Chapter10 Flashcards
1
Q
What are malformations
A
primary error of morphogenesis which there is an intrinsically abnormal developmental process
involves many gene loci
2
Q
What are disruptions
A
result from secondary destrucion of an organ or body region that was normal in development
arise from extrinsic disturbances in morphogenesis
non-hertiable
3
Q
amniotic bands are an example of what type birth defect
A
disruption
4
Q
what are deformations
A
extrinsic disturbance of development
structural abnormalities
5
Q
Give examples of birth deformitites
A
uterine constraint from small or malformed uterus
oligohydramnios causing clubfeet
6
Q
What are birth defect sequences
A
cascade of anomalies triggered by one inititating aberration
7
Q
Describe the cascade resulting from oligohydramnios
A
dec amniotic fluid
potter sequence of flattened facies, positional abnormalities of hands and feet, dislocated hips, lungs are hypoplastic, amnio nodosum (nodules in amnion)
8
Q
What is agenesis
A
complete absence of organ and primordium
9
Q
What is aplasia
A
absence of organ but one due to failure of development of the primordium
10
Q
what is atresia
A
absence of an opening, usually hollow visceral organ
11
Q
what is dysplasia
A
abnormal organization of cell sin context of malformation, NOT neoplasia
12
Q
What type of anomalies result from defects in gametogensis
A
chromosomal abberations
13
Q
what is commonly invovlved in single gene mutations
A
loss of function genes involved in organogenesis
14
Q
what is the most common single gene loss of function mutation?
gain of function?
A
loss: holoprosencaphaly; hedgehog signaling
gain: achondroplasia
15
Q
what are the environmental causes of anomalies
A
viruses, Rx and chemials, radiation, maternal diseases and multifactorial causes
16
Q
What infection leads to cataracts, heart defects, deafness, retardation in infants? when is the greatest risk period?
A
rubella
shortly before conception to 16th week gestation
17
Q
what virus is most at risk during 2nd trimester and what are the symptoms
A
cytomegalovirus
CNS, retardation, microcephaly, deafness and HSM
18
Q
What does thalidomide do
A
down regulation of WNT with HOX genes leading to limb abnormalities
19
Q
what can EtOH do to infants
A
severe structural changes, cognitive and behavioral defects, growth retardation, microcephaly, atrial septal defects, short palpebral fissure, maxillary hypoplasia
20
Q
What development pathways are affected by EtOH
A
hedgehog and retinoic
21
Q
what can be the result of tobacco use during pregnancy
A
spontaneous abortions, premature labor, placental changes, low birth weight, prone to SIDs
22
Q
radiation during organogensis can lead to what
A
malformations, microcephaly, blindness, skull defects, spin bifida
23
Q
what can be the result of maternal DM
A
maternal hyperglycemia inducing fetal hyperinsulinemia with increased body mass and fat, organomegaly, cardiac anomalies, neural tube defects and other CNS problems
24
Q
Describe the periods of insult from teratogens during early embryonic phases
A
first 3 weeks after fertilization: death or abortion
btwn 3-9 wks: increases susceptibility
btwn 4-5 wks: peak susceptibility because organs are being made from germ layers
25
How come during the fetal period there is reduced susceptibility to teratogens
because now just growth and maturation of the organs
26
what is cyclopamine and what does it cause
teratogen from veratrumcalifornicum
| inhibits hedgehog siglaning leading to holosencephaly
27
what is valproic acid used to treat and what does it cause in fetuses
used to treat epilepsy
| disrupts HOX genes so hace abnormal patterning of limbs, vertebrae and craniofacial structure
28
what can vitamin A cause during pregnancy
the retinoic acid form can cause CNS defects, cardiac and craniofacial defects via the TGF-b pathway
29
What does birthweight AGA mean
appropriate for gestational age
| 10-90% percentile
30
What does SGA mean
| LGA
small for gestational age
| large for gestational age
31
what are the gestational classifications
preterm: before 37 weeks
| poster term: after 40 wks
32
what are the top two causes of infant mortality
