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1) The event is a surprise (to the observer)
2) The event has a major effect.
3) After the first recorded instance of the event,
it is rationalized by hindsight, as if it could have
been expected; that is, the relevant data were
available but unaccounted for in risk mitigation
programs. The same is true for the personal
perception by individuals
 The disproportionate role of high-profile,
hard-to-predict, and rare events that are
beyond the realm of normal expectations in
history, science, finance, and technology
 The non-computability of the probability of
the consequential rare events using
scientific methods (owing to the very nature
of small probabilities)
 The psychological biases that make people
individually and collectively blind to
uncertainty and unaware of the massive role
of the rare event in historical affairs
 Unlike the earlier philosophical "black swan
problem," the "black swan theory" refers
only to unexpected events of large
magnitude and consequence and their
dominant role in history. Such events,
considered extreme outliers, collectively
play vastly larger roles than regular
occurrences
Carneus Mole
 Synonym for fleshy mole ...
 A uterine mass occurring
 after fetal death and
 consisting of blood clots,
 fetal membranes, and placenta
 . ... Synonym: blood moles
Subchorionic hemorrhage
Breus Mole
 Maternal blood dissects from the decidua
vera around the placental villi and migrates
to the subchorionic region of the chorionic
plate on the fetal surface of the placenta
 A large proportion of cases end in abortion
or fetal death. Most remaining fetuses
develop IUGR and deliver preterm
Hydatidiform Mole
Partial Hydatidiform Mole
 Features of a partial or incomplete
molar pregnancy include some element
of fetal tissue and hydatidiform changes
that are focal and less advanced. There
is slowly progressive swelling within the
stroma of characteristically avascular
chorionic villi, whereas vascular vili that
have a functioning fetal-placental
circulation are spared
 For a Partial mole the karyotype is typically
triploid – 69, XXX,69XXY, or much less
commonly, 69,XYY. These are each
composed of one maternal and two
paternal haploid sets of chromosome.
Only 3 of 270 molar pregnancies studied
were tetraploid. The nonviable fetus
associated with a triploid partial mole
typically has multiple malformations. In
another study, 82% of fetuses had
symmetrical growth restriction.
 The risk of persistent trophoblastic
disease after a partial mole is substantially
lower than that following a complete molar
preganancy. Moreover, persistent disease
seldom is choriocarcinoma. 0.1% of partial
moles are complicated by
choriocarcinoma.
 Higher postevacuation Beta-hCG levels
correlated with increased risk for
persistent disease. Specifically, levels >=
200 mIU/mL in the third through eighth
week postevacuation were associated
with at least a 35% risk of persistent
disease.
Twin Molar Pregnancy
 a twin gestation composed of a complete diploid
molar pregnancy and a normal pregnancy is not
rare. 5% of diploid moles were part of a twin
pregnancy with a fetus. Survival of the normal
coexisting fetus is variable and depends on
whether the diagnosis is made, if so, whether
problems from the molar component such as
preeclampsia or hemorrhage develop.
Twin Molar Pregnancy
 45% progressed to 28 weeks and of these 70% of
neonates survived.
 A normal placenta supplies nutrition to one twin ,
and the co-pregnancy is a complete molar
gestation. Optimal management is uncertain, but
preterm delivery is frequently required because
bleeding or severe preeclampsia.
Twin Molar Pregnancy
 Compared with partial mole, women with these
types of twin pregnancies have a substantive risk
of developing subsequent gestational
trophoblastic neoplasia. This risk does not
appear greater than following a singleton
complete mole. 21% of pregnancies not
terminated subsequently required chemotherapy
for persistent disease.
Twin Molar Pregnancy
 This rate is not significantly different from the
rate of 16% among women who terminate their
pregnancies. In another series 25% of such twin
pregnancies subsequently needed chemotherapy
Bandl’s Ring
 Localized rings or constrictions of the uterus
develop in association with prolonged
obstructed labor that are seldom encountered
today. The pathological retraction ring of
Bandl is associated with marked stretching and
thinning of the lower uterine segment. The
ring may be seen clearly as a uterine
indentation and signifies impending rpture of
the lower uterine segment.
