Prenatal & Postnatal Diagnosis (Cytogenetics) PDF

CYTOGENETICS College of Allied Health Sciences Bachelor of Science in Medical Laboratory Science 1st Semester | A.Y. 2024-2025 Unit 8: Prenatal and Postnatal Diagnosis Outline: - Prenatal testing provides insights into 1.1 Prenatal Diagn...

CYTOGENETICS College of Allied Health Sciences Bachelor of Science in Medical Laboratory Science 1st Semester | A.Y. 2024-2025 Unit 8: Prenatal and Postnatal Diagnosis Outline: - Prenatal testing provides insights into 1.1 Prenatal Diagnosis the health and development of the 1.2 Purposes of Prenatal Diagnosis fetus enabling healthcare providers to 1.3 Indications of Prenatal Diagnosis guide expected parents on how to 1.4 Methods of Prenatal Diagnosis manage the rest of the pregnancy. 1.5 Amniocentesis → Determining the outcome of the 1.6 Chorionic Villus Sampling pregnancy. 1.7 New Molecular Analytic Techniques - In some cases, tests may reveal 1.8 Postnatal Diagnosis conditions that affect the viability that predict potential outcomes helping parents make informed choices. Remember! → Planning for possible complications with the birth process. - Certain conditions detected through prenatal diagnosis may indicate the need for specialized care during delivery like a caesarian or the presence of specialists at birth. → Planning for problems that may occur in the newborn infant. - If a potential health issue is detected, parents and healthcare providers can prepare necessary interventions immediately after birth. → Deciding whether to continue the Prenatal Diagnosis pregnancy. - In rare cases, the info obtained through Is the process of determining fetal prenatal diagnoses may lead parents anomalies or genetic disorders, to provide to difficult situations about continuing expecting parents with information and the pregnancy. opportunity to modify pregnancy → Finding conditions that may affect future management and/or postnatal care. pregnancies. - Certain genetic conditions may have implications for future pregnancies - The key event that laid the allowing parents to consider options or foundation for prenatal take precautions if they choose to cytogenetic analysis was the have more children. discovery of the ability to determine gender based on the Indications of Prenatal Diagnosis incidence of the sex chromatin body in the nuclei of oral - Critical for healthcare providers and mucosal smears. expected parents as it leads to the - Basically, prenatal diagnosis foundation for active management enabled the diagnosis of and personalized care. a broad spectrum of chromosomal abnormalities, ❑ ADVANCED MATERNAL AGE gene disorders, sex-linked As a woman’s age increases, so does the conditions, neuro tube defects, risk for chromosome aneuploidy in the and infections to be made b4 foetus. the birth of the fetus. 50% - Key component in modern of chromosomally prenatal care. abnormal foetuses are trisomic, with trisomy 16 being Purposes of Prenatal Diagnosis the most frequent Aneuploid is the result of meiotic non- Prenatal diagnosis is helpful for: disjunction, where the failure of homologous chromosomes to separate during anaphase → Managing the remaining weeks of the results in one gamete containing both pregnancy. homologues, the other containing the none. YVONNE MARIANO | BSMLS – 2A 1 CYTOGENETICS College of Allied Health Sciences Bachelor of Science in Medical Laboratory Science 1st Semester | A.Y. 2024-2025 Upon fertilization, the foetus is either Possible disorders that could be inherited monosomic or trisomic. or can affect the pregnancy; - Monogenic disorder: caused by a mutation in a single gene (e.g., Cystic fibrosis and sickle cell anemia) - Polygenic disorder: results from multiple genes interacting (e.g., Note: Review on Non – disjunction!!! heart diseases and diabetes) - Multifactorial disorder: ❑ MULTIPLE MISCARRIAGES AND/OR FETAL LOSS combination of genetic and environmental factors (e.g., Causes for multiple miscarriages can be cleft palate and spina bifida) chromosomal, anatomical, immunological, or hormonal. Confirmed family history, accurate Half of miscarriages are due to diagnosis, and reliable testing are key chromosome abnormality, of these 2% have factors in prenatal diagnosis. unbalanced translocations. - If a genetic disorder is present in the family, the risk of the fetus inheriting it increases. - Recurring miscarriages or often experiences and causes can be - The importance of prenatal complex. diagnosis in this kind of situation - Chromosomal: common cause is it allows parents to plan their of early miscarriages especially child’s care and seek in the first trimester. specialized support. - Anatomical: problems in - Also