Grades
Traditionally, four grades of placenta praevia are defined:
Grade Description
Placenta praevia (placenta previa AE) is an obstetric complication in which the placenta is
inserted partially or wholly in lower uterine segment.[1]It can sometimes occur in the later part
of the first trimester, but usually during the second or third. It is a leading cause of antepartum
haemorrhage(vaginal bleeding). It affects approximately 0.4-0.5% of all labours.[2]
In the last trimester of pregnancy the isthmus of the uterus unfolds and forms the lower
segment. In a normal pregnancy the placenta does not overlie. If the placenta does overlie the
lower segment, as is the case with placenta praevia, it may shear off and a small section may
bleed.
Etiopathogenesis
Exact etiology of placenta praevia is unknown. It is hypothesized to be related to
abnormal vascularisation of the endometrium caused by scarring or atrophy from previous
trauma, surgery, or infection. These factors may reduce differential growth of lower segment,
resulting in less upward shift in placental position as pregnancy advances. [3]
I
Placenta is in lower segment, but the lower edge does not reach internal os
II
Lower edge of placenta reaches internal os, but does not cover it
III
Placenta covers internal os partially
IV
Placenta covers internal os completely
Risk factors
Maternal age ≥ 40 (vs. < 20)
9.1
Previa can be confirmed with an ultrasound.[13] Transvaginal ultrasound has superior accuracy
as compared to transabdominal one, thus allowing measurement of distance between placenta
and cervical os. This has rendered traditional classification of placenta praevia
obsolete.[14][15][16][17]
Illicit drugs
2.8
False positives may be due to following reasons:[18]
≥ 1 previous Cesarean section
2.7
Parity ≥ 5 (vs. para 0)

Overfilled bladder compressing lower uterine segment
2.3

Myometrial contraction simulating placental tissue in abnormally low location
1.9

Early pregnancy low position, which in third trimester may be entirely normal due to
differential growth of the uterus.
The following have been identified as risk Risk factors with their odds ratio
factors for placenta praevia:
Risk factor
Odds ratio





Previous placenta previa (recurrence
rate
4-8%),[5] caesarean
delivery,[6] myomectomy[7] or
endometrium
damage
caused
[5]
by D&C.
Alcohol use during pregnancy.[8]
Parity 2–4 (vs. para 0)
Women who have had previous
pregnancies, especially a large number Prior abortion
of closely spaced pregnancies, are at Smoking
higher risk due to uterine damage.[7]
Congenital anomalies
Smoking during pregnancy;[1] cocaine
Male fetus (vs. female)
use during pregnancy[9][10]
1.9
1.6
In such cases, repeat scanning is done after an interval of 15–30 minutes.
1.7
In parts of the world where ultrasound is unavailable, it is not uncommon to confirm the
diagnosis with an examination in the surgical theatre. The proper timing of an examination in
theatre is important. If the woman is not bleeding severely she can be managed non-operatively
until the 36th week. By this time the baby's chance of survival is as good as at full term.
1.1
Women who are younger than 20 are at Pregnancy-induced hypertension 0.4
higher risk and women older than 35
are at increasing risk as they get older.

Women with a large placentae from twins or erythroblastosis are at higher risk.

Race is a controversial risk factor, with some studies finding that people from Asia and
Africa are at higher risk and others finding no difference.

Placental pathology (Vellamentous insertion, succinturiate lobes, bipartite i.e. bilobed
placenta etc.)[5]
Placenta previa is itself a risk factor of placenta accreta.
Diagnosis
Clinical
History may reveal antepartum hemorrhage. Abdominal examination and usually finds the
uterus non-tender, soft and relaxed. Leopold's Maneuvers may find the fetus in an oblique or
breech position or lying transverse as a result of the abnormal position of the placenta.
Malpresentation is found in about 35% cases.[12] Vaginal examinaton is avoided in known cases
of placenta praevia.[1]
Confirmatory
Management
An initial assessment to determine the status of the mother and fetus is required. Although
mothers used to be treated in the hospital from the first bleeding episode until birth, it is now
considered safe to treat placenta praevia on an outpatient basis if the fetus is at less than 30
weeks of gestation, and neither the mother nor the fetus are in distress. Immediate delivery of
the fetus may be indicated if the fetus is mature or if the fetus or mother are in distress. Blood
volume replacement (to maintain blood pressure) and blood plasma replacement (to maintain
fibrinogen levels) may be necessary.
Mode of delivery
The mode of delivery is determined by clinical state of the mother, fetus and ultrasound
findings. In minor degrees (traditional grade I and II), vaginal delivery is
possible. RCOG recommends that placenta should be at least 2 cm away from internal os for
an attempted vaginal delivery.[19] When a vaginal delivery is attempted, consultant obstetrician
and anesthetists are present in delivery suite. In cases of fetal distress and major degrees
(traditional grade III and IV) a caesarean section is indicated. Caesarian section is
contraindicated in cases of disseminated intravascular coagulation. Obstetrician may need to
divide the anterior lying placenta. In such cases, blood loss is expected to be high and thus
blood and blood products are always kept ready. In rare cases, hysterectomy may be
required.[20]
Complications
Maternal

Antepartum hemorrhage

Malpresentation

Abnormal placentation

Postpartum hemorrhage

Placenta
praevia
increases
the
risk
of puerperal
sepsis and postpartum
haemorrhage because the lower segment to which the placenta was attached contracts
less well post-delivery.
Fetal

IUGR (15% incidence)[5]

Premature delivery

Death
Epidemiology
Placenta previa occurs approximately one of every 250 births. One third of all antepartum
hemorrhage occurs due to placenta previa.[citation needed] It has been suggested that incidence of
placenta praevia is increasing due to increased rate of Caesarian section. [21]
Placental abruption (also known as abruptio placentae) is a complication of pregnancy,
wherein the placental lining has separated from theuterus of the mother. It is the most common
pathological cause of late pregnancy bleeding. In humans, it refers to the abnormal separation
after 20 weeks of gestation and prior to birth. It occurs in 1% of pregnancies worldwide.
Placental abruption is a significant contributor to maternal mortality worldwide; early and skilled
medical intervention is needed to ensure a good outcome, and this is not available in many
parts of the world. Treatment depends on how serious the abruption is and how far along the
woman is in her pregnancy.[1]
Perinatal mortality rate of placenta praevia is 3-4 times higher than normal pregnancies.[22]
Placental abruption has effects on both mother and fetus. The effects on the mother depend
primarily on the severity of the abruption, while the effects on the fetus depend on both its
severity and the gestational age at which it occurs.[2] The heart rate of the fetus can be
associated with the severity.[3]
History
Lasting effects
In places where a Caesarean section could not be performed due to the lack of a surgeon or
equipment, infant could be delivered vaginally. There were two ways of doing this with a
placenta praevia:
On the mother:


A large loss of blood or hemorrhage may require blood transfusions and intensive care
after delivery. 'APH weakens for PPH to kill'.
The baby's head can be brought down to the placental site (if necessary with Willet's
forceps or a vulsellum) and a weight attached to his scalp


The uterus may not contract properly after delivery so the mother may need medication to
help her uterus contract.
A leg can be brought down and the baby's buttocks used to compress the placental site

The mother may have problems with blood clotting for a few days.

If the mother's blood does not clot (particularly during a caesarean section) and too many
transfusions could put the mother into disseminated intravascular coagulation (DIC) due
to increased thromboplastin, the doctor may consider a hysterectomy.
The goal of this type of delivery is to save the mother, and both methods will often kill the baby.
These methods were used for many years before Caesarean section and saved the lives of
both mothers and babies with this condition.

A severe case of shock may affect other organs, such as the liver, kidney, and pituitary
gland. Diffuse cortical necrosis in the kidney is a serious and often fatal complication.

In some cases where the abruption is high up in the uterus, or is slight, there is no bleeding,
though extreme pain is felt and reported.

On the baby:

No coagulopathy

No fetal distress
Class 2: moderate and represents approximately 27% of all cases. Characteristics include
the following:

No vaginal bleeding to moderate vaginal bleeding

If a large amount of the placenta separates from the uterus, the baby will probably be in
distress until delivery and may die in utero, thus resulting in a stillbirth.

Moderate-to-severe uterine tenderness with possible tetanic contractions


Maternal tachycardia with orthostatic changes in BP and heart rate
The baby may be premature and need to be placed in the newborn intensive care unit. He
or she might have problems with breathing and feeding.

Fetal distress

If the baby is in distress in the uterus, he or she may have a low level of oxygen in the
blood after birth.

Hypofibrinogenemia (i.e., 50–250 mg/dL)

The newborn may have low blood pressure or a low blood count.

If the separation is severe enough, the baby could suffer brain damage or die before or
shortly after birth.

The newborn may have learning issues at later development stages, often requiring
professional pedagogical aid.

Symptoms

contractions that don't stop (and may follow one another so rapidly as to seem continuous)

pain in the uterus

tenderness in the abdomen

vaginal bleeding (sometimes)

uterus may be disproportionately enlarged

pallor
Clinical Manifestation


Class 0: asymptomatic. Diagnosis is made retrospectively by finding an organized blood
clot or a depressed area on a delivered placenta.
Class 1: mild and represents approximately 48% of all cases. Characteristics include the
following:

No vaginal bleeding to mild vaginal bleeding

Slightly tender uterus

Normal maternal BP and heart rate
Class 3: severe and represents approximately 24% of all cases. Characteristics include
the following:

No vaginal bleeding to heavy vaginal bleeding

Very painful tetanic uterus

Maternal shock

Hypofibrinogenemia (i.e., <150 mg/dL)

Coagulopathy

Fetal death
Pathophysiology
Trauma, hypertension, or coagulopathy contributes to the avulsion of the anchoring placental
villi from the expanding lower uterine segment, which in turn, leads to bleeding into the decidua
basalis. This can push the placenta away from the uterus and cause further bleeding. Bleeding
through the vagina, called overt or external bleeding, occurs 80% of the time, though
sometimes the blood will pool behind the placenta, known as concealed or internal placental
abruption.
Women may present with vaginal bleeding, abdominal or back pain, abnormal or premature
contractions, fetal distress or death.
Abruptions are classified according to severity in the following manner:

Grade 0: Asymptomatic and only diagnosed through post partum examination of the
placenta.

Grade 1: The mother may have vaginal bleeding with mild uterine tenderness or tetany,
but there is no distress of mother or fetus.

Grade 2: The mother is symptomatic but not in shock. There is some evidence of fetal
distress can be found with fetal heart rate monitoring.

Grade 3: Severe bleeding (which may be occult) leads to maternal shock and fetal death.
There may be maternal disseminated intravascular coagulation. Blood may force its way
through the uterine wall into the serosa, a condition known as Couvelaire uterus.
Risk factors


Pre-eclampsia [2]
Maternal smoking is associated with up to 90% increased

risk.[4]
See also: Smoking and pregnancy

Maternal trauma, such as motor vehicle accidents, assaults, falls or nosocomial infection.

