GENETICS Flashcards
Fanaroff 10, 11,12,14,15,16 11 edition
1
Q
number of chromosomes in humans
A
23 pair of chromosomes
2
Q
autosomes
A
identical chromosomes (22 pairs in both genders)
3
Q
women homologous chromosomes
A
XX
4
Q
men nonhomologous chromosomes
A
XY
5
Q
linear DNA
A
histones (protein) form of chromatin
6
Q
centromere
A
short arm (p arm) and long arm (q arm)
7
Q
metacentric chromosome
A
arm length is equal
8
Q
submetacentric chromosome
A
one arm is longer than the other
9
Q
acrocentric
A
p arm is neglected (example: 13,14,15,21,22)
10
Q
telomeres
A
the ends of each chromosome
11
Q
karotype
A
analyze chromosomes
12
Q
chromosome disorders
A
structural or numerical
13
Q
advanced maternal age
A
35 or more at the expected date of confinement
14
Q
numerical abnormalities
A
triploidy and tetraploidy; aneuploidy;
15
Q
triploid
A
three sets of chromosomes (69 total); fertilization by two sperm; rarely born alive; poor survival
16
Q
tertaploid
A
96 chromosomes, fetus miscarried in the first trimester
17
Q
aneuploidy
A
any genotype in which total chromosome number is not a multiple of 23
18
Q
monosomy
A
type of aneuploidy; only one representative of particular chromosome; not viable expect TURNER syndrome (monosomy X)
19
Q
trisomy
A
type of aneuploidy; three copies of particular chromosome ; chromosomes 13, 18, 21, X, and Y compatible with life
20
Q
structural abnormalities
A
chromosomal breakage followed by anomalous reconstruction; balance or unbalanced; deletions, insertions, ring chromosomes, isochromosomes, translocation
21
Q
Robertsonian translocation
A
two acrocentric chromosomes lose their short arms and fuse near the centrometric region; phenotypically normal but have risk of producing unbalanced gametes involving chromosome 21 (downs)
22
Q
single-gene disorders
A
4000 diseases; Mendelian inheritance; types: autosomal dominant disorders, autosomal recessive disorders, sex-linked disorders
23
Q
alleles
A
variants of gene
24
Q
autosomal dominant disorders
A
vertical pattern of transmission (phenotype in every generation); 50% risk; example: osteogenesis imperfecta;
25
advanced paternal age
40+, not clear;
26
autosomal recessive disorders
individual possessess two mutant alleles that were inherited from heterozygous parents; horizontal transmission (appears in more than one member of the family: sibllings); example: cystic fibrosis
27
consanguineous unions
mating between individuals who are second cousins or closer
28
sex-linked disorders
hemophilia A; X-linked recessive disorder; male disorder
29
Non-Mendelian patterns of inheritance
mitochondrial inheritance; epigenetics and uniparental disomy; trinucleotide repeat expansion
30
mitochondrial inheritance
maternal inheritance, replicative segregation, and heteroplasmy; examples: CNS or MS systems: MERRF, MELAS, NARP, LHON, MNGIE; dysfunction of high energy consuming organs like brain, muscle, heart, kidneys; poor growth, muscle weakness, loss of coordination, developmental delay;
31
epigenetics
modification of genes that determines whether a gene is expressed or not
32
imprinting
phenomenon in which genetic material is differently expressed depending on whether it was inherited from FOB or MOB
33
uniparental disomy
inheritance of a pair of homologous chromosomes from one parent (normally one chromosome is inherited from each parent); example: Prader-Willi syndrome; Angelman syndrome
34
trinucleotide repeat expansion
mutations occur and get passed on to next generation; ; examples: congenital myotonic dystrophy, Huntington disease, Friedreich ataxia, fragile X syndrome
35
Fragile X Syndrome
1 in 4000; at risk for adult onset cerebellar dysfunction; family and personal HX of delay or retardation or tremor should get screened for it
36
Multi-factorial Inheritance /Complex
genetics, environmental and gene-gene interactions; examples: neural tube defects(NTD): spina bifida and anencephaly;
37
Complex Inheritance: ANENCEPHALY
forebrain, meninges, bone and skin are absent; stillborn
38
CompleX Inheritance: NTD
incomplete fusion of vertebral arches; lack of folic acid,
39
Teratogens
medications, maternal conditions, infections
