Gen Path - Class 26

Front 1

What is teratology?

Back 1

Disturbances of development. Fetal malformations.

Front 2

What are teratogens?

Back 2

Causes of fetal abnormalities

Front 3

What are structural chromosomal abnormalities?

Back 3

Deletion of a portion of the chromosome

Front 4

What are four structural chromosomal abnormalities involving Chromosome 11?

Back 4

(1)Wilm’s tumour, (2)Aniridia – lack of iris, (3)Genetic malformation, (4)Mental retardation

Front 5

What is translocation?

Back 5

Translocation of a portion of one chromosome to another chromosomes. SOME cases of Down’s syndrome – translocation of chromosome 21 to chromosome 14.

Front 6

What are numerical chromosomal abnormalities?

Back 6

Loss or gain of chromosomes. Monosomy – loss of one chromosome. Trisomy – gain of an additional chromosome Eg. Trisomy 21

Front 7

What is Trisomy 21?

Back 7

Down’s Syndrome. Most common numerical abnormality. 1 in 800. Maternal origin. 47,XX +21 or 47,XY +21.

Front 8

What are four symptoms of trisomy 21?

Back 8

(1)Mental retardation, (2)Wide face, close set, slanted eyes, macroglossia (large tongue), (3)Abnormal extremities – short, (4)Defects of internal organs – heart, GI, infertility (Men are sterile)

Front 9

What are abnormalities of sex chromosomes?

Back 9

Abnormal segregation of X or Y chromosomes during meiosis in the female or male gonads. Two types: Monosomy or Trisomy

Front 10

What is monosomy?

Back 10

Sperm or ovum may not receive an X or Y. Zygote and embryo develops and lacks one sex chromosome. If lacking an X chromosome – Turner’s syndrome. If lacking a Y chromosome – not viable -- spontaneous abortion

Front 11

What is trisomy?

Back 11

Ovum retains both X chromosomes --

Sperm retains X and Y chromosomes --

Klinefelter’s syndrome

Front 12

What is Turner’s Syndrome?

Back 12

45X. Monosomy X.

Front 13

What are eight clinical features of Turner's Syndrome?

Back 13

(1)Short stature, (2)Webbing of the neck, (3)Abnormal extremities – cubitus valgus, (4)Broad chest with widely spaced nipples, (5)Congenital heart disease, (6)Ovaries – streak gonads – fibrous strands with no oocytes, (7)Never reach puberty, (8)Infertile

Front 14

What is Klinefelter’s Syndrome?

Back 14

47XXY. Trisomy – XXY.

Front 15

What are four clinical features of Klinefelter’s syndrome?

Back 15

(1)Phenotypically males but infertile (Testes unable to produce sperm, atrophied, (2)Secondary sex characteristics don’t develop (Small penis, No pubic hair), (3)Tall, (5)Gynecomastia – enlargement of the breasts

Front 16

What are single gene disorders?

Back 16

Genes are expressed in duplicate and are found on the same site of two homologous chromosomes. Dominant or Recessive. Dominant – over shadow recessive

Front 17

When are recessive genes expressed?

Back 17

Recessive genes are only expressed if they are paired with another recessive

Front 18

Are X or Y chromosomes expressed?

Back 18

X chromosome genes will be expressed rather than Y chromosome genes (Males may inherit recessive genes from their mom)

Front 19

What are four types of genetic disorders?

Back 19

(1)Autosomal dominant, (2)Autosomal recessive, (3)Sex-linked recessive, (4)Sex-linked dominant

Front 20

What are autosomal dominant disorders?

Back 20

Trait is fully expressed even if only one copy of the gene is present. 50% chance of passing the same gene to each offspring. Unaffected offspring do not pass along the trait.

Front 21

What are two autosomal dominant disorders?

Back 21

(1)Marfan’s Syndrome, (2)Familial Hypercholesterolemia

Front 22

What is Marfan’s syndrome?

Back 22

Autosomal dominant. 1 in 5,000. Multisystemic disease – affects connective tissue. Death usually due to heart failure.

Front 23

What is the pathology of Marfan’s syndrome?

Back 23

Dysfunction of the gene that encodes for fibrillin (Tendons, heart valves, blood vessels). Abnormal fibrillin causes loose connective tissue -- cannot support normal function

Front 24

What are three skeletal changes are seen in Marfan's syndrome?

Back 24

(1)slender, long, tall, elongated head, prominent frontal bone, (2)Lax ligaments, (3)Frequent subluxations, spinal deformities

Front 25

What are three cardiovascular changes are seen in Marfan's syndrome?

