Chapter 6 - Genetic Diseases Flashcards
1
Q
Most common chromosomal disorder
A
Down Syndrome
2
Q
Down Syndrome is caused by…
A
Meiotic nondisjunction (95%)
Robertsonian translocation (4%)
Mosaicism due to mitotic nondisjunction during embryogenesis (1%)
3
Q
Down Syndrome: presentation (not obvious)
A
Brushfield spots (speckled appearance of the iris)
Hypotonia
Broad short neck
Palmar (simian)
crease
Congenital heart defects.
4
Q
Down Syndrome: Endocardial cushion defect, if present, leads to…
A
Atrioventricular canal (connection between all 4 heart chambers)
5
Q
Down Syndrome: Additional clinical problems
A
Duodenal atresia
Hirschsprung disease
Increased risk of acute lymphoblastic leukemia (ALL) and Alzheimer disease
6
Q
Down Syndrome: median life expectancy
A
47 years
7
Q
Edwards Syndrome is the trisomy of chromosome… and is caused by…
A
18
nondisjunction
8
Q
Edwards Syndrome: specific characteristics
A
Overlapping flexed fingers
Rocker-bottom feet
9
Q
Patau Syndrome is the trisomy of chromosome… and is caused by…
A
13
nondisjunction
10
Q
Patau Syndrome: specific characteristics
A
Microcephaly
Microphthalmia
Holoprosencephaly
Polydactyly
11
Q
Cri du chat Syndrome is due to deletion of the…
A
Short arm of chromosome 5
12
Q
Cri du chat Syndrome: specific characteristic
A
High-pitched catlike cry
13
Q
Cri du chat Syndrome: microdeletions include…
A
13q14 (retinoblastoma gene)
11p13 (WAGR complex [Wilms tumor, aniridia, genitourinary anomalies])
14
Q
Microdeletions require…to be detected
A
Molecular techniques
15
Q
Klinefelter syndrome is caused by … and is a common cause of …
A
Meiotic nondisjunction
Male hypogonadism
16
Q
Klinefelter syndrome: karyotype
A
47, XXY
17
Q
Klinefelter syndrome: hormones findings
A
↑ FSH and LH
↓ Testosterone
18
Q
Klinefelter syndrome: 3 characteristics
A
Testicular atrophy
High-pitched voice
Gynecomastia
19
Q
Turner syndrome is a common cause of … The most common karyotype is …
A
Female hypogonadism
45, XO
20
Q
Turner syndrome: 4 characteristics
A
Fail to develop secondary sex characteristics
Short stature
Widely spaced nipples
Atrophic streak ovaries
21
Q
Turner syndrome: 4 clinical features
A
Cystic hygroma
Hypothyroidism
Preductal coarctation of the aorta and bicuspid aortic valve
Hydrops fetalis
22
Q
Turner syndrome: females with 45,X/46,XY mosaicism are at risk for
A
Gonadoblastoma
23
Q
In Turner syndrome, there is no…
A
Barr body
24
Q
True hermaphrodite: genetic sex possibilities
A
46 XX, 46 XY, 45 X/XY (mosaics)
25
True hermaphrodite: gonadal sex possibilities
Ovary on one side and testes on the other
Ovotestes: a gonad with both testicular and ovarian tissue
26
Female pseudohermaphroditism: genetic sex:
46 XX
27
Female pseudohermaphroditism: gonadal and ductal sex:
normal female organs
28
Female pseudohermaphroditism: phenotypic sex:
Ambiguous or virilized external genitalia
29
Female pseudohermaphroditism: is caused by
Exposure of a female fetus to androgens in utero:
-congenital adrenal hyperplasia
-androgen-producing tumors (ovarian sertoli-leydig
cell tumor)
-exogenous androgens
30
Male pseudohermaphroditism: genetic sex:
46, XY
31
Male pseudohermaphroditism: gonadal and ductal sex:
Testes present
32
Male pseudohermaphroditism: phenotypic sex:
Ambiguous or female genitalia
33
Male pseudohermaphroditism: most common cause
Testicular feminization (complete androgen insensitivity syndrome)
34
Testicular feminization: genetic defect
Mutation of the androgen receptor (Xq11-12)
35
Mendelian disorders are characterized by
Single gene mutations
36
Mendelian disorders include
Point and frameshift mutations
37
Point mutations occur with a...
