Perthes’ disease and the search for genetic associations

Abstract

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.

Aetiology of Legg-Calvé-Perthes disease: A systematic review

“…Several case reports and studies were reported in our review[42-46]. Their association with the disease was found to be weak in a case study published by Kenet et al[101] involving 119 LCPD affected children and 276 controls, further supported by a review of the literature. In the same study, the absence of significant association with Gaucher's disease and Factor V Leiden alterations was also reported.…”

Kohler’s Disease Secondary to Tarsal Pyogenic Arthritis

“…This theory is supported by the absence of the condition in bones in which centres of ossification are present at birth (e.g., calcaneus, talus, or cuboid) [7]. We have also found evidence in the literature that shows a genetic predisposition for certain osteochondroses [8,9].…”

No correlation to collagen synthesis disorders in patients with Perthes’ disease: a nationwide Swedish register study of 3488 patients

“…Su et al found a mutation of COL2A1 that caused abnormal chondrocytes, disarrangement of fibres and decreased stability in the femoral head cartilage of patients with Perthes’ disease [ 8 ]. Further support for mutations in the COL2A1 gene in patients with Perthes’ disease has been published by several authors [ 3 – 5 , 9 , 10 ].…”