Genetic and Developmental Disorders

Question 1

Egg + sperm =

Answer 1

zygote

Question 2

Zygote cells divide to form

Answer 2

Morula

Question 3

Morula develops into

Answer 3

Blastocyst

Question 4

Three primordial germ layers

Answer 4

Ectoderm
Mesoderm
Endoderm

Question 5

The critical stages of organogenesis are characterized by:

Answer 5

Extensive cell division, migration and interaction; and

Extreme sensitivity to external influences

Question 6

Teratogen

Answer 6

Any agent that causes fetal abnormalities

Question 7

Breakdown of causes of fetal abnormalities:

Answer 7

75% unknown
20% genetic diseases
2% chromosomal abnormalities
2% infection
1% chemical

Question 8

Exogenous teratogens

Answer 8

Physical (X-rays, radiation, etc)

Chemicals

Question 9

Fetal Alcohol Syndrome

Answer 9

Intrauterine growth development, affecting development of brain

Typically presents with small cranium and jaw, thin upper lip, reduced mental processes

Question 10

TORCH

Answer 10

Toxoplasma, Other, Rubella, Cytomegalovirus, Herpes Simplex

Microbial teratogens

Question 11

Congenital Rubella syndrome.

Answer 11

Microcephaly, micropthalmia, congenital heart defects

Inflammation of liver, lungs, lymphosplenomegaly

Question 12

Teratogenic effect of Toxoplasmosis and cytomegalovirus

Answer 12

Brain abnormalities; small eyes with inflammation, cataracts and calcifications

Question 13

Teratogenic effect of Herpes

Answer 13

skin lesions

Question 14

Chromosomal abnormalities can be:

Answer 14

1. Structural
2. Numerical
   - trisomy
   - monosomy

More common in sex chromosomes than autosomes

Question 15

Trisomy 21

Answer 15

Downs Syndrome
Translocation or trisomy of chromosome 21
Associated with mental retardation, facial and limb abnormalities, defects in internal organs, hematologic abnormalities.

Question 16

Turner’s Syndrome

Answer 16

Monosomy X

Short stature, webbing of neck, normal female genitalia, except ovaries don’t develop normally.

Question 17

Klinefelter’s Syndrome

Answer 17

XXY

Infertile males.

Atrophy of testes. Tall, effeminate, gynecomastia

Question 18

Heterozygous

Answer 18

Possess one recessive and one dominant copy of the allele

Question 19

Homozygous

Answer 19

Possess either two recessive or two dominant copies of the gene.

Question 20

Marfan’s Syndrome

Answer 20

Autosomal dominant disorder primarily affecting connective tissue. Defect in gene that codes for fibrilin

1/10000

Causes skeletal, cardiovascular and occular changes

Elongated head, eye abnormalities, aortic aneurysm, floppy mitral valve, vertebral deformity, arachnodactyly

Question 21

Familial Hypercholesterolemia

Answer 21

Autosomal dominant disorder primarily affecting cardiovascular system. Mutation in gene encoding LDL receptor.

LDL cholesterol removal less efficient –> deposition of lipids in arteries

1/500 people

Question 22

Xanthomas

Answer 22

Lipid-rich yellow nodules, consist of macrophages that have phagocytize cholesterol

Question 23

Cystic Fibrosis

Answer 23

Autosomal recessive disorder affecting gene that codes for chloride transport channel in cell membrane.

1/2500 neonates (1/25 estimated carrier)
Almost exclusively found in those with European heritage

Lack of NaCl in glandular secretions –> lack of H2) –> increased viscosity of secretions –> obstruction of organs

In pancreas –> malabsorption of nutrients
In bronchial mucosa –> abnormal respiration
Recurrent bacterial infection

Question 24

Lysosomal Storage Diseases

Answer 24

Autosomal recessive disorders related to deficiency of enzymes involved in intermediary metabolism.

Metabolites that can’t get fully degraded, digested or incorporated get stored in lysosomes

Question 25

Types of Lysosomal Storage Diseases

Answer 25

Lipodoses, glycogenoses, mucopolysaccharidoses, Tay-Sachs Normally classified by type of pathway affected. All characterized by accumulation of metabolites that cannot be processed

Question 26

Tay-Sachs Disease

Answer 26

Lysosomal Storage Disease (autosomal recessive) Defect in the function of hexosaminidase A --> accumulation of ganglioside in the brain Gradual loss of brain function --> often death by age 5

Question 27

Phenylketonuria

Answer 27

PKU Autosomal recessive defect of protein metabolism. Problem with enzyme that metabolizes phenylalanine (phenylalanine hyroxylase -- PAH) into tyrosine. Phenylalanine cannot be metabolized and so accumulates in blood and tissues. Can be controlled with diagnosis at birth and special diet. Without special diet --> mental retardation

Question 28

Hemophilia

Answer 28

X-linked recessive disease - internally hemorrhage, joint deformity resulting from hemarthrosis ``` Two types: Hemophilia A -- defect of Coagulation Factor VIII -- 1/5000 boys -- mild to severe symptoms Hemophilia B -- defect of Coagulation Factor IX -- 1/20000 boys -- always severe ```

Question 29

Muscular Dystrophy

Answer 29

X-linked recessive disease characterized by progressive muscle wasting -inadequate or absent dystrophin Duchenne (most severe), Beckers (less severe)

Question 30

Fragile X Syndrome

Answer 30

X-linked recessive form of mental retardation CGG triplet repeat Currently 80% penetrance, but seems to get more severe with successive generations 1/1250 boys, 1/2500 females

Question 31

Anencephaly

Answer 31

Multifactorial development defect in which the midline structures covering the brain do not fuse, and spinal/brain development is severely disturbed

Question 32

Diabetes Mellitus

Answer 32

Disturbance of intermediate metabolism --> hyperglycemia Multifactorial

Question 33

Forms of prenatal diagnosis

Answer 33

Ultrasound Chorionic villus biopsy (fetal cells) Amniotic fluid analysis Maternal blood analysis (AFP - alpha-fetoprotein; triple-screen marker test)

Question 34

Prematurity

Answer 34

Born before 37th week, and weighing less than 2500g

Question 35

Immaturity

Answer 35

Less than 1500 g and cannot survive outside NICU

Question 36

Most important risk factor for prematurity

Answer 36

Premature rupture of amniotic membrane

Question 37

Neonatal Respiratory Distress Syndrome

Answer 37

In premature infants, immature lungs may not have fully developed alveoli - - alveoli secrete surfactant to decrease surface tension and keep alveoli open - - in immature alveoli, lack of surfactant allows alveoli to collapse. Cells die - - necrotic cells and tissues coagulate and form a hyaline membrane, which further impedes gas exchange - - anoxia can cause death within 48 hours

Question 38

Sudden Infant Death Syndrome

Answer 38

SIDS 1/500 births [1/2000 in Canada] More common with poverty "Back to Sleep"