Predictive Clinical and Biological Criteria for Gene Panel Positivity in Suspected Inherited Autoinflammatory...

Area of Science:

• Genetics
• Immunology
• Clinical Medicine

Background:

• Diagnosing inherited genetic autoinflammatory diseases (I বৈশিষ্ট) requires genetic testing.
• Current guidelines mandate national multidisciplinary staff approval for genetic testing since 2019.
• The need for improved criteria to guide genetic panel selection is apparent.

Purpose of the Study:

• To assess clinical and biological criteria for predicting gene panel positivity in suspected inherited genetic autoinflammatory diseases.
• To evaluate the accuracy and positive predictive value (PPV) of these criteria.
• To determine if these criteria can replace the current national multidisciplinary staff approval process.

Main Methods:

• A case-control study design was employed.
• 119 patients with positive gene panels were matched with 119 patients with negative gene panels.
• Data from a prospectively filled database (June 2012–March 2023) were analyzed for clinical and biological criteria.

Main Results:

• Neonatal symptom onset (92.9% accuracy) and deafness (92.6% accuracy) demonstrated the highest predictive accuracy.
• Despite high accuracy, the Positive Predictive Values (PPVs) for all evaluated criteria did not exceed 50%.
• A statistical association was found between criteria and panel positivity, but predictive power was limited.

Conclusions:

• While certain clinical features like neonatal onset and deafness are highly accurate indicators, their low PPVs limit their utility.
• The evaluated clinical and biological criteria are not sufficient to replace national multidisciplinary staff evaluation for Next-Generation Sequencing (NGS) gene panel testing.
• Expert multidisciplinary review remains essential for appropriate genetic testing in suspected inherited genetic autoinflammatory diseases.