Genetic Diseases and Syndromes Flashcards
(107 cards)
1
Q
What is the most common chromosomal abnormality in live births?
A
Trisomy 21 (Down syndrome).
2
Q
What are the prenatal tests used to screen for Trisomy 21 (Down syndrome)?
A
Quad screen (maternal serum AFP, estriol, hCG, inhibit-alpha). Nuchal translucency
3
Q
What chromosomal abnormalities increase incidence with advancing maternal age?
A
Trisomy 21 (Down syndrome) Age 35 1:400 Age 45 1:35 Trisomy 18 (Edward syndrome) Trisomy 13 (Patau syndrome)
4
Q
Describe Down syndrome.
A
Gamete has two copies of chromosome 21-leads to trisomy when fertilized.
Cause of 95% of Down syndrome cases (4% due to Robertsonian translocation).
Prevelance: 1/500 pregnancies.
Chromosome studies only indicated if trisomy was due to an unbalanced translocation.
5
Q
What is the most common non-lethal trisomy?
A
Down syndrome (trisomy 21).
6
Q
Describe the phenotypic traits of Down syndrome.
A
Intellectual disability Characteristic facial appearance. 40% cardiac defects. 75% hearing loss. >50% visual problems. 7% GI defects. Single transverse palmer crease. Increased social skills in childhood. 1/2 adults with Down syndrome develop Alzheimer disease.
7
Q
What is another name for Trisomy 18.
A
Edwards syndrome
8
Q
What is the popcorn for Edwards syndrome (trisomy 18)?
A
Club foot (rocker bottom feet).
9
Q
What is the second most common autosomal trisomy after trisomy 21 that goes to full term?
A
Trisomy 18 (Edward’s syndrome).
10
Q
Describe trisomy 18 (Edwards syndrome).
A
Usually caused by three copies of chromosome 18, but translocation can occur.
IUGR.
Many die before birth or in first month.
11
Q
What are the characteristics of Trisomy 18 (Edwards syndrome)?
A
Kidney, GI, heart defects. Developmental delay. Club foot (rocker bottom feet). Low set heart, small jaw. 2% 1 year survival rate.
12
Q
What is another name for Trisomy 13?
A
Patau syndrome.
13
Q
What are the characteristics of Trisomy 13 (Patau syndrome)?
A
Severe intellectual disability. Many physical abnormalities. Cleft lip/palate. Seizures. Small jaw. Polydactyly. Heart defects. Brain/spinal cord abnormalities. Many children die within first days or weeks of life.
14
Q
Describe the Etiology of Trisomy 13 (Patau syndrome).
A
Most cases are from three copies of chromosome 13.
Some caused by Robertsonian translocation involving chromosomes 13 and 14 when part of chromosome 13 gets attached to chromosome 14 during formation of gametes. Affected people have 2 normal copies of 13 plus an extra copy attached to another chromosome.
15
Q
Describe Cri-Du-Chat syndrome.
A
deletion of part of short arm of chromosome 5.
Partial monosomy.
Most cases are from spontaneous mutation.
16
Q
Define partial monosomy.
A
when only a portion of a chromosome has one copy instead of two.
17
Q
Describe the characteristics of Cri-Du-Chat syndrome.
A
Cat-like cry of affected children due to abnormal larynx development.
Intellectual disability.
Wide set eyes.
Low ears.
18
Q
How can Cri-Du-Chat syndrome be detected?
A
In utero with CVS.
19
Q
Describe Klinefelter’s Syndrome.
A
Extra X chromosome. 47 total chromosomes. XXY. Occurs at gametogenesis. Accounts for many 1st trimester losses.
20
Q
Describe the characteristics of Klinefelter’s syndrome.
A
Affects male physical and cognitive development.
Physical traits become more apparent after puberty.
Hypogonadism, infertility.
Gynecomastia, reduces hair.
21
Q
What is the most common sex chromosome aneuploidy in males?
A
Klinefelter’s syndrome.
XXY.
