Genetic Diseases Flashcards
1
Q
Down Syndrome
A
- Trisomy 21
- Increased incidence with advanced maternal age
- Gamete has two copies of chromosome 21 when it’s fertilized
2
Q
What is the most common chromosomal abnormality in live births?
A
Down syndrome/trisomy 21
3
Q
Characteristics of Down Syndrome
A
- Intellectual disability
- Characteristic facies
- Cardiac defects
- Hearing loss
- Visual problems
- 50% develop Alzheimer’s
4
Q
Edward Syndrome
A
- Trisomy 18
- Either 3 copies of 18 or translocation
- Most die before or shortly after birth
5
Q
What is the second most common autosomal trisomy after trisomy 21 that goes to full term?
A
Edwards syndrome/trisomy 18
6
Q
Characteristics of Edwards syndrome/trisomy 18
A
- Club foot (rocker bottom feet)
- Kidney and heart defects
- developmental delay
- Low set ears
- Small jaw
7
Q
Trisomy 13
A
-Patau syndrome
8
Q
Characteristics of Trisomy 13/Patau syndrome
A
- Cleft lift or palate
- Severe intellectual disabilities
- Seizures
- Many die within the first days or weeks
9
Q
Cri-du-chat Syndrome
A
- Deletion of part of the short arm (p) of chromosome 5
- Cat-like cry due to abnormal larynx development
- Intellectual disability, wide set eyes, low ears
10
Q
Klinefelter Syndrome
A
- 47 XXY
- Affects male physical and cognitive development
- Hypogonadism and infertility
- Gynecomastia and reduced body hair
11
Q
What is the most common sex chromosome aneuploidy in males?
A
Klinefelter syndrome (XXY, 47)
12
Q
Turner Syndrome
A
- 45 X
- affects development in females
- Nonfunctional ovaries
- Short stature
- Broad chest
- Amenorrhea and infertility
13
Q
Huntington’s disease
A
- Progressive neurodegenerative disease
- Autosomal dominant
- Main symptom: chorea
- Uncontrolled movements, emotional problems, loss of thinking ability
14
Q
What is the Huntington’s genetic defect?
A
HD gene on chromosome 4 that codes for the protein huntingtin
- CAG trinucleotide repeat (36-120 repeats)
- more repeats = worse disease
15
Q
What is the only human disorder of complete dominance?
A
Huntington’s
16
Q
Alzheimer’s disease
A
- neurodegenerative dx
- most common form of dementia
- occurs in older patients
- those with a 1st degree relative are at increased risk
17
Q
What is the pathophysiologic response in Alzheimers?
A
- loss of cholinergic neurons in brain (loss of ACh)
- formation of plaques and tangles in the brain
- atrophy of brain
18
Q
Two forms of Alzheimers genes:
A
- familial (early onset)
- sporadic (late onset)
19
Q
Familial Alzheimer’s disease
A
- early onset AD
- symptoms start before age 65
- mutations on chromosomes 1, 14, or 21
- Rare
- Autosomal dominant
20
Q
What chromosomes are affected in familial Alzheimer’s disease patients?
A
1, 14, 21
21
Q
What mode of inheritance is familial Alzheimer’s disease?
A
Autosomal dominant
22
Q
Gene for increased risk of sporadic Alzheimer’s disease
A
Chromosome 19 apolipoprotein E (APOE)
23
Q
Two major genes in hereditary breast and ovarian cancer syndrome
A
BRCA1
BRCA2
(mutated cancer suppressor genes)
24
Q
Chromosome associated with BRCA1
A
Chromosome 17
25
Chromosome associated with BRCA2
Chromosome 13
26
What inheritance pattern do BRCA1/BRCA2 follow?
Autosomal dominant
27
Which BRCA gene is associated with male breast cancer, ovarian cancer, prostate cancer, and pancreatic cancer?
BRCA2
28
Does the presence of BRCA1/BRCA2 guarantee an individual will have cancer?
No
29
What are the strongest risk factor for colorectal cancer?
Diet, exercise, smoking, and obesity.
| Genetic predisposition is the main risk factor in only a small proportion.
