seminar prenatal genetic screening

of 59/59
PRENATAL GENETIC SCREENING By Dr Sreelasya Kakarla Dept of OBG, SSMC, Tumkur

Post on 13-Apr-2017



Health & Medicine

10 download

Embed Size (px)




By Dr Sreelasya KakarlaDept of OBG,SSMC, Tumkur

Congenital defects may be anatomical or functional.Causes of these defects may be preconceptional or because of post conceptional exposureChromosomal abnormalities : 0.2%Single gene defects : 0.4%Multifactorial : 0.7%Unknown : 0.6%Anomalies due to exposure to teratogen : 0.1%

Prenatal diagnosis is the science of identifying structural and functional abnormalities in the developing fetus.

Diagnostic evaluation typically involves 3 major categories :Fetuses at a high risk for a genetic or congenital disorder.Fetuses at high risk for common congenital abnormalities.Fetuses discovered ultrasonographically to have structural or functional abnormalities.

High risk describes a risk greater than the chance of fetal death associated with the diagnostic procedure considered.

INDICATIONS for prenatal diagnosisIncreased risk for fetal chromosomal abnormalities based on advanced maternal age, previous pregnancy affected by fetal chromosomal abnormality Family history of a known genetic condition or if the couple is a known carrier of gene mutation or balanced translocation.Either of the couple affected by congenital disorder : eg ; congenital cardiac defectsPrevious history of a pregnancy affected by congenital anomalies


Family history of congenital abnormalitiesMaternal medical condition : diabetes, autoimmune diseases, hypertension, hypothyroidism etc.,Abnormal ultrasound findings-soft markers.Medications : anticonvulsants, oral anticoagulants, chemotherapeutic agents.Congenital infections : rubella, cytomegalovirus, chickenpox, syphilis.

METHODS of prenatal diagnosisNON INVASIVE UltrasoundFetal MRIFree fetal DNA

INVASIVE AmniocentesisChorionic villus samplingFetal blood samplingFetal biopsyFetal surgery

Confirmatory tests for prenatal diagnosisChromosome abnormalities

Karyotype by conventional chromosome analysisFluoroscent in situ hybridization (FISH)Multiplex ligation dependent probe amplification (MLPA)Comparative genomic hybridization (CGH)

Single gene analysis

Sanger sequencingNext generation sequencing(NGS)Others : amplification refractory mutations system(ARMs)

SCREENING FOR COMMON CONGENITAL ABNORMALITIESNEURAL TUBE DEFECTS : Screening for NTDs is recommended if the following RISK FACTORS are presentFamily history of neural tube defectsExposure to certain environmental agentsDiabetesHyperthermiaDrugs : anticonvulsants isotretinoinAntifolate receptor antibodies

ALPHA FETO PROTEINGlycoproteinSynthesized early in gestation by fetal yolk sac ; later by fetal gastro intestinal tract and liverConcentration increases steadily in both fetal serum and amniotic fluid until 13 weeks, after which these levels rapidly decrease.Passes into maternal circulation by diffusion across the placental membranes and may also be by placental circulation.


Anechoic stripe visible just internal to the skin stripe at the level of back of the fetal neck.Consequent to the subcutaneous accumulation of fluid in the fetal neck in the 1st trimester.Incidence of chromosomal abnormalities and structural anomalies is related to the thickness rather than the appearance.The translucency usually resolves in the 2nd trimester but may persist as a cystic hygroma or nuchal oedema.

Chromosomal abnormalities are found in 20-30% of fetuses with increased nuchal translucency.50% of these are trisomy 21,Rest are contributed by trisomy 13, 18, turners syndrome.Majority of the cases, NT < 4.5 mm

Aetiology of increased nuchal translucency

Multifactorialcardiac failureSuperior mediastinal compression causing venouscongestion,Altered composition of extracellular matrix,Abnormal or delayed development of lymphatic systemConsequent to decreased fetal movements,Fetal anemia

Criteria for assessment of NT

Fetus to be in true sagital sectionIdeal image includes : nasal skin, echogenic tip of nose, nasal bone, palate in rectangular shape, the translucent diencephalon in the centre and the nuchal translucency posteriorly in the same image.It should definitely not include any part of the zygoma between the nose and the palate.CRL should range between 45 and 84 mm.It is important to exclude the presence of umbilical cord near the fetal neck.

Fetal nasal boneNasal bone is absent or hypoplastic in around 69% of fetuses with trisomy 21 in 11-13 weeks.Technically ,the section for assessment and measurement is same as for nuchal translucency.Transducer should be parallel to the direction of the nose.

3 lines are evident :

skin represented by the top line ,Echogenic nasal bone just below this which is thicker than overlying skin and A line in front of the nose which represents tip of the nose

Maternal serum afp screeningDone between 14-22 weeksMeasured in ng/dlReported as multiples of the median (MoM)Weight, race, diabetic status, gestational age, number of fetuses influence the level.2.0-2.5 MoM : upper limit of normal.2.5-3.5 MoM : indiscriminate zone>3.5 MoM : increased fetal risk .Sensitivity : 90%PPV: 2-6%

Conditions associated with abnormal MS AFPELEVATED LEVELS :Neural tube defects.Pilonidal cystsEsophageal or intestinal obstructionLiver necrosisCystic hygromaSacrococcygeal teratomaAbdominal wall defects : omphalocele, gastroschisisMultifetal gestationUndetermined gestation.


Chromosomal trisomiesGestational trophoblastic disordersFetal deathOverestimated gestational age.

A combination of the MSAFP test + Ultrasonography detects almost all cases of anencephaly and most cases of spina bifida. Also, a NTD can be distinguished from other fetal defects, such as abdominal wall defects, by the use of an acetylcholinesterase test carried out on amniotic fluid. If the level of acetylcholinesterase rises along with AFAFP, it is suspected as a condition of a NTD. However, the MSAFP levels also increase with gestational age, gestational diabetes, twins, pregnancies complicated by bleeding, and in association with intrauterine growth retardation.

Screening for Downs syndromeDepending on the gestational age at pregnancy booking,testing options that can be offered include

Combined screening (11-13 weeks) : NT + serum PAPPA & free B-HcgQuadruple screening (15-18 weeks) : serum AFP,uE3, free B-Hcg & inhibin AIntegrated screen: NT + serum PAPPA+Quadruple screening

Stepwise screening: Combined screening+ Quadruple marker test in all patients with down syndrome risk (DSR)