Diagnostic Approach to Monogenic Inflammatory Bowel Disease in Clinical Practice

A Ten-Year Multicentric Experience

Research output: Contribution to journalArticle

Abstract

BACKGROUND AND AIMS: Multiple monogenic disorders present as very early onset inflammatory bowel disease (VEO-IBD) or as IBD with severe and atypical features. Establishing a genetic diagnosis may change patients' management and prognosis. In this study, we describe the diagnostic approach to suspected monogenic IBD in a real clinical setting, discussing genetic and phenotypic findings and therapeutic implications of molecular diagnosis.

METHODS: Information of patients with VEO-IBD and early onset IBD with severe/atypical phenotypes (EO-IBD s/a) managed between 2008-2017 who underwent a genetic workup were collected.

RESULTS: Ninety-three patients were included, and 12 (13%) reached a genetic diagnosis. Candidate sequencing (CS) was performed in 47 patients (50%), and next generation sequencing (NGS) was performed in 84 patients (90%). Candidate sequencing had a good diagnostic performance only when guided by clinical features specific for known monogenic diseases, whereas NGS helped finding new causative genetic variants and would have anticipated one monogenic diagnosis (XIAP) and consequent bone marrow transplant (BMT). Patients with monogenic IBD more frequently were male (92% vs 54%; P = 0.02), had extraintestinal findings (100% vs 34%; P < 0.001), and had disease onset ≤1 month of life (25% vs 1%; P = 0.006). Genetic diagnosis impacted patient management in 11 patients (92%), 7 of whom underwent BMT.

CONCLUSION: A genetic diagnosis can be established in a significant proportion of suspected monogenic IBD and has an impact on patients' management. Candidate sequencing may be deployed when clinical findings orientate toward a specific diagnosis. Next generation sequencing should be preferred in patients with nonspecific phenotypes.

Original languageEnglish
JournalInflammatory Bowel Diseases
DOIs
Publication statusE-pub ahead of print - Aug 3 2019

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Inflammatory Bowel Diseases
Bone Marrow
Transplants
Phenotype

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@article{c3a9c98a58bd43d5bc72130f23d4e846,
title = "Diagnostic Approach to Monogenic Inflammatory Bowel Disease in Clinical Practice: A Ten-Year Multicentric Experience",
abstract = "BACKGROUND AND AIMS: Multiple monogenic disorders present as very early onset inflammatory bowel disease (VEO-IBD) or as IBD with severe and atypical features. Establishing a genetic diagnosis may change patients' management and prognosis. In this study, we describe the diagnostic approach to suspected monogenic IBD in a real clinical setting, discussing genetic and phenotypic findings and therapeutic implications of molecular diagnosis.METHODS: Information of patients with VEO-IBD and early onset IBD with severe/atypical phenotypes (EO-IBD s/a) managed between 2008-2017 who underwent a genetic workup were collected.RESULTS: Ninety-three patients were included, and 12 (13{\%}) reached a genetic diagnosis. Candidate sequencing (CS) was performed in 47 patients (50{\%}), and next generation sequencing (NGS) was performed in 84 patients (90{\%}). Candidate sequencing had a good diagnostic performance only when guided by clinical features specific for known monogenic diseases, whereas NGS helped finding new causative genetic variants and would have anticipated one monogenic diagnosis (XIAP) and consequent bone marrow transplant (BMT). Patients with monogenic IBD more frequently were male (92{\%} vs 54{\%}; P = 0.02), had extraintestinal findings (100{\%} vs 34{\%}; P < 0.001), and had disease onset ≤1 month of life (25{\%} vs 1{\%}; P = 0.006). Genetic diagnosis impacted patient management in 11 patients (92{\%}), 7 of whom underwent BMT.CONCLUSION: A genetic diagnosis can be established in a significant proportion of suspected monogenic IBD and has an impact on patients' management. Candidate sequencing may be deployed when clinical findings orientate toward a specific diagnosis. Next generation sequencing should be preferred in patients with nonspecific phenotypes.",
author = "Sara Lega and Alessia Pin and Serena Arrigo and Cristina Cifaldi and Martina Girardelli and Bianco, {Anna Monica} and Monica Malamisura and Giulia Angelino and Simona Faraci and Francesca Rea and Romeo, {Erminia Francesca} and Marina Aloi and Claudio Romano and Arrigo Barabino and Stefano Martelossi and Alberto Tommasini and {Di Matteo}, Gigliola and Caterina Cancrini and {De Angelis}, Paola and Andrea Finocchi and Matteo Bramuzzo",
note = "{\circledC} 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.",
year = "2019",
month = "8",
day = "3",
doi = "10.1093/ibd/izz178",
language = "English",
journal = "Inflammatory Bowel Diseases",
issn = "1078-0998",
publisher = "Oxford University Press",