Short umbilical cord

Prolonged rupture of membranes (>24 hours)

Thrombophilia [2]

Retroplacental fibromyoma

Multiparity [2]

Multiple pregnancy[2]

Maternal age: pregnant women who are younger than 20 or older than 35 are at greater
risk.

It is crucial for women to be made aware of the signs of placental abruption, such as vaginal
bleeding, and that if they experience such symptoms they must get into contact with their health
care provider/the hospital without any delay.
Intervention
Placental abruption is suspected when a pregnant mother has sudden localized abdominal
pain with or without bleeding. The fundus may be monitored because a rising fundus can
indicate bleeding. An ultrasound may be used to rule out placenta praevia but is not diagnostic
for abruption. The mother may be given Rhogam if she is Rh negative.
Treatment depends on the amount of blood loss and the status of the fetus. If the fetus is less
than 36 weeks and neither mother or fetus is in any distress, then they may simply be monitored
in hospital until a change in condition or fetal maturity whichever comes first.
Immediate delivery of the fetus may be indicated if the fetus is mature or if the fetus or mother
is in distress. Blood volume replacement to maintain blood pressure and blood
plasma replacement to maintain fibrinogen levels may be needed. Vaginal birth is usually
preferred over caesarean section unless there is fetal distress. Caesarean section is
contraindicated in cases of disseminated intravascular coagulation. Patient should be
monitored for 7 days for PPH. Excessive bleeding from uterus may necessitate hysterectomy.
Prognosis
Previous abruption: Women who have had an abruption in previous pregnancies are at
greater risk.

Previous Caesarean

some infections are also diagnosed as a cause

cocaine intoxication[5]
section[2]
Prevention
Although the risk of placental abruption cannot be eliminated, it can be reduced. Avoiding
tobacco, alcohol and cocaine during pregnancy decreases the risk. Staying away from activities
which have a high risk of physical trauma is also important. Women who have high blood
pressure or who have had a previous placental abruption and want to conceive must be closely
supervised by a doctor.[6]
The risk of placental abruption can be reduced by maintaining a good diet including taking folic
acid, regular sleep patterns and correction of pregnancy-induced hypertension.
The prognosis of this complication depends on whether treatment is received by the patient,
on the quality of treatment, and on the severity of the abruption.
In the Western world, maternal deaths due to placental abruption are rare; for instance a study
done in Finland found that, between 1972 and 2005 placental abruption had a maternal
mortality rate of 0.4 per 1,000 cases (which means that 1 in 2,500 women who had placental
abruption died); this was similar to other Western countries during that period.[7] The prognosis
on the fetus is worse, currently, in the UK, about 15% of fetuses die following this event.[2]
Without any form of medical intervention, as often happens in many parts of the world, placental
abruption has a high maternal mortality rate.
Chromosome abnormality

Deletions: A portion of the chromosome is missing or deleted. Known disorders in humans
include Wolf-Hirschhorn syndrome, which is caused by partial deletion of the short arm of
chromosome 4; and Jacobsen syndrome, also called the terminal 11q deletion disorder.

Duplications: A portion of the chromosome is duplicated, resulting in extra genetic material.
Known human disorders include Charcot-Marie-Tooth disease type 1A which may be
caused by duplication of the gene encoding peripheral myelin protein 22 (PMP22) on
chromosome 17.

Translocations: A portion of one chromosome is transferred to another chromosome.
There are two main types of translocations:

A chromosome anomaly, abnormality, aberration, or mutation is a missing, extra, or
irregular portion of chromosomal DNA.[1] It can be from an atypical number of chromosomes
or a structural abnormality in one or more chromosomes. A karyotype refers to a full set of
chromosomes from an individual which can be compared to a "normal" karyotype for
the species via genetic testing. A chromosome anomaly may be detected or confirmed in this
manner. Chromosome anomalies usually occur when there is an error in cell
division following meiosis or mitosis. There are many types of chromosome anomalies. They
can be organized into two basic groups, numerical and structural anomalies
Numerical disorders
This is called aneuploidy (an abnormal number of chromosomes), and occurs when an
individual is missing either a chromosome from a pair (monosomy) or has more than two
chromosomes of a pair (trisomy, tetrasomy, etc.).
In humans an example of a condition caused by a numerical anomaly is Down Syndrome, also
known as Trisomy 21 (an individual with Down Syndrome has three copies of chromosome 21,
rather than two). Trisomy has been determined to be a function of maternal age.
An example of monosomy is Turner Syndrome, where the individual is born with only one sex
chromosome, an X.
Structural abnormalities
When the chromosome's structure is altered, this can take several forms:
Reciprocal translocation: Segments from two different chromosomes have been
exchanged.

Robertsonian translocation: An entire chromosome has attached to another at the
centromere - in humans these only occur with chromosomes 13, 14, 15, 21 and 22.

Inversions: A portion of the chromosome has broken off, turned upside down and
reattached, therefore the genetic material is inverted.

Insertions: A portion of one chromosome has been deleted from its normal place and
inserted into another chromosome.

Rings: A portion of a chromosome has broken off and formed a circle or ring. This can
happen with or without loss of genetic material.

Isochromosome: Formed by the mirror image copy of a chromosome segment including
the centromere.
Chromosome instability syndromes are a group of disorders characterized by chromosomal
instability and breakage. They often lead to an increased tendency to develop certain types of
malignancies.
Inheritance
Most chromosome abnormalities occur as an accident in the egg or sperm, and therefore the
anomaly is present in every cell of the body. Some anomalies, however, can happen after
conception, resulting in Mosaicism (where some cells have the anomaly and some do not).
Chromosome anomalies can be inherited from a parent or be "de novo". This is why
chromosome studies are often performed on parents when a child is found to have an anomaly.
If the parents do not possess the abnormality it was not initially inherited; however it may be
transmitted to subsequent generations.
Cri du chat

excessive drooling;

small head and jaw;

wide eyes;

skin tags in front of eyes.
Other common findings include hypotonia, microcephaly, growth retardation, a round face with
full cheeks, hypertelorism, epicanthal folds, down-slanting palpebral fissures, strabismus, flat
nasal bridge, down-turned mouth, micrognathia, low-set ears, short fingers, single palmar
creases, and cardiac defects (e.g., ventricular septal defect [VSD], atrial septal
defect [ASD], patent ductus arteriosus [PDA], tetralogy of Fallot). People with Cri du chat are
fertile and can reproduce.
It has also been observed that people with the condition have difficulties communicating. While
levels of proficiency can range from a few words to short sentences, it is often recommended
by medical professionals for the child to undergo some sort of speech therapy/aid with the help
of a professional.
Cri du chat syndrome, also known as chromosome 5p deletion syndrome, 5p- (said
minus) syndrome or Lejeune’s syndrome, is a rare genetic disorder due to a missing part
(deletion) of chromosome 5. Its name is a French term (cat-cry or call of the cat) referring to
the characteristic cat-like cry of affected children. It was first described by Jérôme Lejeune in
1963.[1] The condition affects an estimated 1 in 50,000 live births, strikes all ethnicities, and is
more common in females by a 4:3 ratio.[2]
Signs and symptoms
The syndrome gets its name from the characteristic cry of affected infants, which is similar to
that of a meowing kitten, due to problems with the larynx and nervous system. About 1/3 of
children lose the cry by age 2. Other symptoms of cri du chat syndrome may include:

feeding problems because of difficulty swallowing and sucking;

low birth weight and poor growth;

severe cognitive, speech, and motor delays;

behavioral problems such as hyperactivity, aggression, tantrums, and repetitive
movements;