22
Q
Describe Turner syndrome.
A
45X, affects development in females.
Monosomy. Only one X.
23
Q
What is the popcorn for Turner syndrome?
A
Gonadal dysgenesis (non-functional ovaries).
24
Q
What are the characteristics of Turner syndrome?
A
Gonadal dysgenesis. Short stature. Broad chest. Webbed neck. Amenorrhea. Infertility. Cardiovascular abnormalities.
25
Describe Huntington's Disease.
Neurodegenerative disease-progressive brain disorder.
Autosomal dominant.
Increased anticipation.
HD gene on chromosome 4 that codes for a protein called huntingtin (CAG trinucleotide repeat). >35 repeats=HD.
Abnormal protein causes microscopic deposits of protein in neurons.
Most often inherited but can occur spontaneously.
26
What are the early signs of Huntington's disease?
Depression
Irritability
Poor coordination
Trouble learning
27
Describe adult onset Huntington's disease.
Genetic defect is latent for 3-5 decades, then manifests as progressive neuronal dysfunction.
28
What are the characteristics of Huntington's disease?
Causes uncontrolled jerky movements (chorea), emotional problems, and loss of thinking ability, changes in personality.
29
What is the average time from symptom onset to death in Huntington's disease?
15 years.
30
What referral should be make for Huntington's patients?
Offspring of HD parents should be offered genetic counseling.
31
What is the only human disorder of complete dominance?
Huntington's disease.
| Heterozygotes are just as affected clinically as homozygotes.
32
Describe Alzheimers disease.
Neurodegenerative disease.
Usually begins after age 60; risk increases with age.
Death usually occurs within 10 years.
People with parent, sibling, or child with AD are at increased risk.
33
What is the most common form of dementia in older individuals?
Alzheimer's disease.
Dementia:
65% from Alzheimer's
35% vascular in nature
34
What is the pathophysiology pf Alzheimer's disease?
Loss of cholinergic neurons in brain (loss of acetylcholine).
Formation of plaques and tangles.
Atrophy of brain.
Resultant effect-blocked communication.
35
Describe the mode of inheritance of Alzheimers disease.
Several gene mutations cause predisposition to AD.
36
What are the clinical manifestations of Alzheimers disease?
Progressive mental deterioration: memory loss, confusion, disorientation.
37
What is the popcorn for Alzheimers disease?
Formation of plaques and tangles in the brain.
38
What are the 2 forms of Alzheimers disease?
Familial (early onset).
| Sporadic (late onset).
39
Describe familial Alzheimer's disease (early onset AD).
Many members of multiple generations affected.
Symptoms start before age 65.
Mutations on chromosomes 1, 14, or 21.
Induced formation of a sticky protein that forms clumps in the brain.
Rare- <5% of cases of AD.
Autosomal dominant: 50% of inheritance.
40
Describe sporadic Alzheimers disease (late onset).
Usually develops after 65.
Accounts for most cases of AD.
One gene has been shown to increase risk: chromosome 19 apolipoprotein E (APOE) gene.
Not everyone carrying the gene develops disease.
41
What is a definitive diagnosis for Alzheimers disease?
Autopsy-plaques and tangles.
42
What are the risk factors for hereditary breast and ovarian cancer syndrome?
Gender
Age
Family history
43
What is the mode of inheritance for hereditary breast and ovarian cancer syndrome?
Up to 10% of breast and ovarian cancers are caused by known predisposing genetic factors.
44
What are the clinical manifestations for hereditary breast and ovarian cancer syndrome?
Early age of breast cancer onset (<50).
FH of both breast and ovarian cancer.
Increased bilateral cancers.
Increased development of both cancers in same person.
Increased incidence of prostate cancer in family.
Male breast cancer.
45
What are the 2 major cancer susceptibility genes for hereditary breast and ovarian cancer syndrome?
BRCA 1 and BRCA 2.
They are tumor suppressor genes and control cell growth and death, and DNA repair and stability.
One mutation of either gene and their cancer risk goes up.
