A pilot study of the possible role of familial defects in anticoagulation as a cause for terminal limb reduction malformations.

Terminal limb deficiency defects affect between three and eight babies per 10000 births and are an important cause of disability. Established causes for these malformations include single gene disorders, chromosome abnormalities, teratogens, and amniotic bands. However, the etiology remains unknown in a significant proportion of cases. Several authors have hypothesized that vascular accidents, either bleeds or vessel occlusions, may underlie a substantial number of cases; but, for the most part, the origin of such events remains obscure. Over the past several years, an increasing number of genetic thrombophilias have been recognized and have been associated with increased risks of peri- and post-natal occlusive disease, and with higher rates of recurrent pregnancy loss. The hypothesis to be examined in this pilot study was whether the inherited thrombophilias might be associated with a vascular cause of some terminal limb deficiency defects. Towards that end, protein C, protein S, antithrombin III, factor V Leiden mutation, prothrombin (G20210A) variant, methylenetetrahydrofolate reductase variant, plasma homocysteine, anticardiolipin IgM and IgG antibodies, and lipoprotein (a) were measured in 24 mother-child pairs in which the child had a terminal limb defect. The results provided some evidence that there may be an excess of thrombophilias present in such families and that they may play some etiological role in a subset of these types of limb malformations.