Clinical and genetic characteristics of Legg-Calve-Perthes disease

Abstract

Legg-Calve-Perthes disease (LCPD) is a known childhood form of idiopathic femoral head osteonecrosis. It is characterized by a sequence of events involving the capital femoral epiphysis. The disease process is associated with the disruption of the blood supply to the femoral head. In most cases, LCPD appears in a sporadic form. Occurrences of cases in families have also been reported, with some families having more than two affected individuals. The disease etiology is still unknown, however, various factors have been considered for the pathogenesis of LCPD, including very low body weight or short stature at birth, maternal smoking, and secondhand smoke exposure. Interaction of multiple environmental and genetic factors has also been postulated as an underlying player in the development of the disorder. Hypercoagulability may have a major role in LCPD development. Families segregating LCPD largely demonstrate autosomal dominant inheritance. Variants in coagulations genes (Factor 5 and Factor 2) and collagen encoding gene (COL2A1) have been linked to the disease. However, our knowledge of the LCPD pathogenic factors is limited. A better understanding of the association between LCPD and causative factors, for example, the role of hypercoagulability in osteonecrosis development, might lead to the development of improved treatments, to shorten the acute phase of the disease during childhood as well as to possibly reduce the long-term effects of osteoarthritis in adulthood. Detection of large-effect variants underlying LCPD may help in offering extended screening for all first-degree family members. In this review, we would like to discuss the etiological factors underlying LCPD with special emphasis on the role of coagulation factors and mutations in the genes encoding those coagulation factors.