provides guidance on the the uterus, cervix, and fallopian implications of the diagnosis tubes of expected mothers and possible treatments in the - Immunological: the immune likelihood of future children. system of the mother can attack the developing fetus. - Hormonal: hormones like thyroid ❑ ETHNICITY AT INCREASED RISK FOR GENETIC and progesterone can affect DISEASE pregnancy. Certain ethnic groups have an increased incidence of specific genetic conditions due to lack of migration, genetic drift, or heterozygotes within the given population Importance of Prenatal Diagnosis or geographic area. - Could help pinpoint the specific cause of the miscarriages - For sickle cell anemia, is more leading to more effective common in African people. treatment or management in - For Thalassemia, common in future pregnancy. Mediterranean people. - Also helps the expected parents to understand the cause of Importance: It allows prenatal testing miscarriages or fetal loss could based on the individual’s ethnicity and offer closure and help families associated risk. It also provides early cope with their loss. diagnosis which could lead to prompt treatment and management strategies. ❑ KNOWN OR SUSPECTED FAMILY HISTORY OF ❑ TERATOGENS GENETIC DISEASE OR MULTIFACTORIAL DISORDER - substances or agents that can cause If a monogenic, polygenic, or multifactorial birth defects or increase the risk of birth disorder is in the family history, the defects in the fetus. pregnancy may be affected. YVONNE MARIANO | BSMLS – 2A 2 CYTOGENETICS College of Allied Health Sciences Bachelor of Science in Medical Laboratory Science 1st Semester | A.Y. 2024-2025 - Can interfere with fetal development - Importance: provides further delays and even miscarriages. - E.g., infections such as rubella, investigation. The abnormal cytomegaloviruses, or toxoplasmosis findings of ultrasound from further prenatal testing to Maternal disease (e.g. Insulin-dependent determine the cause and diabetes, maternal phenylketonuria), severity of the abnormalities. infection (e.g. Toxoplasmosis, rubella) or Also, it provides management exposure to internal or external substances planning so it will allow doctors (e.g. Medications, alcohol, radiation) are and parents to plan for not associated with a chromosomal or potential interventions for genetic disease but may lead to fetal support services for the child abnormality, distress or demise. after birth. - Importance: can help identify birth defects or abnormalities associated with teratogen ❑ ABNORMAL MATERNAL SERUM SCREEN RESULTS exposure. Also helps monitor Maternal serum screening may identify fetal health. Regular prenatal women at increased risk of having a child care helps monitor the fetuses in with Down Syndrome, trisomy 18 or an open development and assess neural tube defect (spina bifida). essential impact teratogens In these cases, positive serum screen results exposure often prompt consideration of diagnostic testing by amniocentesis. ❑ ABNORMAL ULTRASOUND FINDINGS - MSS analyzes the mother’s This may prompt invasive prenatal blood for specific proteins and diagnostic measures if fetal structural hormones that are produced in abnormalities or markers associated with different amounts based on the chromosome conditions are identified. fetuses’ health. For example, ultrasound may suggest the - Open neural tube defects: birth presence of chromosomal aneuploidies defects affecting the brain and such as Down Syndrome, genetic spinal cord. syndromes such as dwarfism, hereditary - Importance: to confirm the renal disorders or isolated birth defects. diagnosis. Abnormal screening results often prompt further - Ultrasound scans: provide diagnostic tests like detailed images of amniocentesis or chorionic villus the developing fetus which sampling to confirm diagnosis allows physicians to assess and for early intervention of growth structure and organ appropriate medical function. management and planning. - Ultrasound may reveal structural - In addition, advanced paternal defects such as problems with age is an important indicator of the heart, brain, limbs, or other prenatal cytogenetic diagnosis. organs. It also reveals growth Not connected to fetal issues, the fetus may be too abnormalities however it is small or too large for its associated with a linearly gestational age. increased risk of some autosomal dominant mutations in the offspring due to mutations in the form of single-based pair mutations. YVONNE MARIANO | BSMLS – 2A 3 CYTOGENETICS College of Allied Health Sciences Bachelor of Science in Medical Laboratory Science 1st Semester | A.Y. 2024-2025 Methods of Prenatal Diagnosis Fetal tissue biopsy Prenatal diagnosis employs