1st- congenital anomalies
| 2nd- prematurity
33
what are risk factors for preterm premature rupture of placental membrane PPROPM
prior Hx preterm delivery, preterm labor and/or vaginal bleeding during current preg, maternal smoking, low socioeconomic, poor maternal nutrition, polymorphisms in genes assoc w/ immune regulation or collagen breakdwon
34
What occurs in PPROPM
inflammation of placental membranes, increased collagen degradation by matrix MMPs
35
What is chorioamnionitis
inflammation of placental membranes
36
what is funistitis
inflammation of fetal umbilical cord
37
What are the common microorganisms to cause intrauterine infections
ureaplasmaurealyticum
mycoplasma hominis
gardnerellavaginalis, thrichomonas, gonorrhea and chlamydia
38
What R does LPS from bacteria activate that can lead to preterm labor
TLR-4 that deregulates prostaglandin expression causing uterine smooth m contraction
39
What diseases can be caused by multiple gestations
hyaline membrane disease, necrotizing enterocolitis, sepsis, intraventricular hemorrhage, longterm complications
40
What are the fetal contributors to fetal growth restriction
chromosomal, congenital, congenital infections (TORCH)
41
What is TORCH
group of infections
| taxoplasmosis, rubella, cytomegalovirus, herpesvirus and other viral/bacterial
42
what does fetal caused fetal frowth restriction look like
symmetrical growth restrictions
43
what are the placental contributors to fetal growth restriction
umbilical-placental vascular anomalies, placental abruption, placental previa, placental thrombosis and infarction, placental infection, multple gestaions
44
What does placental caused fetal growth restriction look like
asymmetric, sparing of brain
45
What is the most common cause of fetal growth restriction cause dby placenta
chromosomal trisomies
46
What are the maternal contributors to fetal growth restriction
```
vascular diseases (preeclampsia) chronic HTN, inherited thrombophilias
maternal malnutrition
```
47
What causes neonatal respiratory distress syndrome RDS
hyaline membrane disease due to deposition of hyaline layer of proteinacecous material in peripheral airspaces of infants
48
How do infants with untreated RDS present
preterm AGA, male, maternal DM, delivery by C section
difficulty breathing and cyanotic 30 min post-delivery
rales b/l and x ray showing minute reticulogranular density
49
What is the fundamental defect in RDS
deficiency in pulmonary surfactant causing severe respiratory failure
50
what are the congenital mutations for surfactant deficiency
SFTPB and SFTBC genes
51
when do the type II alveolar cells increase production of surfactant
week 35
52
What can increase surfactant levels
glucocorticoid administration to mom
| and labor
53
what molecule suppresses surfactant production
insulin high blood levels
54
what do the lungs look like in RDS
solid, airless, reddish purple, alveoli poorly developed or collapsed with necrotic cellular debris in terminal bronchioles and alveolar ducts
55
What do an infants lungs look like if survive 48 hrs with RDS
alveolar epithelium proliferates under surface of membrane and there is partial digestion by macrophages
56
what can occur after admin of surfactant O2 to infant with RDS
3-4 days can have oxygen toxicity from ROS
57
What does high O2 in neonate lead to
```
retrolental fibroplasia (retinopathy of prematrutiy in eyes)
from changed expression of VEGF
```
58
What is required for Dx of bronchopulmonary dysplasia
28 days of O2 therapy and beyond 36 weeks post partum age
59
what are the abnormalities in BPD
dec alveolar septation, large SA
| dysmorphic capillary configuration
60
what can cause BPD
```
reversible
hyperoxemia
hyperventilation
prematurity
inflammatory cytokines
vascular meldevelopment
```
61
what is the morphology of BPD
septal fibrosis, hyperplastic smooth muscle around bronchioles, abnormal pleural surface
62
what are neonates that had RDS at risk for
patent ductus arteriosus, intraventriclar hemorrhage, necrotizing enterocolitis
63
What can cause necrotizing enterocolitis in infants
prematurity, enteral feeding, infectious agents, inflammatory mediators like PAF, intestinal ischemia
