Genetic disorders and Neoplasia

Question 1

Autosomal dominant and recessive diseases have opposing features of age of onset, which one is which?

Answer 1

Dominant-Occurs later in life usually

Question 2

Which disorders are dominant?

Answer 2

BAMN

Brugada, Achondroplasia, Marfan syndrome, and Neurofibromatosis

Question 3

What is Brugada Syndrome due to?

Answer 3

Due to defect in gene that codes for Na, K, or Ca channels in the heart

Question 4

What is often the first symptom of someone who has Brugadas?

Answer 4

Sudden cardiac death with structurally normal hearts

Question 5

What causes development of Achondroplasia?

Answer 5

A mutation in the gene for FGF receptor 3

Question 6

80% of individuals with achodroplasia have parents of average height, meaning most cases result from ___ mutations.

Answer 6

De novo

Question 7

What is the paternal age effect?

Answer 7

New, sporadic dominant mutations occurring with advanced paternal age.

Over the age of 40 has an increase risk of passing on a mendelian condition, primarily autosomal dominant ones that were not present in either parent

Question 8

What causes Marfan syndrome?

Answer 8

Dysfunction in a gene that codes for fibrillin 1 needed for production of elastic fibers

Question 9

What are the pleiotropic effects observed in Marfans syndrome?

Answer 9

Disproportionately tall stature, ocular changes, sever myopia, retinal detachments, dislocations of the lenses, hyperextensible skin, bruising easily, poor wound healing

Most serious is dilation of the aortic root, leading to rupture and sudden death

Question 10

What is the genetic defect in Neurofibromatosis?

Answer 10

Defect in a tumor suppressor gene involved in cell division and growth, causing tumor formation by Schwann cells

Question 11

What are the two neurofibromatosis and their manifestations?

Answer 11

NF-1- learning disabilities, ADD, speech abnormalities

NF-2- Absence or minimal cutaneous lesions, progressive deafness and bilateral acoustic neuromas

Question 12

What do autosomal recessive mutations often lead to?

Answer 12

Loss of enzyme function (inborn errors of metabolism)

Question 13

What are the two characteristics of autosomal recessive disorders that distinguish it from a dominant disorder?

Answer 13

AR results in early onset of disease and uniform symptomology

Question 14

What are the four autosomal recessive disorders we discuss?

Answer 14

PaTT

Phenyketonuria, Tay Sachs disease, A1 antitrypsin deficiency, Thalassemias

Question 15

What is the genetic defect in phenylketonuria?

Answer 15

Most commonly lack of phenyalanine hydroxylase, which converts phenyalanine to tyrosine. Excess Phenylalanine is toxic to the brain

Question 16

What are manifestations of PKU? If left untreated?

Answer 16

Mental retardation, microcephaly, seizures, decrease pigmentation
Post natal growth restrictions, intellectual disability, recurrent seizures

Question 17

What deficiency causes Tay Sachs Disease?

Answer 17

Hexominidase A, which breaks down GM2 ganglioside

It ends up accumulating in the lysosomes in this disease when not broken down

Question 18

What are the manifestations of Tay Sachs Disease?

Answer 18

Weakness, muscle flaccidity, decreased attentivenessk blindness

Question 19

What does the progression of Tay Sachs Disease look like?

Answer 19

Normal at birth, symptoms at 3-6 months, death at 4-5

Question 20

What does alpha 1 antitrypsin deficiency cause?

Answer 20

Alveolar damage due to increased elastic fiber destruction and emphysema

Question 21

What can also cause similar symptoms as a1 antitrypsin disease?

Answer 21

Smoking

Question 22

What does Thalassemias result from?

Answer 22

Mutations causing deficient synthesis of alpha or beta globin chain of hemoglobin and compensation by increasing the unaffected chain

Question 23

What does alpha thalassemias cause?

Answer 23

Doesnt really say, but its not as bad as Beta thalassemia

Question 24

What does beta thalassemia cause?

Answer 24

Heinz bodies produced r/t increase alpha chains. The heinz bodies damage the cell and cause lysis

Question 25

What are the two different names of beta thalassemia?

Answer 25

Minor-1 mutations

Major/Cooleys Anemia- 2 Mutations

Question 26

What are the two X linked inherited disorders we discussed?

Answer 26

Chronic granulomatous disease and G6PD

Question 27

What is the most common inherited enzyme deficiency?

Answer 27

G6PD, especially common in African, Middle easter, or south asian decent

Question 28

What can G6PD lead to?

Answer 28

Acute hemolysis when exposed to oxidative stressors like infection or those deadly fava beans

Question 29

What do mitochondrial disorders commonly relate to given their etiology?

Answer 29

Impaired protein synthesis resulting in many different forms of myopathy

Question 30

What causes down syndrome?

Answer 30

Aneuploidy, extra chromosomes
Specifically, it most commonly caused by nondisjunction error in meiosis but can also be due to a translocation event (Robersonian Chromosome)

Question 31

What is Klinefelter a result of?

Answer 31

Extra X, or more, chromosome due to nondisjunction

Question 32

What are the signs and symptoms of Klinefelter?

Answer 32

Increased risk for low bone density, CV and immunological diseases, and psych disorders

It all depends on how many extra X chromosomes there are

Question 33

What is Turner Syndrome due to?

Answer 33

45 chromosomes

Question 34

What are Turner Syndromes signs and symptoms?

Answer 34

Htn, obesity, dyslipidemia, impaired glucose tolerance, insulin resistance, autoimmune disease, CV diseases, hepatic dysfunctions,

Question 35

What is the TMB?

Answer 35

Tumor Mutational Burden

Cancer cells with a higher TMB may be easier to target due to increased neoantigens

Question 36

What are the two viruses mentioned that can promote tumorigenesis?

Answer 36

HCV, HPV