a variety of Invasive and Non-invasive techniques to determine the health - obtaining a small sample of and condition of a developing fetus. fetal tissue usually skin, liver, or muscle for analysis under a INVASIVE METHODS NON-INVASIVE microscope or with other tests. (use needles) METHODS (use - The procedure is primarily to equipment but nit diagnose inherited disorders needles) that cannot be detected AMNIOCENTESIS ULTRASONOGRAPHY through amniocentesis or CHORIONIC VILLUS MAGNETIC chorionic villus sampling. SAMPLING RESONANCE IMAGING - For example, skin disorders like BIOPSY FROM FOETAL CELL FREE-FOETAL DNA epidermolysis bullosa and TISSUE albinism and metabolic CORDOCENTESIS TRIPLE TEST disorders where liver or muscle biopsy can provide insights into Cordocentesis enzyme deficiency. - Typically performed between 17 - also known as Percutaneous and 20 weeks of gestation. umbilical cord blood sampling - The risks are miscarriage, or Funipuncture infections, pre-term delivery, - is an invasive prenatal and hemorrhage. procedure where in needle is inserted through the mother’s abdomen and through AMNIOCENTESIS the umbilical cord to collect a sample of fetal blood. - Amniotic fluid: a fluid that - It is typically performed when surrounds the fetus for the whole other less invasive prenatal tests duration of the pregnancy. A like amniocentesis or chorionic pale-yellow fluid that cushions villus sampling cannot provide and protects the fetus, allows the necessary information or when fetus to move and grow, and results are inconclusive. stabilizes the temperature to - It is used to diagnose a range of protect the fetus from extreme fetal conditions such as temp. changes. Also used in fetal chromosomal abnormalities like biochemical homeostasis and Down Syndrome, Trisomy 18 or permits proper lung 13, blood disorders like anemia, development. Exists within thrombocytopenia, and fetal a protective sac created by the hemolytic conditions. amnion (the innermost - Can also diagnose infections membrane that encloses the like toxoplasmosis and amniotic fluid and the fetus; isoimmunization (when the a membrane that is composed mother’s blood is incompatible of cuboidal cells; it is with the fetus’s blood). metabolically active and - Typically performed after the involved in the exchange of 17th week of pregnancy when water and chemicals between the umbilical cord is developed. the fluid, fetus and maternal - The risk of cordocentesis can circulation. The amount of cause miscarriage, premature amniotic fluid increases in delivery, bleeding, infection, quantity throughout the and cord hematoma. pregnancy. App. 16 milliliters at 12 weeks of gestation and reaching a peak of 801,000 milliliters during 3rd trimester and gradually decreases before delivery. YVONNE MARIANO | BSMLS – 2A 4 CYTOGENETICS College of Allied Health Sciences Bachelor of Science in Medical Laboratory Science 1st Semester | A.Y. 2024-2025 AMNIOCENTESIS EVOLUTION - Trans abdominal/cervical - In 1930, the removal of puncture of the uterus to remove amniotic fluid was done by a small sample of amniotic fluid trans-abdominal needling for genetic testing. following injection of a - Performed for diagnostic and radio-opaque contrast to therapeutic purposes. outline the fetus and placenta. - In 1967, Hoffman and Discovered by Dr. Povl Riis - University of Hollander stated the Copenhagen (1955). importance of placental localization using ultrasound before amniocentesis. HISTORY - In 1972, amniocentesis under ultrasound guidance - In the early 1950s, amniocentesis was implemented in was used for the diagnosis and Copenhagen. determination of severity of - In the late 1970s, there was Rhesus disease. an improvement in - In 1956, James described the use ultrasound real-time of amniotic fluid sediment to scanners for a small number determine fetal sex using of centers that started to the Papanicolaou and Giemsa perform amniocentesis with stain. the simultaneous - In the same year, Fritz Fuchs and visualization of the puncture Povl Riis used cultured amniotic needle tip on the scanner fluid cells to determine fetal sex monitor. through Barr bodies. - In 1984, the use of free-hand - In 1966, Mark Steele and William technique was used in Breg successfully cultured fetal Switzerland. An assistant cells obtained from was holding onto amniocentesis which allowed for a transducer probe that karyotyping of chromosomes. was commonly wrapped in - In 1970, Nadler and Gerbie a sterile adhesive trait. published the role of Performing amniocentesis, 2 amniocentesis in the intrauterine healthcare providers work; diagnosis of genetic defects in the assistant of the the New England Journal of physician