Intestinal pathology in patients with pathogenic ACTG2-variant visceral myopathy: 16 patients from 12 families and review of the literature
Kapur RP, Goldstein AM, Loeff DS, Myers CT, Paschal CR. Intestinal Pathology in Patients With Pathogenic ACTG2-Variant Visceral Myopathy: 16 Patients From 12 Families and Review of the Literature [published online ahead of print, 2022 Jun 12]. Pediatr Dev Pathol. 2022;10935266221107449. doi:10.1177/10935266221107449
Background: Dominant gamma-smooth muscle actin gene (ACTG2) variants cause clinically diverse forms of visceral myopathy. Many patients undergo intestinal resection or biopsy before identification of their genetic defect. The pathology of ACTG2-variant visceral myopathy has not been evaluated systematically.
Methods: Glass slides, ultrastructural images, molecular genetic reports, and clinical records from 16 patients with pathogenic (15) or likely pathogenic (1) ACTG2 variants were reviewed and compared with surgical specimens from controls (no evidence of a primary myopathy or pseudo-obstruction due to Hirschsprung disease) and published descriptions.
Results: The variable clinical manifestations in our cohort matched those in the literature. Only non-specific light and electron microscopic findings observed in non-myopathic controls were encountered in 13 of 16 patients. The remaining 3 patients harbored hyalinized cytoplasmic inclusions in smooth muscle cells and 1 of them had polyglucosan bodies in the muscularis propria.
Conclusions: Apart from hyalinized inclusions, which were only observed in 3/16 patients, intestinal pathology in the majority of patients with ACTG2 variants is not indicative of an underlying visceral myopathy. Molecular testing should be considered even when no diagnostic intestinal pathology is identified.