Pregnancy loss, recurrent, susceptibility to, 1

Miscarriage, the commonest complication of pregnancy, is the spontaneous loss of a pregnancy before the fetus has reached viability. The term therefore includes all pregnancy losses from the time of conception until 24 weeks of gestation. Recurrent miscarriage, defined as 3 or more consecutive pregnancy losses, affects about 1% of couples; when defined as 2 or more losses, the scale of the problem increases to 5% of all couples trying to conceive (summary by Rai and Regan, 2006). Pregnancy losses have traditionally been designated 'spontaneous abortions' if they occur before 20 weeks gestation and 'stillbirths' if they occur after 20 weeks. Subtypes of spontaneous abortions can be further distinguished on the basis of embryonic development and include anembryonic loss in the first 5 weeks after conception (so-called 'blighted ovum'), embryonic loss from 6 to 9 weeks' gestation, and fetal loss from 10 weeks' gestation through the remainder of the pregnancy. These distinctions are important because the causes of pregnancy loss vary over gestational ages, with anembryonic losses being more likely to be associated with chromosomal abnormalities, for example. Possible etiologies for RPRGL include uterine anatomic abnormalities, cytogenetic abnormalities in the parents or fetus, single gene disorders, thrombophilic conditions, and immunologic or endocrine factors as well as environmental or infectious agents (summary by Warren and Silver, 2008). Genetic Heterogeneity of Recurrent Pregnancy Loss Susceptibility to RPRGL2 (614390) is conferred by mutation in the coagulation factor II gene (176930) on chromosome 11p11; RPRGL3 (614391) by mutation in the ANXA5 gene (131230) on chromosome 4q27; and RPRGL4 (see 270960) by mutation in the SYCP3 gene (604759) on chromosome 12q23. Genetic variation in the conceptus itself that results in decreased viability of the embryo or fetus is discussed in the respective gene and/or phenotype entry (see, e.g., MTHFR, 607093.0004; NLRP7, 609661; hydatidiform mole, 231090).

OMIM