30
Patterns of colorectal cancer in a family that exist without a specific mutation are called ____________.
familial CRC
31
Familial Adenomatous Polyposis (FAP)
- <1% of CRC cases
- Autosomal dominant
- Mutation in the adenomatous polyposis coli gene
- Hundreds to thousands of polpys in colon beginning in adolescence
- Cancer in 20's
- Risk of CRC is nearly 100% before 50 yo
32
The gene responsible for familial adenomatous polyposis:
APC (tumor suppressor gene) on chromosome 5
33
Children of patients with FAP should have genetic screening by age ___.
10 yo
34
Once diagnosis of FAP is established, total colectomy is recommended before ___ years old.
20
35
Hereditary nonpolyposis colorectal cancer (HNPCC)
- aka Lynch Syndrome
- 2-3% of all CRCs
- Autosomal dominant
- Cancer occurs in the 30's and 40's
36
Chronic myelogenous leukemia (CML) genetic defect
translocation 9;22 (Philadelphia chromosome)
37
CML characteristics
- More common in men
- Presentation in mid-50's
- Philadelphia chromosome t(9;22)
38
Bleeding disorders caused by mutations in genes that code for coagulation proteins
Hemophilia
39
Genetic defect in hemophilia
mutation on F8 or F9 genes on the X chromosome
40
Hemophilia A
- Factor VIII deficiency
| - More common
41
Hemophilia B
- Factor IX deficiency
- Christmas disease
- less common than hemophilia A/VIII
42
Hemophilia pattern of inheritance
X-linked recessive
| -men mostly affected
43
Sickle Cell Disease
- hemoglobin S
- distorts the RBC into crescent shapes, which breaks them down prematurely
- Anemia, infections, pain, SOB, fatigue
44
Genetic mutation in sickle cell disease
- HBB gene mutation
| - Hemoglobin S
45
Inheritance pattern for Sickle Cell disease
autosomal recessive
46
Inheritance pattern for cystic fibrosis
autosomal recessive
47
What is the genetic mutation for CF?
mutation in the CFTR gene
48
What does the CFTR gene do?
Codes for a protein that regulates chloride channels in epithelial cells
49
What is the hallmark clinical manifestation in CF patients?
Thick, sticky mucous obstructing airways in lungs and pancreatic ducts
50
What is the most common cause of morbidity associated with CF?
pulmonary disease - obstruction and bacterial infections
51
What is the primary test for diagnosis of CF?
sweat chloride test (positive result is an elevated concentration of chloride in sweat)
52
What is the inheritance mechanism for Marfan syndrome?
Autosomal dominant
53
What is the gene affected by an inherited or new mutation in Marfan syndrome?
Fibrillin-1 gene (FBN1)
54
What genetic disease causes defects in connective tissue affecting multiple systems?
Marfan Syndrome
55
What are the clinical manifestations of Marfan Syndrome?
- Tall
- Long thin arms and legs
- Arm span wider than body height
- Long, narrow face
- High, arched palate
- Scoliosis
- Hyperflexible joints
- Chest deformities
56
What are the two key primary features of Marfan syndrome?
Dislocated lens of the eye
| Aortic aneurysm/dissection
57
What are the major cause of morbidity and mortality in people with Marfan syndrome?
heart defects
58
Neurofibromatosis Type I aka
von Recklinghausen disease
59
What is the genetic mutation in neurofibromatosis type I?
NF1 gene on chromosome 17
60
What disease results in neurofibromas (benign tumors that grow on the nerves of skin and brain)?
neurofibromatosis type I
61
What are the main clinical features of NF-1?
- Subcutaneous tumors
- Cafe-au-lait spots
- Lisch nodules in iris
- Freckles in axillae and groin (Crowe sign)
62
What genetic disease causes clusters of fluid-filled sacs to develop in the kidneys?
Polycystic kidney disease
63
What are the two forms of polycystic kidney disease?
Autosomal dominant (PKD1 and PKD2)
Autosomal recessive (PKHD1)
64
What form of polycystic kidney disease is rarer and more lethal?
autosomal recessive (PKHD1)
65
What percentage of newborns have some birth defect?
10%
66
What is the biggest cause of birth defects?
Unknown etiology
67
What is the study of abnormal fetal development?
teratology
68
What is the critical period for teratogenic effects?
3-16 weeks gestation