64
Describe the sequelae of intestinal ischemia
increased mucosal permeability by promoting RBC apoptosis and compromising the tight junctions ultimately leading to sepsis and shock
65
what is the clinical presentation of necrotizing enterocolitis in neonates
bloody stool, abdominal distention, development of circulatory collapse
66
What is penumatosisintestinalis
gas in intestinal wall
67
where anatomically is affected by NEC and what do theses areas look like
ileum, cecum, right colon and they all are distended, friable, congested or gangrenous
mucosal or transmural coagulative necrosis, ulceration, bacterial colonization and submucosal gas bubbles
68
what are the reparative changes of NEC
granulation tissue and fibrosis
69
when to transcervical infections occur
in utero or around time of birth
70
what causes transcervical ifnections
fetus inhales amniotic fluid before birth and may causes inflammation, or even penumonia sepsis and meningitis
71
what type of infections are transplacental
hematologic via chorionic villi
72
When can transplacental infections occur at time of birth
with concurrent HIB or HEP B infection
73
what are two common causes of transplacental infections
Parvobirus B19
| TORCH infection group
74
intrauterine parvovirus leads to what
spontaneous abortion, stillbirth, hydropsfetalis and congenital anemia
75
the TORCH infection group causes what symptoms
fever, encephalitis, chorioretinianemia, vasciular or hemorrhagic skin lesions
76
when is early onset VS late onset sepsis
early: first 7 days of life
| late (7 days-3 months)
77
what are symptoms of early sepsis
pneumonia, sepsis, meningitis
| usually caused by Group B strep
78
what bacteria cause late onset sepsis
candida and lysteria
79
What is fetal hydrops
accumulation of edema fluid in fetus during intrauterine growth
80
what is the most common cause of fetal hydrops
non-immune hydrops
81
What is immune hydrops commonly from
Rh incompatibility
ABO incompatibility
destruction of RBC destruction
82
what is the mech of hydropfetalis in anemia
hypoxic injury to heart and liver leading to a decrease in plasma proteins and cardiace decompensation leading to dec oncotic P so generalized edna and anasarca
83
excessive descruction of RBC in neonates can also lead to what besides hydrops
kernicterus, jaundice
84
What are the 3 major causes of non-immune hydrops
CV defects
CSS anomalies
fetal anemia
85
What chromosomal anomalies cause hydrops
45X Turner, trisomy 1 and 18
86
what type of fetal anemia causes hydrops
homo alpha thalassemia most commonly
87
what are other non common causes of hydropsfetalis
transplacental infection from parvovirus
| monozygous twins with twin-twin transfusion via anastomoses
88
Fetal anemia will lead to what sequelae
fetus and placenta are pale, HSM from cardiac failure and congestion, bone marrow shows compensatory hyperplasia or erythroid precursors, extramedullary hematopoiesis in liver, spleen and nodes
89
what will be present in a blood smear of fetal anemia
large numbers of immature RBC (erythroblastosis fettles)
90
What is the most serious complication of fetal anemia
kernicterus BR>20mg/dL
91
What are the clinical features of fetal hydrops
pallor and HSM
| severe: intense jaundice, generalized edema, signs of neuro involvement
92
What is the inheritance of PKU
autosomal recessive
| bi-alleic mutations for PAH
93
what is the abnomrality in PKU
cannot convert phenylalanine to tyrosine
94
what are the cofactors for conversion by PAH
BH4 and dihydropteridinereductase
95
even though mutations in BH4 alone are only 2% PKU what is important about these
cannot be treated by dietary control of Phe alone
96
What happens with classic PKU
increased phenylpyruvic acid, phenyllactic acid, phenylacetic acid and o hydroxyphenylacetic acid
can impair brain and cause severe mental retardation by 6 mo, seizures and decreased pigmentaion of hair and skin, eczema
97
What occurs with maternal PKU
metabolites cross placenta and affect specific fetal organs
| neonates have microcephaly and congeintal heart disease
98
What is Tx for PKU
diet, BH4 supplementation (molecular chaperone)
99
What is the inheritance of galactosemia
