Genetic Development - Final Exam

Question 1

Four main stages of prenatal development

Answer 1

1. Preimplantation embryonic stage
2. Germ layer formation
3. Early organogenesis
4. Definitive organogenesis

Question 2

Preimplantation stage

Answer 2

First cleavage of zygote and blastocyst formation
Morula (16 cells, day 4)
Blastocyst (day 5)
Trophoblast (dedicated to placenta and extraembryonic tissue)

Question 3

Germ layer formation

Answer 3

Embryo implants in endometrial wall of uterus
Gastrulation occurs after implantation, cells arrange into 3 cellular compartments
Axes of final body plan form

Question 4

Germ layers

Answer 4

1. Ectoderm
2. Mesoderm
3. Endoderm

Question 5

Late organogenesis

Answer 5

Anatomical and funcitonal maturation of organs occur (4-8w)
Position and basic structures of all organs are now established and cellular components necessary for full development are not in place
Neural tube defects form at this stage

Question 6

Causes of neural tube defects (3)

Answer 6

1. Geographical
2. Folic acid deficiency (very early on)
3. MTHFR involved in genetic component of neural tube defects

Question 7

Congenital defects

Answer 7

Present at birth
Organs or other structures
Significant cause of infant death (20%)
Major cause of long term morbidity, intellectual disability, and other dysfunction
Major impact on public health

Question 8

Congenital defect causes (5)

Answer 8

1. 75% - unknown
2. 20% - genetic
3. 2% - chromosomal
4. 2% - infectious
5. 1% - chemical

Question 9

What point of organogenesis is most susceptible to developmental defects?

Answer 9

First trimester

Question 10

Developmental malformation causes (6)

Answer 10

Disturbances in development resulting in development malformations - morphological defect of an organ or larger part of body results from intrinsically abnormal developmental process

1. Genetic factors
2. Exogenous teratogens
3. Chromosomal abnormalities
4. Single-gene disorders
5. Prenatal diagnosis
6. Prematurity, birth injury, SIDS

Question 11

Cleft lip

Answer 11

Incidence increased in some families

Inherited as multifactorial trait

Question 12

Achondroplastic dwarfism

Answer 12

Cause by single gene defect

Mendelian trait

Question 13

Exogenous teratogens (3)

Answer 13

1. Physical (X-rays, corpuscular radiation)
2. Chemical (industrial, drugs, alcohol)
3. Microbial (viruses, bacteria, protozoal parasites)

Question 14

Fetal alcohol syndrome

Answer 14

Caused by prenatal exposure to alcohol
Intellectual and behaviour disabilities
Impairment of internal organs

Question 15

TORCH syndrome

Answer 15

Toxoplasma
Others
Rubella
Cytomegalovirus
Herpes
Can stress mother and lead to low fetal weight
Marked by involvement of several organ systems

Question 16

Other (TORCH)

Answer 16

Less common infectious agents

EBV, varicella virus, listeria monocytogenes, leptospira, etc

Question 17

Brain (TORCH)

Answer 17

Most often affected

Small (microcephaly), mental retardation usually combined with neurological symptoms

Question 18

Eyes (TORCH)

Answer 18

Small (micropthamlia), inflammation of inside layer of eyes, lens clouding

Question 19

Heart (TORCH)

Answer 19

Development defect

Question 20

Liver/lung (TORCH)

Answer 20

Inflammation, reactive enlargement of lymph nodes and spleen

Question 21

Skin lesions (TORCH)

Answer 21

Petechial hemorrhages and vesicles

Especially after herpes virus infection

Question 22

Congenital Rubella Syndrome

Answer 22

Now prevented by maternal immunization
Marked by triad:
1. Microcephaly
2. Microphthalmia
3. CHD

Question 23

Chromosome disorders

Answer 23

Clinical condition caused by abnormal chromosome constitution in which there is duplication, loss or rearrangement of chromosomal material
Structural or numerical

Question 24

What is a chromosome?

Answer 24

1/3 DNA
1/3 RNA
1/3 Protein
Coloured body
Threadlike structures seen in cell nucleus containing chromatin
Single molecular DNA in interphase state

Question 25

What do chromosomes do?

Answer 25

Carry genetic information in a defined structure Somatic cell division Gamete formation

Question 26

How do we study chromosomes?

