VII - Genetic and Pediatric Diseases Flashcards
1
Q
These disorders are derived from one’s parents, transmitted through gametes through the generations, and are therefore familial.
A
Hereditary disorders(TOPNOTCH)
2
Q
This term literally means “present at birth”.
A
Congenital(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.227
3
Q
This term refers to permanent changes in the DNA.
A
Mutations(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.227
4
Q
This type of mutation results from the substitution of a single nucleotide base by a different base, resulting in the replacement of one amino acid by another.
A
Missense mutation(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.227
5
Q
This type of mutation results in the replacement of one amino acid by a stop codon, resulting in chain termination.
A
Nonsense mutation(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.227
6
Q
Missense, nonsense and silent mutations are examples of ________ mutations, wherein only one base pair is replaced.
A
Point mutations(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.227
7
Q
This type of mutation occur when the insertion or deletion of one or two bse pairs alters the reading frame of the DNA strand.
A
Frameshift mutations(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.227
8
Q
These mutations are characterized by amplification of a sequence of three nucleotides.
A
Trinucleotide repeat mutations(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.227
9
Q
Disease characterized by CGG trinucleotide repeats.
A
Fragile X Syndrome(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.227
10
Q
This is a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and psychiatric problems.
A
Huntington’s disease(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.229
11
Q
Genetic mutation in Huntington’s disease?
A
CAG trinucleotide repeats(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.229
12
Q
This disorder is a chronic, slowly progressing inherited genetic disorder characterized by muscle wasting, cataracts, heart conduction defects, endocrine changes and myotonia.
A
Myotonic Dystrophy(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.229
13
Q
Genetic mutation found in myotonic dystrophy?
A
CTG Trinucleotide repeats(TOPNOTCH)
14
Q
A point mutation wherein a single base pair is replaced but codes for the same amino acid, therefore has no effect on the functioning of the protein.
A
Silent mutation(TOPNOTCH)
15
Q
An example of point mutation wherein a purine base is replaced by another purine base or a pyrimidine base is replaced by another pyrimidine base.
A
Transition(TOPNOTCH)
16
Q
A point mutation wherein a purine is replaced by a pyrimidine or vice versa.
A
Transversion (V - Valiktad) (TOPNOTCH)
17
Q
Diseases caused by single gene defects are called?
A
Mendelian Disorders(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.228
18
Q
A condition wherein both dominant and recessive alleles of a gene pair may be fully expressed in the heterozygote.
A
Codominance(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.228
19
Q
The presence of many allelic forms of a single gene is called _______.
A
Polymorphism(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.228
20
Q
This occurs when one gene influences or leads to multiple phenotypic traits.
A
Pleiotropy(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.228
21
Q
A phenomenon wherein a single phenotype or genetic disorder may be caused by mutations of several genetic loci or allele.
A
Genetic heterogeneity Note: compare with pleiotropy(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.228
22
Q
A transmission pattern of inheritance which is manifested in the heterozygous state, wherein at least one parent of an index case is usually affected, both males and females are affected and both can transmit the condition.
A
Autosomal dominant (AD)(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.229 *SEE SLIDE 7.1
23
Q
This pattern of inheritance occur when BOTH of the alleles at a given gene locus are mutants, wherein the parents are not affected, but offspring have 1 in 4 chance (25%) of being affected.
A
Autosomal recessive(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.229 *SEE SLIDE 7.1
24
Q
Pattern of inheritance wherein the disorder is transmitted by heterozygous female carriers only to 50% of the sons. An affected male does not transmit the disorder to sons but all daughters are carriers.
A
X-linked disorders(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.229 *SEE SLIDE 7.2
25
An autosomal dominant disorder of connective tissues characterized by abnormally long legs, arms and fingers, joint hyperextensibility, pectus excavatum, lens subluxation (Ectopia lentis) and increased risk of aortic dissection. *SEE SLIDE 7.3
Marfan Syndrome(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.230
26
Integral component of elastic fibers defective in Marfan Syndrome.
Fibrillin 1(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.230
27
Fibrillin 1 is encoded by what gene?
FBN1 gene (chromosome 15q21)(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.230
28
A collection of disorders caused by defects in collagen synthesis or structure, characterized by hyperextensible skin and joint hypermobility, rupture of internal organs and poor wound healing. *SEE SLIDE 7.4
Ehlers-Danlos SyndromesThere are 6 variants to Ehlers-Danlos (nice to know)(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.231
29
This autosomal recessive inborn error of metabolism is characterized by inability to convert phenylalanine to tyrosine, strong mousy or musty odor of urine and sweat, decreased pigmentation of hair and skin, eczema, seizures and mental retardation.
Phenylketonuria (PKU)(TOPNOTCH)
30
This autosomal dominant disorder is caused by a mutation in the gene that specifies the receptor for LDL, impairing the intracellular transport and catabolism of LDL.
Familial hypercholesterolemia(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.232
31
Enzyme deficient in classic PKU.
