PRENATAL DIAGNOSIS Flashcards
INTRINSIC abnormality “programmed” in development
MALFORMATION
Spina bifida
Omphalocele
Fetus develops abnormally because of EXTRINSIC MECHANICAL FORCES imposed by uterine environment
DEFORMATION
Limb contractures that develop w/ oligohydramnios from bilateral renal agenesis
More severe change in form or function that occurs when genetically normal tissue is modified as a result of a specific insult
DISRUPTION
damage from an amniotic band –> limb reduction defect
Cluster of several anomalies or defects that have the same cause
SYNDROME
Trisomy 18
Anomalies that all developed sequentially from one initial insult
SEQUENCE
Pierre-Robin Sequence - micrognathia, glossoptosis
Group of specific abnormalities that occur frequently but do not seem to be linked etiologically
ASSOCIATION
VACTERL association - > 3 of the ff Vertebral defects Anal atresia Cardiac defects TracheoEsophageal fistula Renal anomalies Limb abnormalities
Inherited from 1 parent w/ the disease via a SINGLE GENE DEFECT
Autosomal Dominant
Required 2 affected alleles
Autosomal Recessive
Carried by MOTHER who is UNAFFECTED and passed only to SONS
X-linked disorders (hemophilia, fragile X)
Mothers –> sons and daughters
Fathers –> daughters
X-linked dominant
Aicardi syndrome - LETHAL in MALE
Presence of one or more extra chromosomes –> trisomy, or loss of chromosome monosomy
ANEUPLOIDY
> 50% of 1st trimester abortions
1st Trimester Aneuploidy Screening
11 and 14 weeks of gestation
human chorionic gonadotropin (hCG)
pregnancy associated plasma protein A (PAPP-A)
sonographic measurement of the nuchal translucency (NT)
DOWN SYNDROME
HIGHER b-hCG and LOWER PAPP-A
Increased nuchal translucency (NT) is associated with
various birth defects - FETAL CARDIAC ANOMALIES
2nd Trimester Aneuploidy Screening
15 - 21 weeks of gestation
DOWN SYNDROME
DECREASED - maternal serum AFP and unconjugated estriol
INCREASED hCG and dimeric inhibin levels
TRISOMY 18
DECREASED - maternal serum AFP, unconjugated estriol, hCG
QUAD SCREEN TEST
- alpha fetoprotein (AFP)
- beta human chorionic gonadotropin (b-hCG)
- unconjugated estriol
- dimeric inhibin A (DIA)
Maternal Serum Estriol Level
DECREASED
Smith Lemli Opitz Syndrome
Steroid Sulfatase Deficiency (X-Linked Ichthyosis)
AR condition
mutations in 7-DEHYDROCHOLESTEROL REDUCTASE GENE
Smith Lemli Opitz Syndrome
abnormalities of the CNS, heart, kidney and extremities
w/ ambiguous genitalia
fetal growth restriction
AR disease
d.t. abnormality in the cystic fibrosis transmembrane conductance regulator (CFTR) - responsible for chloride channels
CYSTIC FIBROSIS
chronic lung disease d.t. recurrent infections –> irreversible lung damage and strain on right ventricle (COR PULMONALE)
pancreatic insufficiency (85%)
AR disease
caused by a SINGLE point mutation in the gene for the BETA chain in hemoglobin –> hemoglobin (Hb S) –> polymers that when deoxygenated –> lose their biconcave shape and sickled appearance
HEMOGLOBIN ELECTROPHORESIS - maternal screen
SICKLE CELL ANEMIA
hemolytic anemia
shortened life expectancy
pain crises
AR lysosomal storage disease
absence of the HEXOSAMINIDASE A –> accumulation of GM2 GANGLIOSIDES in the CNS, progressive neurodegeneration and death
brain - GRAY MATTER - highest concentrations of GANGLIOSIDE
TAY SACHS DISEASE
loss of alertness, hyperacusis
progressive developmental delay and neurologic degeneration
myoclonic and akinetic seizures
CHERRY RED SPOT
paralysis, blindness and dementia
Typical phenotype of Down Syndrome
short stature
