Evaluation of families with recurrent molar pregnancy suggests that dysregulation of normal parental imprinting of genes, with loss of maternally transcribed genes, is likely to contribute to the pathogenesis of molar pregnancy. Familial recurrent hydatidiform mole, is a rare occurrence, characterized by recurrent complete hydatidiform mole of biparental origin, rather than the more usual androgenetic origin (23). Genetic mapping shows that in most families the gene responsible is located in a 1.1 Mb region on chromosome 19q13.4. Mutations in the gene result in dysregulation of imprinting in the female germ line with abnormal development of both embryonic and extraembryonic tissue.
Figure 39.4 The karyotype of partial hydatidiform mole.
Clinical Features Patients with complete molar pregnancy are diagnosed increasingly earlier in pregnancy and treated before they develop the classic clinical signs and symptoms. This is the result of many changes in clinical practice, such as the frequent use of human chorionic gonadotropin (hCG) measurement and transvaginal ultrasonography in early pregnancy for women with vaginal staining and for determining the gestational dates in asymptomatic women. The following is a description of the classic and current clinical features of complete molar pregnancy (24,25).
Vaginal Bleeding Vaginal bleeding is the most common symptom causing patients to
Mole seek treatment for complete molar pregnancy. It had been reported to occur in 97% of cases, whereas currently it is reported to occur in 84% of patients. Molar tissues may separate from the decidua and disrupt maternal vessels, and large volumes of retained blood may distend the endometrial cavity. Because vaginal bleeding may be considerable and prolonged, one-half of these patients had anemia (hemoglobin <10 g/100 mL). Anemia is present in only 5% of patients.
Excessive Uterine Size Excessive uterine enlargement relative to gestational age is one of the classic signs of a complete mole, although it was present in only about half of patients.
Currently, excessive uterine size occurs in only 28% of patients. The endometrial cavity may be expanded by both chorionic tissue and retained blood. Excessive uterine size is generally associated with markedly elevated levels of hCG, because uterine enlargement results in part from trophoblastic overgrowth.
Preeclampsia Preeclampsia was observed in 27% of patients with a complete hydatidiform mole. Preeclampsia is now reported in only 1 of 74 patients with complete mole at the initial visit. Although preeclampsia is associated with hypertension, proteinuria, and hyperreﬂexia,
Figure 39.5 Photomicrograph of a fetal hand demonstrating syndactyly. The fetus had a triploid karyotype, and the chorionic tissues were a partial mole.
eclamptic convulsions rarely occur. Preeclampsia develops almost exclusively in patients with excessive uterine size and markedly elevated hCG levels. Hydatidiform mole should be considered whenever preeclampsia develops early in pregnancy.
Hyperemesis Gravidarum Hyperemesis requiring antiemetic or intravenous replacement therapy occurred in one-fourth of women with a complete mole, particularly those with excessive uterine size and markedly elevated hCG levels. Severe electrolyte disturbances may develop and require treatment with parenteral ﬂuids. Currently, only 8% of patients have hyperemesis.
Hyperthyroidism Clinically evident hyperthyroidism was observed in 7% of patients with a complete molar gestation. These women may have tachycardia, warm skin, and tremor, and the diagnosis can be confirmed by detection of elevated serum levels of free thyroxine (T4) and tri-iodothyronine (T3). Clinical evidence of hyperthyroidism with complete mole is rare.