Phenylalanine hydroxylase (PAH)(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.234 *SEE SLIDE 7.5
32
An autosomal recessive disorder of galactose metabolism characterized by jaundice, liver damage, cataracts, neural damage, vomiting and diarrhea.
Galactosemia(TOPNOTCH)
33
Deficiency of this enzyme can also cause symptoms of phenylketonuria due to decreased synthesis of a cofactor in the conversion of phenylalanine to tyrosine.
Dihydrobiopteridine reductase (DHPR)Enzyme responsible for the reduction of Dihydrobiopterin (BH2) to Tetrahydrobiopterin (BH4).(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.234
34
Enzyme deficient in galactosemia.
Galactose-1-phosphate uridyltransferase(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.235
35
Lysosomal storage disease due to deficiency of glucosylceramidase.
Gaucher disease(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.236
36
Lysosomal storage disease due to deficiency of B-Hexosaminidase A.
Tay-Sachs disease(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.236
37
Lysosomal storage disease due to deficiency of a-Galactosidase A.
Fabry disease(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.236
38
Lysosomal storage disease due to deficiency of Sphingomyelinase.
Niemann-Pick disease(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.236
39
Lysosomal storage disease common among Ashkenazi Jews characterized by motor weakness, mental retardation, blindness, neurologic dysfunction and death.
Tay-Sachs disease(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.236
40
Lysosomal storage disease characterized by accumulation of glucosylceramide in mononuclear phagocytic cells, which enlarge, forming "wrinkled tissue paper" cytoplasmic appearance. *SEE SLIDE 7.6
Gaucher disease(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.238
41
What do you call the pathognomonic cell characterized by "wrinkled tissue paper" cytoplasmic appearance. *SEE SLIDE 7.6
Gaucher cell(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.238
42
These disorders result from the accumulation of mucopolysaccharides in many tissues including the liver, spleen, heart, blood vessels, brain, cornea and joints. Affected patients have coarse facial features.
Mucopolysaccharidoses(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.238
43
Mucopolysaccharidosis characterized by corneal clouding, coronary arterial and valvular depositions, which occurs due to deficiency of a-L-iduronidase, leading to accumulation of dermatan and heparan sulfate.
Hurler syndrome(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.239
44
An X-linked mucopolysaccharidosis which is due to a deficiency of L-iduronate sulfatase. Symptoms are similar to Hurler syndrome, but without corneal clouding.
Hunter syndrome(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.239
45
Glycogen storage disease characterized by hepatomegaly, renomegaly, hypoglycemia, hyperlipidemia and hyperuricemia, leading to gout and skin xanthomas.
von Gierke's disease (Type I)(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.240
46
von Gierke's disease is due to a deficiency of what enzyme?
Glucose-6-phosphatase(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.240
47
Glycogen storage disease characterized by accumulation of glycogen in skeletal muscles leading to painful cramps during strenuous exercise and myoglobinuria.
McArdle syndrome (type V)(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.240
48
Glycogen storage disease characterized by mild hepatomegaly, cardiomegaly, muscle hypotonia, and may lead to cardiorespiratory failure.
Pompe disease (type II)(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.240
49
Enzyme deficient in McArdle syndrome.
Muscle phosphorylase(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.240
50
These disorders may result from alterations in the number or structure of chromosomes and may affect autosomes or sex chromosomes.
Cytogenetic disorders(TOPNOTCH)
51
These disorders may result from alterations in the number or structure of chromosomes and may affect autosomes or sex chromosomes.
Cytogenetic disorders(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.241
52
It is a term used to describe the presence of two or more populations of cells in the same individual.
Mosaicism(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.242
53
This refers to a lack of one chromosome of the normal complement (e.g. XO).
Monosomy(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.244
54
This refers to the presence of three copies of a particular chromosome, instead of two.
Trisomy(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.244
55
This mechanism occurs due to the failure of chromosome pairs to separate properly during meiosis stage 1 or 2.
Nondisjunction(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.243 *SEE SLIDE 7.7
56
This mechanism implies transfer of a part of one chromosome to another chromosome.
Translocation(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.243 *SEE SLIDE 7.7
57
This mechanism involves loss of a portion of a chromosome.
Deletion(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.243
58
Patients with this syndrome have severe mental retardation, flat facial profile, epicanthic folds, cardiac malformations, increased risk of leukemia, and premature development of Alzheimer's disease.
Down syndrome(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.244
59
Down syndrome is also called _________
Trisomy 21(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.245
60
Trisomy 18 is also called ________ syndrome.
Edwards syndrome(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.245
61
Trisomy 13 is also called _________ syndrome.
Patau syndrome(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.244
62
Syndrome characterized by a prominent occiput, low set ears, micrognathia, rocker-bottom feet, renal malformation, mental retardation and heart defects.
Edwards syndrome / trisomy 18(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.245
63
Syndrome characterized by mental retardation, microcephaly, micropthalmia, polydactyly, cleft lip and palate, cardiac and renal defects, umbillical hernia and rocker-bottom feet.