unusual facial features which may change over time;
Less frequently encountered findings include cleft lip and palate, preauricular tags and fistulas,
thymic
dysplasia, intestinal
malrotation, megacolon, inguinal
hernia, dislocated
hips,cryptorchidism, hypospadias, rare renal malformations (e.g., horseshoe kidneys, renal
ectopia or agenesis, hydronephrosis), clinodactyly of the fifth fingers, talipes equinovarus, pes
planus,syndactyly of the second and third fingers and toes, oligosyndactyly, and
hyperextensible joints. The syndrome may also include various dermatoglyphics, including
transverse flexion creases, distal axial triradius, increased whorls and arches on digits, and
a single palmar crease.
Late
childhood
and
adolescence
findings
include
significant
intellectual
disability, microcephaly, coarsening of facial features, prominent supraorbital ridges, deep-set
eyes, hypoplastic nasal bridge, severe malocclusion, and scoliosis.
Affected females reach puberty, develop secondary sex characteristics, and menstruate at the
usual time. The genital tract is usually normal in females except for a report of a bicornuate
uterus. In males, testes are often small, but spermatogenesis is thought to be normal.
Genetics
Cri du chat syndrome is due to a partial deletion of the short arm of chromosome number 5,
also called "5p monosomy". Approximately 90% of cases result from a sporadic, or randomly
occurring, de novo deletion. The remaining 10-15% are due to unequal segregation of a
parental balanced translocation where the 5p monosomy is often accompanied by a trisomic
portion of the genome. These individuals may have more severe disease than those with
isolated monosomy of 5p. A recent study suggests this may not be the case where a trisomy
of chromosome 4q is involved.[3]
Most cases involve total loss of the most distant 10-20% of the material on the short arm. Fewer
than 10% of cases have other rare cytogenetic aberrations (e.g., interstitial
deletions,mosaicisms, rings and de novo translocations). The deleted chromosome 5 is
paternal in origin in about 80% of de novo cases. Loss of a small region in band 5p15.2 (cri du
chat critical region) correlates with all the clinical features of the syndrome with the exception
of the catlike cry, which maps to band 5p15.3 (catlike critical region). The results suggest that
2 noncontiguous critical regions contain genes involved in this condition's etiology. Two genes
in these regions, Semaphorine F (SEMA5A) and delta catenin (CTNND2), are potentially
involved in cerebral development. The deletion of the telomerase reverse
transcriptase (hTERT) gene localized in 5p15.33 may contribute to the phenotypic changes in
cri du chat syndrome as well.
Diagnosis and management
Diagnosis is based on the distinctive cry and accompanying physical problems. Seeing as
these symptoms are quite easily observable, affected children are typically diagnosed by a
doctor or nurse at birth. Genetic counseling and genetic testing may be offered to families with
individuals who have cri du chat syndrome. Prenatally the deletion of the cri du chat related
region in the p arm of chromosome 5 can be detected from amniotic fluid or chorionic villi
samples with BACs-on-Beads technology.G-banded karyotype of a carrier is also
useful.[4] Children may be treated by speech, sound, and occupational therapists. Cardiac
abnormalities often require surgical correction.
the diagnosis are often terminated.[4][5] Regular screening for health problems common in Down
syndrome is recommended throughout the person's life.
Education and proper care has been shown to improve quality of life.[6] Some children with
Down syndrome are educated in regular school classes while others require more specialized
education.[7] Some children with Down syndrome graduate from high school and in adulthood
some individuals work in the community.[8] The degree of independence possible for an
affected individual varies, and some require a more sheltered work environment.[7] Support in
financial and legal matters is often needed.[9] Life expectancy is around 50 to 60 years in the
developed world with proper health care.[3][9]
Down syndrome is the most common chromosome abnormality in humans[3] occurring in about
1 per 1000 babies born each year.[2] It is named afterJohn Langdon Down, the British doctor
who fully described the syndrome in 1866.[10] Some aspects of the condition were described
earlier by Jean-Étienne Dominique Esquirol in 1838 and Édouard Séguin in 1844.[11] The
genetic cause of Down syndrome, an extra copy of chromosome 21, was identified by
Dr. Jérôme Lejeune in 1959.[10]
Signs and symptoms
Down syndrome
Down syndrome (DS) or Down's syndrome, also known as trisomy 21, is a genetic
disorder caused by the presence of all or part of a third copy ofchromosome 21.[1] It is typically
associated with physical growth delays, characteristic facial features and mild to
moderate intellectual disability.[2]The average IQ of a young adult with Down syndrome is
around 50, similar to the mental age of an 8 or 9 year old child.[3]
A drawing of the facial features of Down syndrome
Down syndrome can be identified during pregnancy by prenatal screening or after birth by
direct observation and genetic testing. Since the introduction of screening, pregnancies with
Those with Down syndrome nearly always have physical and mental disabilities. [12] As adults
their mental abilities are typically similar to that of an 8 or 9 year old. [3] They also typically
have poor immune function[13] and developmental milestones generally are reached at a later
age.[9] There is an increased risk of a number of other health problems including: congenital
heart disease, leukemia, thyroid disorders, and mental illness, among others.[10]
Characteristics
Percentage Characteristics
Percentage
Narrow roof of mouth
76%[16]
Strabismus
~35%[2]
Abnormal outer ears
70%[10]
Brushfield spots in the iris
56%[13]
Physical
Stunted growth
90%[14]
Flattened nose
68%[13]
Mental impairment
99%[15]
Abnormal teeth
60%[16]
Increased skin back of neck
80%[10]
Bent fifth finger tip
57%[13]
Umbilical hernia
90%[17]
Separation of 1st and 2nd toes 68%[16]
Feet of a boy with Down Syndrome
Flexible ligaments
75%[13]
Short neck
60%[16]
Low muscle tone
80%[18]
Shortened hands
60%[16]
Flat head
75%[13]
Congenital heart disease
40%[16]
Undescended testicles
20%[19]
Single transverse palmar crease 53%[13]
Eyelid fold
60%[16]
Protruding tongue
Shortened arms and legs
70%
Epicanthic fold
They may have some or all of the following physical characteristics: abnormally small chin,
slanted eyes, poor muscle tone, a flat nasal bridge, a single crease of the palm, a protruding
tongue due to small mouth, and an enlarged tongue.[18] Other common features include: a flat
and wide face,[18] there is a short neck, excessive joint flexibility, extra space between big
toe and second toe, an abnormal patterns on the fingertops and short fingers.[16][18]Instability of
the atlanto-axial joint occurs in approximately 20% and may lead to spinal cord injury in 12%.[3][9] Around half of those with DS haveobstructive sleep apnea.[10] Hip dislocations occur
without trauma in an up to a third.[10]
Growth in height is slower resulting in adults tending to have short stature—the average height
for men is 154 cm (5 feet 1 inch) and for women is 142 cm (4 feet 8 inches).[20] Individuals with
DS are at increased risk for obesity as they age.[10] There are growth charts specifically for
those with Down syndrome.[10]
47%[16]
Neurological
59%[13]
Most individuals with Down syndrome have mild (IQ: 50–70) or moderate intellectual
disability (IQ: 35–50) with some cases having severe (IQ: 20–35) difficulties.[2][21] As they age
they typically perform less well compared to their same aged peers. [21][22] Some after 30 years
of age may lose their ability to speak.[3] Those with mosaic Down syndrome typically have
scores 10–30 points higher.[23] This syndrome causes about a third of cases of intellectual
disability.[13]
Fine motor skills[24] and large scale motor skills are often delayed which can interfere with
cognitive development. Effects of the condition gross motor skills is variable. Some children
will begin walking at around 2 years of age, while others will not walk until age four.
Commonly individuals with Down syndrome have some difficulty speaking with better language
understanding.[10][21] 10 to 45% have either stuttering or rapid and irregular speech making
them difficult to understand.[25] They typically do fairly well with social skills.[10] Behavior
problems are not generally as great as an issue as in other syndromes associated with
intellectual disability.[21] In children with Down syndrome mental illness occurs in nearly 30%
with autism occurring
in
5-10%.[9] While
generally
happy,
symptoms
of depression and anxiety may develop in early adulthood.[3]
Children and adults with DS are at increased risk of epileptic seizures which occur in 5-10% of
children and up to 50% of adults.[3] This includes an increased risk of a specific type of seizure
called infantile spasms.[10] Many (15%) who live past 40s develop dementia of the Alzheimer's
disease type.[26] Of those who reach 60 years, 50-70% have the disease.[3]
Senses
in children with Down syndrome can bring many of the children up to normal hearing
levels.[27] Age related hearing loss of the sensorineural type occurs at a much earlier age
affected 10-70%.[3]
Otitis media with effusion is the most common cause of hearing loss in children with Down's
occurring in 50-70%.[9] Ear infections often start at birth and continue throughout the children's
life.[28]The ear infections are mainly due to poor eustachian tube function.[29] However,
excessive wax can also cause obstruction of the outer ear canal and hearing
problems.[3] Middle ear problems account for 83% of hearing loss in children with Down
syndrome.[30] The degree of hearing loss varies but even a mild degree can have major
consequences for speech understanding, language learning, and academics [2] if not detected
in time and corrected.[31] It is important to rule out hearing loss as a contributing factor in social
and mental deterioration.[32]
Heart
The rate of congenital heart disease in newborns with Down syndrome is around
40%.[16] An atrioventricular septal defect also known as endocardial cushion defect is the most
common form with up to 40% affected. This is closely followed by ventricular septal defect that
affects approximately 35%.[33] Mitral valve problems become common as people age, even in
those without heart problems at birth.[3] Other problems that may occur include: tetralogy of
Fallot and patent ductus arteriosus.[29] People with Down syndrome have a lower risk
of hardening of the arteries.[3]
Cancer
Brushfield spots, visible in the irises of a baby with Down Syndrome.
Hearing and vision disorders occur in more than half of people with DS. [10] Vision problems
occur in 38 to 80%.[2] Between 20 and 50% have strabismus, in which the two eyes do not
move in tandem.[2] Refractive errors requiring glasses or contacts are also
common.[3] Cataracts (opacity of the lens) occur in 15%,[9] and may be present at
birth.[2] Keratoconus (thin, cone-shaped corneas),[3] and glaucoma (increased eye pressures)
are also more common.[2] Brushfield spots (small white or grayish/brown spots on the periphery
of the iris) are present in 38 to 85%.[2]
Hearing problems are found in 38-78% of children with Down syndrome compared to 2.5% of
normal children.[2] Diagnosis and aggressive treatment of chronic ear disease (e.g.otitis media)
Although the general incidence of cancer amongst individuals with Down syndrome is the same
as in the general population,[34] there is a reduced risk of solid cancers and an increased risk
of leukemia and testicular cancer.[3] Solid cancers are believed to be less common due to
the tumor suppressor genes present on chromosome 21.[35]
Cancers of the blood are 10 to 15 times more common in children with DS.[10] In
particular, acute
lymphoblastic
leukemia is
20
times
more
common
and
the megakaryoblastic form of acute myelogenous leukemia is 500 times more
common.[36] Transient myeloproliferative disease, a disorder of blood cell production that does
not occur outside of Down syndrome, affects 3-10% of infants.[36][37] The disorder is typically
not serious but occasionally can be.[37] It resolves most times without treatment; however, in
those who have had it there is a 20 to 30 percent risk of developing acute lymphoblastic
leukemia at a latter time.[37]
Endocrine
Problems of the thyroid gland occur in 20-50%.[3][10] Low thyroid is the most common, occurring
in almost half of those with DS.[3] Thyroid problems can be due to a poorly or non functioning
thyroid at birth (known as congenital hypothyroidism) which occurs in 1%[9] or can develop
latter due to an attack on the thyroid by the immune system resulting in Graves
disease or autoimmune hypothyroidism.[38] Type 1 diabetes mellitus is also more common.[3]
can give rise to Down syndrome include Robertsonian translocation, isochromosomes, ring
chromosomee, which contain additional material from chromosome 21. These findings occurs
in approximately 2.5% of cases.[10][41] Isochromosomes result when the two long arms separate
together on one chromosome.[42]
Trisomy 21
Gastrointestinal
Constipation occurs in nearly half of people with DS and may result in changes in
behavior.[10] One potential cause is Hirschsprung's disease, which is due to a lack of nerve cells
controlling thecolon, which occurs in 2 to 15%.[39] Other frequent congenital problems
include: duodenal
atresia, pyloric
stenosis, Meckel
diverticulum and imperforate
anus.[29] Celiac disease affects about 7-20%[3][10] and gastroesophageal reflux disease is also
more common.[29]
Fertility
Males with Down syndrome usually do not father children, while females have lower rates of
fertility relative those who are unaffected.[40] Fertility is estimated to be present in 30-50% of
women[41] and they often have
difficulties
with miscarriages, premature births,
and labor. Menopause typically occurs at an earlier age.[3] The poor fertility in men is thought
to be due to problems with sperm development; however, it may also be related to not being
sexually active.[40] As of 2006 there have been three recorded instances of males with DS
fathering children and 26 cases of women having children.[40] Without assisted reproductive
technologies, approximately half of the pregnancies of someone with Down syndrome will also
have the syndrome.[40][42]
Genetics
Main article: Genetics of Down syndrome
Down syndrome is caused by having three copies of the genes on chromosome 21, rather than
the usual two.[1][43] The parents of the affected individual are typically genetically
normal.[13] Those who have one child with Down syndrome have about a 1% risk of having a
second child with the syndrome, if both parents are found to have normal karyotypes. [41]
The extra chromosome content can arise through several different mechanisms. The most
common cause (approximately 92-95% of cases) is a complete extra copy of chromosome 21,
resulting in trisomy 21.[42][44] In 1 to 2.5%, some of the cells in the body are normal and others
have trisomy 21, known as mosaic Down syndrome.[41][45] The other common mechanisms that
Karyotype for trisomy Down syndrome. Notice the three copies of chromosome 21
Trisomy 21 (also known by the karyotype 47,XX,+21 for males and 47,XY,+21 for females)[46] is
caused by a failure of the chromosomes to separate during egg or sperm development.[42] As
a result, a sperm or egg cell is produced with an extra copy of chromosome 21; this cell thus
has 24 chromosomes. When combined with a normal cell from the other parent,
the embryo and baby has 47 chromosomes, with three copies of chromosome 21. Trisomy 21
is the cause of approximately 92 to 95% of cases of Down syndrome, [1][42] with 88% of cases
resulting from non separation of the chromosomes in the mother and 8% coming from non
separation in the father.[47]
Translocation
The extra chromosome 21 material may also occur due to a Robertsonian translocation in 24% cases.[41][48] This may be a new mutation or previously present in one of the parents.[49] In
this case, the long arm of chromosome 21 is attached to another chromosome,
often chromosome 14 known as 45XY,t(14q21q) in males.[50][51] The risk of this type of Down
syndrome is not related to the mothers age.[50] The parent with such a translocation is usually
normal physically and mentally;[50] however, during production of egg or sperm cells there is a
higher chance of creating reproductive cells with extra chromosome 21 material. [48] This results
in a 15% chance of having a child with DS when the mother is affected and a less than 5% risk
if the father is affected.[49] Additionally some children may inherit this translocation while not
have DS but are subsequently at higher risk of having children with DS themselves. [50] In this
case it is sometimes known as familial Down syndrome.[52]