holds the Medicine. These two described ultrasound scanner and the the use of amniocentesis for the physician inserts the needle. detection of cytogenetic and - In 1985, the single-operator biochemical abnormalities in 155 two-hand technique was women at increased risk for established; the opposite of these cytogenetic and the freehand technique. biochemical disorders. The doctor holds the probe with their hand while the other hand manually inserts the needle. There is no assistant needed; the physician performs both the task of holding the probe and inserting the needle. Allows coordinated approach. From then on, newer needles were marketed with special external coating and ecoluminance to enhance needle placement. YVONNE MARIANO | BSMLS – 2A 5 CYTOGENETICS College of Allied Health Sciences Bachelor of Science in Medical Laboratory Science 1st Semester | A.Y. 2024-2025 Invasive procedure performed at 15-18 - Initially, amniocentesis was weeks of gestation. performed in a conventional Procedure for obtaining a sample of period so around 15 to 24 weeks amniotic fluid from pregnant women. Amniotic fluid contains exfoliated fetal cells or 15 to 20 weeks (some that may be cultured to reveal fetal references) to detect genetic karyotype, and/or perform biochemical abnormalities. testing and molecular analysis. - Recently, amniocentesis has In 3rd trimester of pregnancy, the been utilized in the 3rd trimester amniotic fluid can be analyzed for focusing on fetal lung maturity the determination of fetal lung maturity. and managing potential late This is important when the fetus is below 35 pregnancy complications. to 36 weeks of gestation, because the lungs - Conventional amniocentesis: may not be mature enough to sustain life. common time period for performing amniocentesis procedure. The culture of Early Amniocentesis amniotic fluid cells is optimal - Usually described as one that (ideal condition for achieving occurs before the 15th week of the desired results) at this time gestation. It has been shown in period both from the studies that the earlier perspective of the rapidity of cell the prenatal diagnosis growth and the culture failure procedure is performed, the rate is less than 5% in higher the fetal loss rate. experimental labs. - According to physicians, the - Why is conventional placenta is more widely spread. amniocentesis considered The amniotic fluid volume is optimal? much lower compared to the volume of amniotic fluid in (1) sufficient fetal cells; the mid-trimester. And the adequate concentration of fetal amniotic membrane is not cells in amniotic fluid by the mid- adherent to the uterine wall so trimester. Fetal cells are there is tenting that’s why the necessary for culturing and American College of conducting genetic analyses. Obstetricians and Gynecologists doesn’t recommend this (2) low risk of miscarriage procedure because it poses a because the amniotic sac is high risk of miscarriage and well-developed so there is a pregnancy complications reduced likelihood of issues such compared to conventional as fluid leakage and infections. amniocentesis. (3) optimal volume of amniotic fluid; the amniotic fluid is sufficient to collect the amount needed. Some references indicate that 30-40 milliliters amount of amniotic fluid are withdrawn from the needle. Some are 20-30 mL for culture without impacting the overall volume. YVONNE MARIANO | BSMLS – 2A 6 CYTOGENETICS College of Allied Health Sciences Bachelor of Science in Medical Laboratory Science 1st Semester | A.Y. 2024-2025 Indication of 3rd-trimester amniocentesis - (1) assessment of fetal lung maturity. It is often done when early delivery is anticipated due to maternal or fetal health issues. Tests like lecithin sphingomyelin ratio (LS ratio: common test for the levels of lecithin and sphingomyelin are measured; lecithin increases as the lungs mature while sphingomyelin THE USE OF AMNIOCENTESIS IS RESTRICTED TO remains relatively stable; 2:1 or CERTAIN CIRCUMSTANCES: higher LS ratio generally indicates lung maturity) and When the mother is over age 35. The risk of phosphatidylglycerol having children with chromosome (phospholipid that appears later abnormalities increases dramatically after in lung development; each this age. The majority of all amniocentesis procedures are performed because of presence in amniotic fluid advanced maternal age. indicates that lungs are mature) When the mother has already had a child level measures. with a chromosomal aberration. The reoccurrence risk in such cases is 1-2%. - (2) detection of intra-amniotic infections. In cases of suspected intra-amniotic infection, - Amniocentesis should only be amniocentesis can confirm the offered