Patau syndrome/Trisomy 13(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.245
64
Syndrome characterized by thymic hypoplasia with diminished T-cell immunity and parathyroid hypoplasia with hypocalcemia.
DiGeorge syndrome(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.245
65
Syndrome characterized by congenital heart disease affecting outflow tracts, facial dysmorphism and developmental delay.
Velocardiofacial syndrome(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.245
66
Deletion of genes from this chromosome gives rise to DiGeorge and velocardiofacial syndromes.
22q11.2Remember mnemonic CATCH22(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.245
67
The q from 22q11.2 refers to ________.
"Long arm" of chromosome 22.(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.246
68
Syndrome defined as male hypogonadism that develops when there are at least two X chromosomes and one or more Y chromosomes.
Klinefelter syndrome(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.246
69
Syndrome manifested by a eunochoid body habitus, reduced facial, body and pubic hair, gynecomastia, testicular atrophy, decreased serum testorerone and increased urinary gonadotropin levels. It is the most common cause of hypogonadism in males.
Klinefelter syndrome (TOPNOTCH)Robbins Basic Pathology, 8th Ed p.246 *SEE SLIDE 7.8
70
Most common chromosomal derangement in Klinefelter syndrome.
47XXY(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.246
71
Syndrome which results from the partial or complete monosomy of the short arm of the X chromosome.
Turner syndrome(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.247 *SEE SLIDE 7.8
72
Inheritance associated with mitochondrial DNA.
Maternal inheritance(TOPNOTCH)
73
Neurodegenerative disease which manifests as progressive bilateral loss of central vision that leads to blindness. This is the prototypical disorder of mutations in mitochondrial genes.
Leber hereditary optic neuropathy(TOPNOTCH)
74
Inheritance associated with mitochondrial DNA.
Maternal inheritance(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.247
75
An epigenetic process wherein certain genes are differentially "inactivated" during paternal and maternal gametogenesis.
Genomic imprinting(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.252
76
This refers to transcriptional silencing of the maternal allele.
Maternal imprinting(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.251
77
Refers to the transcriptional silencing of the paternal allele.
Paternal imprinting(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.251
78
Syndrome characterized by mental retardation, short stature, hypotonia, obesity, small hands and feet, and hypogonadism. Paternal imprinting.
Prader-Willi syndrome(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.251 *SEE SLIDE 7.9
79
Syndrome manifested as mental retardation, ataxic gait, seizures and inappropriate laughter. Also called the "happy puppet syndrome". Maternal imprinting.
Angelman syndrome(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.251 *SEE SLIDE 7.9
80
These represent primary errors of morphogenesis due to an intrinsically abnormal developmental process. *SEE SLIDE 7.10
Malformations(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.254
81
These result from secondary destruction of an organ or body region that was previously normal in development, due to an extrinsic disturbance in morphogenesis. *SEE SLIDE 7.11
Disruptions(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.254
82
These are due to generalized compression of the growing fetus by abnormal biomechanical forces, for example uterine constraint. *SEE SLIDE 7.12
Deformations(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.254
83
This refers to multiple congenital anomalies that result from secondary effects of a single localized aberration in organogenesis. The initiating event may be a malformation, deformation or disruption.
Sequence(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.254
84
This refers to the presence of several defects that cannot be explained on the basis of a single localizing initiating error in morphogenesis.
Malformation syndrome(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.253
85
Elements of the TORCH complex.
ToxoplasmaTreponema pallidumRubellaCytomeglovirusHerpesvirus(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.256
86
Most common cause of neonatal mortality.
Congenital anomalies(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.253
87
Second most common cause of neonatal mortality.
Prematurity(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.257
88
Lungs of infants with this disease are normal size but are heavy and relatively airless. They have a mottled purple color, with poorly developed atelectatic alveoli.
Neonatal Respiratory Distress Syndrome / Hyaline Membrane Disease(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.257
89
Characteristic eosinophilic membranes line the respiratory bronchioles, alveolar ducts and random alveoli, which contain necrotic epithelial cells admixed with extravasated plasma proteins. *SEE SLIDE 7.13
Hyaline Membrane Disease / Neonatal RDS(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.257
90
Two well known complications of high concentration ventilator administered oxygen in infants suffering from RDS.
Retrolental fibroplasia / retinopathy of prematurityBronchopulmonary dysplasia(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.258
91
Characteristic lesion in the retina of infants suffering from retrolental fibroplasia?
Neovascularization or retinal vessel proliferation(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.258
92
Main component of pulmonary surfactant.
Dipalmitoylphosphatidylcholine (DPPC) ~40%(TOPNOTCH)
93
Characteristic abnormality in bronchopulmonary dysplasia?
Alveolar hypoplasia or a decrease in the number of mature alveoli.(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.258
94
What is the fundamental abnormality in neonatal RDS?
Insufficient pulmonary surfactant(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.258
95
This condition occurs more commonly in very-low-birth-weight infants, as a result of intestinal ischemia, bacterial colonization of gut and formula milk feeding.
