Megacystis microcolon intestinal hypoperistalsis syndrome: evidence of a primary myocellular defect of contractile fiber synthesis.

Two infant boys with megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) are reported. Presenting with neonatal intestinal obstruction, they underwent laparotomies that showed megacystis, microcolon, and aperistaltic shortened small bowel without any mechanical obstruction. Patient 1 gradually improved and is developing normally at home, on a normal diet without genitourinary or gastrointestinal complaints (now 11 years old). Patient 2, who underwent vesicoamniotic drainage antenatally, never developed adequate gastrointestinal or genitourinary function in spite of appropriate diversion and pharmacologic support. He showed progressive deterioration and died at the age of 7 months. Detailed histo-immuno- and ultrastructural pathology assessment, although confirming results in the existing literature in some aspects, showed previously unreported neuronal dysplastic changes associated with increased laminin and fibronectin. Although patient 1 showed ultrastructural features of vacuolar degeneration of smooth muscle as reported in the literature, patient 2 showed ultrastructural and histochemical evidence of excessive smooth muscle cell glycogen storage with severely reduced contractile fibres displaced to the extreme periphery of the cells, suggesting a fundamental defect of glycogen-energy utilization. A deficiency of fiber synthesis as the alternative primary defect is discussed. In both cases, a two-step genetic defect may explain the variability in clinical outcome and pathological findings.