Diagnostic Approach to Monogenic Inflammatory Bowel Disease in Clinical Practice: A Ten-Year Multicentric Experience.
Inflamm Bowel Dis
; 26(5): 720-727, 2020 04 11.
Article
en En
| MEDLINE
| ID: mdl-31375816
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedades Inflamatorias del Intestino
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Pruebas Genéticas
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Análisis de Secuencia
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Secuenciación de Nucleótidos de Alto Rendimiento
Tipo de estudio:
Clinical_trials
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Diagnostic_studies
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Observational_studies
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Prognostic_studies
Límite:
Child, preschool
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Female
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Humans
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Infant
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Male
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Newborn
Idioma:
En
Revista:
Inflamm Bowel Dis
Asunto de la revista:
GASTROENTEROLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Italia