Mechanism
In general, extra chromosome 21 DNA leads to an over-expression of certain genes.[43] This
over expression is about 50%.[41] It is estimated that chromosome 21 contains around 310
genes.[43]Some research has shown that the parts of the chromosome which are of greatest
importance are bands 21q22.1-q22.3.[53] This area includes genes for amyloid, superoxide
dismutase, and likely the ETS-2 proto oncogene.[54] Other research has not confirmed these
findings.[43]
Ultrasound of fetus with Down syndrome showing a large bladder
The dementia which occurs in Down syndrome is due to too much amyloid beta peptides being
produced in the brain.[55] Senile plaques and neurofibrillary tangles are present in nearly all by
35 years of age even though dementia may not be present. [13] Those with DS lack a normal
number of lymphocytes and produce less antibodies which contributes to there increased risk
of infection.[10]
Screening
Guidelines recommend that screening for Down syndrome be offered to all pregnant women,
regardless of age.[56][57] A number of tests can be used, with varying levels of accuracy. They
are usually used in combination to increase their detection rate, while maintaining a low false
positive rate, but are not definitive.[10] If screening is positive either amniocentesis or chorionic
villous sampling is required to confirm the diagnosis.[56] Screening in both the first and second
trimesters is better than just screening in the first trimester. [56] The different screening
techniques in use are able to pick up 90 to 95% of cases with a false positive rate of between
2 and 5%.[58]
Ultrasound
Enlarged NT and absent nasal bone in a fetus at 11 weeks with Down syndrome
Ultrasound imaging can be used to screen for Down syndrome. Finding that increase the risk,
when seen at 14 to 24 weeks of gestation include: a small or no nasal bone, large ventricles,
nuchal fold thickness, and an abnormal right subclavian artery among others.[59] The presence
or absence of many markers is more accurate.[59]
Increased fetal nuchal translucency (NT) indicates an increased risk of Down syndrome picking
up 75-80% of cases and being falsely positive in 6%.[60]
Blood tests
Several blood markers can be measured that to predict the risk of Down syndrome during the
second trimester.[61] Often two or three or used in combination with two or three of: αfetoprotein, unconjugated estriol, total hCG, and free βhCG detecting about 60-70% of
cases.[61] First trimester screening with markers is not as accurate and thus is not generally
recommended by itself.[62]
Testing of the mother's blood for fetal DNA is being studied and appears promising in the first
trimester.[63][64] The International Society for Prenatal Diagnosis considers it a reasonable
screening option for those women whose pregnancies are at a high risk for trisomy
21.[65] Accuracy has been reported at 98.6% in the first trimester of pregnancy.[10] Confirmatory
testing by invasive techniques (amniocentesis, CVS) is still required to confirm the screening
result.[65]
Diagnosis
The diagnosis can typically be made based on the appearance of the child at birth. [9] An
analysis of the child's chromosomes is recommended to confirm the diagnosis and determine
if a translocation is present as if it this may help determine the risk of the child's parents having
further children with DS.[9] Parents generally wish to know the possible diagnosis once it is
suspected and do not wish pity.[10]
Management
Efforts such as early childhood intervention, screening for common problems, medical
treatment where indicated, a good family environment, and work related training can improve
the development of children with Down syndrome. Education and proper care can
improve quality of life.[6] Typical vaccinations are recommended.[10]
Health screening
Recommended screening
Before birth
When screening tests predict a high risk of Down syndrome, a more invasive diagnostic test
(amniocentesis or chorionic villus sampling) is needed to confirm the diagnosis.[56] If Down
syndrome occurs in 1 in 500 pregnancies and the test used has a 5% false positive rate, this
means that of 28 women who test positive on screening only 1 will have Down syndrome
confirmed.[58] If the screening test has a 2% false positive rate this improves to 1 out of 10 who
test positive on screening having a fetus with DS.[58] Amniocentesis and chorionic villus
sampling are more reliable; however, carry an increased risk of miscarriage of between 0.5 and
1%.[66] There is also an increased risk of limb problems in the offspring due to the
procedure.[66] The risk from the procedure is greater the earlier it is preformed and thus
amniocentesis is not recommended before 15 weeks gestational age and chorionic villus
sampling before 10 weeks gestational age.[66]
Testing
Children[68]
Adults[3]
Hearing
6 months, 12 months, then yearly
3–5 years
T4 and TSH
6 months, then yearly
Eyes
6 months, then yearly
About 92% of pregnancies in the United Kingdom and Europe with a diagnosis of Down
syndrome are terminated.[5] In the United States termination rates are around 67%; however
this varies significantly depending upon the population looked at. [4]
Teeth
2 years, then every 6 months.
When non pregnant people are asked if they would have a termination if their fetus tested
positive 23-33% said yes, when high risk pregnant women were asked 46-86% said yes, and
when women who screen positive are asked 89-97% say yes.[67]
Coeliac disease
Between 2 and 3 years of age,
or earlier if symptoms occur.
Abortion rates
After birth
3–5 years
Medications
Sleep study
3 to 4 years, or earlier if symptoms
of obstructive sleep apnea occur.
Neck X-rays
Between 3 and 5 years of age
A number of health organizations, have issued recommendations for screening those with
Down syndrome for particular diseases.[68] It is recommended that this be done
systematically.[10]
At birth all children should get an electrocardiogram and ultrasound of the heart.[10] Surgical
repair of heart problems may be required around three months of age.[10] Heart valve problems
may occur in young adults and further ultrasound evaluation may be needed when in
adolescents and early adulthood.[10] Due to the elevated risk of testicular cancer some
recommend checking the person's testicles yearly.[3]
Cognitive development
Hearing aids or other amplification devices can be useful for language learning in those with
hearing loss of any degree.[10] Early communication intervention help language skills.
Language assessments can help determine strengths and weaknesses; for example, it is
common for understanding to exceed expressive skills. As those with Down's typically have
good hand eye coordination, learning sign language may be possible.[21]
Speech therapy may be useful and it is recommended that it be started around 9 months of
age.[10] Augmentative and alternative communication methods, such as pointing, body
language, objects, or graphics are often used to aid communication. Relatively little research
has focused on the effectiveness of communications intervention strategies.[69]
Education programs before reaching school age may be useful.[2] When of school age children
with Down syndrome may benefit from mainstreaming (whereby students of differing abilities
are placed in classes with their chronological peers) provided that some adjustments are made
to the curriculum.[70] Evidence to support this however is not very strong.[71] In the United States
theIndividuals with Disabilities Education Act of 1975 requires that public school generally allow
attendance by students with Down's.[72]
Behavioral issues and mental illness are typically managed with counselling and or
medications.[9]
Efforts to prevent respiratory syncytial virus (RSV) with human monoclonal antibodies should
be considered, especially in those with heart problems.[2] In those who develop dementia there
is no evidence for memantine,[73] donepezil,[74] rivastigmine,[75] or galantamine.[76]
Edwards syndrome (also known as Trisomy 18 [T18]) is a genetic disorder caused by the
presence of all or part of an extra 18th chromosome. This genetic condition almost always
results from nondisjunction during meiosis. It is named after John Hilton Edwards, who first
described the syndrome in 1960.[1] It is the second most common autosomal trisomy,
after Down syndrome, that carries to term.
Edwards syndrome occurs in around one in 6,000 live births and around 80 percent of those
affected are female.[2] The majority of fetuses with the syndrome die before birth.[2] The
incidence increases as the mother's age increases. The syndrome has a very low rate of
survival, resulting from heart abnormalities, kidney malformations, and other internal organ
disorders.
Signs and symptoms
Children born with Edwards syndrome may have some or all of the following characteristics:
kidney malformations, structural heart defects at birth (i.e., ventricular septal defect, atrial
septal defect, patent ductus arteriosus), intestines protruding outside the body
(omphalocele), esophageal atresia, intellectual disability, developmental delays, growth
deficiency, feeding difficulties,breathing difficulties, and arthrogryposis (a muscle disorder that
causes multiple joint contractures at birth).[3][4]
Some physical malformations associated with Edwards syndrome include small head
(microcephaly) accompanied by a prominent back portion of the head (occiput); low-set,
malformed ears; abnormally small jaw (micrognathia); cleft lip/cleft palate; upturned nose;
narrow eyelid folds (palpebral fissures); widely spaced eyes (ocular hypertelorism); drooping
of the upper eyelids (ptosis); a short breast bone; clenched hands; choroid plexus cysts;
underdeveloped thumbs and or nails, absent radius, webbing of the second and
third toes; clubfoot or Rocker bottom feet; and inmales, undescended testicles.[3][4]
Trisomy 18 (47,XX,+18) is caused by a meiotic nondisjunction event. With nondisjunction,
a gamete (i.e., a sperm or egg cell) is produced with an extra copy of chromosome 18; the
gamete thus has 24 chromosomes. When combined with a normal gamete from the other
parent, the embryo has 47 chromosomes, with three copies of chromosome 18.
Clenched hand and overlapping fingers: index finger overlaps third finger and fifth finger overlaps fourth
finger, characteristically seen in Trisomy 18.
In utero, the most common characteristic is cardiac anomalies, followed by central nervous
system anomalies such as head shape abnormalities. The most common intracranial
anomaly is the presence of choroid plexus cysts, which are pockets of fluid on the brain.
These are not problematic in themselves, but their presence may be a marker for trisomy
18.[5][6] Sometimes excess amniotic fluid or polyhydramnios is exhibited.[3]
Genetics
Edwards syndrome is a chromosomal abnormality characterized by the presence of an extra
copy of genetic material on the 18th chromosome, either in whole (trisomy 18) or in part
(such as due to translocations). The additional chromosome usually occurs
before conception. The effects of the extra copy vary greatly, depending on the extent of the
extra copy, genetic history, and chance. Edwards syndrome occurs in all human populations
but is more prevalent in female offspring.[7]
A healthy egg and/or sperm cell contains individual chromosomes, each of which contributes
to the 23 pairs of chromosomes needed to form a normal cell with a typical
human karyotype of 46 chromosomes. Numerical errors can arise at either of the
two meiotic divisions and cause the failure of a chromosome to segregate into the daughter
cells (nondisjunction). This results in an extra chromosome, making the haploid number 24
rather than 23. Fertilization of eggs or insemination by sperm that contain an extra
chromosome results in trisomy, or three copies of a chromosome rather than two. [8]
A small percentage of cases occur when only some of the body's cells have an extra copy of
chromosome 18, resulting in a mixed population of cells with a differing number of
chromosomes. Such cases are sometimes called mosaic Edwards syndrome. Very rarely, a
piece of chromosome 18 becomes attached to another chromosome (translocated) before or
after conception. Affected individuals have two copies of chromosome 18 plus extra material
from chromosome 18 attached to another chromosome. With a translocation, a person has a
partial trisomy for chromosome 18, and the abnormalities are often less severe than for the
typical Edwards syndrome.
Prognosis
In 2008/2009, there were 495 diagnoses of Edwards syndrome (trisomy 18)
in England and Wales, 92% of which were made prenatally. There were 339 abortions,
49 stillbirths/miscarriages/fetal deaths, 72 unknown outcomes, and 35 live births.[9] Because
approximately 3% of cases with unknown outcomes are likely to result in a live birth, the total
number of live births is estimated to be 37 (2008/09 data are provisional). Major causes of
death include apnea and heart abnormalities. It is impossible to predict an
exact prognosis during pregnancy or the neonatal period.[7] Half of infants with this condition
do not survive beyond the first week of life.[10] The median lifespan is 5–15 days.[11][12] About
8% of infants survive longer than 1 year.[13] One percent of children live to age 10, typically in
less severe cases of the mosaic Edwards syndrome.[7] Parents with surviving children who
take part in support groups report that these children enriched their family and their couple
irrespective of the length of their lives.[14]
Epidemiology
Edwards syndrome occurs in approximately 1 in 6,000 live births, but more conceptions are
affected by the syndrome because the majority of those diagnosed with the condition
prenatally will not survive the prenatal period.[2][15] Although women in their 20s and early 30s
may conceive babies with Edwards syndrome, the risk of conceiving a child with Edwards
syndrome increases with a woman's age. The average maternal age for conceiving a child
with this disorder is 32½.[16]
Patau syndrome
Patau syndrome /ˈpætaʊ/ is a syndrome caused by a chromosomal abnormality, in which
some or all of the cells of the body contain extra genetic material from chromosome 13. This
can occur either because each cell contains a full extra copy of chromosome 13 (a disorder
known as trisomy 13or trisomy D), or because each cell contains an extra partial copy of
the chromosome (i.e., Robertsonian translocation) or because of mosaic Patau syndrome.
Full trisomy 13 is caused by nondisjunction of chromosomes during meiosis (the mosaic form
is caused by nondisjunction during mitosis). The extra genetic material from chromosome 13
disrupts the normal course of development, causing multiple and complex organ defects. Like
allnondisjunction conditions (such as Down syndrome and Edwards syndrome), the risk of
this syndrome in the offspring increases with maternal age at pregnancy, with about 31 years
being the average.[1] Patau syndrome affects somewhere between 1 in 10,000 and 1 in
21,700 live births.[2]
chromosome 13. Although they do not have signs of Patau syndrome, people who carry this
type of balanced translocation are at an increased risk of having children with the condition.
Manifestations and physical findings
Causes
Patau's syndrome is the result of trisomy 13, meaning each cell in the body has three copies
of chromosome 13 instead of the usual two. A small percentage of cases occur when only
some of the body's cells have an extra copy; such cases are called mosaic Patau.
Patau syndrome can also occur when part of chromosome 13 becomes attached to another
chromosome (translocated) before or at conception in aRobertsonian translocation. Affected
people have two copies of chromosome 13, plus extra material from chromosome 13
attached to another chromosome. With a translocation, the person has a partial trisomy for
chromosome 13 and often the physical signs of the syndrome differ from the typical Patau
syndrome.
Most cases of Patau syndrome are not inherited, but occur as random events during the
formation of reproductive cells (eggs and sperm). An error in cell division called nondisjunction can result in reproductive cells with an abnormal number of chromosomes. For
example, an egg or sperm cell may gain an extra copy of the chromosome. If one of these
atypical reproductive cells contributes to the genetic makeup of a child, the child will have an
extra chromosome 13 in each of the body's cells. Mosaic Patau syndrome is also not
inherited. It occurs as a random error during cell division early in fetal development.
Patau syndrome due to a translocation can be inherited. An unaffected person can carry a
rearrangement of genetic material between chromosome 13 and another chromosome. This
rearrangement is called a balanced translocation because there is no extra material from
A 37 2/7 week gestational age male infant with Patau syndrome demonstratingpolydactyly
Of those fetuses that do survive to gestation and subsequent birth, common abnormalities
may include:

