The Principles of Clinical Cytogenetics - Extra Materials - Springer

Cytogenetics of Spontaneous Abortion 331
Fig. 1. Gestational sac with very small embryo, consistent with an underlying cytogenetic abnormality,
often a nonviable trisomy or, as in this case, monosomy X.
present for evaluation. Some affected individuals might never be identified. The mild phenotypic
expression at birth appears to reflect an absence of markedly deleterious effects during embryogenesis.
This would explain the relatively low frequency of sex chromosome trisomies of 0.2% among
spontaneous abortuses (23).
Monosomy X gestations vary considerably in phenotype and might exhibit marked dysmorphism.
The majority undergo early embryonic growth arrest and present as an empty gestational sac or as an
umbilical cord ending with a small nodule of necrotic embryonic tissue (see Fig. 1). A lesser number
survive into the second trimester, at which time the phenotype is often that of an hydropic fetus with
massive cystic hygroma (see Fig. 2). Renal and cardiac anomalies are frequently seen as well. During
the third trimester, the appearance might be similar to that seen in the second trimester, with cystic
hygroma and dorsal edema over the hands and feet, the classic Turner syndrome phenotype. There
are also 45,X infants who appear minimally affected and might not be recognized at birth, presenting
later in childhood or adolescence with hypogonadism and short stature.
Several explanations have been proposed for the wide variability in phenotype. Although the majority
of 45,X conceptuses surviving to term appear to have a maternally derived X, parental origin of
the monosomy does not appear to affect phenotype or viability (38,39). Rather, survival of the early
pregnancy could be dependent on presence, in some tissues, of a second sex chromosome, either
another X or a Y. The nonmosaic 45,X conceptus appears unlikely to survive, whereas a mosaic
gestation with a second sex chromosome, regardless of whether it is an X or a Y, has a better chance
of undergoing orderly morphogenesis early in gestation and of surviving to term (39,40). This second
cell line could be absent from many tissues and is often difficult to detect with routine cytogenetic
studies, but could sometimes be identified using multiple sampling sites or FISH techniques. Although
extensive efforts at identification of a second cell line might not be justified in routine evaluation of
a monosomy X abortus, such techniques are often helpful in evaluation of Turner syndrome patients
with suspected low-level Y chromosome mosaicism. The presence of genes originating on the Y
chromosome may place the patient at increased risk for gonadoblastoma.