Back 25

(1)large vessels are weak, (2)Aortic aneurysm, weakening of vessel wall, (3)Floppy valves – loose cardiac valves -- malfunction

Front 26

What are three occular changes are seen in Marfan's syndrome?

Back 26

(1)Subluxation of the lens, (2)Cataracts, (3)Retinal detachment

Front 27

What is Familial Hypercholesterolemia?

Back 27

1 in 500 Americans. Mutation in the gene encoding for LDL receptor. Less cholesterol is removed from the blood -- hypercholesterolemia -- depositing of lipids in arteries -- atherosclerosis. No cure. Low fat diet. Drugs - statins.

Front 28

What are autosomal recessive disorders?

Back 28

For trait to be expressed, the gene must be inherited from each parent. Parents are usually asymptomatic carriers.

Front 29

What are three autosomal recessive disorders?

Back 29

(1)Cystic Fibrosis, (2)Lysosomal storage disease, (3)Phenylketonuria

Front 30

What is Cystic Fibrosis?

Back 30

1 in 2500. 1 in 25 is an asymptomatic carrier. Extremely rare an any race other than Caucasian. Defect in the transport of chloride across the cell membrane. Lack of sodium chloride in secretions of exocrine glands (Especially pancreas, intestine, bronchi, Secretions contain less water -- thick, mucous). Obstruction of the lumen.

Front 31

What are five clinical features of cystic fibrosis?

Back 31

(1)Prevention of pancreatic juice into intestine -- malabsorption, steatorrhea -- malnutrition, (2)Bronchial mucus transforms into plugs -- recurrent bacterial infections(bronchitis/pneumonia) -- bronchiectasis and pulmonary fibrosis, (3)Sweat glands cannot reabsorb chloride -- salty sweat, (3)Incurable, (4)Life span is generally 20 years old (Pulmonary infection)

Front 32

What are Lysosomal Storage Diseases?

Back 32

Deficiency in enzymes. Metabolites are not fully digested or removed -- accumulate inside affected cells (Most often in lysosomes). Many different diseases depending on the metabolic pathway affected: Lipidoses, Glycogenoses, Etc

Front 33

What are two clinical features of Lysosomal Storage Diseases?

Back 33

(1)Accumulation of metabolizes, (2)Variable symptoms

Front 34

What is Phenylketonuria?

Back 34

Error in protein metabolism. Deficiency of phenylalanine hydroxylase. Phenylalanine accumulates in blood and tissues -- ketones, acids formed and excreted in urine.

Front 35

What are five clinical features of Phenylketonuria?

Back 35

(1)Initially healthy, (2)Fair skin, fair hair, blue eyes, (3)“mousy odour”, (4)Routine screening at time of birth, (5)Affects CNS if untreated

Front 36

What are X-Linked Recessive Disorders?

Back 36

Recessive traits encoded by recessive genes on the X chromosome but NOT on the Y chromosome. Rarely expressed in females – would have to get from both parents. Males –Y chromosomes does not overshadow the X chromosome. Gene is transmitted by an asymptomatic mother. Sisters of an affected male are asymptomatic (May be carriers or may not). Unaffected brothers do not carry the gene and do not express the trait. All daughters of affected male are asymptomatic carriers. All sons of affected male do not get the gene.

Front 37

What are two X-Linked Recessive Disorders?

Back 37

(1)Hemophilia, (2)Muscular Dystrophy

Front 38

What is hemophilia?

Back 38

Mutation of the gene that codes for coagulation factor VIII or IX. Mild to severe forms. Inherited or new mutation.

Front 39

What can happen in severe cases of hemophilia?

Back 39

Hemorrhage due to minor trauma, spontaneous. Hemarthrosis is common.

Front 40

How is science helping hemophilia patients?

Back 40

Genes for coagulation factors VIII and IX have been cloned. Clotting factors made in lab to treat patients.

Front 41

What is muscular dystrophy?

Back 41

Progressive muscle wasting. Most commonly seen in males. Lack of dystrophin -- muscle cells cannot retain proper form -- disintegrate. Most commonly effects skeletal muscle.

Front 42

What are two types of muscular dystrophy?

Back 42

(1)Duchenne’s muscular dystrophy, (2)Becker’s muscular dystrophy

Front 43

What is Duchenne’s muscular dystrophy?

Back 43

Males only. Dx usu pre-school age- tire easily &cannot keep-up with friends. Symm. weakness of pelvic mm. Calf pseudo-hypertrophy. Often incapacitated by 10; death, 20

Front 44

What is Becker's muscular dystrophy?

Back 44

Appears later, less severe and slower to progress