46
Describe the first gene associated with breast cancer.
BRCA 1 on chromosome 17.
Mutation is inherited in autosomal dominant manner.
Not all families with this gene get hereditary breast cancer.
47
Describe the second gene associated with breast cancer.
BRCA 2 on chromosome 13.
Mutation is inherited in autosomal dominant manner. Associated with male breast cancer, ovarian cancer, prostate cancer, and pancreatic cancer.
48
Explain genetic testing in relation to hereditary breast and ovarian cancer syndrome.
Preferred to first test an individual who is affected by cancer before testing unaffected family members.
Helps to identify whether a detectable BRCA1 or BRCA2 mutation could be responsible for the cancer.
An individual can inherit a BRCA1 or 2 mutation yet never develop cancer.
49
Describe colorectal cancer.
Results from the interaction of both genetic and environmental factors.
Genetic predisposition is the main risk factor in only a small portion of people.
May occur sporadically or from familial inheritance.
Most are sporadic/random.
Many cancer syndromes include colon cancer.
50
What are the risk factors for colorectal cancer?
Diet, exercise, smoking, obesity are strong risk factors in most people.
51
What are the types of colon cancer?
Familial colorectal cancer.
Hereditary colorectal cancer syndromes: arise from specific mutations in genes that code for susceptibility to cancer. FAP <1%
Lynch syndrome 2-3%.
52
Describe familial colorectal cancers.
Patterns within a family that exist without identifying a specific mutation.
A FH of one or more people with colorectal cancer or premalignant polyps is considered a positive FH.
May be due to:
Chance, shared exposure to carcinogen or diet/lifestyle, combination of mutations and environmental factors.
53
What is the pattern of inheritance for familial adenomatous polyposis (FAP)?
Autosomal dominant:
| 50% chance of passing it to each offspring.
54
Describe familial adenomatous polyposis.
Mutation in APC (adenomatous polyposis coli) gene on chromosome 5. Tumor supressor gene.
55
What are the clinical manifestations of familial adenomatous polyposis?
Hundreds to thousands of polyps in colon beginning in adolescence.
Cancers develop in 20's.
Risk of developing colorectal cancer is near 100%, usually before 50.
Time from polyp to cancer development is 10+ years.
56
What is the treatment for FAP once diagnosis is established.
Total colectomy is recommended before age 20.
57
When considering familial adenomatous polyposis, who would get genetic counseling and testing?
Should be offered to all patients with a suspected diagnosis of FAP as identifies by colonoscopy.
Should be offered to all relatives at risk.
Children of patient with FAP should have genetic screening by age 10.
58
What is another name for hereditary nonpolyposis colorectal cancer (HNPCC)?
Lynch syndrome.
59
What is the pattern of inheritance of hereditary nonpolyposis colorectal cancer?
Autosomal dominant.
60
Describe hereditary nonpolyposis colorectal cancer.
A mutation in one of many genes that code for DNA repair.
More rapid transition from adenoma to cancer than FAP.
Cancers occur earlier 30s and 40s.
50% chance of cancer in women, 70% in men.
61
What cancers are also associated with HNPCC?
Uterus, ovaries, stomach, urinary tract, small bowel. bile ducts.
62
What is the difference between hereditary nonpolyposis colorectal cancer and FAP?
HNPCC: colorectal cancer can occur when a small number or no polyps are present.
FAP: thousands of polyps develop.
63
What is the maintenance if genetic testing reveals a HNPCC gene mutation?
Regular colonoscopy starting age 25 for relatives or beginning 5 years younger than the age of diagnosis of the youngest affected family member.
Upper endoscopy every 2 years to screen for gastric cancer.
Screening for endometrial and ovarian cancer in women at age 25-35.
64
Describe chronic myelogenous leukemia.
A myeloproliferative disorder.
Translocation between chromosomes 9 and 22.
Philadelphia chromosome (22). Produces a protein that codes for an enzyme that causes too many stem cells to develop into WBCs.
