review of clinical indications for genetic testing in gastroenterology

Clinical indications for genetic testing in gastroenterology primarily focus on identifying hereditary gastrointestinal conditions that have significant implications for management, surveillance, and familial risk counseling.

Genetic testing is strongly indicated in patients with suspected hereditary colorectal cancer syndromes such as Familial Adenomatous Polyposis (FAP), where clinical criteria include the presence of multiple (classically hundred or more) adenomas in the colon and rectum, or in attenuated forms (10 to <100 adenomas), as well as family history suggestive of such syndromes Zare and Monahan KJ. 2025. Genetic confirmation of an APC gene mutation is critical in these cases, enabling precise diagnosis, guiding surveillance intervals, surgical decisions, and cascade testing of relatives Zare and Monahan KJ. 2025 Tóth et al. 2026 Zare & Monahan 2025.

In inflammatory bowel disease (IBD), genetic testing is indicated particularly for patients with features suggestive of monogenic forms of IBD, which often present in infancy or early childhood (onset <6 years), those with family history of monogenic disorders, consanguinity, recurrent or atypical infections suggestive of primary immunodeficiency, and extraintestinal manifestations such as immune dysregulation, hemophagocytic lymphohistiocytosis, or malignancies PubMed. Next-generation sequencing technologies, including targeted gene panel sequencing that cover known monogenic IBD genes, exome, or genome sequencing, are recommended to confirm diagnosis, inform prognosis, and identify specific treatments such as hematopoietic stem cell transplantation in select immunodeficiency-related IBDs Uhlig et al. 2021 PubMed. Genetic testing is not recommended routinely for all IBD patients, but selectively based on clinical phenotype, age of onset, and associated features PubMed.

Genetic testing is also indicated for other inherited gastrointestinal disorders such as genetic sucrase-isomaltase deficiency in patients with gastrointestinal symptoms resembling disorders of gut-brain interaction especially in pediatric populations, where analysis of the SI gene combined with dietary challenges can confirm diagnosis and guide treatment Demir et al. 2026 Demir et al. 2026.

More broadly, clinical indications for genetic testing in gastroenterology encompass patients with early-onset disease, multiple affected family members, syndromic features, or unusual presentations not explained by common multifactorial etiologies SmPC Gastrografin. Identifying monogenic causes allows tailored management, reduces morbidity, and enables predictive testing of relatives SmPC Gastrografin Goodman & Chung 2016.

Thus, the decision to perform genetic testing in gastroenterology should consider:

• Presence of multiple colorectal adenomas, especially >10, with or without family history Zare and Monahan KJ. 2025 Zare & Monahan 2025.
• Very early-onset or infantile onset IBD, or pediatric/young adult onset with atypical features or immune dysregulation PubMed Uhlig et al. 2021.
• Family history suggestive of hereditary gastrointestinal cancer syndromes or monogenic IBD PubMed,Zare and Monahan KJ. 2025 Uhlig et al. 2021 Zare & Monahan 2025.
• Unexplained extraintestinal manifestations, immunological abnormalities, or atypical infections in IBD or other GI conditions PubMed Uhlig et al. 2021.
• Suspicion of rare metabolic or absorption disorders, such as genetic sucrase-isomaltase deficiency in relevant clinical context Demir et al. 2026 Demir et al. 2026.

Genetic testing approaches include multi-gene panel testing for hereditary cancer syndromes, targeted monogenic IBD gene panels, and broader exome or genome sequencing where indicated, ideally performed in specialized multidisciplinary clinical settings PubMed,Zare and Monahan KJ. 2025 Uhlig et al. 2021 Zare & Monahan 2025. The choice depends on clinical context, available resources, and the specific suspected condition.