Читать книгу Genetic Disorders and the Fetus - Группа авторов - Страница 157

CHMs are generally the result of androgenetic (paternal only) development and are observed in about 1/800 human pregnancies.¹²⁷ Diagnosis is characterized by cystic, edematous chorionic villi (fluid accumulation within the placental villi), trophoblastic hyperplasia (overgrowth of the outer layer of the villi), and, generally, absent amnion, chorion, and fetal development (Figure 4.1a, b). Pathological diagnosis is aided by absence of p57^KIP2 staining, a protein expressed only from the maternal allele of the CDKN1C gene and, consequently, negative in CHMs. Most CHMs are diandric diploid with genomic contribution from either one or two sperm.¹²⁸ The abnormal development of embryos lacking a maternal genome can be explained by loss of expression of developmentally important paternally imprinted (maternally expressed) genes.^{129, 130} A small portion of CHMs are biparental in origin and these are more likely to be recurrent and familial. Maternal homozygous and compound mutations in NLRP7 have been detected in the majority of women experiencing recurrent biparental hydatidiform moles.^{131, 132} Mutations in c6orf221 have also been reported.¹³³ Biparental moles generally exhibit abnormal maternal imprints, although the extent of this and loci involved are variable.^134–136

Figure 4.1 (a) Complete hydatidiform mole (CHM) gross – cystic villi; (b) CHM microscopic – cystic villi with cisterns, circumferential trophoblastic hyperplasia, stromal karyorrhexis; (c) partial hydatidiform mole (PHM) gross – cystic villi; (d) PHM microscopic – normal and cystic villi, focal trophoblastic hyperplasia, fetal vessels, and blood cells present; (e) placental mesenchymal dysplasia (PMD) gross – abnormal extension of vessels and Wharton's jelly into placenta parenchyma; (f) PMD micro – large, myxomatous stem villi with abnormal and dilated vessels.