40
all or non period
first two weeks after conception; lethal or no adverse effect
41
diagnostic imaging
ionizing radiation; ; dental xray ok(less than 5 rad); exposure more than 10 rad increase rick for malformations; iodinated contrast: might effect fetal thyroid); MRI not contradicted; US not contradicted
42
congenital abnormalities occur in
3-4% live births
43
congenital abnormalities categories
malformation, deformation, disruption
44
malformation
intrinsic abnormalities in the genetic programs controlling development;
45
deformation
extrinsic factors physically imprinting on otherwise normal tissue;
46
arthrogryposis
contractures of the extremities due to prolonged leakage of AF resulting in fetal crowding
47
disruptions
consequence of fetal tissue destruction: vascular insufficiency or mechanical damage
48
ultrasound examination categories
limited(placental location), standard(18-20 weeks check up), specialized/targeted(fetal ECHO)
49
first trimester US (10-13.6 weeks)
confirm pregnancy, estimate GA, evaluate pelvic anatomy; aneuploidy screening: nuchal transluency (70% downs) ; in the future might be replaced by NIPS;
50
second trimester US (15-22.6 weeks)
fetus anatomy : fetal number, presentation, cardiac activity, AF and placental characteristics; fetal organ survey
51
triple screen
maternal serum AFP, hCG, unconjugated estriol
52
cell free DNA screening
maternal blood screen; non-invasive prenatal screening (NIPS)-cant replace prenatal diagnosis;
53
NIPS non invasive prenatal screening
tests for aneuploidy (trisomy), (not recommended for microdeletions,) deletions and duplications
54
Serum Alpha-fetoprotein (AFP)
(15-20 weeks); screens for NTDs; false positive if contaminated with blood
55
screening for hemoglobinopathies
CBC early in pregnancy; for all women; if at rick then test FOB
56
carrier screening for Cystic Fibrosis
mutation of chromosome 7; s&s: chronic pulmonary disease, pancreatic insufficiency, liver disease; CTFR gene;
57
Jewish Carrier Screening
Ashkenazi heritage
58
carrier screening for Spinal Muscular Atrophy (SMA)
progressive neuromuscular disease resulting from degeneration of spinal alpha neurons; offered to all couples
59
diagnostic modalities
chorionic villus sampling (CVS), amniocentesis, cordocentesis
60
Chorionic Villus Sampling
small sample of the placenta; 10-13 weeks; often same karyotype as fetus; NOT for Alpha-fetoprotein, NOT for NTDs;
61
Amniocentesis
withdrawal of AF (20-30 ml) from the uterine cavity; prenatal genetics and lung maturity; 15-22 weeks; used to test NTDs, FISH
62
karyotyping
Giemsa stain; analysis of banding pattern; advantage: whole genome analyzed at one time
63
FISH
fluorescence microscopy; advantage: can be applied to non-dividing and dividing cells; ; disadvantage: structural abnormalities can be missed;
64
microarray technology
gene expression analysis; detect smaller changes than karyotype;
65
future in PRENATAL diagnostics
next generation sequencing, WES and WGS;
66
Assisted Reproductive Technologies
IVF
67
Genetic Evaluation and Counseling
family and personal HX; ethnic background; tetatogen exposure; abnormal US; previous pregnancy loss
68
Fetal Imaging Techniques
B-mode: standard (confirmation of cardiac activity and fetal movement; M-mode (arrhythmia, myocardial contractility, pericardial effusions); doppler US (color and power): sound and color; three-dimensional US;
69
diagnostic US energy
bioeffects: heating and cavitation;
70
application of US
genetic screening, assisted reproduction(complications), multiple gestation(3% of all pregnancies); standard method for recognition of fetal anomalies
71
US fetus with Downs anomalies
endocardial cushion defect, duedenal atresia, small atrioseptal and vantriculoseptal cardiac defects; thickened nuchal fold
72
monochorionic TTTS
shared perfusion: restricts growth and AF production in the donor, and causes volume overload, cardiac dysfunction, polyhydramnios in the reciepient
73
Twin Reversed Arterial Perfusion TRAP
"pump twin" vs "acardiac/parabiotic twin" flow in the artery and veins are reversed
74
sonographic measurements and US parameters