Nervous system

Intellectual disability and motor disorder

Microcephaly

Holoprosencephaly (failure of the forebrain to divide properly).

Structural eye defects, including microphthalmia, Peters anomaly (a type of eye
abnormality), cataract, iris and/or fundus (coloboma), retinal dysplasia or retinal
detachment, sensory nystagmus, cortical visual loss, and optic nerve hypoplasia


Meningomyelocele (a spinal defect)
Musculoskeletal and cutaneous

Polydactyly (extra digits)

Cyclopia



Proboscis

Low-set ears[3]

Prominent heel

Deformed feet known as rocker-bottom feet
palate. Physical, occupational, and speech therapy will help individuals with Patau syndrome
reach their full developmental potential. Surviving children are described as happy and
parents report that they enrich their lives.[9] The cited study grouped Edwards syndrome,
which is sometimes survivable beyond toddlerhood, along with Patau, hence the median age
of 4 at the time of data collection.

Omphalocele (abdominal defect)
Prognosis

Abnormal palm pattern
More than 80% of children with Patau syndrome die within the first year of life.[10]

Overlapping of fingers over thumb

Cutis aplasia (missing portion of the skin/hair)

Cleft palate
Urogenital

Abnormal genitalia

Kidney defects
Other

Heart defects (ventricular septal defect) (Patent Ductus Arteriosus)

Dextrocardia

Single umbilical artery[4]
Diagnosis
Diagnosis is usually based on clinical findings, although fetal chromosome testing will show
trisomy 13. While many of the physical findings are similar to Edward's syndrome there are a
few unique traits, such as polydactyly. However, unlike Edward's syndrome and Down
syndrome, the quad screen does not provide a reliable means of screening for this disorder.
This is due to the variability of the results seen in fetuses with Patau. [5]
Treatment[edit]
Medical management of children with Trisomy 13 is planned on a case-by-case basis and
depends on the individual circumstances of the patient. Treatment of Patau syndrome
focuses on the particular physical problems with which each child is born. Many infants have
difficulty surviving the first few days or weeks due to severe neurological problems or
complex heart defects. Surgery may be necessary to repair heart defects or cleft lip and cleft
Trisomy 8
Trisomy 8, also known as Warkany syndrome 2,[1] is a human chromosomal
disorder caused by having three copies (trisomy) of chromosome 8. It can appear with or
without mosaicism.
Characteristics
Complete trisomy 8 causes severe effects on the developing fetus and can be a cause
of miscarriage.[2] Complete trisomy 8 is usually an early lethal condition, whereas trisomy
8 mosaicism is less severe and individuals with a low proportion of affected cells may exhibit
a comparatively mild range of physical abnormalities and developmental delay. [3][4] Individuals
with trisomy 8 mosaicism are more likely to survive into childhood and adulthood, and exhibit
a characteristic and recognizable pattern of developmental abnormalities. Common findings
include retarded psychomotor development, moderate to severe mental retardation, variable
growth patterns which can result in either abnormally short or tall stature, an expressionless
face, and many musculoskeletal, visceral, and eye abnormalities, as well as
other anomalies.[5] A deep plantar furrow is considered to be pathognomonic of this condition,
especially when seen in combination with other associated features.[6] The type and severity
of symptoms are dependent upon the location and proportion of trisomy 8 cells compared to
normal cells.
Other conditions
Trisomy 8 mosaicism affects wide areas of chromosome 8 containing many genes, and can
thus be associated with a range of symptoms.




Mosaic trisomy 8 has been reported in rare cases of Rothmund-Thomson syndrome, a
genetic disorder associated with the DNA helicase RECQL4 on chromosome 8q24.3.
The syndrome is "characterized by skin
atrophy, telangiectasia, hyper- and hypopigmentation, congenital skeletal abnormalities,
short stature, premature aging, and increased risk of malignant disease".[7]
Some individuals trisomic for chromosome 8 were deficient in production of coagulation
factor VII due to a factor 7 regulation gene (F7R) mapped to 8p23.3-p23.1.[8]
G/BBB Syndrome, Cayler Cardiofacial Syndrome.The effects of this disorder are different in each
individual but similarities exist such as heart defects, immune system problems, a distinctive facial
appearance, learning challenges, cleft palate, hearing loss, kidney problems, hypocalcemia, and
sometimes psychiatric issues.
22q11 microduplication syndrome[3] is the opposite of the 22q11 deletion syndrome, in this
condition, a band of q.11.2 section of chromosome 22 is duplicated. Individuals carrying this
Trisomy and other rearrangements of chromosome 8 have also been found in tricho–
rhino–phalangeal syndrome.[9]
deficiency are relatively “normal” as in they don’t possess any major birth defects or major medical
Small regions of chromosome 8 trisomy and monosomy are also created by recombinant
chromosome 8 syndrome (San Luis Valley syndrome), causing anomalies associated
with tetralogy of Fallot, which results from recombination between a typical chromosome
8 and one carrying a parental paracentric inversion.[10]
phenotype of the individuals.
illnesses. This microduplication is more common than the deletion; this might be due to the milder
Phelan-McDermid Syndrome / 22q13 Deletion Syndrome[4] is a condition caused by the
deletion of the tip of the q arm on chromosome 22. Most individuals with this disorder experience
cognitive delays as well as low muscle tone and sleeping, eating and behavioural issues.