to women who are at presence of bacteria or high risk of carrying a fetus with inflammation markers guiding chromosomal or genetic treatment and management. disorders. - (3) evaluation of POTENTIAL ADVANTAGES AND DISADVANTAGES isoimmunization. If there is RH incompatibility, amniocentesis ADVANTAGES DISADVANTAGES can assess the degree of fetal Early Diagnosis Miscarriage while anemia by testing bilirubin levels performing (the risk is in the amniotic fluid. So, results considered less than 1% help determine whether after the procedure in interventions like intra-uterine the 2nd trimester of transfusions or early delivery are pregnancy, only slightly higher than the normal necessary. risk of miscarriage) Cell culture Needle might hit the baby (Nowadays, we PROCEDURE: have the ultrasound so Outpatient procedure either with the use of it avoids this kind of local anesthetic or without it. advantage but there is First, ultrasonography is used to locate the a higher chance that position of fetus in the uterus. the baby might hit with A long sterile needle is inserted through the needle without using abdominal wall into the amniotic sac. ultrasound) About 30-40 mL of amniotic fluid is Source of fetal DNA Mother may withdrawn from the needle. experience side effects From that, 2-3 mL of fluid is taken in a 5 mL (cramping, leaking of syringe and the fluid along the syringe is fluid, and irritation discarded. around the area of This is done because the first mL of fluids are the puncture) likely to contain maternal blood cells, muscle cells, fibroblast, etc. YVONNE MARIANO | BSMLS – 2A 7 CYTOGENETICS College of Allied Health Sciences Bachelor of Science in Medical Laboratory Science 1st Semester | A.Y. 2024-2025 LIMITATIONS ❖ CVS doesn't provide information on Neural Tube Defects. So women who are - Difficulties of procedure: if undergoing CVS need to follow blood tests. Anteriorly placed placenta - When the placenta is located at the - Biopsy placental tissue between front wall of the uterus, it can obstruct 10 – 13 weeks of gestation for the path of the needle during prenatal genetic testing. amniocentesis. - The primary advantage of CVS Multiple pregnancy. is earlier genetic results in - Twins, triplets, quadruplets, etc., each pregnancy so this knowledge fetus has its own amniotic sac making amniocentesis more complicated. So, provides patients with the the physician may need to insert the opportunity to seek counseling needle multiple times to sample for obstetric management and amniotic sacs separately increasing risk recommendation. and technical difficulty. - Relies on sampling cells from the Maternal obesity chorion and essential fetal - Increased abdominal fat can make it membrane that plays a crucial harder to locate the exact position of role in early pregnancy. the fetus and amniotic sac using - Chorion: the outermost layer of ultrasound guidance. fetal membrane; a membrane Oligohydramnios that forms part of the fetal sac, - Involves a low amount of amniotic fluid it gives rise to the fetal aspect of making it harder to extract a sample the placenta to protect and without risk of inherited fetus or other complications. The physician must be nourish the developing embryo. extra cautious to ensure they collect Within the chorion are chorionic enough fluid for testing without causing villi which are collected by CVS. harm. - Chorionic villi: small finger-like projections that maximize COMPLICATIONS surface area for the nutrient Pregnancy loss 0.3 – 1.0% and gas exchange between Increase risk: mother and fetus. It also – Needle larger than 18g anchors the placenta to the – Multiple needle insertion uterine wall and it enables – Discoloration of the fluid efficient transfer of essential – High AFP, multiple late abortions, substances; contains the previous vaginal bleeding – Placental perforation genetic make-up of the fetus. – recent studies didn’t find a correlation RISK OF INVASIVE PROCEDURE Early amniocentesis: PROCEDURE: – High pregnancy loss A catheter is passed via the vagina through – High fetal malformations the cervix and into the uterus to the – High rate of multiple needle insertions developing placenta under ultrasound (4.7%) guidance. – High-rate laboratory failures (1.8%) Alternative approaches are: Late amniocentesis: ▪ TRANSCERVICAL – “Low” pregnancy loss (0.3-1%) - Uses a thin flexible plastic catheter. This – Low rate of multiple needle insertions catheter is carefully guided through (1.7%) the cervix and their ultrasound – Low-rate laboratory failures (0.2%) guidance to the chorionic villi. So, the barrel of the syringe is attached to the CHORIONIC VILLUS SAMPLING catheter which is used to suction a small