Bandl’s Ring
 Following birth of a first twin, a pathological
ring may still develop occasionally as
hourglass constrictions of the uterus. The
ring can sometimes be relaxed and delivery
effected with appropriate general
anesthesia, but occasionally prompt
cesarean delivery offers a better prognosis
for the second twin.
Chromosomal Microdeletions
 Some deletions are not large enough to be recognized
by traditional karyotyping and thus, molecular
cytogenetic techniques are required….These deletions
cause clinically recognizable syndromes that my
include serious but unrelated phenotypic
abnormalities. Deletions can occur in any region,
however, several are found more frequently than
expected by chance alone. This is thought to result
from a greater propensity for certain regions to break.
Chromosomal Deletions
Microarray
Chromosomal Deletions
Microarray
Microarray
 A DNA microarray (also commonly known as
DNA chip or (biochip) is a collection of
microscopic DNA spots attached to a solid
surface. Scientists use DNA microarrays to
measure the expression levels of large numbers
of genes simultaneously or to genotype
multiple regions of a genome. Each DNA spot
contains picomoles (10−12 moles) of a specific
DNA sequence, known as probes (or reporters
or oligos).
MICROARRAY
 These can be a short section of a gene or other
DNA element that are used to hybridize a
cDNA or cRNA (also called anti-sense RNA)
sample (called target) under high-stringency
conditions. Probe-target hybridization is
usually detected and quantified by detection of
flourophor-, silver-, or chemiluminecencelabeled targets to determine relative
abundance of nucleic acid sequences in the
target.
The Microarray
 Since an array can contain tens of thousands of probes, a
microarray experiment can accomplish many genetic tests
in parallel.
 In standard microarrays, the probes are synthesized and
then attached via surface engineering to a solid surface by
a covalent bond to a chemical matrix
 Specific arrays are designed to find sequences of bases
which have been identified with specific chromosomal
deletion areas in human disease
Wolf-Hirschorn Syndrome
 Wolf-Hirschhorn syndrome (WHS) refers to a
condition that is caused by a missing part (deletion) of
the short arm of chromosome 4. This missing genetic
material results in severe developmental delays, a
characteristic facial appearance, and may include a
variety of other birth defects.
 Some patients who have WHS may have a small
deletion on 4p, while others may be missing up to half
of 4p. For this reason, some individuals have a less
severe case of WHS than others do. The band 4p16.3
needs to be deleted in order for an individual to have
full expression of WHS.
Wolf-Hirschorn Syndrome
 WHS frequently presents prenatally with slow growth
(intrauterine growth delays). Some infants with WHS can
be stillborn or die shortly after birth. As many as one-third
of reported patients have died in the first year of life.
Individuals with WHS have been described as having a
characteristic facial appearance likened to a “Greek Helmet
facies.” This can be described as having a small head size
(microcephaly), eyes spaced widely apart (ocular
hypertelorism), downturned mouth, short upper lip and
short groove between the upper lip and nose (philtrum) or
bilateral cleft lip and small chin (micrognathia).
Wolf-Hirschorn Syndrome
 These children have severe developmental delays. Other
significant problems can include heart defects, cleft lip
and/or palate, hearing impairment, and eye problems.
Most children who have WHS have seizures
(approximately 90%). Seizures are one of the major health
concerns in children with WHS. These seizures begin
between five and 23 months of age, however
approximately 50% of the individuals stop having seizures
between age three and 11. Sleeping problems are also
common in children who have WHS. Although it seems
that most of the literature focuses on children who have
WHS, there are adults who have WHS.