Necrotizing enterocolitis (TOPNOTCH)Robbins Basic Pathology, 8th Ed p.258
96
Microscopic features of NEC.
Presence of submucosal gas bubbles, transmural coagulative necrosis, ulceration and bacterial colonization.(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.259
97
Defined as the sudden death of an infant under 1 year of age which remains unexplained after a thorough investigation.
Sudden Infant Death Syndrome / SIDS(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.260
98
Characteristic findings include multiple petechiae of the thymus, visceral and parietal pleura and epicardium, congested lungs with vascular engorgement with or without pulmonary edema. There is also hypoplasia of the arcuate nucleus.
Sudden Infant Death Syndrome(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.260
99
Results from antibody-induced hemolytic disease in the newborn that is caused by blood group incompatibility between mother and fetus, leading to edema fluid accumulation.
Immune Hydrops(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.261
100
Erythroid precursors with large homogenous, intranuclear inclusions and a surrounding peripheral rim of residual chromatin can be seen in the bone marrow aspirate of an infant infected with this virus. This leads to development of non-immune hydrops.
Parvovirus B19(TOPNOTCH)
101
Isolated postnuchal fluid accumulation in fetuses with hydrops.
Cystic hygroma(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.261
102
A lethal condition characterized by generalized edema of the fetus.
Hydrops fetalis(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.261
103
Increased hematopoietic activity leading to the presence of large number of immature red cells, including reticulocytes, normoblasts and erythroblasts. Characteristic finding in fetal anemia-associated hydrops.
Erythroblastosis fetalis(TOPNOTCH)
104
Primary gene defect in cystic fibrosis.
Abnormal CFTR (CF transmembrane conductance regulator). Most severe mutation involves deletion of nucleotides for phenylalanine (F508 position). (TOPNOTCH)Robbins Basic Pathology, 8th Ed p.262
105
Lungs with extensive mucous plugging and dilated tracheobronchial tree. Pancreatic ducts dilated and plugged with eosinophilic mucin, atrophic parenchymal glands replaced by fibrous tissue. Azoospermia, infertility, and bilateral absence of the vas deferens in males are some of the features of this disease.
Cystic fibrosis(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.262
106
Patients with cystic fibrosis are prone to developing infections caused by these three organisms.
S. aureusH. InfluenzaeP. aeruginosa(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.266
107
How is cystic fibrosis diagnosed?
Persistently elevated sweat chloride concentration(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.267
108
Most common tumors of infancy.
Hemangioma(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.267
109
Microscopically normal cells or tissues that are present in abnormal locations.
Heterotopia or choristoma(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.267
110
Port wine stains are associted with these syndromes. (2) *SEE SLIDE 7.14
von Hippel-Lindau Sturge-Weber syndromes(TOPNOTCH)
111
This refers to an excessive but focal overgrowth of cells and tissues native to the organ in which it occurs.
Hamartoma(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.267
112
Large, flat to elevated, irregular, red-blue masses in the skin. *SEE SLIDE 7.14
Port wine stains(Large hemangiomas)(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.267
113
These represent the lymphatic counterpart of hemangiomas characterized as cystic and cavernous spaces lined by endothelial cells and surrounded by lymphoid aggregates,usually containing pale fluid.
Lymphangiomas(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.268
114
What do you call the rosettes found in neuroblastomas?
Homer-Wright pseudorosettes. Tumor cells are concentrically arranged around a neuropil (eosinophilic fibrillary material that corresponds to neuritic processes of neuroblasts) (TOPNOTCH) Robbins Basic Pathology, 9th ed., p 259 *SEE SLIDE 7.15
115
Most common germ cell tumors of childhood,associated with meningocoele and spina bifida.
Sacrococcygeal teratomas(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.268
116
Tumors arising from neural crest cells. Composed of small, primitive-appearing cells with dark nuclei, scant cytoplasm, and poorly defined cell borders growing in solid sheets within a finely fibrillar matrix (neuropil). *SEE SLIDE 7.16
Neuroblastomas(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.269
117
This is used in the screening of patients with neuroblastoma.
Urinary vanillylmandelic acid and homovanillic acid (VMA/HVA)(TOPNOTCH)
118
Differentiated lesions containing more large cells with vesicular nuclei and abundant eoinophilic cytoplasm, in the absence of neuroblasts, usually accompanied by mature spindle shaped Schwann cells.
Ganglioneuroma(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.270
119
Disseminated neuroblastoma with multiple cuteaneous metastases with deep blue discoloration to the skin.
"Blueberry muffin baby"(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.270
120
This tumor is composed of small, round cells with large hyperchromatic nuclei and scant cytoplasm, with characteristic structures consisting of clusters of cuboidal or short columnar cells arranged around a CENTRAL LUMEN. The nuclei are displaced away from the lumen, which appears to have a limiting membrane. *SEE SLIDE 7.17
Retinoblastoma(Differentiate with neuroblastoma)(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.271
121
Rosettes in retinoblastoma are called _______. *SEE SLIDE 7.17
Flexner-Wintersteiner rosettes. (TOPNOTCH)Robbins Basic Pathology, 8th Ed p.271
122
Clinicial findings include poor vision, strabismus, whitish hue to the pupils ("cat's eye reflex"), pain and tenderness to the eye. *SEE SLIDE 7.18
Retinoblastoma(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.271
123
Most common primary tumor of the kidney in children.