65
What is a popcorn for chronic myelogenous leukemia?
Philadelphia chromosome (22).
66
What is the population for chronic myelogenous leukemia?
More common in men.
| Median age at presentation is 55 years.
67
What is the pathophysiology for chronic myelogenous leukemia?
Increased production of abnormal WBCs that are nonfunctional. These large numbers take up bone marrow space meant for healthy WBCs, RBCs, and platelets.
68
What is the clinical presentation for chronic myelogenous leukemia?
Insidious onset, slow progression over months to years of infections, anemia, bleeding.
Fever, night sweats, fatigue.
69
How is chronic myelogenous leukemia diagnosed?
Upon bone marrow aspiration for karyotype.
70
Describe hemophilia.
Mutation on F8 or F9 genes, located on the X chromosome.
F8 mutation: factor VIII deficiency (more common, hemophilia A).
F9 mutation: factor IX deficiency (hemophilia B, Christmas disease).
Bleeding disorders caused by mutations in genes that code for coagulation proteins.
71
What is the pattern of inheritance for hemophilia?
x-linked recessive.
Genes associated are on the X chromosome.
Most people affected are males.
72
What are the clinical manifestations of hemophilia?
hemarthroses (spontaneous bleeding into a joint).
Bleeding into muscles/other tissues; prolonged bleeding or oozing of blood after injury/surgery.
Severity can vary.
73
What is a popcorn for hemophilia?
hemarthroses (spontaneous bleeding into a joint).
74
What is the pathophysiology for sickle cell disease?
Atypical hemoglobin molecules (Hemoglobin S).
Distorts the red blood cell into a crescent shape.
Abnormally shaped RBCs break down prematurely.
Mutation on the HBB gene.
75
What are the clinical manifestations of sickle cell disease?
Anemia, infections, episodic pain, SOB, fatigue, delayed growth.
76
What is the pattern of inheritance for sickle cell disease?
Autosomal recessive.
Most common in people whose ancestors came from Greece, Africa, Turkey, Italy, Arabian Peninsula, India, South America, Central America, Caribbean.
77
What is the pattern of inheritance for cystic fibrosis?
Autosomal recessive.
78
Describe cystic fibrosis.
Mutation in the CFTR gene (cystic fibrosis transmembrane conductance regulator). Codes for protein that regulates chloride channels in epithelial cells.
When mutated, a defective protein is made, causing a disruption of chloride and water transport- water balance in secretions is disrupted.
79
What are the clinical manifestations of cystic fibrosis?
```
Thick sticky mucous obstructing airways in lungs and ducts in pancreas.
Difficulty breathing, lung infections, chronic sinus infections, nutrient digestion (buildup of mucous prevents pancreatic enzymes from reaching intestine).
FTT, poor growth rate.
Meconium Ileus (newborn intestinal obstruction due to thick fecal waste products.
Can affect pancreas, intestines, GU tract, hepatobiliary system, exocrine glands.
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80
What is a popcorn for cystic fibrosis?
Meconium ileus: newborns intestinal obstructions due to thick fecal waste.
81
What is the most common cause of morbidity associated with CF?
Pulmonary disease.
| Pulmonary system can't defend against pathogens well-leads to sinusitis and bronchitis.
82
What abnormal organisms cause infections in CF patients?
S. aureus.
P. aeruginosa
Aspergillus.
83
Additional info about cystic fibrosis.
Common genetic disease in the white population in the US.
Carrier incidence: 1 in 25
Disease incidence: 1 in 3500 white newborns
Most cases diagnosed by age 1.
84
What is the primary test for cystic fibrosis diagnosis?
Sweat chloride test.
Defective chloride channel doesn't allow chloride to be reabsorbed.
Concentration of chloride in sweat is elevated in CF.
Genetic testing used to confirm results.
85
What is the mode of inheritance for Marfan syndrome?
Autosomal dominant.
86
Describe Marfan syndrome.
Either an inherited or new mutation to the fibrillin-1 gene (FBN1).