classic facies
developmental delay
mental retardation - 40 - 90
cardiac defects
duodenal atresia
stenosis
short limbs
1st trimester screen (TRIPLE SCREEN)
nuchal translucency
PAPP-A
hCG
Lethal aneuploidy; nearly all neonates dies in the first 2 years of life
TRISOMY 18 (EDWARD Syndrome)
associated w/ MULTIPLE CONGENITAL ANOMALIES
clenched fists, OVERLAPPING digits and ROCKER BOTTOM FISTS
cardiac defects - VSD, TOF omphalocele congenital diaphragmatic hernia neural tube defects choroid plexus cysts
Has many similar findings w/ Trisomy 18
holoprosencephaly cleft lip and palate UMBILICAL HERNIA cystic hygroma single nostril or absent nose omphalocele
cardiac anomalies - hypoplastic left heart
limb anomalies - clubfoot and clubhand, polydactyl and overlapping fingers
The MC sex chromosome aneuploidies
Turner syndrome (45, X or monosomy X) Klinefelter syndrome (47, XXY)
Phenotypically FEMALE, SHORT STATURE
Turner syndrome (45, X or monosomy X)
primary amenorrhea, sexual infantilism, webbed neck, low set ears, low posterior hairline, epicanthal folds
wide carrying angle of the arms, shield like chest
wide set nipples
short 4th metacarpal
renal anomalies
lymphedema
COARCTATION OF THE AORTA
The only anomaly in Turner syndrome seen in ultrasound
CYSTIC HYGROMA
Klinefelter syndrome (47, XXY)
infertility
gynecomastia
mental retardation
elevated gonadotropin levels d.t. decreased levels of circulating androgens
Formation of neural tube begins on
Days 22-23 (WEEK 4) - 4th and 6th somites
ANTERIOR neuropore (FUTURE BRAIN) - closes on day 25
POSTERIOR neuropore (FUTURE SPINAL CORD) - closes on day 27
Neural Tube Defects (NTDs)
Spina Bifida
Anencephaly
Classic Ultrasound Findings of Spina Bifida
“lemon” sign - concave frontal bones
“banana” sign - cerebellum that is pulled caudally and flattened
Neural Tube Defects (NTDs)
Spina Bifida
Anencephaly
Classic Ultrasound Findings of Spina Bifida
“lemon” sign - concave frontal bones
“banana” sign - cerebellum that is pulled caudally and flattened
Typically performed b/w 10 and 13 weeks gestation
Specimen is sent for karyotyping or CMS
Chorionic Villus Sampling
Results from RENAL FAILURE –> anhydramnios –> pulmonary hypoplasia and contractures/deformations of the limbs in the fetus
Potter Sequence
bilateral renal agenesis
Kidneys development begins in
WEEK 4
PRONEPHROS
MESONEPHROS- WEEK 5 – mesonephric duct (Wolffian duct)
- URETERIC BUD - offshoot of the mesonephric duct that dilates and subdivides to form URINARY COLLECTING SYSTEM (collecting tubules, calyces, renal pelvis and ureter)
- (+) testosterone –> mesonephric duct (males) –> vas deferens, epididymis, ejaculatory duct and seminal vesicles
- (+) testosterone –> mesonephric duct (females) –> degenerates EXCEPT for the vestigial Gartner’s duct
METANEPHROS - week 5; WEEK 9 - FUNCTIONING
ureteric bud from the mesonephric duct contacts the metanephros and induces it to form nephrons
RENAL AGENESIS - failure of contact
Renal anomalies that are without much consequence
Horseshoe kidney
Ectopic kidney
Double ureter
Common Risks of Amniocentesis
pregnancy loss infection (chorioamnionitis) PPROM fetal injury (w/ needle) exposure to the mother of fetal cells (alloimmunization of mother)
ELEVATED MSAFP
spina bifida
meningomyelocele
anencephaly
omphalocele
gastroschisis
previa, accreta
Increased incidence of NTD
diabetes
women with seizure disorders - AED - carbamazepine, valproic acid
Ultrasound findings in Down syndrome
AV CANAL DEFECT - classic cardiac anomaly
PYLORIC STENOSIS
