A decision tree for genetic diagnosis of hereditary periodic fever in unselected patients.
BACKGROUND
The diagnostic value of molecular analysis of the familial Mediterranean fever (FMF) gene (Mediterranean fever (MEFV)) has been well established only in patients selected on the basis of ethnic background or clinical criteria. Genetic diagnosis for other hereditary periodic fever syndromes has been poorly evaluated.


OBJECTIVE
To determine the diagnostic contribution of genetic tests for hereditary periodic syndromes in a large, unselected series of patients.


METHODS
A retrospective study was conducted on 1941 patients referred to us for FMF genetic tests between 1997 and 2005. MEFV genotypes were compared with clinical data to appraise criteria for FMF diagnosis. Genetic tests for tumour necrosis factor receptor-associated periodic syndrome (TRAPS), hyperimmunoglobulinaemia D syndrome (HIDS) and cryopyrin-associated periodic syndromes (CAPS) were also reviewed.


RESULTS
71% of the 1574 patients with enough data had a clinical diagnosis of FMF according to the widely used Israeli criteria. Two MEFV mutations were found in only 409 patients of this subgroup (sensitivity = 37%) and in 15 (3.3%) of the patients with an improbable clinical diagnosis of FMF (specificity = 97%). Molecular diagnosis for alternate hereditary periodic syndromes was carried out in 456 of the patients having a non-conclusive FMF genetic test. A positive diagnosis was obtained in 31 of these patients (TRAPS (n = 19), HIDS (n = 4) and CAPS (n = 8)).


CONCLUSIONS
First-line MEFV mutation screening in patients with clinically typical FMF may be appropriate only in particular areas. To optimise genetic diagnosis, we propose a decision tree, which, with the advice of an expert practitioner, could help redirect test indications towards non-FMF hereditary periodic syndromes.
Federici
L
L
Laboratoire de Génétique, Hôpital A de Villeneuve, CHU de Montpellier, 34295 Montpellier Cedex 5, France.
Rittore-Domingo
C
C
Koné-Paut
I
I
Jorgensen
C
C
Rodière
M
M
Le Quellec
A
A
Touitou
I
I
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D003663:Decision Trees; D003937:Diagnosis, Differential; D010505:Familial Mediterranean Fever / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000071198:Pyrin; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D000071198:Pyrin