Maternal screening:- Part 2 – Prenatal Screening For Genetic Abnormalities (Chromosomal)
Sample for Maternal screening
- The serum of the patient is taken during the second trimester.
- Ideally, around the 18th week is the best time.
Purpose of Maternal screening
- Prenatal screening is done to diagnose:
- Neural tube defect
- Trisomy 18
- Down’s syndrome
Significance of Maternal screening
- This is done for pregnant ladies to prepare them mentally for abnormal babies.
Indications for Maternal screening
- This test is advised for the ladies who:
- Has a family history of birth defects.
- Ladies 35 years or older age group.
- If there is a history of drugs used during pregnancy which may be harmful to the fetus.
- Diabetic ladies using insulin.
- If there is a history of viral infection during pregnancy.
- If the lady is exposed to radiation, even on routine X-rays.
- This test may be advised in case of multiple pregnancies.
- Many chromosomal abnormalities are:
- Autosomal does not involve the sex chromosomes.
- Sex-linked abnormalities are called inherited through sex chromosomes.
- There may be total or partial deletion of the chromosome.
- Presence of the extra chromosome attached to the pair of chromosomes (trisomy).
- There may be translocation, where part of a chromosome is broken and attached to another chromosome.
- Other genetic abnormalities or the deficiency of the enzyme or abnormality.
- Triple screening measures the level of AFP, HCG, and estriol.
- This is a screening test and not confirmatory for fetal abnormalities.
- There may be a false positive test.
- This can be supported by ultrasound.
- For more accuracy, advised amniocentesis in positive cases.
Neural tube defect
- Neural tube defect is due to failure of fusion of the neural tube.
- Neural tube defects may show as follows:
- Spina bifida (open)
- Anencephaly is a serious condition; most babies die within a few hours of birth.
- The incidence of neural tube defects is one per 1300 pregnancies.
- Another source says 1 in 500 live birth.
Diagnosis of Neural tube defect:
- Normal HCG.
- Increased AFP
- Decreased UE.
- Maternal AFP is raised.
- Ultrasound of the abdomen may help to diagnose the neural tube defect. It will confirm the single pregnancy.
- Ultrasound establishes normal pregnancy, fetal viability, and identifiable congenital defects.
- Amniotic fluid level of AFP:
- AFP > 2.5 MoM (multiple of the median) will find in 90% of cases of anencephaly.
- AFP >2.5 MoM diagnoses in 80% of the cases of spinal bifida.
- Electrophoresis of amniotic fluid shows two bands of nonspecific cholinesterase and acetylcholinesterase (ACHE).
- There is a third copy of chromosome 18 in most of the cells.
- An extra chromosome is attached to a pair of chromosome 18 (trisomy).
- This is a chromosomal abnormality showing aneuploidy.
- Clinical presentation of trisomy 18:
- Congenital heart disease.
- Renal abnormality.
- Intellectual abnormality.
- The ears are low-set.
- Fists are clenched.
- The incidence is 1 per 4100 pregnancies.
- The incidence of trisomy 18 abnormality increases with the age of the mother.
- Baby with trisomy 18 abnormality, 60% die in the first month of life.
- While 90% die within the first year of life.
- Trisomy 18 usually shows a characteristic pattern that there is:
- Decreased HCG.
- Decreased AFP
- Decreased UE
- About 80 % of Trisomy 18 cases were detected by the above screening.
- Women >35 years of age need genetic analysis Of amniotic fluid.
- Genetic picture:
- This syndrome is characterized by trisomy 21 and is common autosomal aneuploidy.
- Clinical presentation of Down’s syndrome:
- Down’s syndrome baby shows:
- Retarded growth.
- There is a lack of muscle tone.
- There is an intellectual abnormality.
- The incidence increases with the increasing age of the mother.
- The incidence is 1 per 750 live birth of the baby.
Laboratory Diagnosis of down’s syndrome:
- The triple screen:
- This test consists of the estimation of the following:
- Human chorionic gonadotropin (HCG).
- Alpha-fetoprotein (AFP)
- Unconjugated estriol (UE)
- The sensitivity of this panel to Down’s syndrome is 70 %.
- Quad screening:
- This test consists of the following:
- Human chorionic gonadotrophin (HCG).
- Alpha-fetoprotein (AFP).
- Unconjugated Estriol (UE).
- Dimeric inhibin A
- The accuracy of the quad test for Down’s syndrome is 80 %.
- The combined serum test and ultrasonographic measurement of nuchal fold thickness led to a more than 90 % sensitivity.
- Amniotic fluid analysis is the gold standard for ladies above the age of 35 years.
Down’s syndrome shows the following pattern:
- Increased HCG
- Decreased AFP.
- Decreased UE.
- Ultrasound will be helpful in evaluating the gestational age, excluding the multiple gestations, and can find anatomical abnormalities.
- Amniotic fluid may be obtained by amniocentesis to estimate AFP and acetylcholinesterase.
|Abnormality||HCG||AFP||UE||Dimeric Inhibin A|
|Neural tube defect||normal||increased||decreased|
- Genetic picture:
- The patient looks male, but the sex chromosome is XXY instead of XY.
Presentation of Klinefelter’s syndrome patient:
- The external genitalia is usually normal except for small testes.
- There is a tendency for androgens hormone deficiency that will lead to gynecomastia and decreased body hair.
- In some patients above findings are mild or absent.
- There is a tendency for mental retardation, but patients with normal mental status may be seen.
- These patients are always sterile.
- Diagnosis of Klinefelter syndrome:
- Testicular biopsy is diagnostic, showing marked atrophy of the seminiferous tubules.
- The buccal smear shows one barr body due to XX chromosome.
- 10% of the cases have mosaic cell patterns.
- Chromosome karyotyping is the procedure of choice.
- This is also called ovarian agenesis.
- This is the most common abnormality of genetics in females.
- Genetic picture:
- One X female chromosomes is deleted, so the patient has only 45 chromosomes. There is only one X chromosome instead of two XX chromosomes.
- Presentation of Turner’s syndrome:
- Typically affected females have short stature but normal body proportion.
- Secondary-sex characters are not developed, and there is small genitalia.
- Body hairs usually have a normal distribution.
- Some patients may have a webbed neck, coarctation of the aorta, and short fingers.
- These ladies usually do not menstruate because of the lack of ovaries.
- Diagnosis of Turner’s syndrome:
- Buccal smears are negative. In the case of positive cases, do chromosomal karyotyping. The reason is that some cells are positive, and some cells are negative (mosaic pattern).
Conditions associated with increased maternal AFP are:
- Neural tube defect.
- Fetal death.
- Feto-maternal hemorrhage.
- Sacrococcygeal Teratoma.
- Cystic teratoma.
- Cystic hygroma.
- Intestinal obstruction.
- Renal anomalies.
- Turner syndrome.
Questions and answers:
Question 1: How many chromosomes in Klinefelter's syndrome?
There is one extra X chromosome.
Question 2: What is a picture of karyotyping in Turner's syndrome?
One X chromosome is missing.