Defects in connective tissue affecting multiple systems.
Bones, ligaments, muscles, blood vessels, heart valves.
87
What are the clinical manifestations of Marfan syndrome?
```
Tall stature.
Long, thin arms and legs.
Arm span wider than body height.
Long, narrow face.
High arched palate.
Overcrowded teeth.
Scoliosis.
Hyperflexible joints.
Chest deformities.
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88
What is the popcorn for Marfan syndrome?
Tall stature, long, thin arms and legs, arm span wider than body height.
89
What are the key primary features of Marfan syndrome?
Dislocated lens of the eye (vision problems).
| Aortic aneurysm/dissection.
90
What is the major cause of morbidity and mortality in Marfan syndrome?
Heart defects.
Affected individuals are advised to avoid contact sports, caffeine, and decongestants due to increased stress placed on CV system.
91
What is another name for Neurofibromatosis Type 1?
Recklinghausen disease.
92
What is the pattern of inheritance for neurofibromatosis type 1?
autosomal dominant.
93
Describe Neurofibromatosis type 1 (recklinghausen disease).
Mutation on NF1 gene of chromosome 17. Tumor suppressor gene.
Results in neurofibromas; benign tumors that grow on nerves of skin and brains and changes in skin pigmentation (darker).
94
What are the clinical manifestations for NF-1 gene mutations of neurofibromatosis type 1?
Subcutaneous tumors.
Hyperpigmented skin lesions called cafe-au-lait spots.
Lisch nodules in iris.
Freckles in axillae and groin.
95
What is a popcorn for neurofibromatosis type 1?
axillary or inguinal freckling (Crowe sign).
96
What are the diagnostic features of neurofibromatosis type 1?
```
large cafe-au-lait spots.
neurofibromas.
axillary or inguinal freckling (Crowe sign).
Optic glioma.
Lisch nodules.
1st degree relatives with NF1.
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97
What is the pathophysiology for polycystic kidney disease?
Clusters of fluid filled sacs develop in kidneys.
Affects ability to filter the blood properly.
Kidneys become enlarged and can fail.
98
What are the clinical manifestations of polycystic kidney disease?
```
Hypertension.
Back pain.
Hematuria.
UTI.
Kidney stones.
Others: liver cysts, heart valve abnormalities, increased risk of aortic aneurysm and brain aneurysm.
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99
What are the two forms of polycystic kidney disease?
Autosomal dominant: sx start in adulthood. usually inherited. PKD1 and PKD2 genes.
Autosomal recessive: rare, lethal early in life. PKHD1 gene.
100
Describe congenital abnormalities.
Approximately 10% of all newborns have some birth defect. Ranges from minor biochemical problem to sever physical deformity.
Caused by variety of biochemical, chemical, and physical agents.
Contributors: mutant genes, chromosomal defects, multifactorial components.
101
What is the biggest cause of birth defects?
unknown etiology.
102
Define teratology.
study of abnormal development.
Teratogens: anything capable of disrupting embryonic or fetal development and producing malformation.
Timing of exposure determine which systems are affected.
103
Critical period for teratogenic effects is?
3-16 weeks.
104
What is newborn screening?
Biochemical analysis that determines whether certain proteins (enzymes) are present/absent.
Typically autosomal recessive conditions.
Referred to as "inborn errors of metabolism" cause genetically mediated and involved in metabolism.
105
For newborn screening, how many tests are there and when are they?
2 tests.
1st test: baby is 24-36 hours old.
2nd test: 1st office visit, between 5-10 days old.
106
Describe genetic counselors.
Master's trained health care professionals. Employed by physician offices, medical centers, advocacy organizations, governmental agencies, public health departments, biotech companies.
107
Define medical geneticist.
Clinical genetics specialist. Practice of clinical medicine with regard to hereditary disorders.
Recognized by the American Board of Medical Specialties.
Residencies in clinical genetics are accredited.
Applicants must be MD or DO who has already completed 24 months of another residency.