Wilm's tumor / Nephroblastoma(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.271
124
Components of the WAGR syndrome.
Wilm's tumorAniridiaGenital abnormalitiesMental retardation(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.272
125
Presents grossly as a large, solitary, well-circumscribed mass. On cut-section, tumor is soft, homogenous, and tan to gray, with occasional foci of hemorrhage, cystic degeneration and necrosis.
Wilm's tumor(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.272
126
Microscopically, a combination of blastemal, stromal and epithelial cell types is observed. (Triphasic combination) Blastemal components described as sheets of small blue cells with few distinctive features. Stromal cells are fibrocytic or myxoid in nature. Epithelial cells take the form of abortive tubules or glomeruli. *SEE SLIDE 7.19
Wilm's tumor(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.272
127
Associated with inactivation of the WT1 gene of chromosome 11p13.
WAGR syndrome and Denys-Drash syndrome(TOPNOTCH)Robbins Basic Pathology, 8th Ed p.272
128
Patient presents with mental retardation, motor incoordination, and blindness. Ophthalmologic exam showeed cherry-red spots on the macula. Brain showed neurons ballooned with cytoplasmic vacuoles. What is the enzyme deficiency? *SEE SLIDE 7.20
Hexosaminidase A. (Case of Tay-Sachs Disease) (TOPNOTCH)
129
An 18 y/o male was recently diagnosed with a genetic disorder. His parents do not manifest the disease, but one of his parent carries the gene with phenotypic expression. Some of his relatives manifest the same disease but with different presentation. What type of Mendelian disorder does the patient most likely have?
Autosomal dominant disorder. With this type, some patient do not have affected parents, has variations in penetrance and expressivity, age at onset is delayed. (TOPNOTCH) Robbins Basic Pathology, 9th ed., p. 140
130
True or False. Male patient with hemophilia does not transmit the disorder to his sons, but all daughters are carriers.
True. Hemophilia is an X-linked disorder. (TOPNOTCH)
131
True or False. Female hemophilia carrier will transmit the disease to half her sons and half her daughter.
False. X-linked disorders are transmitted by heterozygous females to their sons, who manifest the disease. (TOPNOTCH) Robbins Basic Pathology, 9th ed., p. 142
132
True or False. Female hemophilia carrier will manifest with decrease Factor VIII.
False (TOPNOTCH)
133
True or False. In female hemophilia carrier, only one of the X chromosome shows abnormality.
True (TOPNOTCH)
134
True or False. In X-linked disorders, female carriers are usually protected because of random inactivation of one X chromosome.
True (TOPNOTCH)
135
True or False. In X-linked disorders, heterozygous female carrier will never manifest the disease.
False (TOPNOTCH)
136
A 26 y/o male was referred to a cardiologist due to presence of murmur at the aortic area. On history, patient suffered from severe myopia at the age of 6. His development was normal except that he was taller than the rest of his family members and friends. Examination of abdomen showed visible pulsation above the umbilicus. The most striking feature in this syndrome is:
Skeletal abnormalities. (case of Marfan Syndrome) (TOPNOTCH)
137
The most life-threatening feature of Marfan syndrome
Cardiovascular lesions (TOPNOTCH) Robbins Basic Pathology, 9th ed., p. 145
138
The 2 most common lesions of Marfan Syndrome
Mitral valve prolapse and dilation of ascending aorta (TOPNOTCH) Robbins Basic Pathology, 9th ed, p. 145
139
A 4 y/o male presented with cutaneous xanthomas on the extensor surfaces of his arms, knees, and elbow since he was 1 year old. He was found to have serum cholesterol greater than 1000 mg/dl and triglyceride level of 170 mg/dl. Both parents had high cholesterol levels. What is the cause of hypercholesterolemia in this condition?
Impared transport of LDL into the cells (Case of Familial Hypercholesterolemia) (TOPNOTCH)
140
A 6 mo old infant presented with failure to thrive, vomiting, fever, and hepatosplenomegaly. Progressive deterioration of the infant led to death. Autopsy finding showed lipid laden phagocytic foam cells widely distributed in the spleen, liver, lymph nodes, GIT and lungs. Tissue cells are enlarged, with innumerable vacuoles staining for fat, and lysosome contain concentric lamellated myelin figures. The patient is deficient of what enzyme?
Sphingomyelinase (case of Niemann-Pick Disease Type A) (TOPNOTCH)
141
A 1 y/o infant succumbed to death. Autopsy finding showed shrunken gyri and widened sulci. There is vacuolation and ballooning of neurons noted. Cells are enlarged with innumerable small vacuoles of uniform size, imparting foaminess to the cytoplasm. This is a case of:
Niemann-Pick Disease (TOPNOTCH)
142
Presents with fractures, bone pain and thrombocytopenia. Morphologic findings of distended phagocytic cells and have fibrillary type of cytoplasm, intensely positive for PAS staining.
