Genetics

1. Genetics Denice Gardner, MSN, NNP-BC

2. Objectives • Discuss genetics and its affects on the newborn

4. Genetics • Pictures included in presentation were obtained from the Mosby’s Nursing Consult web site • Graphics used in presentation were created by the author

5. Terminology • Genetics- study of heredity • Chromosome- structural element in a cell that contains the genes and all the genetic information; human cells have 23 pairs of chromosomes • DNA- double-stranded nucleotide that carries genetic material • Gene- segments of the DNA that are responsible for inherited traits; contain the “blueprint for everything that will make “you”

6. Terminology • Allele- variations in a gene; segregates during meiosis; receive only one pair from each parent; only 2 alleles can be present in one person • Autosome- one of the 22 chromosomes that do NOT determine the sex of a person • Sex chromosome- the X & Y chromosome that determines the sex of a person

7. Terminology • Gamete- one of the 2 cells that joins together during sexual reproduction to create a new being • Genotype- genetic make-up of a person • Phenotype- biochemical, physiologic, & morphologic characteristics of a person (hair color, skin type, etc.) & is determined by his/her genotype and environment

8. Terminology • Haploid- number of chromosomes in a gamete; half the number of chromosomes in a person, 23 chromosomes • Diploid- contains a set of maternal & paternal chromosomes to equal 46 total chromosomes • Locus- location of the gene in the chromosome • Penetrance- degree to which an inherited trait will be expressed in a person

9. Dominant & Recessive Genes • Dominant- expressed & transmitted even if only ONE parent has the gene • Recessive- expressed only when BOTH parents have the gene • Homozygous- two identical alleles for a particular gene (one from each parent) • Heterozygous- two different alleles for a particular gene

10. Possible Combinations • Both can be dominant (AA) • Both can be recessive (aa) • One can be dominant & one can be recessive (Aa)

11. Autosomal Dominant • Appears in every generation without skipping • Either parent can pass the gene on to their children • Risk for affected individuals to have affected children is 50% with every pregnancy • If 2 affected parents mate, 75% of their children will be affected • Unaffected individuals do NOT have affected children • Trait is found equally in males and females

12. Autosomal Dominant

13. Autosomal Recessive • Expressed only when both parents transmits it to their offspring • Alternates generations • If 2 affected people mate, all children with be affected • If 2 carriers mate, the risk of having an affected offspring is 25% • If a carrier & an affected person mate, the risk of having an affected offspring is 50% • Risk of an unaffected carrier having a child who is a carrier is 50% with each pregnancy

14. Autosomal Recessive

15. X-Linked Dominant • Female children of affected males are ALL affected • Male children of affected males are unaffected • Trait appears in every generation • All children of affected females MAY be affected • X-Linked dominant problems affect twice as many females as males

16. X-Linked Dominant

17. X-Linked Recessive • Only Male children are affected. (Female may be affected if mother is a carrier and father is affected) • Traits cannot be transmitted from father to son because the father only contributes the Y chromosome • Transmission of the trait occurs from father to all daughters (who will be carriers)

18. X-Linked Recessive • Heterozygous females transmit the gene to half of their sons, who will be affected, & to half their daughters, who will be carriers • Transmission is horizontal among males of the same generation & then skips a generation • Carrier females transmit the disorder

19. X-Linked Recessive

20. Chromosomal Defects: Abnormal Number • Polyploidy- contains more than 2 sets of chromosomes, showing multiples of the haploid number; usually dies as embryos or fetuses • Nonmultiples- designated by the suffix “-somy” • Monosomy- one less than the diploid number (45 chromosomes) • Trisomy- one more than the haploid number (47 chromosomes)

21. Chromosome Defects: Abnormal Number • Causes- • Nondisjunction- failure of paired chromosomes to separate during cell division; most common cause of all chromosome disorders • Chromosome lag- failure of a chromosome to travel to the correct daughter cell • Anaphase lag- failure of a chromosome or chromatin to be incorporated into one of the daughter nuclei following cell division as a result of delayed movement during anaphase

