Genetic counseling It is the process of evaluating family history & medical records, ordering genetic tests, evaluating the results of this investigation & helping parents understand & reach decisions about what to do next. Genetic test are done by analyzing small samples of blood or body tissues. They determine whether you or your partner or your baby carry genes for certain inherited disorders.
WHO NEEDS GENETIC COUNSELLING ? Those who can benefit from genetic counselling include those who have a history of: A known genetic disorders e.g. Cystic Fibrosis, Hemophilia, Down’s syndrome Birth defects e.g. Spina Bifida, Cleft Lip and Palate, Congenital heart disease, club foot Inherited Cancers e.g. Breast and Bowel Cancers Intellectual disability Hearing or visual disability Infertility or multiple miscarriages or infant deaths Genetic defects occurring frequently in special ethnic and rational groups e.g. Tay-Sachs disease, Sickle cell Anemia, Thalassemia.
Genetic counselling deals with the problem of giving advice tofamilies having, or likely to have, children with genetic disorders. Causation of human diseases Genetic Inborn errors of metabolism. e.g.Phenylketonuria,Galactosemia,Duchenne muscular dystrophy Rarer, simple Mendelian inheritance. High risk of recurrence Genetic & Environmental Pyloric stenosis, Club-foot, Congenital dislocation of hip, Diabetes mellitus Commoner, Multifactorial. Low risk of recurrence
Genetic counselling refers to the giving ofscientific advice under following circumstances 1. Risk of recurrence of a hereditary disease in a family. 2. Risk attending the progeny from consanguineous marriages. 3. Genetic basis in cases of abnormal sexual development, infertility, recurrent abortion & congenital malformations. 4. Problem of child adoption. 5. Cases of disputed paternity. 6. Risks of acquiring common diseases. 7. Detection of carrier.
Risk of recurrence of a hereditary disease in afamily Determining the risk: Autosomal dominant disorder(Brachydactyly, Achondroplasia): risk of recurrence is 50% - 100% Autosomal recessive(Albinism,Phenylketonuria): chances of affected child is 1 in 4. X-linked disorder(Haemophilia,G6PDdeficiency, Partial colour blindness): In male – male progeny – nil; female progeny- 100%. In female – male progeny -50%; female progeny- 50%.
Sporadic case of hereditary abnormality:when normal parents have child with a rare congenital abnormality; the following must be considered to calculate the risk of same abnormality to future children.1. Rule out the effect of teratogenic agent.2. Find out possibility of new mutation in the gametes.3. In autosomal recessive disorder,(Phenylketonuria) the parents of the affected child may be related consanguinously.4. Known X- linked recessive disorder(Colour blindness)- distinction should made from an autosomal recessive disorder.5. Rule out Down’s syndrome, 13 trisomy syndrome, 18 trisomy syndrome & cri du chat syndrome. When anomalies involves more than one system, karyotyping should be done to find out if any translocation. During genetic counselling , the phenomenon of genetic heterogeneity should be kept in mind.
Problem of child adoption Determining the risk of inherited disorders in child. The main difficulties are encountered when there is a family history of disease, which is not recognisable clinically or biochemically in the earlier years of child’s life e.g. Marfan’s syndrome, Huntington’s chorea.
Cases of disputed paternity. Paternity could not be proved with certainty, but it can be disproved without doubt. Paternity can be often disproved on the basis of blood groups of child & putative father.
Risks of acquiring common diseases Some of the common conditions such as cleft lip- palate,idiopathic epilepsy, pyloric stenosis, spina bifida, early onset of diabetes mellitus etc. have no simple mode of inheritance.some are heterogenous having number of etiologically different disorders. Others due to effect of many genes or environment. In such conditions only empiric risks of recurrence can be given. An Empiric risk is defined as the probability of occurrence of a specified event based upon prior experience and observations rather than on prediction by a general theory. It is calculated by estimating the frequency of the condition in the relatives of the affected persons. In multifactorial disorders, the rate of recurrence in first degree relatives is equal to the sqare root of the prevalence in the general population
Antenatal diagnosis of genetic disease Procedures- Transabdominal amniocentesis . Cytological & biochemical study of amniotic fluid detects gross anomaly. Carried out at about 16 wks of gestation. Radiography Ultrasonography- to determine viability of fetus, gestational age, multiple gestations, placental & fetal positions & gross fetal malformations. Fetoscopy. Placentocentesis.
Treatment of genetic disease Replacement of deficient enzyme or protein Drugs Viral therapy Prevention –avoiding harmful drugs. Surgical removal of diseased tissue. Transplantation of normal tissue. Genetic screening of the newborn is carried out to detect inborn errors of metabolism by examination of maternal blood, cord blood, blood & urine of newborn.
