Faculty Collaboration Database

The diagnostic approach to monogenic very early onset inflammatory bowel disease. Gastroenterology 2014 Nov;147(5):990-1007.e3

Date

07/25/2014

Pubmed ID

25058236

Pubmed Central ID

PMC5376484

DOI

10.1053/j.gastro.2014.07.023

Scopus ID

2-s2.0-84908262165 (requires institutional sign-in at Scopus site)   495 Citations

Abstract

Patients with a diverse spectrum of rare genetic disorders can present with inflammatory bowel disease (monogenic IBD). Patients with these disorders often develop symptoms during infancy or early childhood, along with endoscopic or histological features of Crohn's disease, ulcerative colitis, or IBD unclassified. Defects in interleukin-10 signaling have a Mendelian inheritance pattern with complete penetrance of intestinal inflammation. Several genetic defects that disturb intestinal epithelial barrier function or affect innate and adaptive immune function have incomplete penetrance of the IBD-like phenotype. Several of these monogenic conditions do not respond to conventional therapy and are associated with high morbidity and mortality. Due to the broad spectrum of these extremely rare diseases, a correct diagnosis is frequently a challenge and often delayed. In many cases, these diseases cannot be categorized based on standard histological and immunologic features of IBD. Genetic analysis is required to identify the cause of the disorder and offer the patient appropriate treatment options, which include medical therapy, surgery, or allogeneic hematopoietic stem cell transplantation. In addition, diagnosis based on genetic analysis can lead to genetic counseling for family members of patients. We describe key intestinal, extraintestinal, and laboratory features of 50 genetic variants associated with IBD-like intestinal inflammation. In addition, we provide approaches for identifying patients likely to have these disorders. We also discuss classic approaches to identify these variants in patients, starting with phenotypic and functional assessments that lead to analysis of candidate genes. As a complementary approach, we discuss parallel genetic screening using next-generation sequencing followed by functional confirmation of genetic defects.

Author List

Uhlig HH, Schwerd T, Koletzko S, Shah N, Kammermeier J, Elkadri A, Ouahed J, Wilson DC, Travis SP, Turner D, Klein C, Snapper SB, Muise AM, COLORS in IBD Study Group and NEOPICS

Author

Abdul Aziz Elkadri MD Associate Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Age of Onset
Colitis, Ulcerative
Crohn Disease
Genetic Predisposition to Disease
Genetic Testing
Humans
Phenotype
Predictive Value of Tests
Prognosis
Risk Factors