Answer 26

Stained to give regular lines

Question 27

Aneuploidy

Answer 27

Any chromosome number that is not an exact multiple of haploid number Gain or loss of entire chromosome

Question 28

Hyperdiploidy

Answer 28

2n+

Question 29

Hypodiploidy

Answer 29

2n-

Question 30

Monosomy

Answer 30

Loss of a single chromosome

Question 31

Trisomy

Answer 31

Gain of a single chromosome

Question 32

Trisomy 21 (Down's Syndrome)

Answer 32

``` Non-disjunction in M1 Mental retardarion Unique facial features Eye abnormalities Gaping mouth and large tongue Heart diseases Intestinal defects Hand abnormalities (shortened fingers, curved) Abnormalities of toes (wide gap) ```

Question 33

Pathogenesis of sex chromosome abnormalities

Answer 33

More common in clinical practice | Less lethal and cause less fetal wastage

Question 34

Turner's syndrome

Answer 34

Usually diagnosed at puberty, or at infancy with excessive webbing Short stature, heart-shaped face, webbing of neck, heart disease, broad chest, cubitus valgus, streak ovaries, hypoplastic uterus, amenorrhea

Question 35

Klinefelter Syndrome

Answer 35

``` Groups of chromosomal disorders where there is at least one extra X in male karyotype OR translocation of SRY to XX Tall, long arms and legs Lack of beard, body hair and pubic hair Gynecomastia (breasts) Female-like hips Testicular atrophy, infertility ```

Question 36

WAGR syndrome

Answer 36

11p12-p14 deletions - deletion of short arm Wilms tumour of kidney Aniridia Genital malformations Mental retardation Results in loss of important genes, such as WT1 - deletion of chromosome 13 causing retinoblastoma (RB1)

Question 37

Reciprocal translocation

Answer 37

Transfer of one segment of one chromosome to another chromosome (two non-homologous chromosomes) 1/500 newborns

Question 38

Balanced reciprocal translocations

Answer 38

Generally no loss or gain of genetic information Position change but no phenotypic consequences Reproductive consequences

Question 39

Down's Syndrome - Translocation form

Answer 39

4% have 46 chromosomes Reciprocal translocation between chromosome 21 and another acrocentric chromosome (14 or 22) No maternal age effect, but may be the result of familial translocation Parental karyotypes required for follow up

Question 40

Robertsonian translocations

Answer 40

Rare form of chromosomal rearrangement that, in humans, generally occurs in the five acrocentric chromosome pairs, namely 13, 14, 15, 21 and 22

Question 41

Autosomal dominant disorders

Answer 41

Apparent in heterozygotes Trait is expressed in every generation that carries dominant trait Unaffected offspring of symptomatic carrier do not transmit trait

Question 42

Marfan's syndrome

Answer 42

Autosomal dominant disease affecting connective tissue Structural defect in fibrillin, causing connective tissue to be loose and disjointed Elongated head, eye abnormalities, aortic aneurysm with dissection and exsanguination, floppy mitral valve, vertebral deformity, long fingers

Question 43

Familial hypercholesterolemia

Answer 43

Autosomal dominant disease affecting CVS 1/500 Mutation in LDL receptor Lipid deposits in tissues, especially arteries Accelerated atherosclerosis and coronary artery disease Nodules in hands, not curable but manageable with strict, low fat diet Statins can help

Question 44

Adult polycystic kidney disease

Answer 44

Autosomal dominant disease affecting kidney

Question 45

Wilm's tumour

Answer 45

Autosomal dominant disease affecting kidney

Question 46

Huntington's disease

Answer 46

Autosomal dominant disease affecting nervous system

Question 47

Neurofibromatosis

Answer 47

Autosomal dominant disease affecting nervous system

Question 48

Familial polyposis coli

Answer 48

Autosomal dominant disease affecting GI tract

Question 49

Autosomal recessive disorders

Answer 49

Gene is apparent only in homozygotes

Question 50

Cystic fibrosis

Answer 50

Autosomal recessive disorder Disorder in Cl ion transport channel Positive sweat chloride test and DNA testing Many fluid in body are highly viscous Affects pancreas, affecting absorption - failure to thrive Fetal intestines Can be detected by ultrasound Lungs start to fill up with viscous fluid, increased chance of bronchitis and pneumonia

