Phenotypic diversity in clinical and manometric characteristics of pediatric patients with ACTG2 mutations

Heterogenous missense variants in ACTG2 have been identified in individuals with visceral myopathy and megacystis, microcolon, intestinal hypoperistalsis syndrome (MMIHS). Though varying degrees of severity of chronic intestinal pseudo obstruction have been correlated to the disease phenotype when ACTG2 is mutated, little is known about the details of motility disorder affecting different regions of the gastrointestinal tract. This is a case series of 5 patients, age 9 months to 9 years, with ACTG2 mutations who underwent gastrointestinal manometry testing at an academic pediatric hospital. Esophageal manometry was performed in two patients with p.R257C mutations. Each was abnormal. Antral fed response with low amplitude response to azithromycin was found in one patient with a p.R257H mutation. Antral activity differed in the patients with p.R257C mutations, two having normal gastric motility (contractions in response to feeding and normal response to erythromycin), and the other having gastric dysmotility (absent fed response and no response to erythromycin). Small bowel and colonic motility did not differ significantly among patients. All patients required gastrostomy tubes and diverting ileostomies, with differing reliance on supplemental parenteral nutrition. These findings suggest that ACTG2 mutations can have varied manometric presentations within different segments of the gastrointestinal tract, which may translate to differing patient outcomes.