The role of heritable thrombophilic risk factors in the pathogenesis of the
Perthes' disease is controversial. The clinical and radiological findings of
Perthes' disease may be indistinguishable from those of
Gaucher's disease, and the most common Jewish N370S Gaucher mutation is threefold greater in patients with
Perthes' disease. Familial
osteonecrosis of the femoral head is associated with variant mutations of
collagen type II (COL2A1 mutations). We therefore studied the potential role of genetic
thrombophilia and the Gaucher and COL2A1 mutations in children with
Perthes' disease. Genomic
DNA of 119 children with radiologically-confirmed
Perthes' disease diagnosed between 1986 and 2005 was analysed for the thrombophilic polymorphisms
Factor V Leiden, 677T-MTHFR and FIIG20210A. The results were compared with those of a group of 276 children without
Perthes' disease.
DNA was also analysed for the Gaucher mutations N370S, G insertion (84GG), L444P, Intron 2 (IVS2+1G>A) and R496H. Enzymic assays confirmed the
Gaucher disease status.
Collagen (COL2A1) mutations of the 12q13 gene were also analysed. The prevalence of thrombophilic markers was similar among the 119 patients with
Perthes' disease and the 276 control subjects. The prevalence of the Gaucher mutation was consistent with Israeli population carriership data and did not confirm an earlier-claimed association with
Perthes' disease. All 199 patients were negative for the studied COL2A1 mutations. We found no genetic association between
Perthes' disease and either
Gaucher's disease or COL2A1 mutations or increased genetic
thrombophilia among our patients compared with the control group. A systematic review of case-control studies suggested that there was a positive association between
Perthes' disease and
Factor V Leiden. The impact of this association upon the disease, although not consistent across the studies, remains unclear.