basis for accurate GA and detection of fetal growth abnormalities
75
Biparietal diameter
parietal bone calsification in 12 week; closest correlation with GA in the 2nd trimester
76
US fetal growth assessment/ fetak biometry
BPD (biparietal diameter), head circumference, abdominal circumference, femoral length; no golden standard, in third semester usually undetected
77
Placental abnormalities US
US is ultimate diagnosis for placental DX; placental location;
78
funic
umbilical cord
79
vasa previa
fetal vessels overlying the os
80
placenta previa
common source of severe third semester bleeding
81
Amniotic Fluid Volume
16weeks done by renal production; 24h turnover; 1000ml
82
polyhydramnios
malformations of esophagus and upper GI, inhibited fetal swallowing, aneuploidy, intermittent renal obstruction, maternal DM, TTTS, dwarfisms, fetal hydrops; usually idiopathic; more than 2000ml
83
oligohydramnios
after membrane rupture, urogenital anomalities; maternal dehydration; meds: indomethacin, ACE inhibitors;
84
cervical length US
correlates with duration of gestation; under 25mm increase premature labor; cerclage
85
doppler US
identification and localization of blood flow; abnormal doppler US presese growth restriction and maternal HPT complications;
86
Biophysical Profile (BPP)
non-invasive US-based clinical tool; (1) tidal fetal breathing, (2)AF pocket (3)three fetal movements (4)fetal tone (5) reactive NST
87
Hydrocephalus
raised intracranial pressure, not done by US; does NOT happen with NTDs;
88
fetal ventriculomegaly
10mm
89
Meningomyelocele and Chiari Malformation (type II)
downward displacement of the hindbrain;
90
"lemon sign"
altered appearance of calvarium; 18-24 weeks; DX of spina bifida
91
"banana sign"
abnormal cerebral positioning; DX of spina bifida
92
anencephaly
absence of normal brain; 10 weeks; alpha fetoprotein very elevated; cause abnormal prolongation of pregnancy; no survival
93
encephalocele
extracranial protrusion of brain tissue
94
holoprosencephaly
malformation of brain resulting from early failure of division; trisomy 13; 11-14 weeks, butterfly sign
95
Choroid Plexus Cyst
usually resolve by early 3rd trimester; normal karyotype; associated with trisomy 18
96
spine US
3D imaging; sacrococcygeal tetratomas (SCTs) congenital germ cell tumors; uncomplicated SCTs prognosis is excellent;
97
head and neck US
14 weeks; orbits, facial clefting; nasal bones;
98
cystic hygroma US
mass arising from neck and occipital region secondary to lymphatic malformation; monosomy X;
99
heart US
18-22 weeks; four chambers and great arteries at 13-14 weeks;
100
GI US
esophageal atresia and Tracheoesophageal Fistula; small bowel obstruction( "double-bubble", trisomy 21) anterior abdominal wall defect (omphalocele, gastroschisis); Diaphragmatic hernia and thoracic lesion (fluid filled intrethoracic bowel loops, mass effect on lungs causing: pulmonary hypoplasia, and secondary pulmonary HPT; fetal hydrops (accumulation of fluid); gallbladder and bile ducts
101
GU US
kidneys 12-14 weeks; bladder;
102
Potter syndrome
prolonged oligohydramnios, characteristic facial apperance, limb deformities, pulmonary hypoplasia
103
anhydramnios
no measurable fluid in the bladder
104
pyelectasis
dilation of the renal pelvis, 4-7mm
105
hydronephrosis
dilation of the renal pelvis 1cm
106
MS US
skeletal dysplasia (falling below 3SD measure)
107
phocomelia
extreme generalized limb reduction or absence
108
micromelia
overall limb shorthening
109
rhizomelia
proximal reduction (femurs and humeri)
110
mesomelia
more distal reduction (forearms and lower legs)
111
acromelia
most distal reduction (hands and feet)
112
dysostosis
absence of various skeletal portions
113
two vessel umbilical cord
restricted growth, serial third trimester examination recommended
114
antepartum
testing done remote from delivery
115
intrapartum
testing done during labor
116
antepartum fetal surveillance
MOB subjective assessment "kick counts"; non-stress test (NST), CST, Biophysical profile, AF volume assessment; doppler flow velocimetry; if normal then usually performed on weekly basis
117
what alteres fetal biophysical paremeters?