Gaucher disease (TOPNOTCH)
143
A 21 y/o female of short stature presented with primary amenorrhea, shield-shaped chest, "thick neck", and absence of secondary female characteristics. Estrogen level were decreased, while FSH and LH are increased. What is the most likely diagnosis? *SEE SLIDE 7.8
Turner syndrome (TOPNOTCH)
144
The most common chromosomal disorder
Down Syndrome(TOPNOTCH)Robbins Basic Pathology, 9th ed., p. 161
145
The most common genetic cause of mental retardation.
Down Syndrome(TOPNOTCH)Robbins Basic Pathology, 9th ed., p. 161
146
Most common pathogenesis of Trisomy 21
Meiotic nondisjunction (TOPNOTCH)
147
Most common congenital heart defects in Trisomy 21
Endocardial cushion defects(TOPNOTCH)Robbins Basic Pathology, 9th ed., p. 163
148
Why are patients with DiGeorge syndrome has T-cell immunodeficiency?
Because of thymic hypoplasia (TOPNOTCH)Robbins Basic Pathology, 9th ed., p. 163
149
A 14 y/o male presented with gynecomastia and small testes. He was noted to have difficulties in school when he was 8. He was tall for his age. You would suspect:
Klinefelter syndrome (TOPNOTCH) *SEE SLIDE 7.8
150
Classic karyotype patttern of Klinefelter syndrome
47,XXY(TOPNOTCH)
151
Single most important cause of primary amenorrhea
Turner syndrome (TOPNOTCH)Robbins Basic Pathology, 9th ed., p. 166
152
Most important cause of increased mortality in children with Turner syndrome.
Cardiovascular abnormalities (TOPNOTCH)Robbins Basic Pathology, 9th ed., p. 166
153
Patient presents with mental retardation, long face with large mandible, large everted ears, and large testicles. *SEE SLIDE 7.21. The most likely diagnosis is:
Fragile X Syndrome (TOPNOTCH) Robbins Basic Pathology, 9th ed., p. 169
154
Most distinctive feature of Fragile X syndrome
Macro-orchidism(TOPNOTCH) Robbins Basic Pathology, 9th ed., p. 169
155
The neonate was noted to have microcephaly, short palpebral fissure, maxillary hypoplasia, growth retardation, and psychomotor disturbances. The mother denies intake of drugs during pregnancy. SEE SLIDE 7.22. The most likely cause
Alcohol (TOPNOTCH)
156
Deficiency in homogentisic oxidase results in this condition which manifests black discoloration of the urine
Alkaptonuria (TOPNOTCH)
157
Most common cause of respiratory distress in the newborn
Hyaline Membrane Disease (TOPNOTCH) Robbins Basic Pathology, 9th ed., p. 457
158
This teratogenic drug disrupts expression of homeobox (HOX) proteins implicated in the patterning of limbs, vertebrae, and craniofacial structures.
Valproic acid (TOPNOTCH) Robbins Basic Pathology, 9th ed., p. 456
159
Most commonly responsible for fetal growth restriction.
TORCH infections (TOPNOTCH) Robbins Basic Pathology, 9th ed., p. 457
160
Most common maternal condition associated with SGA infants
Vascular diseases (chronic hypertension, preclampsia) (TOPNOTCH) Robbins Basic Pathology, 9th ed, p. 457
161
A 28 week old male delivered via CS by a diabetiic mother presented with dyspnea and cyanosis. Fine rales are heard over both lung fields. CXR revealed uniform minute reticulogranular densities, producing a ground glass appearance. The fundamental defect in this condition is:
Pulmonary surfactant (Case of RDS) (TOPNOTCH)
162
The most common cause of mortality in children ages 1-4 years old.
Accidents (TOPNOTCH) Robbins Basic Pathology, 9th ed., p. 452
163
A 28 week old male dies 20 hours after birth. Autopsy findings showed a solid, airless, and reddish purple lungs with poorly developed alveoli. Necrotic cellular debris incorporated within eosinophilic hyaline membranes lines the respiratory bronchioles, alveolar ducts and alveoli. SEE SLIDE 7.13. The most likely cause of death of the neonae is:
Respiratory distress syndrome/Hyaline membrane disease (TOPNOTCH)
164
Premature infant, bottle-fed, developed bloody stool, abdominal distention. Abdominal radiograph showed pneumotis intestinalis. Diagnosis:
Necrotizing enterocolitis(TOPNOTCH)
165
Morphology: intestinal segment is distended, friable and congested, with transmural coagulative necrosis, ulceration, bacterial colonization, and submucosal bubbles.