autosomal recessive
100
what is the most common form of galactosemia
lack of galactose-1-phosphate uridyltransferase GALTwhich converts glucose and galactose to glucose
101
lack of GALT leads to what
accumulation of galactose-1-phosphate in liver, spleen, lens, kidneys, heart muscle, cerebral Cx, RBCs
102
What is the clinical presentations of galactosemia
liber, eyes brain, Hepatomegaly, catarcts, nonsepcific changes in CNS
103
What occurs in infants with galactosemia
fail to thrive, vomiting, dirrhea, jaundice, hepatomegaly
cataracts after few weeks
impairment of AA transport in kidney 6-12 mo leading to aminoaciduria
104
what occurs in older patients with galactosemia
speech disorder and gonadal failure
105
What is the mutation in galactosemia in whites vs african americans
white: glutamine to arginine at codon 188
aa: serine to leucine at 135
106
what is the Dx for galactosemia
deficiency of transferase in leukocytes and RBCs
107
how can you prevent early symptoms from galactosemia
removal of galactose from diet for at least 2 yrs
108
What is cystic fibrosis
disorder of ion transport in epithelial cells that affects fluid secretion in exocrine glands and the epithelial lining of the respiratory, GI and repro tracts
109
What results from abnormal viscous secretions that obstruct organs in CF
chronic lung disease from infections, pancreatic insufficiency, steatorrhea, malnutrition, hepatic cirrhosis, intestinal obstruction and male infertility
110
what is the inheritance of CF
autosomal recessive
| but heterozygotes can be at risk too
111
What cofactors are essential for opening of the pore NBD assoc with CFTR
ATP and hydrolysis
112
What is the primary defect in CF
abnormal function in epithelial Cl channel protein encoded on CFTR 7q31.2
113
Describe interaction of CTFR with ENaC
ENaC is on the apical surface of exocrine epithelial cells and is responsible for Na uptake from luminal fluid leaving th fluid hypotonic
ENaC is inhibited by CFTR
114
What is the exception to increased ENaC activity in CF
In CF: sweat ducts, decrease in ENaC activity which leaves the luminal fluid hypertonic
115
What is the role of CFTR in respiratory and intestinal epithelium
active secretion of Cl
mutations: loss or reduction of Cl secretion into the lumen and increase active luminal Na absorption: increase passive water reabsorption from the lumen: lower water content of surface
116
what occurs with a lower water content on surface of respiratory and intestinal epithelium
defective mucociliary action and accumulation of hyperconcentrated, viscid secretions that obstruct the air passages and predispose to pulmonary infections
117
What bicarb exchanger is expressed with CFTR
SLC26
118
Mutant CFTRs secrete acid leading to what
increase mucin and plugging of ducts
increase binding o bacteria to plugged mucins
pancreatic insufficiency present with abnormal bicarb conductance
119
What is class I CF
defective protein synthesis, complete lack of CFTR on surface
120
what is class II CF
abnomral protein folding, processing and trafficking
| degraded before reach surface
121
what is the most common class II mutation
deletion of 3 NT for phe at 508
122
what is class III CF
defective regulation: prevent activation of CFTR by preventing ATP binding
123
What is class IV CF
decreased conductance, mutations in transmembrane domain of CFTR which forms ionic pore for Cl transport
124
What is class V CF
reduced abundance that affect intronic splice sites of the CTFR promoter reducing the amount of normal protein
125
What is class VI CF
altered regulation of separate ion channels
| affects conductance by CFTR as regulation of other ion channels
126
What classes of CF are the most severe
I II and III
127
what are the symptoms of class I II III CF
pancreatic insufficiency, sinopulmonary infections and GI
128
what genes have polymorphisms assoc with CF pulmonary Sx
MBL2 and TGFb1
129
what type of infeciton is common in CF
pseudomonas aeruginosa
the static mucus creates hypoxic environment which produces alginate and biofilm that protects bacteria from Abs leading to chronic destructive lung disease
130