hypoxemia and acidosis
118
non-stress test
NST: monitor FHR for up to 40 minutes, observe for HR accelerations; peak up 15bpm and last 15 sec; usually starts at 32-34 weeks
119
contraction stress test
CST: evaluate FHR in response; to maternal contractions; MOB had at least 3* 40 sec contractions in 10 minute period
120
biophysical profile
NST and US; 30 minute period, score can be only even number: 0-10;
121
AF volume assessment
US: measuring and adding the maximal vertical pockets of fluid
122
Doppler flow velocimetry
evaluation of fetus with possible IUGR
123
fetus respiratory acidosis
carbon dioxide accumulates secondary to impaired clearance by the lungs/placenta;
124
respiratory vs metabolic acidosis
check base deficit; high base deficit is caused by metabolic process
125
metabolic processes
more concerning than respiratory; excess tissue lactate generation; longer time to correct; result of prolonged or severe deprivation of oxygen, triggers lactate production in fetal tissues
126
respiratory acidosis
low umbilical ph, low 1-minute apgar; faster to correct through proper ventilation
127
continuous electronic FHR monitoring
externally and internally(contradicted with hepatitis and HIV);
128
continuous FHR recordings
FHR baseline 110-160bpm;
129
primary response to hypoxemia
tachycardia secondary to sympathetic discharges
130
FHR variability
fluctuation in FHR baseline of two cycles per minute or greater, with irregular amplitude and inconstant frequency
131
FHR accelerations
periodic elevations above baseline, always reassuring; but absence is not concerning
132
FHR decelerations
episodic decreases below the baseline; "early": increases in intracranial pressure; "variable":systemic vascular resistance; "late": hypoxemia ; recurrent(50%) or prolonged(2 minutes)
133
early decels
shallow and symmetric, gradual in onset and recovery same time as the peak of contraction; Cushing reflex; unrelated to fetal oxygenation and acid-base balance
134
variable decels
abrupt onset and abrupt return to baseline; vary in shape, duration, and depth; associated with compression of umbilical cord(can lead to presence of umbilical cord compression, oligohydramnios, prolapse of cord through the cervix); maternal position changes can solve "decels"
135
late decels
more gradual onset and return baseline (30sec); occur after the contraction; caused by hypoxemia and tissue level hypoxia; resolved my positional change, oxygen supplementation, two mechanisms of action ;)
136
fetal tracing categories
category I: normal (110-160, moderate variability, absence of late and variable decels; early decels ok, accelerations may or may not be present
category II: indeterminate tracing
category III: abnormal (absent baseline with any of these:-recurrent late decels, recurrent variable decels, bradycardia; and sinusoidal pattern
137
how to manage patterns during labor?
rule out immediate delivery: cord prolapse, placental abruption, or uterine rupture
rule out meds and MOB BP
rule out frequent contractions not allowing for recovery (oxytocin)
change maternal position: lateral recumbent
give supplemental oxygen
give fluids: amnioinfusion
138
The Developmental Origins of Health and Disease / DOHaD
field of study that explores the relationship between exposure to environmental stressors during critical periods of fetal development and adverse health outcomes that occur across a lifetime; originally published by Baker
139
preconceptual effects
epigenome; maternal and paternal exposures
140
epigenetics
study of phenotypic changes occurring in the absence of modification of DNA sequence; genomic imprinting; mechanism: DNA methylation, alternation of expression patterns in micro RNA, modification of histone proteins
141
genomic imprinting
silencing of one parental allele leading to monoallelic gene expression; differential expression of specific genes according to parental origins
142
maternal exposure
active smoking; environmental toxicants; DES (given to prevent miscarriage) can cause your offspring infertility
143
paternal exposure
environmental toxicants: pesticides, can cause offspring infertility and/or cancer, and birth defects
144
maternal body burden
adipose tissue stores chemicals, bones store lead and fluoride; PCBs ; Lead
145
maternal exposures concurrent with pregnancy
occupation and paraoccupational: lead, mercury, pesticides, organic solvents, ionizing radiation; air pollution; drinking water; diet
146
pathways of fetal exposure
placenta-dependent: by crossing the placenta
| placenta- independent: radiation, heat, noise,
147
fetal pharmacokinetics
