genetic counseling & prenatal diagnosis

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Genetic Counseling and Antenatal Diagnosis

Genetic Counseling & Prenatal DiagnosisDr. Dilip ChoudharyModerator: Dr. D. Singh124/02/2016


Genetic Counseling


Learning Objectives-1. What is genetic counseling?2. Why it is needed?3. What are the clinical situations (indications) where it is important?4. Types of genetic counseling5. What are the steps of genetic counseling?324/02/2016


Introduction: Genetic counseling is communicative process which deals with human problems associated with occurrence and or recurrence of a genetic disorder in a family. An individual who seek genetic counselling is known as a consultand.


This involves an attempt by counsellor to help the consultand to:Understand the medical facts including diagnosis, probable course of disorder and available management.Understand the mode of inheritance of the disorder and the risk of developing and/or transmitting it. Understand the alternatives for dealing with the risk of recurrence.Choose the course of action which is appropriate for them.Make the best possible adjustment to the disorder in an affected family member and or to the risk of recurrence of the disorder.


Purpose of genetic counselingProvide concrete, accurate information about inherited disorders.Reassure people who are concerned that their child may inherit a particular disorder that the disorder will not occur.Allow people who are affected by inherited disease to make informed choice about future reproduction.Educate people about inherited disorder and the process of inheritance.Offer support by skilled health care professionals to people who are affected by genetic disorders.


Indications1. Advanced parental age:- Maternal age 35 yrs Paternal age 50 yrs2. Previous child with or family H/O:- Congenital anomaly Dysmorphism Intellectual disability Isolated birth defect Metabolic disorder Chromosomal abnormality3.Adult onset genetic disorder (presymptomatic testing):- Cancer4.Consanguinity724/02/2016

5.Teratogen exposure 6.Repeated pregnancy loss or infertility7.Pregnancy screening abnormality Maternal serum -feto protein Maternal triple or quad test Fetal ultrasonography Fetal karyotype8.Heterozygote screening based on ethnic risk Sickle cell anemia Tay- sachs, Canavan, Gaucher disease Thalassemia9.Follow up to abnormal neonatal genetic testing824/02/2016

Types of Genetic Counseling Two types of genetic counseling:(A) Prospective genetic counseling:This allows for the true prevention of disease.This requires to identify heterozygous individuals for any particular defect by screening.Explaining to them the risk of their having affected children if they marry another heterozygote for the same gene.If heterozygous marriage can be prevented or reduced, the prospects of giving birth to affected children will diminish.Ex: Sickle cell anaemia Thalassemia



(B) Retrospective genetic counseling:Most genetic counseling at present is retrospective, (the hereditary disorder has already occurred within the family).Ex. Mental retardation Psychiatric illness Inborn errors of metabolismThe methods which could be suggested under retrospective genetic counseling are: Contraception Pregnancy termination. Sterilization


Areas of genetic counseling:Prenatal Genetic Counseling: Several different reasons a person or couple may seek prenatal genetic counseling. If a woman is of age 35 or older and pregnant, then there is an increased chance that her fetus may have a change in the number of chromosomes present.24/02/201611

(B) Pediatric Genetic Counseling:Families or pediatricians seek genetic counseling when a child has features of an inherited condition. Any child who is born with more than one defect, mental retardation or dysmorphic features has an increased chance of having a genetic syndrome. A common type of mental retardation in males for which genetic testing is available is fragile X-syndrome.24/02/201612

Steps of genetic counseling1324/02/2016


Prenatal diagnosis


Introduction: procedures which are used to detect genetic disorders during early stages of pregnancy.

Indications ;To identify fetal disease when abortion is being considered.Direct fetal treatment 1624/02/2016

Methods of prenatal diagnosis(a) Imaging- Ultrasound Fetoscopy MRI (b) Fluid analysis- Amniocentesis Cordocentesis (c) Fetal tissue analysis- Chorionic villus sampling (d) Maternal serum tests- -feto protein Triple test Quad test (e) Maternal cervix- Fetal fibronectin Fluid Bacterial culture



ImagingUltrasound Real time USG can detect fetal growth abnormalities- by biometric measurement of biparietal diameter, femoral length, or head or abdominal circumference.Fetal anomalies eg. Hydrocephalus, NTDs, duodenal atresia, diaphragmatic hernia, renal agenesis, limb anomalies, omphalocele, gastroschisis, hydrops.Also help in performing BPP, cordocentesis and other invasive proceduresDoppler USG- for velocimetry and detection of increased vascular resistence due to fetal hypoxia.