Describe pancreas morphology in CF
ducts have mucus accumulation and become plugged that leads to atrophy and fibrosis
the dec exocrine impairs fat absorption and leads to squamous metaplasia of lining of epithelium in ducts
meconium ileus
131
what is the liver morphology in CF
the bile canaliculi are plugged with mucinouse material and ductal proliferation
focal biliary cirrhosis leads to diffuse hepatic nodularity
132
what is the morphology of salivary glands in CF
progressive dilation of the ducts, squamous metaplasia of lining epithelium and glandular atrophy with fibrosis
133
what is the morphology in the lungs in CF
bronchioles are distended with thick mucus associated with hyperplasia and hypertrophy of the mucus secreting cells
superimposed infections cause severe chronic bronchitis and bronchiectasis
134
What is the most common organism that causes lung infections in CF
staphylococcus aureus, hemophilius influenzae and pseudomonas aeruginosa
135
What is the most common finding in men with CF and infertility
azoospermia and congenital b/l absent vas deferens
136
What are the CV complications in CF
persistent lung infections leading to COPD leading to core pulmonale
also P aeruginosa infections
recurrent sinusoidal polyps
137
describe the liver in patients with CF
asymptomatic hepatomegaly
| diffuse biliary cirrhosis
138
What is SIDS
sudden death of an infant under 1 yr of age which is unexplained after autopsy, exam of death scene and review of clinical Hx
139
In what position do infants usually die
in prone or side position
140
90% of SIDS deaths occur when
in first 6 mo
| usually btwn 2 and 4 mo
141
What was thought to be the risk for SIDS
apparent life threatening event ALTE
142
what is the triple risk for SIDS
vulnerable infant, critical development period in homeostatic control and exogenous stressor
143
what is the current hypothesis for SIDS
delayed development of arousal and cardiorespiratory control
| there are abnormalities in serotonin-dependent signaling in brainstem
144
What are the vulnerability factors for SIDS
```
preterm or SGA
male
genetic predisposition (sibling)
no abuse
prior Hx of mild respiratory tract
```
145
how areURI linked to chemoreceptros
the change the laryngeal chemoreceptors to increase volume of secretions and impair swallowing
146
what are the maternal risk factors for SIDS
smoking
young mom
frequent childbirths
inadequate prenatal care
147
what are noxious sleep stimuli
hypoxia, hypercarbia and thermal stress
148
what is the most common cause of sudden unexpected death
infection
149
what is the morphology of SIDS
multiple petichiae, usually on thymus, visceral and parietal pleura and epicardium
the lungs are congested with vascular engorgement
upper respiratory tract signs of recent infections
astrogliosis of brain stem and cerebellum, hypoplasia of arcuate nucleus
150
What must you rule out before Dx SIDS
unsuspected infection, congenital anomaly, genetic disorder or child abuse
151
what is a herotopia or choristoma
normal cells or tissues that are present in abnormal locations
like pancreatic tissue in stomach
152
what is a hamartoma
excessive focal overgrowth of cells and tissue native to the organ in which it occurs
not normal architecture
can be clonal like neoplasm
153
what are the common tumors in children
soft tissue tumors of mesenchymal derivation
154
what is the most common type of tumor in infancy
hemangioma
155
what do hemangiomas look like
flat to elevated, irregular, red-blue masses
156
what disease do hemangiomas present in
VHL
157
what are the familial hemangiomas
CNS cavernouse
158
What are lymphangiomas characterized by
cystic and cavernous spaces
| may occur in skin but more common in deeper regions: neck, axilla, mediastinum, retroperitoneal tissue
159
what causes lymphangiectasis
abnormal dilation of preexisting lymph channels
diffuse swelling of part of all of an extremity
distortion and deformation as consequence of spongy, dilated subQ and deeper lymph
lesion is not progressive and does not extend beyond original location
160
fibromatosis
richly cellular lesions indistinguishable from fibrosarcomas in adults
161
describe genes involved with fibrous tumors