Single nucleotide base substitution
38
Frameshift mutations occur when ... of bases leads to a shift in the reading frame of the gene.
insertion or deletion
39
Autosomal recessive diseases: onset
Early
40
Autosomal dominant diseases: onset
Varies
41
Autosomal recessive diseases: usually affects...
Enzyme protein
42
Autosomal dominant diseases: usually afects...
Structural protein or receptor
43
Most common lethal genetic disorder in Caucasians
Cystic fibrosis
44
Cystic fibrosis is due to mutation of the...
Chloride channel protein CFTR (Cystic fibrosis transmembrane conductance regulator).
45
Location of CFTR (cystic fibrosis transmembrane conductance regulator) gene
Chromosome 7
46
In Cystic Fibrosis, CFTR gene most commonly has been damaged by a deletion of the...
Amino acid phenylalanine at position 508 (ΔF508)
47
Cystic Fibrosis manifestations: lungs
Recurrent infections
Chronic bronchitis
Bronchiectasis
48
Cystic Fibrosis manifestations: pancreas
Atrophy, fibrosis and pancreatic insufficiency
49
Cystic fibrosis: pancreatic insufficiency consequences
fat malabsorption, steatorrhea, and deficiency of fat-soluble vitamins
50
Cystic Fibrosis manifestations: male reproductive system
Absence or obstruction of the vas deferens and epididymis - infertility
51
Cystic Fibrosis manifestations: liver
Biliary cirrhosis
52
Cystic Fibrosis manifestations: small intestines
Obstruction (meconium ileus)
53
Cystic Fibrosis: diagnosis
Sweat test (elevated NaCl) or DNA probes
54
Cystic Fibrosis: 3 most common pulmonary infections
S. aureus, H. influenzae and P. aeruginosa
55
Phenylketonuria (PKU) is a deficiency of ... , resulting in toxic levels of phenylalanine and a lack of ...
Phenylalanine hydroxylase
Tyrosine
56
Phenylketonuria (PKU): clinical onset
Intellectual development disorder with 6 months
57
Phenylketonuria (PKU): the lack of tyrosine causes
Light-colored skin and hair
58
Mousy or musty odor to the sweat and urine secondary to metabolite [...] accumulation is seen in...
Phenylacetate
Phenylketonuria (PKU)
59
Phenylketonuria (PKU): treatment
Restriction of phenylalanine
Avoid aspartame!
60
Alkaptonuria (ochronosis): deficiency of ... results in the accumulation of ...
Homogentisic acid oxidase
Homogentisic acid
61
Alkaptonuria (ochronosis): presentation
Urine that turns black upon standing
Black-stained cartilage - discoloration of the nose and ears
Early degenerative arthritis
62
Albinism is caused by a lack of...
Tyrosinase
63
Albinism increases the risk of...
Basal and squamous cell carcinomas
64
Glycogen storage diseases: concept
deficiencies of one of the enzymes of glycogen metabolism
→ glycogen accumulates in liver, heart, and skeletal muscle.
65
Glycogen storage diseases: Type I - deficiency and symptoms
von Gierke disease: glucose-6-phosphatase
Hepatomegaly and hypoglycemia.
66
Glycogen storage diseases: Type II - deficiency and symptoms
Pompe disease: lysosomal α-1,4-glucosidase (acid maltase)
Hepatomegaly, hypotonia, cardiomegaly, and death from cardiac failure in 2 years.
67
Glycogen storage diseases: Type V - deficiency and symptoms
McArdle syndrome: muscle glycogen phosphorylase
Exercise-induced muscle cramps
68
Tay-Sachs disease is a deficiency of
Hexosaminidase A (due to mutation of HEXA gene on chromosome 15)
69
Tay-Sachs disease leads to accumulation of...
GM2 ganglioside in the lysosomes of the CNS and retina.
70
Tay-Sachs disease is common in
Ashkenazi Jews
71
Tay-Sachs disease: clinical findings
Cherry-red spots in the retina due to accentuation of the macula
Dilated neurons with cytoplasmic vacuoles
72
Tay-Sachs disease: presentation
6 months: progressive mental deterioration and motor incoordination
2-3 years: death
73
Tay-Sachs disease: Electron microscopy shows...
distended lysosomes with whorled membranes
74
Tay-Sachs disease: diagnosis
Enzyme assays and DNA probes
75
Niemann-Pick disease is caused by a deficiency of
Sphingomyelinase
76
Niemann-Pick disease leads to the accumulation of
Sphingomyelin in lysosomes of CNS and reticuloendothelial system (monocytes and macrophages)
77
Niemann-Pick disease is common in
Ashkenazi Jews
78
Zebra bodies: concept
concentric lamellated inclusions seen in the cytoplasm on electron microscopy.
