth muscle cells in bowel and bladder and thus play an important role in peristalsis and voiding. Central vacuolar degenerative changes in smooth muscle cells of bowel and bladder, often in combination with extensive transmural interstitial fibrosis points to a degenerative disease in the eyes of some investigators. Other studies suggest a role of the β-4/α-3 subunits of the neuronal nicotinic acetylcholine receptors, which were found to be significantly decreased in some bowel and bladder specimens.

Diagnosis

Based on the clinical picture and family history. Progressive fetal megacystis (in almost 90% of patients) with bilateral hydroureteronephrosis (in about half the cases) usually becomes noticeable in the second trimester of pregnancy allowing for antenatal ultrasonographic or MRI diagnosis. The stomach may appear enlarged and the bowel loops transiently dilated. The amniotic fluid volume may be normal (in approximately 60%) or increased (polyhydramnios; in about 33%) or decreased (in 7%) and its analysis may reveal elevated γ-glutamyl transpeptidase and aminopeptidase M in conjunction with a normal intestinal alkaline phosphatase concentration, which appears to yield ...

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