Trisomy is also found in some cases of chronic myeloid leukaemia, potentially as a result
of karyotypic instability caused by the bcr:abl fusion gene.
Chromosome Ring 22[5] is a rare disorder caused by the break and re-join of both ends of
Trisomy 22
chromosome 22, forming a ring. The effects on the individual with this disorder are dependent on
From Wikipedia, the free encyclopedia
disorder are mental retardation, muscle weakness and lack of coordination.
Trisomy 22 is a chromosomal disorder in which there are three copies of chromosome 22 rather
Cat Eye Syndrome / Schmid Fraccaro Syndrome[6] is a condition caused by a partial trisomy or
than two. It is a frequent cause of spontaneous abortion during the first trimester of pregnancy.
tetrasomy in chromosome 22. A small extra chromosome is found, made up of the top half of
Progression to the second trimester and livebirth are rare. This disorder is found in individuals with
chromosome 22 and a portion of the q arm at the q11.2 break. This chromosome can be found
an extra copy or a variation of chromosome 22 in some or all cells of their body. There are many
three or four times. This syndrome is referred as “Cat Eye” due to the eye appearance of reported
kinds of disorders associated with Trisomy 22:
affected individuals who have coloboma of the iris ; however, this feature is only seen in about half
Emanuel Syndrome [1] is named after the genetic contributions made by researcher Dr. Beverly
of the cases.
Emanuel. This condition is assigned to individuals born with an unbalanced 11/22 translocation.
Mosaic trisomy 22[7] is a disorder in which an extra chromosome 22 is found only in some cells of
That is, when a fragment of chromosome 11 is moved, or translocated to chromosome 22.
the body. The severity of each case is determined by the number of cells with this extra copy.
22q11 Deletion Syndrome [2] is a rare condition which occurs in approximately 1 in 4000 births.
Some characteristics of individuals with this condition are cardiac abnormalities, growth
This condition is identified when a band in the q11.2 section of the arm of chromosome 22 is
retardation, mental delay, etc..
missing or deleted. This condition has several different names, The 22q11.2 Deletion Sydrome,
Velocardiofacial syndrome, DiGeorge Syndrome, Conotruncal Anomaly Face syndrome, Opitz
the amount of genetic information lost during the break/re-join. Major characteristics for this
Complete Trisomy 22[8] is in contrast with Mosaic trisomy 22; this disorder is characterized by an
extra copy of chromosome 22 which is found in each cell of the body of the affected individual.
These cases are very rare, and most of the affected individuals die before birth or shortly after.
Klinefelter syndrome or Klinefelter's syndrome is the set of symptoms resulting from additional
Klinefelter syndrome
X genetic material in males. Also known as47,XXY or XXY, Klinefelter syndrome is a genetic
disorder in which there is at least one extra X chromosome to a standard human male karyotype,
for a total of 47 chromosomes rather than the 46 found in genetically typical humans.[1] While
Klinefelter syndrome
females have an XX chromosomal makeup, and males an XY, individuals with Klinefelter
syndrome have at least two X chromosomes and at least one Y chromosome.[2] Because of
Classification and external resources
the extra chromosome, individuals with the condition are usually referred to as "XXY males", or
"47,XXY males".[3]
This chromosome constitution (karyotype) exists in roughly between 1:500 to 1:1000 live male
births[4][5][note 1] but many of these people may not show symptoms. If the physical traits associated
with the syndrome become apparent, they normally appear after the onset of puberty.[10]
In humans, 47,XXY is the most common sex chromosome aneuploidy in males[11] and the second
most common condition caused by the presence of extra chromosomes. Other mammals also
have the XXY syndrome, including mice.[12]
Principal effects include hypogonadism and sterility. A variety of other physical and behavioural
47,XXY
differences and problems are common, though severity varies and many XXY boys have few
detectable symptoms.
Signs and symptoms[edit]
A person with typical untreated (surgery/hormones) Klinefelter 46,XY/47,XXY mosaic, diagnosed at age 19.
Scar from biopsy may be visible on left nipple.
There are many variances within the XXY population, just as within the 46,XY population.
While it is possible to characterise XXY males with certain body types and physical
characteristics, that in itself should not be the method of identification as to whether or not
someone has XXY. The only reliable method of identification is karyotype testing. The degree
to which XXY males are affected, both physically and developmentally, differs widely from
person to person.
Physical
As babies and children, XXY males may have weaker muscles and reduced strength. As they
grow older, they tend to become taller than average. They may have less muscle control and
coordination than other boys their age.[4]
During puberty, the physical traits of the syndrome become more evident; because these
boys do not produce as much testosterone as other boys, they have a less muscular body,
less facial and body hair, and broader hips. As teens, XXY males may have larger breasts,
weaker bones, and a lower energy level than other boys.[4]
By adulthood, XXY males look similar to males without the condition, although they are often
taller. In adults, possible characteristics vary widely and include little to no signs of
affectedness, a lanky, youthful build and facial appearance, or a rounded body type with
some degree of gynecomastia (increased breast tissue).[13] Gynecomastia is present to some
extent in about a third of affected individuals, a slightly higher percentage than in the XY
population. About 10% of XXY males have gynecomastia noticeable enough that they may
choose to have cosmetic surgery.[3]
Affected males are often infertile, or may have reduced fertility. Advanced reproductive
assistance is sometimes possible.[14]
The term hypogonadism in XXY symptoms is often misinterpreted to mean "small testicles" or
"small penis". In fact, it means decreased testicular hormone/endocrine function. Because of
this (primary) hypogonadism, individuals will often have a low serum testosterone level but
high serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels.[15] Despite
this misunderstanding of the term, however, it is true that XXY men may also
have microorchidism (i.e., small testicles).[15]
XXY males are also more likely than other men to have certain health problems, which
typically affect females, such as autoimmune disorders, breast cancer, venous
thromboembolic disease, and osteoporosis.[4][16] In contrast to these potentially increased
risks, it is currently thought that rare X-linked recessive conditions occur less frequently in
XXY males than in normal XY males, since these conditions are transmitted by genes on the
X chromosome, and people with two X chromosomes are typically only carriers rather than
affected by these X-linked recessive conditions.
Cognitive and developmental
Some degree of language learning or reading impairment may be present,[17] and
neuropsychological testing often reveals deficits in executive functions, although these
deficits can often be overcome through early intervention.[18] There may also be delays in
motor development which can be addressed through occupational therapy and physical
therapy.[19] XXY males may sit up, crawl, and walk later than other infants; they may also
struggle in school, both academically and with sports. [4]
Cause
The extra X chromosome is retained because of a nondisjunction event during meiosis
I (gametogenesis). Nondisjunction occurs when homologous chromosomes, in this case the
X and Y sex chromosomes, fail to separate, producing a sperm with an X and a Y
chromosome. Fertilizing a normal (X) egg produces an XXY offspring. The XXY chromosome
arrangement is one of the most common genetic variations from the XY karyotype, occurring
in about 1 in 500 live male births.[4]
Another mechanism for retaining the extra X chromosome is through a nondisjunction event
during meiosis II in the female. Nondisjunction will occur when sister chromatids on the sex
chromosome, in this case an X and an X, fail to separate. (meiosis) An XX egg is produced
which, when fertilized with a Y sperm, yields XXY offspring.
In mammals with more than one X chromosome, the genes on all but one X chromosome are
not expressed; this is known as X inactivation. This happens in XXY males as well as normal
XX females.[20] However, in XXY males, a few genes located in the pseudoautosomal
regions of their X chromosomes, have corresponding genes on their Y chromosome and are
capable of being expressed.[21]
The first published report of a man with a 47,XXY karyotype was by Patricia Jacobs and John
Strong at Western General Hospital in Edinburgh, Scotland in 1959.[22] This karyotype was
found in a 24-year-old man who had signs of Klinefelter syndrome. Jacobs described her
discovery of this first reported human or mammalian chromosome aneuploidy in her 1981
William Allan Memorial Award address.[23]
Variations
48,XXYY and 48,XXXY occur in 1 in 18,000–50,000 male births. The incidence of 49,XXXXY
is 1 in 85,000 to 100,000 male births.[24] These variations are extremely rare. Additional
chromosomal material can contribute to cardiac, neurological, orthopedic and other
anomalies.
Males with Klinefelter syndrome may have a mosaic 47,XXY/46,XY
constitutional karyotype and varying degrees of spermatogenic failure. Mosaicism
47,XXY/46,XX with clinical features suggestive of Klinefelter syndrome is very rare. Thus far,
only about 10 cases have been described in literature.[25]
There have been some reports of individuals with Klinefelter syndrome who also have other
chromosome abnormalities, such as Down syndrome.[37]
Analogous XXY syndromes are known to occur in cats—specifically, the presence
of calico or tortoiseshell markings in male cats is an indicator of the relevant abnormal
karyotype. As such, male cats with calico or tortoiseshell markings are a model organism for
Klinefelter syndrome.[26]
The genetic variation is irreversible. Often individuals that have noticeable breast tissue
or hypogonadism experience depression and/or social anxiety because they are outside of
social norms. This is academically referred to as psychosocial morbidity.[38] At least one study
indicates that planned and timed support should be provided for young men with Klinefelter
syndrome to ameliorate current poor psychosocial outcomes.[38]
Diagnosis
diagnosis.[28]
About 10% of Klinefelter cases are found by prenatal
The first clinical features
may appear in early childhood or, more frequently, during puberty, such as lack of secondary
sexual characters and aspermatogenesis,[29] while tall stature as a symptom can be hard to
diagnose during puberty. Despite the presence of small testes, only a quarter of the affected
males are recognized as having Klinefelter syndrome at puberty[30][31] and 25% received their
diagnosis in late adulthood: about 64% affected individuals are not recognized as
such.[32] Often the diagnosis is made accidentally as a result of examinations and medical
visits for reasons not linked to the condition.[33]
The standard diagnostic method is the analysis of the
chromosomes' karyotype on lymphocytes. In the past, the observation of the Barr body was
common practice as well.[31] To confirm mosaicism, it is also possible to analyze the
karyotype using dermal fibroblasts or testicular tissue.[34]
Other methods may be: research of high serum levels of gonadotropins (follicle-stimulating
hormone and luteinizing hormone), presence ofazoospermia, determination of the
sex chromatin,[35] and prenatally via chorionic villus sampling or amniocentesis. A 2002
literature review of elective abortion rates found that approximately 58% of pregnancies in the
United States with a diagnosis of Klinefelter syndrome were terminated.[36]
Differential diagnosis
The symptoms of Klinefelter syndrome are often variable; therefore, a karyotype analysis
should be ordered when small testes, infertility, gynecomastia, long legs/arms, developmental
delay, speech/language deficits, learning disabilities/academic issues and/or behavioral
issues are present in an individual.[1] The differential diagnosis for the Klinefelter syndrome
can include the following conditions: fragile X syndrome, Kallmann syndrome and Marfan
syndrome. The cause of hypogonadism can be attributed to many other different medical
conditions.
Treatment
By 2010 over 100 successful pregnancies have been reported using IVF technology with
surgically removed sperm material from males with Klinefelter syndrome.[39]
Prognosis
Children with XXY differ little from other children. Although they can face problems
during adolescence, often emotional and behavioural, and difficulties at school, most of them
can achieve full independence from their families in adulthood. Most can lead a normal,
healthy life.
The results of a study carried out on 87 Australian adults with the syndrome shows that those
who have had a diagnosis and appropriate treatment from a very young age had a significant
benefit with respect to those who had been diagnosed in adulthood.[40]
There is research suggesting Klinefelter syndrome substantially decreases life
expectancy among affected individuals, though the evidence is not definitive.[41] A 1985
publication identified a greater mortality mainly due to diseases of the aortic valve,
development of tumors and possible subarachnoid hemorrhages, reducing life expectancy by
about 5 years.[42] Later studies have reduced this estimated reduction to an average of 2.1
years.[43] These results are still questioned data, are not absolute, and will need further
testing.[41]
Epidemiology
This syndrome, evenly spread in all ethnic groups, has a prevalence of 1-2 subjects every
1000 males in the general population.[30][44][45][46] 3.1% of infertile males have Klinefelter
syndrome. The syndrome is also the main cause of male hypogonadism.[47]
According to a meta-analysis, the prevalence of the syndrome has increased over the past
decades; however, this does not appear to be correlated with the increase of the age of the
mother at conception, as no increase was observed in the prevalence of other trisomies of
sex chromosomes (XXX and XYY).[48]
diseases.[6] Finally, a specific pattern of cognitive deficits is often observed, with particular
difficulties in visuospatial, mathematical, and memory areas.[7]
History
Turner syndrome is named after Henry Turner, the endocrinologist who first described it in
1938.
The syndrome was named after Harry Klinefelter, who, in 1942, worked with Fuller
Albright at Massachusetts General Hospital in Boston, Massachusetts and first described it in
the same year.[13][29] The account given by Klinefelter came to be known as Klinefelter
syndrome as his name appeared first on the published paper, and seminiferous tubule
dysgenesis was no longer used.
Signs and symptoms
See also

