A138 A NEW ACTG2 VARIANT MUTATION CAUSING CHRONIC INTESTINAL PSEUDO OBSTRUCTION. (15th March 2019) - Alqahtani, S
Abstract: Background: A limited number of novel genes have been recently identified as a cause for pediatric chronic intestinal pseudo-obstruction (CIPO). Aims: We describe a case of a child with a new variant ACTG2 mutation causing bladder and intestinal dysmotility. Methods: CASE REPORT Results: Case description: A 3-year-old male patient with a history of severe constipation starting at 1 year of age was referred to the care of the intestinal failure program at the Hospital for Sick Children for further diagnostic and therapeutic work-up. At 2 years of age he was not responding to laxatives and required manual dis-impaction. Rectal biopsy was negative for Hirschsprung's disease. He continued to have significant ongoing abdominal and bladder distension and was taken to the operating room for ileostomy and Mitrofanoff creation. Following the procedure, abdominal distension, recurrent vomiting and signs of intestinal obstruction persisted. Abdominal CT demonstrated diffusely dilated small bowel loops. Upper intestinal fluoroscopy demonstrated 35 cm of severely dilated small bowel loops in the distal ileum. Total bowel transit time was 5 hours and 30 minutes. The transit time in the normal appearing bowel was 2 hours. After introduction of Cisapride, the child's dysmotility improved and he weaned off parenteral nutrition. The family history was significant for gastrointestinal dysmotility without evidence of bladder distension in the mother and maternal grandmother. Both underwent colectomies. Whole exome sequencing revealed a heterozygous P323L mutation in ACTG2 gene (c.968C>T, p.Pro323Leu) in the patient and his mother. ACTG2 gene mutations have been previously described in Megacystis-microcolon-intestinal hypoperistalsis syndrome. The Gene encodes γ-2 actin that plays a pivotal role in intestinal and urinary tract smooth muscle contraction. Conclusions: Severe motility disorders can present a diagnostic challenge in children and may be associated with monogenic genetic defects. We identified a new autosomal dominant variant of the ACTG2 gene (P323L) causing chronic intestinal pseudo-obstruction and bladder distension. Whole exome sequencing can lead to definitive diagnosis, identification of new variants associated with CIPO and assists in genetic counselling with families. Funding Agencies: None