Clinical Cytogenetics PDF

CYTOGENETICS LESSON 11: CLINICAL CYTOGENETICS | 2MT06 - 52% due to autosomal trisomies (Extra Topic Outline: copy of chromosomes from Chromosome Definition of Terms...

CYTOGENETICS LESSON 11: CLINICAL CYTOGENETICS | 2MT06 - 52% due to autosomal trisomies (Extra Topic Outline: copy of chromosomes from Chromosome Definition of Terms 1-22) Cytogenetic Abnormalities - 1 for every 3 spontaneous abortions Prenatal Cytogenetic Abnormalities have chromosomal abnormalities ○ Prenatal Chromosomal Analysis Amniocentesis - Seen in 6:1000 live births Chorionic Villus Biopsy ○ Trisomy 18: Edward's Syndrome - Umbilical Cord Blood Biopsy Babies get stuck at 6 months level if Alpha Fetoprotein (AFP) they survive. ○ Postnatal Chromosomal Analysis ○ Trisomy 13: Patau's Syndrome - ○ Childhood and Adult Cytogenetics Cytogenetic Disorder Most striking feature = Eye fusion; ○ Chromosomal Aneuploidy Syndromes Cyclops Sex Chromosome Aneuploidies ○ Trisomy 16 - Fetal loss in the First ○ 47,XXX Females, 47,XXY Males Trimester ○ Klinefelter Syndrome ○ Polysomic X (47,XXX / 48XXXY) Rate of biological elimination: ○ Turner Syndrome ○ 95% of 45, X ○ Other Sex Chromosome Abnormalities ○ 90% of Trisomy 13 ○ Female Pseudo-hermaphroditism ○ 80% of Trisomy 18 ○ Male Pseudo-hermaphroditism ○ 65% of Trisomy 21 Microdeletion Syndrome ○ Angelman Syndrome - 15% of recognized genetically abnormal ○ Prader-Willi Syndrome pregnancy end in spontaneous fetal loss - 80% occur during the 1st trimester l. DEFINITION OF TERMS A. PRENATAL CHROMOSOMAL ANALYSIS Aneuploidy - Done to screen for any possible genetic - An abnormal amount of DNA alterations - Usually used in reference to an - Usually done for those who become abnormal number of chromosomes pregnant at an older age Karyotype Advanced maternal age = incidence of - Number of chromosomes in the chromosomal abnormalities normal diploid cell, as well as their ○ TYPES: size distribution 1. Amniocentesis 2. Chorionic Villus Biopsy ll. CYTOGENETIC ABNORMALITIES 3. Umbilical Cord Blood - Can be found in apparently normal looking individuals a. AMNIOCENTESIS - Patients with phenotypic/trait anomalies - Collecting amniotic fluid and culturing the - Patients with diagnosed genetic disorders cells to create a karyotype of the growing fetus inside - Can also be done by measuring the amount of Alpha fetoprotein (AFP) in the fluid lll. PRENATAL CYTOGENETIC ABNORMALITIES - Responsible for 50%-60% spontaneous abortion ✿|1 CYTOGENETICS LESSON 11: CLINICAL CYTOGENETICS | 2MT06 b. CHORIONIC VILLUS BIOPSY ENCEPHALOCELE - Transcervical/transabdominal chorionic - Part of brain protrudes from the occipital sutures. venous sampling - Enlarges due to presence of Insertion of a long tube into the Cerebrospinal fluid (CSF) Vagina up to the Cervix until it SPINAL BIFIDA reaches the Uterus. - Part of the spinal cord Puncture of the abdomen, through protrudes at the bottom of the guidance of ultrasound, until it spine reaches the placenta. - The chorionic villi are wispy projections of placental tissue that share the baby's a. INDICATIONS FOR PRENATAL genetic makeup CHROMOSOMAL ANALYSIS Screening for maternal age-related risk Family history of previous child with chromosomal abnormality Abnormal levels of AFP in a screening test A fetal abnormality detected on ultrasound A parent who is carrier of unbalanced gametes A parent who is a carrier of X-linked genetic c. UMBILICAL CORD BLOOD BIOPSY disorder - Aka Cordocentesis - Fetal blood is extracted, cultured, and B. POSTNATAL CHROMOSOMAL ANALYSIS assessed for any abnormalities - 0.6% - 1.0% newborns have gross chromosomal abnormality - Karyotype analysis is needed Indications: - Presence of multiple congenital anomalies - Suspected aneuploidy e.g. features of Down Syndrome C. CHILDHOOD AND ADULT CYTOGENETICS Indications: - Unexplained mental retardation or developmental delay Turner Syndrome - Suspected sex chromosomal abnormality d. ALPHA FETOPROTEIN (AFP) Prader-Willi Syndrome - Suspected - Detects neural tube defects which occur in unbalanced autosome 2:1000 pregnancies ○ Loss of function of genes in - Not related to mother’s age Chromosome 15 - Can also predict Down’s syndrome ○ Begins as hypotonia, feeding difficulties, delayed ANENCEPHALY - Exposed brain / Undeveloped development skull ○ During childhood - - Once called "Monkey-looking babies" insatiable appetite, overeating, obesity ✿|2 CYTOGENETICS LESSON 11: CLINICAL CYTOGENETICS | 2MT06 ○ During adulthood - Diabetes mellitus type 2 Indications: - Suspected Fragile-X Syndrome - Infertility - Multiple spontaneous abortions lV. CYTOGENETIC DISORDERS A. CHROMOSOMAL ANEUPLOIDY Transverse palmar creases (simian crease) SYNDROMES Heart defects (40%) Autosomal Aneuploidies - Ostium primum 1. Trisomy 21 or Down Syndrome - Atrial septal defects 2. Trisomy 13 or Patau Syndrome - A-V valve malformations 3. Trisomy 18 or Edwards Syndrome - Ventricular septal defects Sex Chromosome Aneuploidies Hypogonadism 1. 47XXX females and 47XYY males Risk: 2. Klinefelter Syndrome ○ Acute Leukemia 3. Turner Syndrome ○ Acute lymphoblastic leukemia 4. Pseudo-hermaphroditism ○ Acute myeloblastic leukemia ○ Infections a. TRISOMY 21 or DOWN SYNDROME ○ Alzheimer’s Disease - Most common of the chromosomal disorder - Major cause of mental retardation b. TRISOMY 13 or PATAU SYNDROME - US – 1:700 live births - Triple copies of chromosome 13 - Incidence = 1:4000 to 1:15000 live births - Caused by: Meiotic nondisjunction Translocation type (46XX,+13,del(13,14)(q10;q10)) Mosaic type (46,XX/47,XX+13) - Associated with increase in Maternal age Karyotypic Abnormalities: - 92.5% - 95% of Trisomy 21 are 47,XX+21 Due to non-disjunction in Signs and Symptoms: parental meiosis ○ Microcephaly -