Drs. Gattorno and Sormani contributed equally to this work.
A diagnostic score for molecular analysis of hereditary autoinflammatory syndromes with periodic fever in children
Article first published online: 31 MAY 2008
Copyright © 2008 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 58, Issue 6, pages 1823–1832, June 2008
How to Cite
Gattorno, M., Sormani, M. P., D'Osualdo, A., Pelagatti, M. A., Caroli, F., Federici, S., Cecconi, M., Solari, N., Meini, A., Zulian, F., Obici, L., Breda, L., Martino, S., Tommasini, A., Bossi, G., Govers, A., Touitou, I., Woo, P., Frenkel, J., Koné-Paut, I., Baldi, M., Ceccherini, I. and Martini, A. (2008), A diagnostic score for molecular analysis of hereditary autoinflammatory syndromes with periodic fever in children. Arthritis & Rheumatism, 58: 1823–1832. doi: 10.1002/art.23474
- Issue published online: 31 MAY 2008
- Article first published online: 31 MAY 2008
- Manuscript Accepted: 11 FEB 2008
- Manuscript Received: 7 AUG 2007
- Italian Ricerca Corrente Ministeriale
- Fondazione C. Golgi, Brescia, Italy
To identify a set of clinical parameters that can predict the probability of carrying mutations in one of the genes associated with hereditary autoinflammatory syndromes.
A total of 228 consecutive patients with a clinical history of periodic fever were screened for mutations in the MVK, TNFRSF1A, and MEFV genes, and detailed clinical information was collected. A diagnostic score was formulated based on univariate and multivariate analyses in genetically positive and negative patients (training set). The diagnostic score was validated in an independent set of 77 patients (validation set).
Young age at onset (odds ratio [OR] 0.94, P = 0.003), positive family history of periodic fever (OR 4.1, P = 0.039), thoracic pain (OR 4.6, P = 0.05), abdominal pain (OR 33.1, P < 0.001), diarrhea (OR 3.3, P = 0.028), and oral aphthosis (OR 0.2, P = 0.007) were found to be independently correlated with a positive genetic test result. These variables were combined in a linear score whose ability to predict a positive result on genetic testing was validated in an independent data set. In this latter set, the diagnostic score revealed high sensitivity (82%) and specificity (72%) for discriminating patients who were genetically positive from those who were negative. In patients with a high probability of having a positive result on genetic testing, a regression tree analysis provided the most reasonable order in which the genes should be screened.
The proposed approach in patients with periodic fever will increase the probability of obtaining positive results on genetic testing, with good specificity and sensitivity. Our results further help to optimize the molecular analysis by suggesting the order in which the genes should be screened.