ETV6-TRKC constitutively active and stimulates signaling thru oncogenic RAS and PI-3K/AKT
ETV6-NTRK3 fusion transcript is unique to infantile fibrosarcomas
162
differentiate between mature and immature teratomas
mature is benign: well differentiated cystic and more common <4 mo old
immature: lesion of intermediate potential
163
what is the most common teratoma in infants
sacrococcygealteratoma- 40% all cases
| more common in girls and associated with congenital anomalies
164
what are the main differences of malignant tumors in adults and children
incidence and type
close relationship between development(teratogenesis) and tumor induction (oncogenesis)
tendency of fetal and neonatal malignancies regress spontaneously
improved survival for childhood tumors
165
what are the most common tumors from in children
hematopoietic, nervous system, soft tissue, bone and kidney
166
what is the most common leukemia
acute lymphoblastic leukemia, more deaths in kids under 15 than other cancers combined
167
what are other common childhood tumors that arise before 10 years old
```
neuroblastomas
wilms tumor
hepatoblastoma
retinoblastoma
rhabdomyosarcoma
teratoma
ewing sarcoma
juvenile astrocytoma
medulloblastoma
ependymoma
```
168
differentiate between mature and immature teratomas
mature is benign: well differentiated cystic and more common <4 mo old
immature: lesion of intermediate potential
169
what is the most common teratoma in infants
sacrococcygealteratoma- 40% all cases
| more common in girls and associated with congenital anomalies
170
what are the main differences of malignant tumors in adults and children
incidence and type
close relationship between development(teratogenesis) and tumor induction (oncogenesis)
tendency of fetal and neonatal malignancies regress spontaneously
improved survival for childhood tumors
171
what are the most common tumors from in children
hematopoietic, nervous system, soft tissue, bone and kidney
172
what is the most common leukemia
acute lymphoblastic leukemia, more deaths in kids under 15 than other cancers combined
173
what are other common childhood tumors that arise before 10 years old
```
neuroblastomas
wilms tumor
hepatoblastoma
retinoblastoma
rhabdomyosarcoma
teratoma
ewing sarcoma
juvenile astrocytoma
medulloblastoma
ependymoma
```
174
what is a blastoma
primitive rather than pleomorphic-anaplastic appearance
175
what do blastomas look like histologically
small round blue cell tumors
176
neuroblastic tumors include what other structures
sympathetic ganglia and adrenal medulla because are derived from primordial neural crest cells
177
what is the most freq Dx tumor of infancy
neuroblastoma
178
what germline mutation is associated with neuroblastomas
ALK
179
what is the survival range for children with neuroblastomas
5yr for 40%
180
which agegroup of children has a better prognosis for neuroblastomas?
younger than 18 mo
181
40% neuroblastomas are where
adrenal medulla
182
what are the other common places for neuroblastomas
paravertebreal region of abdomen and posterior mediastinum
183
what do neuroblastomas look like
soft gray-tan tissue sometimes with a pseudo capsule
| larger ones have an area of necrosis and systic softening and hemorrheage
184
what do the cells look like in a neurooblastoma
small with dark nuclei, scant cytoplasm and poorly defined cell borders growing in solid sheets
185
What is neurophil
eosinophilic fibrillary material that corresponds to neuritic processes of the primitive neuroblasts
186
what is a ganglioneuroblastoma
ganalgion cells in various stages of maturation found in tumors admixed with primitve neuroblasts
187
what is a ganglioneuroma
better differentiated lesions with many more large cells resembling mature ganglion cells with few residual neuroblasts
188
What are schwann cells indicative of in a neuroblastoma
malignant clone
189
what is a stage 1 neuroblastoma
localized tumor with complete gross excision, ipsilateral nonadherent nodes, negative for tumor
190
what is a stage 2A neuroblastoma
localized tumor with incomplete gross resection, ipsilateral nonadherent nodes negative for tumor
191
what is a stage 2B neuroblastoma
