Abstrakt
Introduction: Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS; MIM 249210) is a rare multisystem syndrome where its name reflects most commonly affected organs. Although ACTG2, LMOD1, MYH11, MYL9, MYLK have been associated with the disease, 55% of all cases remain undiagnosed by genetic testing. Hereby, we report two additional cases with pathogenic variants in ACTG2, and a case where a pathogenic variant in KCNMA1 was found.
Materials and Methods: Next generation sequencing (NGS) was performed. Sanger sequencing was used to verify NGS results and determine the segregation of the presumably pathogenic variants in available first degree relatives.
Results: Two previously described de novo heterozygous pathogenic variants in the ACTG2 /(c.119G>A p.(Arg40His) and c.770G>A (p.Arg257His)/ where detected. A de novo heterozygous Class 4 variant c.1132G>A (p.Gly375Arg) was detected in the KCNMA1 gene.
Conclusions: Only 47 patients with ACTG2 related MMIHS have been reported thus far. We identified another two cases which will contribute to the better understanding of this heterogeneous disorder. Variants in KCNMA1 have also been associated with Liang-Wang multiple malformation syndrome (LIWAS; MIM:618729), where available literature is unfortunately sparse. Previously reported cases with LIWAS bearing the same variant, have among other pathognomonic features also megacystis and impaired bowel motility. Clinical presentation of LIWAS in the neonatal period could be similar to MMIHS with bowel and urinary bladder problems being dominant clinical signs. Therefore, LIWAS should be considered in the differential diagnosis of MMIHS, in particular during early childhood.
Supported by MH CZ - DRO, Motol University Hospital, Prague, Czech Republic 00064203.