Two paternal and one maternal sets of chromosome( triploid) leads to partial mole( abnormalities in placenta with normal fetal growth

Two maternal and one paternal sets( triploid) leads to small placenta but fetus with IUGR.

These features are called imprinting. Thus few genes are active in paternal chromosomes and few are active in maternal chromosomes ,even though both the chromosomes are called homologues.

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Dr.D’Pankar Banerji

Tips of screening for fetal chromosomal anomalies

• Chorionic villus sampling at 10 to 13 weeks' gestation has a 0.6% to 4.6% risk for fetal loss and a 97.8% cytogenetic diagnosis rate.

• Amniocentesis at 16 to 18 weeks' gestation has a 1 in 370 to 1% risk for fetal loss and a 99.4% cytogenetic diagnosis rate.

• First-trimester screening methods include nuchal translucency and combined screening.

• Nuchal translucency, measured by standardized ultrasonography of the posterior fetal neck, detects approximately 70% to 71% of Down's syndrome, with a 3.5% to 5% false-positive rate.

• Nuchal translucency more than 3.5 mm is linked with major congenital heart defects, defects of the great vessels, malformations, dysplasias, deformations, disruptions, and syndromes.

• Abnormal nuchal translucency warrants diagnostic testing; normal diagnostic testing warrants targeted ultrasonography or fetal echocardiogram.

• Combined screening is a nuchal translucency test plus serum PAPP-A and hCG.

• Combined screening has a 78.7% to 89% detection rate, with a 5% false-positive rate for Down's syndrome and a 90% detection rate with a 2% false-positive rate for trisomy 18.

• Low PAPP-A and hCG levels are linked with adverse pregnancy outcomes, including fetal loss, hypertension, preterm birth, stillbirth, and low birth weight.

• Second-trimester serum screening methods include triple and quadruple tests.

• The triple screen of serum AFP, hCG, and unconjugated estriol testing has a 69% detection rate and a 5% false-positive rate for Down's syndrome.

• The quadruple screen of triple-screen tests plus inhibin A testing has a detection rate of 81% and a less than 3% to 5% false-positive rate for Down's syndrome.

• The evidence to recommend routine second-trimester ultrasonography is insufficient.

• If second-trimester ultrasonography results are abnormal, diagnostic testing is recommended.

• Second-trimester ultrasonography combined with quadruple screen has almost 90% sensitivity and a 3.1% false-positive rate.

• Nuchal fold thickening with normal ultrasonography and normal karyotype results is linked with a higher risk for poor pregnancy outcomes.

• Isolated elevated AFP levels are linked with a greater risk for poor pregnancy outcomes.

• Combined first-trimester and second-trimester testing as integrated, stepwise sequential, or contingency screening, has a 92% to 96% detection rate and a 5% false-positive rate for Down's syndrome.

• Integrated screening is a single assessment of risk based on PAPP-A and nuchal translucency tests in the first trimester, quadruple screen in the second trimester, and age.

• In stepwise sequential screening, if first-trimester risk is increased based on age, PAPP-A, and nuchal translucency, then invasive diagnostic testing or second-trimester triple or quadruple screen is recommended.

• In contingency screening, cutoff values for first-trimester risk based on age, PAPP-A, and nuchal translucency will determine recommendations for invasive diagnostic testing, no additional testing, or second-trimester serum screening.

• For women who present in the first trimester, the most effective screening test is the integrated screening with the nuchal translucency test, or the maternal serum-integrated test if the nuchal translucency test is unavailable.

• For women who present in the second trimester, the recommended screen is the quadruple test.

• All pregnant women should have access to counseling.

• In multiple gestation cases, nuchal translucency testing followed by invasive diagnostic testing if indicated can be useful, but maternal serum results are less sensitive.

Pearls for Practice

• For women who present for prenatal care in the first trimester of pregnancy, the most effective method of screening for fetal chromosomal abnormalities is an integrated screening of PAPP-A and nuchal translucency testing in the first trimester and quadruple screen in the second trimester.

• For women who present for prenatal care in the second trimester of pregnancy, the most effective method of screening for fetal chromosomal abnormalities is the quadruple screen.

2.Genetics of Hydatidiform mole

Complete hydatidiform mole:

A complete hydatidiform mole is diploid, i.e. the presence of 46 chromosomes, but all chromosomes is of paternal origin. As always in the case of the uniparental origin of one or more chromosomes, this requires at least two sequential errors. The most frequent mechanism of origin is the fertilization of an oocyte without nucleus (or with inactivated nucleus) by a single sperm, followed by duplication of the haploid genome. In the remainder (~20-25 %), an enucleated oocyte is fertilized by two sperms cells. A third possible cause, the fertilization of an empty oocyte by a diploid sperm cell, is extremely rare. How an enucleated oocyte is generated is not clear, but on possible error is a non-disjunction of all chromosomes during meiosis, with all chromosomes ending up in one of the polar bodies. Since 46 YY has never been observed (and thus probably non-viable), cytogenetic investigation usually reveals a 46,XX Karyotype and in a minority a 46 XY Karyotype is found

This embryo is called androgenotic embryos (both pronuclei are of paternal origin) and they fail to develop an embryoblast whereas the trophoblast proliferates excessively, resulting in a hydatidiform mole.

If both the pronuclei are of maternal origin (gynogenotes, equivalent of parthenogenesis), no extra embryonic components are formed and the embryoblast develops into a teratom

Partial hydatidiform mole:

Partial mole is caused by triploidy, the presence of three copies of each chromosome .The extra haploid set of chromosomes can have either a maternal origin (and then it is called digynic triploidy) or paternal (diandric triploidy)

Diandric triploidy is associated with placental features of partial mole and normal growing fetus where as digynic triploidy is associated with small placenta but the fetus with IUGR and macro cephalic

These features indicate that both maternal and paternal genes are essential for normal embryonic development. Certain maternal genes are required for development of the embryo proper; where as extra embryonic components depend on the presence of active paternal genes. This is regulated by a process called genomic imprinting, where by certain genes are differently expressed, solely depending on whether they are on the maternal or paternal chromosome.

Extra dose of paternal chromosome creates defect of placenta and extra dose of maternal chromosomes creates fetal anomaly
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