22. Mosaicism: Chromosomal Defects: Abnormal Number • Mosaicism: • Nondisjunction of an anaphase lag that occurs during cell division after fertilization • Cells within the same person that have different genetic make-up

23. Chromosomal Defects: Abnormal Structure • Deletion- loss of part of a chromosome • Translocations- displacement of part of a chromosome to an abnormal site, whether on another chromosome or in the wrong position on the same chromosome • Polygenic effects- type of inheritance in which a trait is dependent on many different gene pairs with cumulative effects

24. Chromosome Defects: Abnormal Structure • Environmental influences- nutrition, drugs, & living environment (radiation, pollution, bacteria, virus) that affect the genetic make-up & developing embryo while in utero • Duplication- duplication of an area of the DNA that contain contains a gene; results in mutations that have no deleterious affects on a person

25. Chromosomal Defects: Abnormal Structure • Inversion- area of a chromosome breaks off and then reattaches itself in the opposite direction • Nonreciprocal translocation- one-way transfer of genes from one chromosome to another

26. Chromosomal Defects: Abnormal Structure • Basic Generalizations • Loss of an entire chromosome is usually incompatible with life • One X chromosome is necessary for life & development • If the Y-chromosome is missing, life & development may continue but will follow female pathways

27. Chromosomal Defects: Abnormal Structure • Extra entire chromosomes, translocations of extra chromatin material, & insertion of extra chromatin material are often compatible with life & development • Multiple congenital structural defects are present when gross aberrations are present

28. Prenatal Testing • Alpha-Fetoprotein Test (AFP) • Usually done at 16-18 weeks gestation • Is a screening test, not a diagnostic test • If abnormal, ultrasound should be obtained

29. Prenatal Testing • Elevated AFP may indicate • Greater gestational age than expected • Multiple gestation • Risk of neonatal complications, including spontaneous abortion, PTL, or IUGR • Fetal structural defects: neural tube, abdominal wall, esophageal or intestinal obstruction, or renal anomalies

30. Prenatal Testing • Multiple Marker Screen (“Quad Screen”) • Measures AFP, hCG, unconjugated estriol (uE3), & dimeric inhibin-A (DIA) • Useful in detecting conditions like trisomies • Usually done between 15-20 weeks gestation • If, abnormal, ultrasound should be obtained

31. Prenatal Testing • Ultrasonography- uses high-frequency sound waves to display sectional planes of the uterine contents on a monitor • Recommended by 16-20 weeks of age for gestational age verification & assessment • Used to detect abnormalities of the fetus, placenta, amniotic fluid, & uterus & to monitor changes in anatomy & growth with serial ultrasounds • Only as good as the person’s training-not just on the equipment

32. Prenatal Testing • Amniocentesis- removal of amniotic fluid through a needle placed through the abdomen, usually in conjunction with ultrasonography, for the purpose of chromosome analysis & other biochemical tests • Usually done between 16-18 weeks gestation • Indications for procedure: • Advanced maternal age (>35yrs at time of delivery) • Previous fetus with a neural tube

33. Prenatal Testing • More indications for procedure • Both parents known heterozygous carriers of autosomal recessive chromosome • Both parents known carriers of sex-linked recessive disorder • Patient or partner with balanced chromosomal translocation of his or her chromosomes • High or low AFP with accurate gestational age • Previous fetus with Down’s Syndrome

34. Prenatal Testing • Chorionic Villi Sampling- insertion of a needle through either the cervical os or through the abdomen, in conjunction with ultrasound, to obtain a sample of fetal tissue from the growing placenta for chromosomal analysis & other biochemical tests • Usually done at 8-10 weeks • Indications: • Patient prefers to make decision regarding pregnancy in the 1st trimester • Severe oligohydramnios

35. Prenatal Testing • Complications: • Multiple gestation • Uterine bleeding during this pregnancy • Active genital herpes or other cervical infection • Uterine fibroids • Takes 24-48 hours for initial results

36. Prenatal Testing • Percutaneous Umbilical Cord Sampling-removal of blood through a needle inserted through the abdomen and into the umbilical vein, in conjunction with ultrasound • Performed from 18 weeks until term • Indications: • Patient wants fast results to support decision regarding pregnancy • Abnormality is identified late in pregnancy

