Morphological characteristics of monosomy X in spontaneous abortions

From a morphologic and cytogenetic study of 160 spontaneous abortion specimens with 45,X, as well as data from the literature, we conclude that monosomy X has characteristics which can suggest the diagnosis in prenatal life in the absence of a karyotype. Specimens in our study could be classified into four groups: (I) 49% consisted of a chorionic and amniotic sac, usually ruptured, containing a well-defined umbilical cord with a fragment of embryonic tissue at its end. (II) 25% consisted of small macerated embryos of 40-44 days developmental age, with pronounced retrognathia and lack of nasofrontal angle. Two specimens had a neural tube defect, one had cleft lip and palate, and two had an isolated cleft palate. The developmental age of the embryos was 5-6 weeks behind their gestational age. (III) 5% were very macerated second trimester fetuses with cystic hygromata, lymph-edema of the hands and feet, ascites, hydrothorax, and hypoplastic lungs. Four had coarctation of the aorta, three had single umbilical artery, and two had persistent left cardinal vein. Horseshoe kidney, ventricular septal defect, and anomalous subclavian artery were found once. (IV) The remaining 21% consisted only of fragments of ruptured sacs without an umbilical cord insertion site, pieces of fetal membranes or chorionic villi only. The spectrum of anomalies observed suggests that the pathogenetic mechanism for early death in 45,X embryos and fetuses may be related to vascular abnormalities or to abnormal fluid balance, leading to disturbed embryo-placental circulation, and excess fluid volume in the fetus. The 45,X karyotype is compatible with quite normal morphological development up to the fetal stage, and no specimens were found where development had ceased at a very early stage. The usual lethality of monosomy X may be explained by the presence of genes, essential for survival, on the pseudoautosomal segment of the X and Y. Lethality could result from recessive lethal mutations in this region, or from the necessity for two copies of this regions for normal development.