}

TY - JOUR

T1 - Diagnostic Approach to Monogenic Inflammatory Bowel Disease in Clinical Practice

T2 - A Ten-Year Multicentric Experience

AU - Lega, Sara

AU - Pin, Alessia

AU - Arrigo, Serena

AU - Cifaldi, Cristina

AU - Girardelli, Martina

AU - Bianco, Anna Monica

AU - Malamisura, Monica

AU - Angelino, Giulia

AU - Faraci, Simona

AU - Rea, Francesca

AU - Romeo, Erminia Francesca

AU - Aloi, Marina

AU - Romano, Claudio

AU - Barabino, Arrigo

AU - Martelossi, Stefano

AU - Tommasini, Alberto

AU - Di Matteo, Gigliola

AU - Cancrini, Caterina

AU - De Angelis, Paola

AU - Finocchi, Andrea

AU - Bramuzzo, Matteo

N1 - © 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PY - 2019/8/3

Y1 - 2019/8/3

N2 - BACKGROUND AND AIMS: Multiple monogenic disorders present as very early onset inflammatory bowel disease (VEO-IBD) or as IBD with severe and atypical features. Establishing a genetic diagnosis may change patients' management and prognosis. In this study, we describe the diagnostic approach to suspected monogenic IBD in a real clinical setting, discussing genetic and phenotypic findings and therapeutic implications of molecular diagnosis.METHODS: Information of patients with VEO-IBD and early onset IBD with severe/atypical phenotypes (EO-IBD s/a) managed between 2008-2017 who underwent a genetic workup were collected.RESULTS: Ninety-three patients were included, and 12 (13%) reached a genetic diagnosis. Candidate sequencing (CS) was performed in 47 patients (50%), and next generation sequencing (NGS) was performed in 84 patients (90%). Candidate sequencing had a good diagnostic performance only when guided by clinical features specific for known monogenic diseases, whereas NGS helped finding new causative genetic variants and would have anticipated one monogenic diagnosis (XIAP) and consequent bone marrow transplant (BMT). Patients with monogenic IBD more frequently were male (92% vs 54%; P = 0.02), had extraintestinal findings (100% vs 34%; P < 0.001), and had disease onset ≤1 month of life (25% vs 1%; P = 0.006). Genetic diagnosis impacted patient management in 11 patients (92%), 7 of whom underwent BMT.CONCLUSION: A genetic diagnosis can be established in a significant proportion of suspected monogenic IBD and has an impact on patients' management. Candidate sequencing may be deployed when clinical findings orientate toward a specific diagnosis. Next generation sequencing should be preferred in patients with nonspecific phenotypes.

AB - BACKGROUND AND AIMS: Multiple monogenic disorders present as very early onset inflammatory bowel disease (VEO-IBD) or as IBD with severe and atypical features. Establishing a genetic diagnosis may change patients' management and prognosis. In this study, we describe the diagnostic approach to suspected monogenic IBD in a real clinical setting, discussing genetic and phenotypic findings and therapeutic implications of molecular diagnosis.METHODS: Information of patients with VEO-IBD and early onset IBD with severe/atypical phenotypes (EO-IBD s/a) managed between 2008-2017 who underwent a genetic workup were collected.RESULTS: Ninety-three patients were included, and 12 (13%) reached a genetic diagnosis. Candidate sequencing (CS) was performed in 47 patients (50%), and next generation sequencing (NGS) was performed in 84 patients (90%). Candidate sequencing had a good diagnostic performance only when guided by clinical features specific for known monogenic diseases, whereas NGS helped finding new causative genetic variants and would have anticipated one monogenic diagnosis (XIAP) and consequent bone marrow transplant (BMT). Patients with monogenic IBD more frequently were male (92% vs 54%; P = 0.02), had extraintestinal findings (100% vs 34%; P < 0.001), and had disease onset ≤1 month of life (25% vs 1%; P = 0.006). Genetic diagnosis impacted patient management in 11 patients (92%), 7 of whom underwent BMT.CONCLUSION: A genetic diagnosis can be established in a significant proportion of suspected monogenic IBD and has an impact on patients' management. Candidate sequencing may be deployed when clinical findings orientate toward a specific diagnosis. Next generation sequencing should be preferred in patients with nonspecific phenotypes.

U2 - 10.1093/ibd/izz178

DO - 10.1093/ibd/izz178

M3 - Article

JO - Inflammatory Bowel Diseases

JF - Inflammatory Bowel Diseases

SN - 1078-0998

ER -