Necrotizing enterocolitis(TOPNOTCH)
166
Most common cause of early-onset neonatal sepsis and early-onset bacterial meningitis
Group B streptococcus(TOPNOTCH) Robbins Basic Pathology, 9th ed., p. 460
167
The most serious threat of fetal hydrops
CNS damage -kernicterus (TOPNOTCH) Robbins Basic Pathology, 9th ed., p. 463
168
Most common site of neuroblastoma
Adrenal medulla (40%). Other sites include abdomen (25%) and posterior mediastinum (15%) (TOPNOTCH) Robbins Basic Pathology, 9th ed., p 259
169
Presents with a large abdominal mass crossing the midline, hematuria, intestinal obstruction, and hypertension.
Wilm's tumor (TOPNOTCH)
170
A 22 year old male consults an ophthalmologist for sudden blindness on the right. He is found to have lens subluxation. He is unusually tall and lean, with long limbs and fingers. These findings are due to abnormalities in fibrillin 1, which is secreted by (A) megakaryocytes (B) fibroblasts (C) histiocytes (D) fibroclasts
fibroblasts (TOPNOTCH)Robbins Basic Pathology, 8th Ed, p 230
171
A lysosomal storage disease with a mutation in the gene that encodes glucosylceramidase presents with an accumulation of glucosylceramide in mononuclear phagocytic cells in the liver, spleen, and marrow. These pathognomonic cells are (A) enlarged, with a "wrinkled tissue paper" cytoplasm (B) epithelioid, with "slipper-shaped" nuclei (C) multinucleated, with 8 to 20 nuclei (D) studded with reddish brown cytoplasmic granules
enlarged, with a "wrinkled tissue paper" cytoplasm (TOPNOTCH)Robbins Basic Pathology, 8th Ed pp237-238 *SEE SLIDE 7.6
172
A baby is born with epicanthic folds, flat facial profile, simian crease, and a gap between the first and second toe. Auscultation reveals a holosystolic murmur. The clinical findings are due to an extra chromosome that is most commonly caused by (A) meiotic duplication (B) meiotic nondisjunction (C) fertilization by two spermatozoa (D) translocation
meiotic nondisjunction (TOPNOTCH)Robbins Basic Pathology, 8th Ed p 244
173
A premature female neonate admitted at the PICU develops sepsis, with blood cultures showing growth of Candida sp. She is also found to be persistently hypocalcemic. She dies on her 7th day. On autopsy, she was found to have fungal endocarditis and thymic hypoplasia. She most likely has (A) an extra chromosome 22 (B) a deletion in chromosome 22 (C) a 9:22 chromosomal translocation (D) a duplication in chromosome 22
a deletion in chromosome 22 (TOPNOTCH)Robbins Basic Pathology, 8th Ed pp 245-246
174
A stillborn fetus is found to have polydactyly, an umbilical hernia, and cleft lip and palate. Autopsy showed a ventral septal defect, renal dysplasia, and holoprosencephaly. Karyotyping will likely show (A) Monosomy X (B) Deletion in chromosome 5 (C) Trisomy 13 (D) Trisomy 18
Trisomy 13 (TOPNOTCH)Robbins Basic Pathology, 8th Ed p 245.
175
A 19 year old female consults a gynecologist for primary amenorrhea. Apart from her short stature, there are no other unusual clinical findings. Why must Turner Syndrome be ruled out? (A) mosaicism or partial monosomy may produce a mild form of the syndrome (B) 45,X abnormalities manifest in only half of females by the age of 18 (C) when combined with Fragile X, the typical features such as neck webbing and cubitus valgus are masked (D) supplementation with folate during gestation masks the typical features of neck webbing and cubitus valgus
mosaicism or partial monosomy produces a milder form (TOPNOTCH)Robbins Basic Pathology, 8th Ed pp247-248
176
A stillborn male fetus delivered to a 41 year old G7P7 is found to have flattened facies and clubbed feet. Autopsy showed renal agenesis and pulmonary hypoplasia. What is the main culprit of the findings in the fetus? (A) maternal age (B) multiparity (C) renal agenesis (D) pulmonary hypoplasia
renal agenesis (TOPNOTCH)Robbins Basic Pathology, 8th Ed pp 253-254
177
A G3P3 mother has premature rupture of membranes at 35 weeks age of gestation, and delivers a live baby boy with poor APGAR scores. The obstetrician delivered a placenta with dull-looking membranes, which showed chorioamnionitis on histopathology. Culture of which organism from the placental tissue suggests an transcervical origin of infection? (A) Group B Streptococcus (B) Toxoplasma (C) Plasmodium (D) Rubella
Group B Streptococcus (TOPNOTCH)Robbins Basic Pathology, 8th Ed p. 256
178
A G1P1 preeclamptic mother delivers a live baby boy at 27 weeks age of gestation. The baby develops respiratory distress a few minutes later and is admitted at the PICU. He dies the next day, and is sent for autopsy. Which of the following supports respiratory distress syndrome of the newborn? (A) thickened alveolar septa with lymphocytic infiltrates (B) alveolar spaces filled with neutrophils (C) eosinophilic material lining the alveolar walls (D) hemosiderin laden macrophages in the alveolar spaces