Fluid AnalysisChorionic villous samplingTransvaginal or transabdominal chorionic villous biopsy, whichprovides fetal cells.The placenta contains tissue that is genetically identical to fetus.Timing: In first trimester, shouldnt be performed before 10wk, commonly performed between 11 and 13 wks.Indications: for karyotype, enzyme assay, molecular DNA genetic analysis.


Method of CVS: two ways to perform a CVS, transabdominally (TA) and transcervically (TC), depends on the location of the villi in the uterus. Transabdominal approach-When the villi are anterior, under all aseptic precautions ultrasound guided needle is passed through abdominal Wall and the uterus to reachthe villi. A syringe attached to the needle is used to suction out a small amount of villi.


Transcervical approach- When the villi are in the lower part of the uterus and posterior TC approach is used. A thin flexible plastic catheter is carefully guided through the cervix under ultrasound guidance to the villi. A syringe attached to the catheter is used to suction out a small amount of villi as the catheter is withdrawn.The CVS procedure collects larger samples and provides faster resultsthan amniocentesis.Different from amniocentesisin that it does not allow fortesting for neural tube defects.


Associated risk/ Complications: 1.miscarriage/ fetal loss (1% - 2%). 2. Oromandibular limb hypoplasia. 3.Isolated limb reduction defect- Increased risk is associated with decreased gestational age at the time of CVS, highest susceptibility when CVS if performed before 9 wks.Mechanism: thromboembolization or fetal hypoperfusion through hypovolemia or vasoconstriction (based on assumption that caused by some form of vascular disruption). The limbs and mandible are susceptible to such disruption before 10 weeks gestation.Overall risk for transverse limb deficiency from CVS is 0.03%0.10% 4.Rh- isoimmunization.


AmnicentesisUSG guided percutaneous withdrawal of amniotic fluid for diagnostic purpose.Timing- between 14- 16wks.Indications: Karyotype (advanced maternal age)Fetal maturity (L:S ratio, phosphatidylcholine or phosphatidylglycerol)Biochemical enzyme/amino acid/hormone analysis.Molecular genetic DNA diagnosis.- fetoprotein(for NTDs) and 17-ketosteroid (for adrenogenital syndrome) determination


Method of amniocentesis:Performed transabdominally (TA). During the procedure, a needle is passed through the abdomen and into the amniotic sac under continuous ultrasound guidance. The needle stilette is removed once the needle is in the correct position. A small sample of amniotic fluid (1020ml) is then removed using a syringe attached to the needle.24/02/201625

Complications of amniocentesis:1.Miscarriage (risk about 1%). Before 14 weeks of gestation (early amniocentesis) has a higher fetal loss rate.2.Preterm labor (stimulation of uterine contraction) or PROM.3.Injury to fetus4.Placental puncture and bleeding with secondary damage to fetus.5.Infection6. Maternal sensitization to fetal blood (Rh-isoimmunization) :- Anti D immunoglobulin to be given to Rh ve mother.2624/02/2016

CVSAmniocentesisWhat does it involve?Small sample of placenta under ultrasound guidancesmall sample of amniotic fluid under ultrasound guidanceWhen is the procedure usually performed?Between 10 and 14 weeks of pregnancyAfter 15 weeks of pregnancyWhat is the risk of miscarriage?About 1 to 2 in 100 women (1-2%) About 1 in a 100 women (1%) What technique is used?transabdominally (TA) and transcervically (TC)transabdominally (TA)


CordocentesisCordocentesis, or PUBS (Percutaneous Umbilical Blood Sampling), is the sampling ofblood from the umbilical cord.Objective: (a) prenatal diagnosis and (b) fetal therapy.Timing: can be performed as early as 16 wks of gestation but commonly performed between 18-22 wks of gestation for prenatal diagnosis.


Indication of cordocentesis:(a) Pre