37. Prenatal Testing • More indications: • Patient has been exposed to infectious disease that could affect development of fetus • Blood incompatibility (Rh disease) • Drug or chemical level is fetal blood needs to be assessed • Fetal blood analysis 3 days

38. Postnatal Testing • Chromosome analysis/karyotype- photograph of the chromosomal make-up of an individual, including the number of chromosomes & any abnormalities • Polymerase Chain Reaction (PCR)- technique to copy small segments of DNA for analysis; useful in disorders with recurring mutations • High-resolution banding/prometaphase banding- useful for identification of subtle chromosomes

39. Postnatal Testing • Microarray- assesses the ability of mRNA molecules to and interact with DNA molecules; assesses gene expression within a single sample or in comparison to 2 different cell types or tissue samples; need only a small sample of blood or tissue; can be done on healthy or diseased tissue

40. Postnatal Testing • Fluorescence in situ hybridization (FISH)- cytogenic technique that can be used to detect and localize the presence or absence of specific DNA sequences on chromosomes; uses fluorescent probes that bind to only those parts of the chromosome with which they show a high degree of sequence similarity

41. Genetic Counseling • Goal- to assist the family in understanding • Diagnosis • Role of heredity • Recurrence risks & options • Possible courses of actions • Methods of ongoing adjustment

42. Genetic Counseling • Indications • Previously affected child, parent, or grandparent • Congenital malformation • Sensory defect • Metabolic disorder • Mental retardation • Known or suspected chromosome abnormality • Neuromuscular disorder • Degenerative CNS disease

43. Genetic Counseling • More indications • Previously affected cousins • Muscular dystrophy • Hemophilia • Hydrocephalus • Consanguinity • Hazards of ionizing radiation • Recurrent miscarriages • Concern for teratogenic effect • Advanced maternal age • High or low AFP

44. Newborn Care: Terminology • Birth defect- structural or functional abnormality of the body that is present from birth • Syndrome- group of anomalies that cannot otherwise be explained & occurs in similar patterns of expressions (ex. Fetal alcohol syndrome) • Sequence- primary anomaly that sets a pattern for other anomalies (Ex. Pierre Robin)

45. Newborn Care: Terminology • Association- nonrandom occurrence of multiple anomalies in 2 or more people (ex. CHARGE) • Malformation- abnormality of morphogenesis due to intrinsic problems within the developing structures (ex. Neural tube defect) • Deformation- abnormality of morphogenesis due to intrinsic problems within the developing structures (ex. uterine position defects)

46. Newborn Care: Terminology • Disruption- abnormality of morphogenesis due to disruptive forces or pressure acting on the developing structures (ex. Amniotic bands) • Genetic heterogeneity- different causes may produce different characteristics (ex. Hydrocephalus, cleft lip & palate)

47. Newborn Care • History • Family • History of 3 generations • Defects in the family history related to the problem with the child • History of consanguinity • Reproductive history (frequent miscarriages???) • Pattern of inheritance of the problem

48. Newborn Care • Prenatal • Length of gestation • Fetal activity level • Maternal exposure: infection, illness, high fever, meds, alcohol, smoking, X-rays, known teratogens, illicit or prescription drug use • Obstetric factors: uterine malformations, labor complications, presenting fetal part • Neonatal factors: birth weight, length, HC, Apgar score

49. Newborn Care: Assessment • Physical Exam • General: asymmetry, inappropriate size & length • Face: configuration; centered features with normal spacing; round, triangular, birdlike, elfin, or expressionless characteristics • Head: size of anterior fontanelle, prominence of frontal bone, flattened or prominent occiput, abnormalities in shape (large or small)

50. Newborn Care: Assessment • Skin: intact, presence of skin tags, open sinuses, tracts, etc. • Hair: texture, presence of whorls • Eyes: structure, color of iris, presence of colobomas, centering & spacing of epicanthal folds, ptosis, slanting, eyelash length • Ears: protruding or prominent shape, location, low set, unilateral or bilateral defect, presence &/or degree of rotation