79
Zebra bodies are present in:
Niemann-Pick disease, Fabry disease and Hurler syndrome
80
Niemann-Pick disease: presentation
Massive splenomegaly and lymphadenopathy
Progressive mental and motor manifestations
81
Niemann-Pick disease: onset of symptoms
6 months
82
Niemann-Pick disease, like Tay-Sachs disease, affects the retina and CNS, but also...
Reticuloendothelial system
83
Niemann-Pick disease type C: a defect in ... causes ...
Cholesterol transport
Ataxia, dysarthria, and learning difficulties.
84
Niemann-Pick disease: most common type
C
85
In Niemann-Pick types A and B, there is a mutation affecting an...
Enzyme that metabolizes lipids
86
T or F?
All forms of Niemann-Pick disease is lethal
True
87
Most common lysosomal storage disorder:
Gaucher disease
88
Gaucher disease is a deficiency of:
Glucocerebrosidase
89
Gaucher disease: glucocerebroside accumulates predominantly in the...
Lysosomes of the reticuloendothelial system
90
Gaucher disease: Type I represents 99% of cases and presents in adulthood with...
Hepatosplenomegaly;
thrombocytopenia/pancytopenia
lymphadenopathy
and bone marrow involvement that may lead to bone pain, deformities, and fractures.
91
Gaucher disease: Central nervous system manifestations occur in types...
II and III
92
Gaucher cells: concept
Enlarged macrophages with a fibrillary (tissue paper–like) cytoplasm
93
Mucopolysaccharidosis (MPS): concept
Deficiencies in lysosomal enzymes that degrades mucopolysaccharides (glycosaminoglycans).
94
Mucopolysaccharidosis (MPS): clinical features
Cloudy cornea
Hepatosplenomegaly
Skeletal deformities
Coarse facial features
Cardiac lesions
95
MPS I: is a deficiency of ... and is the ... form
α-L-iduronidase
severe
96
MPS I is also called...
Hurler syndrome
97
MPS II is also called...
Hunter syndrome
98
MPS II: inheritance
X-linked recessive
99
MPS II is a deficiency of
L-iduronate sulfatase
100
Most common inherited disorder
Familial hypercholesterolemia
101
Familial hypercholesterolemia is due to a mutation in...
LDL receptor gene (LDLR) on chromosome 19
102
Familial hypercholesterolemia: mutations in the LDLR gene causes...
Increased levels of circulating cholesterol
Loss of feedback inhibition of HMG-CoA reductase
Increased phagocytosis of LDL by macrophages
103
Familial hypercholesterolemia: Class I defect
No LDL receptor synthesis
104
Familial hypercholesterolemia: Class II defect
Transport out of the endoplasmic reticulum
105
Familial hypercholesterolemia: Class III defect
LDL receptor binding
106
Familial hypercholesterolemia: Class IV defect
Ability to internalize bound LDL
107
Familial hypercholesterolemia: Class V defect
Recycling of the LDL receptor
108
Familial hypercholesterolemia: clinical features
Elevated serum cholesterol
Skin xanthomas (collections of lipid-laden macrophages)
Xanthelasma around the eyes
Premature atherosclerosis
109
Marfan syndrome is due to a mutation of the
Fibrillin gene (FBN1) on chromosome 15q21
110
Marfan syndrome: skeletal changes
Hyperextensible joints
Pectus excavatum and pectus carinatum
Ectopia lentis (bilateral subluxation of the lens)
111
Marfan syndrome: process that leads to the cardiovascular complications
Cystic medial degeneration of the media of elastic arteries with a loss of elastic fibers and smooth muscle cells
112
Marfan syndrome: cardiovascular complications
Dissecting aortic aneurysm
Aortic valve insufficiency and/or mitral valve prolapse.
113
Ehlers-Danlos syndrome (EDS) is a group of inherited connective tissue diseases that have in common a...
Defect in collagen structure or synthesis.