eosinophilic material lining the alveolar walls (TOPNOTCH)Robbins Basic Pathology, 8th Ed pp 257-258 *SEE SLIDE 7.13
179
A premature male neonate who was delivered at 33 weeks AOG and admitted at the PICU develops abdominal distention, bloody stools, and hypotension. An abdominal radiograph shows gas within the intestinal wall. What is the expected histologic findings of the involved intestine? (A) coagulative necrosis of the mucosa and muscularis (B) arteriovenous fistulas in the submucosa (C) melanosis of the mucosa (D) crypt abscesses and noncaseating granulomas
coagulative necrosis of the mucosa and muscularis (TOPNOTCH)Robbins Basic Pathology, 8th Ed p 259
180
What is the most common autopsy finding in sudden infant death syndrome? (A) patent ductus arteriosus (B) multiple petechiae in the thymus and pleural surfaces (C) bilateral adrenal hemorrhage (D) flattening of gyri in the cerebral cortex
multiple petechiae on the thymus and visceral surfaces (TOPNOTCH)Robbins Basic Pathology, 8th Ed p 260
181
How does parvovirus B19 infection cause fetal hydrops? (A) it causes a chronic myocarditis leading to heart failure (B) it infects the lymphatic ducts causing peripheral fluid accumulation (C) it causes placental villi atrophy, exposing the fetal circulation to maternal antibodies (D) it infects erythroid precursors, causing anemia
it infects erythroid precursors, causing anemia (TOPNOTCH)Robbins Basic Pathology, 8th Ed p 262
182
A 4 month old infant with abdominal enlargement presents with multiple bluish-gray subcutaneous nodules. Workup showed a 10 cm mass in the paravertebral region. Biopsy of the nodules showed small round cells with dark nuclei scanty cytoplasm, some forming rosettes arranged in a finely fibrillar matrix. SEE SLIDE 7.15. Immunohistochemical studies showed the cells to be positive for neuron specific enolase and negative for leucocyte common antigen. These tumor cells are derived from (A) antigen presenting cells in the dermis (B) neural crest (C) nephrogenic rests (D) lymphoid precursors
neural crest (TOPNOTCH)Robbins Basic Pathology, 8th Ed pp 269-270
183
A 2 year old male is noticed to have a whitish pupil on photographs. Workup showed a tumor in the posterior chamber. The eye is enucleated, and the tumor shows sheets of small round cells with hyperchromatic nuclei and scant cytoplasm. Occasional clustering around central lumens are seen. On further history, a cousin also had a similar tumor and died. The patient has an increased risk of developing which tumour later in life: (A) hepatoblastoma (B) pheochromocytoma (C) osteosarcoma (D) Wilms tumour
osteosarcoma (TOPNOTCH)Robbins Basic Pathology, 8th Ed p 271
184
A 4 year old female undergoes left nephrectomy for Wilms tumor. Which of the following findings in the nephrectomy specimen is associated with an increased risk of developing the same tumor in the right kidney? (A) nephrogenic rests (B) abortive tubules or glomeruli (C) extensive fibrosis (D) adipose tissue, cartilage, and osteoid
nephrogenic rests (TOPNOTCH)Robbins Basic Pathology, 8th Ed p 272
185
Marfan syndrome is to fibrillin as Ehlers-Danlos is to _____
Collagen (TOPNOTCH)
186
Abnormal proteins in hereditary spherocytosis
Spectrin, ankyrin, protein 4.1 (TOPNOTCH)Robbins Basic Pathology, 9th Ed p 219
187
Abnormal proteins in SCID
Adenosine deaminase (TOPNOTCH)Robbins Basic Pathology, 9th Ed p 219
188
Fragmentation of the elastic fibers in the tunica media of the aorta seen in (but not specific for) Marfan Syndrome
Cystic medionecrosis (TOPNOTCH)Robbins Basic Pathology, 9th Ed p 221
189
ABSORBS or SECRETES: The CFTR protein in sweat glands ____ chloride
ABSORBS. CFTR also augments sodium absorption by the ENaC channel. Hence, when it is defective as in cystic fibrosis, there is increased sodium chloride in the sweat test. (TOPNOTCH)Robbins Basic Pathology, 9th Ed p 224
190
ABSORBS or SECRETES: The CFTR protein in the lungs and intestinal epithelium _____ chloride
SECRETES. Hence, when it is defective as in cystic fibrosis, there is dehydration of the linings. (TOPNOTCH)Robbins Basic Pathology, 9th Ed p 224
191
While S. aureus, H. influenzae, and P. aeruginosa are the three most common organisms that cause lung infections in cystic fibrosis patients, this opportunistic bacterium can also infect patients and can cause fulminant illness called Cepacia Syndrome.
Burkholderia cepacia. (TOPNOTCH)Robbins Basic Pathology, 9th Ed p 225
192
Parts of the brain prone to bilirubin deposition in hyperbilirubinemia
Basal ganglia and brain stem. (TOPNOTCH)Robbins Basic Pathology, 9th Ed p 256