absorption: increase in progesterone prolongs gastric emptying, slows GI; hyperventilation...then increases overall exposure
distribution: increased fat, increased fluid volume, AF, prolongs elimination....causing prolonged overall exposure
metabolism: increase, ontogeny of fetal phase I and phase II metabolism in the liver, genetic polymorphisms in drug metabolizing enzymes
148
specific exposure
cigarette smoking, ethanol, pesticides, Bisphenol A, S, f; Phthalates, organic solvents,
149
epigenetic transgenerational inheritance
epimutations in the germline (egg or sperm) that are passed to future generations and leads to variations in phenotypic expressions
150
active cigarette smoking during pregnancy
reduced fertility, placental dysfunctions, spontaneous abortions, IUGR, PTL, congenital anomalities, SIDS
151
Fetal Alcohol Spectrum Disorder vs FAS
extreme end spectrum: characteristic facial features, and neurodevelopmental impairment
152
pesticides
neurotoxins; endocrine disruptors, immunotoxicants, carcinogens
153
BPA and phthalates (PVC)
plastic, BPA- estrogeic, PVC-anti-androgenic
154
Organic solvents
household cleaning supplies, teratogens
155
"normal" fetal growth
10-90 percentile for GA
156
SGA
less than 10 percentile
157
IUGR
all fetuses with evidence of malnutrition or in utero growth restriction, can include infants above 10 percentile; 10% of all live born infants; suboptimal nutrient and oxygen provision to the fetus, often secondary to poor placental perfusion; fetal growth less that its genetic potential
158
complications of IUGR
short: hypoglycemia, hyperbili, hypothermia, RDS
long: neurodevel delays, cardiometabolic (obesity, DM2, CV disease)
159
asymmetric IUGR
decrease in intrauterine nutrition and oxygen; nutrients go to vital organs: brain and heart; disproportionately HC compared to weight; manifests in third semester; "head-sparing"; more common; placental insufficiency
160
symmetric IUGR
proportionately low measurements of HC, weight and length; less common; detected earlier in pregnancy, genetics or chromosomal; pregnancy infections (rubella, TORCH, malaria)
161
etiology of IUGR
maternal, fetal, placental, environmental factors, or combination
162
fetal IUGR
asymmetric: genetics;
symmetric: chromosomal trisomy 13, 18, 21; structural
163
maternal IUGR
asymmetric: age, parity, race, nutrition; medical conditions and DX,
symmetric: advanced maternal disease: severe HPT
164
environmental IUGR
asymmetric: teratogen exposure, substance abuse, altitude, assisted reproductive technology
symmetric: infectious disease(malaria, rubella, CMV, syphilis)
165
placental IUGR
multiple gestation, insufficiency(most common of all for IUGR), placental disorders and umbilical cord abnormalities;
166
pathophysiology IUGR
chromosomal (decrease number of fetal cells); hormones: insulin, thyroid, adrenal, pituitary
167
antenatal screening IUGR
maternal and family HX; maternal physical exam (fundal height measurment); fetal US (four biometric measurements) : best predictor- abdominal circumference; Doppler velocimetry: umbilical artery (absent or reverses end-diastolic flow)
168
hypoglycemia IUGR
suboptimal glycogen stores, impaired gluconeogenesis; formula, gavage, IVF
169
hypothermia IUGR
decreased brown fat; exogenous heat (incubator)
170
RDS IUGR
pulmonary vascular remodeling; support respiratory care
171
NEC IUGR
especially AEDF and REDF; exclusive breast milk, trophic feeds
172
other issues DX with IUGR
IVH, electrolyte abnormalities, jaundice/polycythemia, abnormal immunity
173
adaptive mechanisms and intrauterine environment
create finely crafted "thrifty" phenotype that may tip towards a disease state
174
imprinting disorders due to IVF
Beckwith-Wiedemann, Angelman, Prader-Willi syndromes, hypomethylation syndrome
175
low weight and slow growth pattern followed by exponential growth during childhood causes what?
metabolic syndrome
176
postnatal "catch-up" growth
result in adiposity (too much white adipose tissue), sets adults for metabolic syndrome, DM, and coronary artery disease
177
mismatch concept
the earlier the deprivation phase is followed by catch-up growth, the more significant the consequences in adult life
178
placental abnormalities and adult chronic disease
HPT and CHD
179
Gestational DM and long-term effect on offspring
obesity, insulin resistance, DM2
180
high estrogen in pregnancy effects on offspring
high estrogen in advanced maternal age, twins and LGA can cause PIH, cancer
181
chronic antenatal and postnatal stress
neurodevelopmental impairments;
182
tocometry
contractions monitoring