Aneuploidy

Intersex

Mosaic (genetics)

True hermaphroditism

Turner Syndrome

XXYY syndrome

Non-Klinefelter XXY
Turner syndrome
Turner syndrome or Ullrich–Turner syndrome (also known as "Gonadal dysgenesis"[1]:550),
45,X, encompasses several conditions in humanfemales, of which monosomy X (absence of
an entire sex chromosome, the Barr body) is most common. It is a chromosomal
abnormality in which all or part of one of the sex chromosomes is absent or has other
abnormalities (unaffected humans have 46 chromosomes, of which two are sex
chromosomes). In some cases, the chromosome is missing in some cells but not others, a
condition referred to as mosaicism[2] or "Turner mosaicism".
Occurring in 1 in 2000[3] – 1 in 5000 phenotypic females,[4] the syndrome manifests itself in a
number of ways. There are characteristic physical abnormalities which affect many but not all
people with Turner syndrome, such as short stature, swelling, broad chest, low hairline, lowset ears, andwebbed necks.[5] Girls with Turner syndrome typically experience gonadal
dysfunction (non-working ovaries), which results in amenorrhea (absence of menstrual cycle)
and sterility. Concurrent health concerns may also be present, including congenital heart
disease, hypothyroidism (reducedhormone secretion by
the thyroid), diabetes, vision problems, hearing concerns, and many autoimmune
Lymphedema, puffy legs of a newborn with Turner syndrome
The following is a list of common symptoms of Turner syndrome. It is important to note that
an individual may have any combination of symptoms and is unlikely to have all symptoms.

Short stature

Lymphedema (swelling) of the hands and feet

Broad chest (shield chest) and widely spaced nipples

Low hairline

Low-set ears

Reproductive sterility

Rudimentary ovaries gonadal streak (underdeveloped gonadal structures that later
become fibrosed)

Amenorrhoea, or the absence of a menstrual period

Increased weight, obesity
In the majority of cases where monosomy occurs, the X chromosome comes from the
mother.[10] This may be due to a nondisjunction in the father. Meiotic errors that lead to the
production of X with p arm deletions or abnormal Y chromosomes are also mostly found in
the father.[11] Isochromosome X or ring chromosome X on the other hand are formed equally
often by both parents.[11]Overall, the functional X chromosome mostly comes from the
mother.

Shield shaped thorax of heart

Shortened metacarpal IV

Small fingernails

Characteristic facial features

Webbed neck from cystic hygroma in infancy

Aortic valve stenosis

Coarctation of the aorta

Bicuspid aortic valve
In most cases, Turner syndrome is a sporadic event, and for the parents of an individual with
Turner syndrome the risk of recurrence is not increased for subsequent pregnancies. Rare
exceptions may include the presence of a balanced translocation of the X chromosome in a
parent, or where the mother has XO mosaicism restricted to her germ cells. [12]

Horseshoe kidney
Diagnosis

Visual impairments sclera, cornea, glaucoma, etc.
Prenatal

Ear infections and hearing loss

High waist-to-hip ratio (the hips are not much bigger than the waist)

Attention Deficit/Hyperactivity Disorder or ADHD (problems with concentration, memory,
attention with hyperactivity seen mostly in childhood and adolescence)

Nonverbal Learning Disability (problems with math, social skills and spatial relations)
Other features may include a small lower jaw (micrognathia), cubitus valgus,[8] soft upturned
nails, palmar crease, and drooping eyelids. Less common are pigmented moles, hearing loss,
and a high-arch palate (narrow maxilla). Turner syndrome manifests itself differently in each
female affected by the condition, therefore, no two individuals will share the same features.
Cause
Turner syndrome is caused by the absence of two complete copies of the X chromosome in
some or all the cells. The abnormal cells may have only one X (monosomy) (45,X) or they
may be affected by one of several types of partial monosomy like a deletion of the short p
arm of one X chromosome (46,XdelXp) or the presence of an isochromosome with two q
arms (46XiXq)[9] In mosaic individuals, cells with X monosomy (45,X) may occur along with
cells that are normal (46,XX), cells that have partial monosomies, or cells that have a Y
chromosome (46,XY).[9] The presence of mosaicism is estimated to be relatively common in
affected individuals (67-90%).[9]
Inheritance
45,X karyotype, showing an unpaired X at the lower right
Turner syndrome may be diagnosed by amniocentesis or chorionic villus sampling during
pregnancy.
Usually, fetuses with Turner syndrome can be identified by abnormal ultrasound findings (i.e.,
heart defect, kidney abnormality, cystic hygroma,ascites). In a study of 19 European
registries, 67.2% of prenatally diagnosed cases of Turner Syndrome were detected by
abnormalities on ultrasound. 69.1% of cases had one anomaly present, and 30.9% had two
or more anomalies.[13]
An increased risk of Turner syndrome may also be indicated by abnormal triple or quadruple
maternal serum screen. The fetuses diagnosed through positive maternal serum screening
are more often found to have a mosaic karyotype than those diagnosed based on
ultrasonographic abnormalities, and conversely those with mosaic karyotypes are less likely
to have associated ultrasound abnormalities.[13]
Although the recurrence risk is not increased, genetic counseling is often recommended for
families who have had a pregnancy or child with Turner syndrome.
Postnatal
Turner syndrome can be diagnosed postnatally at any age. Often, it is diagnosed at birth due
to heart problems, an unusually wide neck or swelling of the hands and feet. However, it is
also common for it to go undiagnosed for several years, typically until the girl reaches the age
of puberty/adolescence and she fails to develop properly (the changes associated with
puberty do not occur). In childhood, a short stature can be indicative of Turner syndrome. [14]
A test, called a karyotype or a chromosome analysis, analyzes the chromosomal composition
of the individual. This is the test of choice to diagnose Turner syndrome.
Prognosis
While most of the physical findings are harmless, there can be significant medical problems
associated with the syndrome.
Prenatal
Despite the excellent postnatal prognosis, 99% of Turner-syndrome conceptions are thought
to end in spontaneous abortion or stillbirth,[15] and as many as 15% of all spontaneous
abortions have the XO karyotype.[16] Among cases that are detected by routine amniocentesis
or chorionic villus sampling, one study found that the prevalence of Turner syndrome among
tested pregnancies was 5.58 and 13.3 times higher respectively than among live neonates in
a similar population.[17]
Cause
According to Sybert, 1998 the data are inadequate to allow conclusions about phenotypekaryotype correlations in regard to cardiovascular malformations in Turner syndrome
because the number of individuals studied within the less common karyotype groups is too
small. Other studies also suggest the presence of hidden mosaicisms that are not diagnosed
on usual karyotypic analyses in some patients with 45,X karyotype.
In conclusion, the associations between karyotype and phenotypic characteristics, including
cardiovascular malformations, remain questionable.
Prevalence of cardiovascular malformations
The prevalence of cardiovascular malformations among patients with Turner syndrome
ranges from 17% (Landin-Wilhelmsen et al., 2001) to 45% (Dawson-Falk et al., 1992).
The variations found in the different studies are mainly attributable to variations in noninvasive methods used for screening and the types of lesions that they can characterize (Ho
et al., 2004). However Sybert, 1998 suggests that it could be simply attributable to the small
number of subjects in most studies.
Different karyotypes may have differing prevalence of cardiovascular malformations. Two
studies found a prevalence of cardiovascular malformations of 30% [19] and 38%[20] in a group
of pure 45,X monosomy. But considering other karyotype groups, they reported a prevalence
of 24.3%[19] and 11%[20] in patients with mosaic X monosomy, and a prevalence of 11% in
patients with X chromosomal structural abnormalities.[19]
The higher prevalence in the group of pure 45,X monosomy is primarily due to a significant
difference in the prevalence of aortic valve abnormalities and coarctation of the aorta, the two
most common cardiovascular malformations.
Cardiovascular
Congenital heart disease
Cardiovascular malformations are a serious concern as it is the most common cause of death
in adults with Turner syndrome. They play an important part in the 3-fold increase in overall
mortality and the reduced life expectancy (up to 13 years) associated with Turner syndrome.
Price et al. (1986 study of 156 female patients with Turner syndrome) showed a significantly
greater number of deaths from diseases of the circulatory system than expected, half of them
due to congenital heart defects — mostly coarctation of the aorta. When patients with
congenital heart disease were omitted from the sample of the study, the mortality from
circulatory disorders was not significantly increased.[18]
The most commonly observed are congenital obstructive lesions of the left side of the heart,
leading to reduced flow on this side of the heart. This includes bicuspid aortic
valve and coarctation(narrowing) of the aorta. Sybert, 1998 found that more than 50% of the
cardiovascular malformations observed in her study of individuals with Turner syndrome were
bicuspid aortic valves or coarctation of the aorta, alone or in combination.
Other congenital cardiovascular malformations, such as partial anomalous venous drainage
and aortic valve stenosis or aortic regurgitation, are also more common in Turner syndrome
than in the general population. Hypoplastic left heart syndrome represents the most severe
reduction in left-sided structures
Bicuspid aortic valve
Aortic dilation, dissection, and rupture
Up to 15% of adults with Turner syndrome have bicuspid aortic valves, meaning that there
are only two, instead of three, parts to the valves in the main blood vessel leading from
the heart. Since bicuspid valves are capable of regulating blood flow properly, this condition
may go undetected without regular screening. However, bicuspid valves are more likely to
deteriorate and later fail.Calcification also occurs in the valves,[21] which may lead to a
progressive valvular dysfunction as evidenced by aortic stenosis or regurgitation.[22]
Two studies have suggested aortic dilatation in Turner syndrome, typically involving the root
of the ascending aorta and occasionally extending through the aortic arch to the descending
aorta, or at the site of previous coarctation of the aorta repair.[24]
With a prevalence from 12.5%[19] to 17.5% (Dawson-Falk et al., 1992), bicuspid aortic valve is
the most common congenital malformation affecting the heart in this syndrome. It is usually
isolated but it may be seen in combination with other anomalies, particularly coarctation of
the aorta.
Coarctation of the aorta
Between 5% and 10% of those born with Turner syndrome have coarctation of the aorta, a
congenital narrowing of the descending aorta, usually just distal to the origin of the left
subclavian artery(the artery that branches off the arch of the aorta to the left arm) and
opposite to the duct (and so termed "juxtaductal"). Estimates of the prevalence of this
malformation in patients with Turner syndrome ranges from 6.9%[19] to 12.5% . A coarctation
of the aorta in a female is suggestive of Turner syndrome, and suggests the need for further
tests, such as a karyotype.
Partial anomalous venous drainage
This abnormality is a relatively rare congenital heart disease in the general population. The
prevalence of this abnormality also is low (around 2.9%) in Turner syndrome. However, its
relative risk is 320 in comparison with the general population. Strangely, Turner syndrome
seems to be associated with unusual forms of partial anomalous venous drainage. [19][23]
In the management of a patient with Turner syndrome it is essential to keep in mind that
these left-sided cardiovascular malformations in Turner syndrome result in an increased
susceptibility to bacterial endocarditis. Therefore prophylactic antibiotics should be
considered when procedures with high risk endocarditis are performed, such as dental
cleaning.[22]
Turner syndrome is often associated with persistent hypertension, sometimes in childhood. In
the majority of Turner syndrome patients with hypertension, there is no specific cause. In the
remainder, it is usually associated with cardiovascular or kidney abnormalities, including
coarctation of the aorta.

