A Novel ANO1 Gene Variant is Associated with Intestinal Dysmotility Syndrome Masquerading as Hirschsprung Disease: A Case Report

Abstract

Anoctamin 1 (ANO1)-related intestinal dysmotility syndrome (OMIM: 620045) is an extremely rare disorder with only 2 cases reported in the medical literature. We present the clinical scenario of a 2-month-old male infant that presented to our center with diarrhea, vomiting, and abdominal distension. Routine investigations did not yield a clear diagnosis. Whole-exome sequencing showed a novel homozygous nonsense ANO1 pathogenic variant (c.1273G>T) with a protein alternation of p.Glu425Ter that fits the patient's phenotype. Sanger sequencing revealed the same ANO1 variant in both parents in a heterozygous form confirming an autosomal recessive mode of inheritance. The patient experienced multiple bouts of diarrhea-related metabolic acidosis, dehydration, and severe electrolyte imbalances that required intensive care unit monitoring. The patient was managed conservatively and being followed regularly in an outpatient setting.

Keywords: ANO1; intestinal dysmotility syndrome; novel mutation.

FIGURE 1.

Gastrografin barium enema illustrated a reversed rectosigmoid ratio with the lower rectum being smaller in caliber compared to the sigmoid and the rest of the colon (A). Histopathological examination of the rectal biopsy indicated the presence of colonic ganglionic cells as highlighted by the black arrow (B–D). Pedigree of the affected family (E) and Sanger electropherograms of the family members (F).