localized tumor with or without complete gross excision, ipsilateral non adherent nodes positive for tumor
enlarged contralateral nodes negative for tumor
192
What is a stage 3 neuroblastoma
unresectable unilateral tumor infiltrating across midline with or without regional lymph involvement or localized unilateral tumor with contralateral regional lymph node involvement
193
what is a stage 4 neuroblastoma
any primary tumor with dissemination to distant nodes, bones, bone marrow, liver and skin
194
what is a stage 4S neuroblastoma
localized primary tumor with disssemination limited to skin, liver and or bone marrow
infants younger than 1y/o
195
what are symptoms of neuroblastoma
usually under 2 present with abdominal masses, fever and possible weight loss
older children have bone pain, respiaratory symptoms or GI complaints
196
how do neuroblastomas metastasize
through blood or lymph
| raccoon eyes
197
What explains the neonate blueberry muffin baby phenomenon in neuroblastomas
multiple cutaneous metastases that cause dark blue discoloration of the skin
198
What is commonly secreted in neuroblastomas
catecholamines
199
What molecular event in neuroblastomas has most profound prognostic impact
the amplification of the N-MYC oncogene
200
Where is the N-MYC
2p23-24
201
what does near diploid NB mean
more aggressive, harbor genetic instability with unbalanced translocations and chromosomal rearrangements
202
what does hyper-diploid NB mean
better prognosis
203
what deletion is correlated with N-MYC amplification
hemizygous deletion 1p36
| hemizygous loss 11q
204
what mutation is assoc with NB that does not involve amplification of N-MYC
gain of distal long arm chromosome 17
205
What is a favorable prognostic factor in NB that we can trace
high TrkA
206
What is the most common primary renal tumor of childhood
Wilms tumor
207
when does wilmd tumor peak
between 2 and 5 years old
208
What is WAGR syndrome and what is it assoc with
```
aniridia, genital anomalies, mental retardation
deletion 11p13
WT1 wilms tumor assoc gene
PAX6 gene for aniridia
"first hit" for Wilms tumor
33% likely to develop Wilms tumor
```
209
what is Denys-Drash syndrome
gonadal dysgenesis
glomerular lesion (diffuse mesangial sclerosis)
missense mutation of WT1 gene
higher risk for Wilms
210
What is Beck-Wiedmann syndrome BWS and what is it assoc with
organomegaly, macroglossia, hemihypertophy, omphalocele, adrenal cytomegaly
WT2 11p15.5 normally expressed on one allele other imprinted
so imprinting abnormality of IGF2
increased risk for Wilms tumor
also increased risk for hepatoblastoma, pancreatoblastoma, adrenocortical tumors and rhabdomyosarcomas
211
What is the role of B-catenin in wilms tumors
gain of function mutations in 10%
212
what are nephrogenic rests
putative precursor lesions in renal parenchyma seen with wilms tumors
100% with b/l tumors
213
a nephrogenic rest in the R kidney means what
increased risk of wilms tumor in L kidney
214
what do wilms tumors look like
solitary, well-circumscribed mass
| soft, homogenous tan and gray with occasional foci of hemorrhage, necrosis and cyst formation
215
What is the triphasic combination of wilms tumors
blastemal, stromal and epithelial
216
what is the epithelial differentiation in wilms tumors
abortive tubules or glomeruli
| stromal cells-fibrocytic or myxoid
217
what additional mutation is present in wilms tumors rendering them resistant to chemo
p53 mutations causing hyperchromatic pleomorphic nuclei with abnormal mitoses
218
What are signs of wilms tumor in a child
large abdominal mass that is unilateral or may exten across midline and down to pelvis
hematuria, pain in abdomen, intestinal obstruction and appearance of HTN
could have pulm metastasis
219
Are wilms tumors curable
yes if don't have p53 mutation (anaplastic)
220
which genetic defects of wilms have adverse prognosis
loss of DNA on 11q, 16q and gain on 1q in tumor cells
221
even if wilms patients survive what are they at increased risk of
second primary tumor from treatment
222
where do the galactose metabolites build up first in the brain
dentate of cerebellum and olivary nuclei of the medulla