De Novo Deletion
 Approximately 85–90% of cases of WHS occur as the
result of a new deletion in the affected individual. This
is also known as a de novo deletion and simply means
that the affected individual’s parents did not have any
chromosome arrangement that led to the deletion. In
this case, the chance for recurrence in
future pregnancies of a couple whom has an affected
child is not increased. In the remaining 10–15% of
cases, one of the parents of the affected individual
carries a balanced translocation.
Balanced Translocation
 When a parent is identified as being a carrier of a
balanced translocation, with each pregnancy they
have an increased chance for having a child with an
unbalanced chromosome arrangement. The chance of
this is determined by the individual’s specific
translocation, how it was identified, and which parent
is the carrier of the translocation. Genetic counseling
should be offered for any family in which a child is
diagnosed to have WHS. Other family members
should also be offered counseling and chromosome
analysis to determine if they are carriers of a balanced
translocation.
Angelman Syndrome
 dysmorphic facies – “happy puppet” appearance, mental
retardation, ataxia, hypotonia and seizures. 15q11.2q13
(maternal genes).
 normal stature and weight
severe mental
retardation
absent speech
seizure
disorder
ataxia and jerky arm movements
Paroxysms of inappropriate laughter
In about 70% of cases, Angelman’s is
caused by a microdeletion of disruption of the maternal
15q11-q13. In 2%, the syndrome is caused by paternal
uniparental disomy; and another 2-3 % are due to
imprinting with the maternal genes activated.
Uniparental Disomy
 both members of one pair of chromosomes are inherited
from the same parent, instead of one member being
inherited from each parent. Often, uniparental disomy
does not have clinical consequences. Some exceptions are
when it involves chromosomes 6, 7, 11, 14, 15. These
offspring are at increased risk for an abnormality tht
results from parent-of-origin differences in gene
expression. Although several genetic mechanisms may
cause uniparental disomy, the most common is ‘trisomic
rescue’. After a nondisjunction event produces a trisomic
conceptus, one of the three homologues may be lost. This
may result in uniparental disomy for that chromosomes in
a third of cases.
IMPRINTING
 a process by which certain genes are inherited in an
inactivated or transcriptionally silent state at one of the
parental loci in the offspring. This type of gene
inactivation is determined by the gender of the
transmitting parent and may be reversed in the next
generation. Imprinting affects gene expression by
epigenetic control; that is, it changes the phenotype by
altering gene expression and not by permanently altering
the genotype. When a gene is inherited in an imprinted
state, gene function is directed by the co-gene inherited
from the other parent, so imprinting exerts an effect by
controlling the dosage of specific genes.
Imprinting
 Selected diseases can involve imprinting. Two very
different diseases that may be caused by, uniparental
disomy, or imprinting for the 15q11-q13 region of DNA
are Prader-Wili Syndrome and the Angelman
Syndrome.
Prader-Willi Syndrome
 obesity and hyperphagia
short
stature
small hands and feet
small external genitalia
mild
mental retardation
 In over 70% of cases, Prader-Willi is caused
by microdeletion or disruption for the
paternal 15q11-q13. The remainder of cases
are due to imprinting with the paternal
genes inactive.
External Parasitic Twins
Grossly defective fetus or merely fetal parts attached
externally to a relatively normal twin. The parasitic
twin usually consists of supernumerary limbs, often
with some viscera. Classically, a heart and brain are
absent. Attachment mirrors those sites described for
conjoined twins. Parasites are believed to result from
the demise of the defective twin, with its surviving
tissue attached to and vascularized by its normal
twin.
Fetus in Fetu
Fetus in fetus – Early in development, one embryo
may be enfolded inside the twin. Normal
development of this rare parasitic twin usually arrests
at the first trimester. As a result, normal spatial
arrangement of and presence of many organs is lost.
Classically, vertebral or axial bones are found in these
fetiform masses, whereas heart and brain are lacking.
These masses are typically supported by their host by
a few large parasitic vessels.