114
Ehlers-Danlos syndrome (EDS): clinical features
Hyperextensible skin that is easily traumatized and hyperextensible joints
115
Ehlers-Danlos syndrome (EDS): complications
Poor wound healind
Joint dislocations
Diaphragmtaic hernias (EDS Type 1)
Retinal detachment and kyphoscoliosis (type 6)
Arterial or colonic rupture (type 4)
116
EDS: AD types
3, 4 and 6
117
EDS: most common type
3
118
EDS Type 4: defect is in
Type III collagen gene
119
EDS Type 6: defect is in
Lysyl hydroxylase gene
120
EDS Type 9: inheritance
XLR
121
EDS Type 9: defect is in
Copper metabolism
122
Neurofibromatosis Type 1 is also known as...
(von Recklinghausen disease)
123
Neurofibromatosis Type 1 is due to a mutation of the...
Tumor suppressor gene NF1 located on chromosome 17 (17q11.2)
124
The gene NF1 (mutated in Neurofibromatosis Type 1) normally inhibits...
p21 ras oncoprotein
125
Neurofibromatosis Type 1: presentation
Multiple neurofibromas
Benign tumors of peripheral nerves
Pigmented skin lesions (6 or more “cafe- au-lait spots”)
Pigmented iris hamartomas (Lisch nodules)
126
Neurofibromatosis Type 1 increases the risk of
Meningiomas
Pheochromocytoma
Adrenal tumor
127
Neurofibromatosis Type 2 (bilateral acoustic): there is a mutated...
Tumor suppressor gene NF-2 (22q12.2) on chromosome 22
128
Neurofibromatosis Type 2 (bilateral acoustic): clinical features
Vestibular schwannomas (acoustic neuromas)
Increased risk of meningioma and ependymoma
129
von Hippel-Lindau disease is due to a mutation of the...
Tumor suppressor gene VHL on chromosome 3p (3p26-p25)
130
The gene suppressed in von Hippel-Lindau disease encodes a protein which function is...
To tag proteins with ubiquitin for degradation
131
von Hippel-Lindau disease: clinical manifestations
Hemangioblastomas of the retina, cerebellum, brain stem, and spinal cord
Cysts of the liver, pancreas, and kidneys
Multiple bilateral renal cell carcinomas
132
Lesch-Nyhan syndrome results from deficiency of ... which impairs ...
Hypoxanthine-guanine phosphoribosyl transferase (HGPRT)
Salvaging of hypoxanthine and guanine
133
Lesch-Nyhan syndrome: clinical features
Intellectual disability
Hyperuricemia
Self-mutilation
134
In Menkes disease, a mutation of the ... impairs ...
ATP7A gene
copper distribution
135
Example of X-dominant disease
Alport syndrome
136
Alport syndrome: clinical features
Hereditary glomerulonephritis
Nerve deafness
137
Triplet repeat mutations
Fragile X syndrome
Huntington disease
138
Fragile X syndrome: the nucleotide sequence ... repeats typically hundreds to thousands of times.
CGG
139
Fragile X syndrome: the mutation occurs in the ... on the
FMR-1 gene
X chromosome (Xq27.3)
140
Fragile X syndrome: characteristic phenotype
Elongated face with a large jaw, large everted ears, and macroorchidism
141
Huntington disease is due to the triplet repeat mutation (...)
CAG
142
Huntington disease envolves production of an abnormal protein that is...
Neurotoxic and causes atrophy of the caudate nucleus
143
Huntington disease: age of onset
20-50 years
144
Huntington disease: presentation
Progressive dementia with choreiform movements
145
Prader-Willi syndrome is due to a ... on ...
Microdeletion
Paternal chromosome 15
146
Prader-Willi syndrome: presentations
Intellectual disability, obesity, hypogonadism, and hypotonia
147
Angelman syndrome is due to a ... on ...
Microdeletion
Maternal chromosome 15
148
Angelman syndrome: presentation
Intellectual disability, seizures, ataxia, and inappropriate laughter
149
In mitochondrial disorders, the inhiretance is only from...
Mother
150
Leber hereditary optic neuropathy causes...
Loss of retinal cells, which leads to central vision loss.
151
Myoclonic epilepsy with ragged red fibers (MERRF) is a mitochondrial disorder characterized by...
Epilepsy, ataxia, peripheral neuropathy and deterioration in cognitive ability
152
Myoclonic epilepsy with ragged red fibers (MERRF): phenotypic
Short stature and cardiomyopathy
153
Myoclonic epilepsy with ragged red fibers (MERRF): muscle biopsy finding
Ragged red fibers
154
MULTIFACTORIAL INHERITANCE: examples
Open neural tube defects and DM2