Allen et al., 1986 who evaluated 28 girls with Turner syndrome, found a significantly
greater mean aortic root diameter in patients with Turner syndrome than in the control
group (matched for body surface area). Nonetheless, the aortic root diameter found in
Turner syndrome patients were still well within the limits.[25]

This has been confirmed by the study of Dawson-Falk et al., 1992 who evaluated 40
patients with Turner syndrome.[26] They presented basically the same findings: a greater
mean aortic root diameter, which nevertheless remains within the normal range for body
surface area.
Sybert, 1998 points out that it remains unproven that aortic root diameters that are relatively
large for body surface area but still well within normal limits imply a risk for progressive
dilatation.[27]
Prevalence of aortic abnormalities
The prevalence of aortic root dilatation ranges from 8.8%[24] to 42%[22] in patients with Turner
syndrome. Even if not every aortic root dilatation necessarily goes on to an aortic
dissection(circumferential or transverse tear of the intima), complications such as dissection,
aortic rupture resulting in death may occur. The natural history of aortic root dilatation is still
unknown, but it is a fact that it is linked to aortic dissection and rupture, which has a high
mortality rate.[28]
Aortic dissection affects 1% to 2% of patients with Turner syndrome. As a result any aortic
root dilatation should be seriously taken into account as it could become a fatal aortic
dissection. Routine surveillance is highly recommended.[22]
Risk factors for aortic rupture
It is well established that cardiovascular malformations (typically bicuspid aortic valve,
coarctation of the aorta and some other left-sided cardiac malformations) and hypertension
predispose to aortic dilatation and dissection in the general population. At the same time it
has been shown that these risk factors are common in Turner syndrome. Indeed these same
risk factors are found in more than 90% of patients with Turner syndrome who develop aortic
dilatation. Only a small number of patients (around 10%) have no apparent predisposing risk
factors. It is important to note that the risk of hypertension is increased 3-fold in patients with
Turner syndrome. Because of its relation to aortic dissection blood pressure needs to be
regularly monitored and hypertension should be treated aggressively with an aim to keep
blood pressure below 140/80 mmHg. It has to be noted that as with the other cardiovascular
malformations, complications of aortic dilatation is commonly associated with 45,X
karyotype.[22]
Pathogenesis of aortic dissection and rupture
The exact role that all these risk factors play in the process leading to such fatal
complications is still quite unclear. Aortic root dilatation is thought to be due to a
mesenchymal defect as pathological evidence of cystic medial necrosis has been found by
several studies. The association between a similar defect and aortic dilatation is well
established in such conditions such asMarfan syndrome. Also, abnormalities in
other mesenchymal tissues (bone matrix and lymphatic vessels) suggests a similar primary
mesenchymal defect in patients with Turner syndrome.[24]However there is no evidence to
suggest that patients with Turner syndrome have a significantly higher risk of aortic dilatation
and dissection in absence of predisposing factors. So the risk of aortic dissection in Turner
syndrome appears to be a consequence of structural cardiovascular malformations and
hemodynamic risk factors rather than a reflection of an inherent abnormality in connective
tissue (Sybert, 1998). The natural history of aortic root dilatation is unknown, but because of
its lethal potential, this aortic abnormality needs to be carefully followed.
syndrome. Congenital heart disease needs to be explored in every female newly diagnosed
with Turner syndrome. As adults are concerned close surveillance of blood pressure is
needed to avoid a high risk of fatal complications due to aortic dissection and rupture.
Skeletal
Normal skeletal development is inhibited due to a large variety of factors, mostly hormonal.
The average height of a woman with Turner syndrome, in the absence of growth hormone
treatment, is4 ft 7 in (140 cm). Patients with Turner's mosaicism can reach normal average
height.
The fourth metacarpal bone (fourth toe and ring finger) may be unusually short, as may the
fifth.
Due to inadequate production of estrogen, many of those with Turner syndrome
develop osteoporosis. This can decrease height further, as well as exacerbate the curvature
of the spine, possibly leading to scoliosis. It is also associated with an increased risk of bone
fractures.
Kidney
Approximately one-third of all women with Turner syndrome have one of three kidney
abnormalities:
Pregnancy
1. A single, horseshoe-shaped kidney on one side of the body.
Turner syndrome is characterized by primary amenorrhea, premature ovarian failure, streak
gonads and infertility. However, technology (especially oocyte donation) provides the
opportunity of pregnancy in these patients.
2. An abnormal urine-collecting system.
As more women with Turner syndrome complete pregnancy thanks to modern techniques to
treat infertility, it has to be noted that pregnancy may be a risk of cardiovascular
complications for the mother. Indeed several studies had suggested an increased risk for
aortic dissection in pregnancy.[24] Three deaths have even been reported. The influence
of estrogen has been examined but remains unclear. It seems that the high risk of aortic
dissection during pregnancy in women with Turner syndrome may be due to the increased
hemodynamic load rather than the high estrogen rate.[22] Of course these findings are
important and need to be remembered while following a pregnant patient with Turner
syndrome.
Cardiovascular malformations in Turner syndrome are also very serious, not only because of
their high prevalence in that particular population but mainly because of their high lethal
potential and their great implication in the increased mortality found in patients with Turner
3. Poor blood flow to the kidneys.
Some of these conditions can be corrected surgically. Even with these abnormalities, the
kidneys of most women with Turner syndrome function normally. However, as noted above,
kidney problems may be associated with hypertension.
Thyroid
Approximately one-third of all women with Turner syndrome have a thyroid disorder.[citation
needed] Usually it is hypothyroidism, specifically Hashimoto's thyroiditis. If detected, it can be
easily treated with thyroid hormone supplements.
Diabetes
Women with Turner syndrome are at a moderately increased risk of developing type 1
diabetes in childhood and a substantially increased risk of developing type 2 diabetes by
adult years. The risk of developing type 2 diabetes can be substantially reduced by
maintaining a healthy weight.
Cognitive
Turner syndrome does not typically cause intellectual disability or impair cognition. However,
learning difficulties are common among women with Turner syndrome, particularly a specific
difficulty in perceiving spatial relationships, such as nonverbal learning disorder. This may
also manifest itself as a difficulty with motor control or with mathematics. While it is noncorrectable, in most cases it does not cause difficulty in daily living. Most Turner Syndrome
patients are employed as adults and lead productive lives.
There is also a rare variety of Turner Syndrome, known as "Ring-X Turner Syndrome", which
has an approximate 60 percent association with intellectual disability. This variety accounts
for approximately 2–4% of all Turner Syndrome cases.[29]
Treatment
As a chromosomal condition, there is no cure for Turner syndrome. However, much can be
done to minimize the symptoms. For example:[34]

Growth hormone, either alone or with a low dose of androgen, will increase growth and
probably final adult height. Growth hormone is approved by the U.S. Food and Drug
Administration for treatment of Turner syndrome and is covered by many insurance
plans.[34][35] There is evidence that this is effective, even in toddlers.[36]

Estrogen replacement therapy such as the birth control pill, has been used since the
condition was described in 1938 to promote development of secondary sexual
characteristics. Estrogens are crucial for maintaining good bone integrity, cardiovascular
health and tissue health.[34] Women with Turner Syndrome who do not have spontaneous
puberty and who are not treated with estrogen are at high risk for osteoporosis and heart
conditions.

Modern reproductive technologies have also been used to help women with Turner
syndrome become pregnant if they desire. For example, a donor egg can be used to
create an embryo, which is carried by the Turner syndrome woman.[34]

Uterine maturity is positively associated with years of estrogen use, history of
spontaneous menarche, and negatively associated with the lack of current hormone
replacement therapy.[37]
Reproductive
Women with Turner syndrome are almost universally infertile. While some women with
Turner syndrome have successfully become pregnant and carried their pregnancies to term,
this is very rare and is generally limited to those women whose karyotypes are not
45,XO.[30][31] Even when such pregnancies do occur, there is a higher than average risk
of miscarriage or birth defects, including Turner Syndrome or Down Syndrome.[32] Some
women with Turner syndrome who are unable to conceive without medical intervention may
be able to use IVF or other fertility treatments.[33]
Usually estrogen replacement therapy is used to spur growth of secondary sexual
characteristics at the time when puberty should onset. While very few women with Turner
Syndrome menstruate spontaneously, estrogen therapy requires a regular shedding of the
uterine lining ("withdrawal bleeding") to prevent its overgrowth. Withdrawal bleeding can be
induced monthly, like menstruation, or less often, usually every three months, if the patient
desires. Estrogen therapy does not make a woman with nonfunctional ovaries fertile, but it
plays an important role in assisted reproduction; the health of the uterus must be maintained
with estrogen if an eligible woman with Turner Syndrome wishes to use IVF (using
donated oocytes).
Turner syndrome is a cause of primary amenorrhea, premature ovarian failure
(hypergonadotropic hypogonadism), streak gonads and infertility. Failure to develop
secondary sex characteristics (sexual infantilism) is typical.
Especially in mosaic cases of Turner syndrome that contains Y-chromosome (e.g.
45,X0/46,XY) due to the risk of development of ovarian malignancy (most common is
gonadoblastoma) gonadectomy is recommended.[citation needed]
Epidemiology
Approximately 99 percent of all fetuses with Turner syndrome result in spontaneous
termination during the first trimester.[38] Turner syndrome accounts for about 10 percent of the
total number of spontaneous abortions in the United States.[citation needed] The incidence of
Turner syndrome in live female births is believed to be around 1 in 2000.[3]
History
The syndrome is named after Henry Turner, an endocrinologist from Illinois, who described it
in 1938.[39] In Europe, it is often called Ullrich–Turner syndrome or even Bonnevie–
Ullrich–Turner syndrome to acknowledge that earlier cases had also been described by
European doctors.
The first published report of a female with a 45,X karyotype was in 1959 by Dr. Charles Ford
and colleagues in Harwell, Oxfordshire and Guy's Hospital in London.[40] It was found in a 14year-old girl with signs of Turner syndrome.
References:
http://www.wikipedia.com