Uterine Incarceration
– On rare occasions the growing uterus is incarcerated
in the hollow of the sacrum. As the uterus grows, the
cervix is pushed forward behind the symphysis to
impinge on the bladder neck. The patient is usually
first seen complaining of abdominal discomfort and
the inability to void. As pressure forms the full bladder
increases, small amounts of urine are passed
involuntarily, but the bladder never empties.
Uterine Incarceration
After the bladder is emptied, the uterus can usually
be pushed out of the pelvis when the patient is
placed in the knee-chest position; anesthesia is
seldom needed
Rarely, the persistently entrapped retroverted uterus
produces a few symptoms; it can lead to late first
trimester pregnancy loss and it can lead to anterior
sacculation.
Neonatal Alloimmune
Thrombocytopenia
 In Rh isoimmunization the mother develops an
antibody to the antigens on the surface of the red
blood cell
 In Alloimmune thrombocytopenia the mother
develops an antibody to the antigens on the
surface of the platelet
 The most common antibody is HPA-1a ( PLA1)
Other antigens are HPA-5b, HPA-3a, and HPA-1b
 There is no evidence of thrombocytopenia in the
mother when NAT exists
Neonatal Alloimmune
Thrombocytopenia
 Generally, the first indication of the
thrombocytopenia is intracranial
hemorrhage in the fetus
 Therapy is with weekly IVIg 1
grams/Kg/week
 When a previous pregnancy is affected with
intracranial hemorrhage, a subsequent
pregnancy is treated with Prednisone in the
third trimester, daily.
 There are three species of zebras: the plains
zebra, the Grévy's zebra and the mountain
zebra. The plains zebra and the mountain
zebra belong to the subgenus Hippotigris, but
Grévy's zebra is the sole species of subgenus
Dolichohippus. The latter resembles an ass, to
which it is closely related, while the former two
are more horse-like. All three belong to the
genus Equus, along with other living equids.
Neural Tube Defects
 Almost 95% of NTDs occur in the absence of
recognized risk factors or family history; thus
routine screening is needed.
 Levels of AFP after the 13th week increase
rapidly. The normal gradient between fetal
plasma and maternal serum is on the order of
50,000:1. Fetal body wall defects, permit AFP
to leak into the amniotic fluid, resulting in
maternal serum AFP levels that may be
dramatically increased.
Cystic Hygroma
 A cystic hygroma (also known as cystic lymphangioma
and macrocystic lymphatic malformation) is a
congenital multiloculated lymphatic lesion that can arise
anywhere, but is classically found in the left posterior
triangle of the neck. This is the most common form of
lymphangioma. It contains large cyst-like cavities
containing watery fluid. Microscopically cystic hygroma
consists of multiple locules filled with lymph. In the depth
the locules are quite big but they decrease in size towards
the surface.
Cystic Hygroma
 Cystic hygromas are benign, but can be disfiguring. It is
a condition which affects children; very rarely it can
present in adulthood.[
 Cystic hygroma is also known as lymphatic
malformation. Nowadays, the medical field prefers to
use the term lymphatic malformation because the term
cystic hygroma means water tumor. Lymphatic
malformation is more commonly used now because it is
a sponge-like collection of abnormal growth that
contains clear lymphatic fluid. The fluid collects within
the cysts or channels, usually in the soft tissue.
Cystic Hygroma
 Cystic hygromas are filled with lymph which is
the fluid that travels in the lymphatic system of
the body. Cystic hygromas occur when the lymph
vessels that make up the lymphatic system aren't
formed properly.
 There are two types of lymphatic malformations.
They are macrocystic lymphatic malformations
(large cysts) and microcystic (small cysts). A
person may have only one kind of the
malformation or can have a mixture of both
macro and micro cysts.
Cystic Hygroma
 Cystic hygroma can be associated with a
nuchal lymphangioma or a fetal hydrops.
Additionally, it can be associated with
Turner syndrome or with Noonan's
syndrome.
 A lethal version of this condition is known
as Cowchuck Wapner Kurtz syndrome that,
in addition to cystic hygroma, includes
lymphedema and cleft palate.