amount of villi as the catheter is ❖ Discovered by Giuseppe Simoni. withdrawn. ❖ A major disadvantage of amniocentesis is ▪ TRANSABDOMINAL that the cell obtained must be cultured - Approach that uses needle and before a genetic test can be performed. So ultrasound guidance. The needle is takes time to obtain the test results. passed through the abdominal wall ❖ An invasive procedure by which a sample and the wall of the uterus to reach the of some of the placental tissue is obtained. chorionic villi. The syringe is used to YVONNE MARIANO | BSMLS – 2A 8 CYTOGENETICS College of Allied Health Sciences Bachelor of Science in Medical Laboratory Science 1st Semester | A.Y. 2024-2025 suction out a small amount of villi as the needle passes through the chorionic NEW MOLECULAR ANALYTIC TECHNIQUES villi. If an adequate amount of tissue is Fetal cells obtained by CVS and obtained in the first attempt, maybe Amniocentesis can be used for prenatal Dx. the 2nd attempt can be undertaken. For congenital anomalies by following new techniques; The introduction of the catheter allows 1. Southern blotting: the sampling of cells from the placental Cleavage of chromosomal DNA at specific chorionic villi. sites and used for tests The tip of the tube is placed in contact with - Molecular technique used to detect the chorion (the outer layer of specific DNA sequences within a the placenta). sample. It involves cleaving Suction is then applied and a small piece of chromosomal DNA at specific sites chorion is removed. using restriction enzymes separating Chorionic tissue containing a millions of the DNA fragments via gel actively dividing fetal cells that can be used electrophoresis and then hybridizing directly in many genetic tests. with a labeled DNA probe that binds to The most common test employed on cells the target sequence. obtained by CVS is chromosome analysis to 2. PCR determine the karyotype of the fetus. 3. FISH The cells can also be grown in culture for biochemical or molecular biological - Advances in molecular analysis. diagnostics using either FISH with chromosomes-specific DNA probes or Quantitative Fluorescence Polymerase chain reaction (QFPCR/PCR) with chromosomes-specific small tandem repeat markers can be applied to diagnose the common aneuploidies within 1-2 days. - Compared to karyotyping, FISH and PCR these two would be faster to generate results ASSOCIATED RISK/ COMPLICATIONS: because, in karyotyping, it would 1. miscarriage/ fetal loss (1% - 2%). take up to 14 days or more to - Due to invasiveness of procedure release results. The sensitivity and 2. Oromandibular limb hypoplasia. - Lower jaw and limbs are specificity of FISH and underdeveloped. PCR/QFPCR are collectively 3. Isolated limb reduction defect described as rapid aneuploidy - Limbs are not fully developed. testing (demonstrated in large- Increased risk is associated with decreased scale studies and compared gestational age at the time of CVS, highest favorably with traditional susceptibility when CVS is performed before karyotyping for the diagnosis of 9 weeks of gestation. common aneuploidies, currently Mechanism: Thromboembolization it is being used to give rapid (blockage of blood flow due to blood clots) results for the common or fetal hypoperfusion (reduced blood flow) aneuploidies as an adjunct to through hypovolemia (low blood volume) or karyotyping. vasoconstriction (narrowing of blood vessels). (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. - The immune system of mothers creates antibodies against Rh-positive cells. YVONNE MARIANO | BSMLS – 2A 9 CYTOGENETICS College of Allied Health Sciences Bachelor of Science in Medical Laboratory Science 1st Semester | A.Y. 2024-2025 - In addition, we can also use Purpose of Postnatal Cytogenetic Testing aCGH, in contrast to RAT, aCGH Diagnosis: Postnatal cytogenetic testing helps is a comprehensive high- diagnose chromosomal disorders that may be resolution genome-wide causing developmental delays, physical screening strategy for detecting abnormalities, or other health issues. gains or losses of DNA segments - Range from common conditions like in a single test. It is rapid, less- Down Syndrome to the rarest labor intensive and readily condition. amendable to automation compared to traditional Prognosis: Understanding the specific chromosomal karyotyping. abnormality helps predict the potential course of the condition and guide management strategies. - Allowing healthcare providers to anticipate potential complications - We also use karyotyping, a that develop personalized care. traditional method for prenatal diagnosis that involves the Treatment: In some cases, specific treatments or analysis of banded-metaphase