Prenatal diagnosis forms an integral step in genetic counselling. Prenatal diagnosis can be done in:1. It is essential for genetic disorder in which treatment is either absent or unsatisfactory.2. Where there can be accurate prenatal diagnosis.3. Abnormality detected by ultrasonography.4. Stillborn infant or recurrent miscarriages.
Prenatal dignosis is must in1. Maternal age more than 35 yrs.2. One of the parent is balanced translocation carrier.3. Family history of genetic disorder4. History of exposure to teratogens5. Parent already has a child with neural tube defect.
Prenatal Diagnostic Procedures Includes both screening and diagnostic test. Common procedures: Alpha-fetoprotein test Triple marker screening blood test Ultrasound Amniocentesis Chorionic villus sampling Cordocentesis Ivf diagnosis
Alpha-fetoprotein (AFP) Test Procedure Used mainly as a screening test Performed at 15-20 weeks Blood test measures the amount of AFP High levels reflect neural-tube defects Low levels reflect chromosonal abnomalities Advantages and Risks Minimal invasiveness High false positives
Triple Marker Screening Procedure Conducted at 15-16 weeks Blood test (triple marker) Human chorionic gonadotropin (hcG) Conjugated estriol (uE3) Alpha-fetoprotein (AFP) Used for detecting Chromosomal abnomalities (Downs, Edwards) Neural tube defects Advantages and Risks Minimal invasiveness Only 40%-60% accuracy rate
Ultrasound Sonogram Transmitter on abdomen High frequency sound waves echo off the fetus Computer enhanced picture Used to detect Head size Length of gestation Placement and structure of placenta Multiple pregnancies Anatomical abnormalities
Ultrasound Advantages No pain / no injection Minimal time (30 mins) No confirmed adverse biological effects on patients or operators (Rosen & Hoskins, 2000)
Amniocentesis Procedure Employed only when mother is at high risk Done between 14 - 16 weeks. Needle inserted through abdominal wall Ultrasound is used to guide needle placement 10 – 20 cc of fluid from amniotic sac removed Fetal cells tested to determine abnormalities Used to detect Chromosomal abnormalities (Down Syndrome, Edwards Syndrome) Neural tube defects (Spina Bifida)
Advantages and Risks 99% accuracy of abnormality detection Needle may damage fetus Procedure linked to miscarriages in 1 in 200 pregnancies
Chorionic Villus Sampling (CVS) Procedure Employed only when mother is at highest risk Administered between 10-12 weeks Needle inserted through abdominal or cervix Ultrasound is used to guide needle placement Sample of the villi of the chorion collected from placenta and tested Advantages and Risks Can detect abnormalities earlier than amniocentesis Carries a greater risk than amniocentesis (1 in 100 has problems, 3 in 200 linked to miscarriage)
A plastic catheter is inserted through the cervix, guided by ultrasound Method 1: Chorionic Villus Sampling
A biopsy needle is inserted through the abdominal wall and guided by ultrasound
Definition “methods used to achieve pregnancy by artificial or partially artificial means.” Infertility Genetic reasons Communicable diseases, e.g. AIDS. Sperm donor etc…
In vitro fertilization technique of letting fertilization of the male and female gametes (sperm and egg) occur outside the female body. Embryo transfer
Expansions of IVF Transvaginal ovum retrieval (OCR) is the process whereby a small needle is inserted through the back of the vagina and guided via ultrasound into the ovarian follicles to collect the fluid that contains the eggs. Assisted zona hatching (AZH) is performed shortly before the embryo is transferred to the uterus.
zygote intrafallopian transfer (ZIFT), egg cells are removed from the womans ovaries and fertilized in the laboratory; the resulting zygote is then placed into the fallopian tube. gamete intrafallopian transfer (GIFT) a mixture of sperm and eggs is placed directly into a womans fallopian tubes using laparoscopy following a transvaginal ovum retrieval.
Artificial insemination (AI) is when sperm is placed into a females uterus (intrauterine) or cervix (intracervical) using artificial means rather than by natural copulation. Surrogacy, where a woman agrees to become pregnant and deliver a child for a contracted party. It may be her own genetic child, or a child conceived through in vitro fertilization or embryo transfer using another womans ova.
surgical sperm retrieval (SSR) the reproductive urologist obtains sperm from the vas deferens, epididymis or directly from the testis in a short outpatient procedure.
cryopreservation, eggs, sperm and reproductive tissue can be preserved for later IVF.