Question 51

Anemias

Answer 51

Sickle cell anemia, thalassemia | Autosomal recessive disorder

Question 52

Lipodoses

Answer 52

Tay-Sachs disease, Niemman-Pick disease | Autosomal recessive disorder

Question 53

Mucopolusaccharidoses

Answer 53

Hurler's syndrome Hunter's syndrome Autosomal recessive disorder

Question 54

Amino acid disorders

Answer 54

Phenylketonuria Albinism Autosomal recessive disorder

Question 55

Lysosomal storage diseases

Answer 55

Autosomal recessive disorder Deficiencies in enzymes in intermediate metabolism things accumulate in cells

Question 56

Phenylketonuria

Answer 56

Autosomal recessive disorder Phenylpyruvic acid accumulation as phenylalanine does not get converted into tyrosine Can only detect when children start eating phenylalanine Slow, progressive, irreversible mental retardation

Question 57

Tay Sachs Disease

Answer 57

Autosomal recessive disorder Increased substrates in vacuoles Affects brain and eyes

Question 58

X-linked recessives

Answer 58

Gene effected is usually evident only in males, rarely in females Gene is transmitted from asymptomatic, heterozygous mother Son of female has 50% chance of being affected >100 genes on X chromosome, many linked to important diseases

Question 59

Hemophilia A and B

Answer 59

Hereditory bleeding disorders Mutations in genes involved in coagulation Factor 8: 1/5000 males larger, more room for mutation), Factor 9: 1/30000 males 50% inherited, 50% new mutations

Question 60

X-linked muscular dystrophy (2)

Answer 60

1. Duchenne's | 2. Becker's

Question 61

X-linked congenital immunodeficiencies (4)

Answer 61

1. Agammaglobulinemia 2. Wiskott-Aldrich syndrome 3. X-linked immunodeficiency 4. Lymphoproliferative disorders

Question 62

Fragile X syndrome

Answer 62

``` X-linked recessive disorder CGG triple nucleotide repeat Most common mental retardation in males 1/1250 males 1/1200 female (carrier) Normal number of repeats is 5-44 200 greater repeats is pathologic ```

Question 63

Multifactorial inheritance

Answer 63

Trait or disease is product of several genes Inheritance cannot be explained in terms of Mendelian single-gene inheritance Exogenous and endogenous factors influence expression of the trait and determine severity of the disease Genes encoding trait or disease have dose effect More severe form: more likely to transmit to offspring

Question 64

Ancephaly and Craniorachischisis

Answer 64

Multifactorial inheritance Failure of neural tube to close Complete absence of brain Folic acid deficiency

Question 65

Diabetes type II

Answer 65

Multifactorial inheritance 50% of affected persons have relatives with diabetes High incidence in populations with high rate of intermarriage High concordance among monozygotic twins Not entirely environmental

Question 66

Prenatal diagnosis

Answer 66

Many genetic diseases and chromosomal abnormalities can be diagnosed prenatally Usually for highrisk pregnancies

Question 67

Techniques for prenatal diagnosis (4)

Answer 67

1. Utrasonographic examination 2. Chorionic villus biopsy (10-15w) 3. Amniotic fluid analysis 4. Maternal blood analysis

Question 68

Prematurity

Answer 68

<30w <2500g Immaturity <1500g

Question 69

Immaturity

Answer 69

<1500g Anatomical and functionally immature - more noticeable in brain and lungs Cannot survive without medical assistance NICU

Question 70

Causes of prematurity (3)

Answer 70

5-10% pregnancies terminate prematurely 1. Maternal factors 2. Fetal factors 3. Placental factors

Question 71

Maternal factors of prematurity (2)

Answer 71

1. Malnutrition, smoking, substance abuse | 2. Infection

Question 72

Fetal factors of prematurity (3)

Answer 72

1. Infections 2. Fetal malformations 3. Genetic diseases

Question 73

Placental factors of prematurity

Answer 73

Placental insufficiency

Question 74

Neonatal respiratory distress syndrome

Answer 74

Immature Type II pneumocytes Surfactant deficiency Atelectasis, alveolar, endothelial injury of lungs Hypoxia of the hyaline membrane

Question 75

Hypoxia of hyaline membrane

Answer 75

Can cause cerebral intraventricular hemorrhage | Hemorrhagic intestinal necrosis

Question 76

Birth injury

Answer 76

Various lesions caused by mechanical trauma | Skull fractures, intracranial hemorrhage, peripheral nerve injury, fractures of long bones

Question 77

Sudden infant death syndrome

Answer 77

``` Sudden, unexpected death of infants Cause unknown Maternal risk factors Fetal risk factors Most common cause of death beyond immediate neonatal period 2mo ```