interventions may be available based on the chromosomes from cultured identified chromosomal amniotic fluid cells or chorionic abnormality. villi. All 23 pairs of chromosomes are examined. Genetic Counseling: Cytogenetic testing results provide valuable information for genetic counseling, helping families understand the implications of the diagnosis, potential risks for future pregnancies, and available resources. FLUORESCENT IN SITU HYBRIDIZATION - Provide support and guidance as FISH allows the detection & localization of families navigate the emotional and specific DNA sequences in interphase or practical challenges associated with metaphase. chromosomal disorders. Advantage – results available in 24-48 h. Disadvantage – failure to detect big Common Postnatal Indications structural rearrangements Identify 80% clinically relevant Developmental Delays or Physical abnormalities, helpful for early decision Abnormalities about further management of affected - Common indications for cytogenetic pregnancies. testing as chromosomal disorders can often cause a wide range of SUMMARY developmental and physical issues. Infertility or Recurrent Miscarriages The most common indication of prenatal - Due to chromosomal abnormality. diagnosis is advanced maternal age, family Cancer Diagnosis history of chromosome, single gene or - Cytogenetic testing is often used in the structural abnormality and multiple diagnosis and classifications of cancer pregnancies. particularly hematologic malignancies like Leukemia and Lymphoma. POSTNATAL DIAGNOSIS Monitoring Treatment: - Monitor the effectiveness of cancer - Identifying health conditions after a treatment and detect any changes in baby is born. tumor's chromosomal makeup. - Involves a range of tests and examinations. - Sample requirements: Lithium heparin whole blood specimens are required – Why do we need a postnatal diagnosis? gently mixed to prevent clotting and must not be frozen. See the sample stability - Remember that prenatal section for cytogenetic samples. Sample diagnosis has limitations which volumes may be reduced for children (2– include that not all conditions 4ml) and neonates (1-2ml). can be detected. So, some abnormalities can be detected - Turnaround time: The usual turnaround time after the birth of the fetus. is 2–3 weeks; however, the laboratory will endeavor to respond to urgent requests. YVONNE MARIANO | BSMLS – 2A 10 CYTOGENETICS College of Allied Health Sciences Bachelor of Science in Medical Laboratory Science 1st Semester | A.Y. 2024-2025 Where a major trisomy is suspected, a rapid Key Points to Remember: PCR screen may be performed to provide an urgent provisional result. Postnatal cytogenetics is a valuable tool for diagnosing and managing a wide range of conditions related to chromosomal Laboratory Analysis abnormalities. It plays a crucial role in understanding the 1. Cell Culture – a sample of blood is genetic basis of various diseases and collected and cultured to allow cells to guiding treatment decisions. grow and divide. Advances in cytogenetic testing, such as 2. Chromosome Preparations – The microarray analysis, have significantly cultured cells are treated to stop cell improved the sensitivity and accuracy of division at a specific stage allowing detecting chromosomal abnormalities. chromosomes to be visualized. 3. Karyotyping – analyze samples. 4. FISH – uses fluorescent probes that bind to specific DNA sequences on chromosomes allowing for the detection of smaller deletions or duplications that may not be visible with karyotyping. 5. Microarray Analysis – advanced techniques that use a chip with thousands of DNA probes that cover the entire genome. Interpreting Results Karyotype: Results are reported using a standardized system, showing the number and arrangement of chromosomes. FISH: Results are interpreted based on the presence or absence of fluorescent signals at specific locations on the chromosomes. Microarray: Results are displayed as a plot showing the intensity of fluorescence across the genome. Importance of Postnatal Cytogenetics Early Diagnosis: Postnatal cytogenetic testing allows for early diagnosis of chromosomal disorders, which can lead to more timely interventions and support for individuals and families. Personalized Medicine: Cytogenetic testing helps personalize medical care by identifying specific genetic abnormalities and guiding treatment decisions based on individual needs. Genetic Counseling: Cytogenetic testing results provide essential information for genetic counseling, helping families understand the implications of the diagnosis, potential risks for future pregnancies, and available resources. YVONNE MARIANO | BSMLS – 2A 11