SCREENING DAN DIAGNOSIS DOWN SYNDROME PADA KEHAMILAN

Arga Aditya & Zaras Yudhistira Saga

Human Chromosome
22 pairs of autosome and 1 pairs of gonosom
Female
o 44A + XX
22AA + X 22AA + X

Male
o 44A + XY
22AA + X 22AA + Y

Down Syndrome
Down syndrome (trisomy 21) is the most commonly recognized genetic cause of mental retardation. The risk of trisomy 21 is directly related to maternal age.

Patients who will be 35 years or older on their due date should be offered chorionic villus sampling or second-trimester amniocentesis. Women younger than 35 years should be offered maternal serum screening at 16 to 18 weeks of gestation. The maternal serum markers used to screen for trisomy 21 are alphafetoprotein, unconjugated estriol and human chorionic gonadotropin. The use of ultrasound to estimate gestational age improves the sensitivity and specificity of maternal serum screening

Frequency of Dysmorphic Signs in Neonates with Trisomy 21

Dysmorphic sign Flat facial profile Poor Moro reflex Frequency (%) 90 85

Hypotonia
Hyperflexibility of large joints Loose skin on back of neck Slanted palpebral fissures Dysmorphic pelvis on radiographs Small round ears Hypoplasia of small finger, middle phalanx Single palmar crease

80
80 80 80 70 60 60 45

Down Syndrome

Complications in Persons with Down Syndrome

Disorder Mental retardation and Growth retardation Early Alzheimer's disease Congenital heart defects Hearing loss (related to otitis media with effusion or sensorineural) Incidence (%) > 95 Affects 75% by age 60 40 40 to 75

Ophthalmic disorders (congenital cataracts, glaucoma, strabismus)

Epilepsy Gastrointestinal malformations (duodenal atresia, Hirschsprung disease) Hypothyroidism Leukemia Atlantoaxial subluxation with spinal cord compression

60
5 to 10 5 5 1 <1

Infertility

99% in men anovulation in 30% of women

Pregnancy With Down Syndrome Risk Factor

Maternal Age
As a womans ovum age, there is a higher risk of the chromosomes dividing incorrectly.

Previous child with Down syndrome

first child with Down syndrome have a slightly increased risk (about 1%) of having a second child with Down syndrome.

A carrier parent
Parents who are carriers of the genetic translocation for Down syndrome have an increased risk depending on the type of translocation, therefore prenatal screening and genetic counseling are important.

Screening And Diagnostic Test In High Risk Pregnancy Women

Screening
Genetic History Maternal Blood Fetal cell Ultrasound

Diagnostic
Amniocentesis
performed after week 15.

Chorionic villus sampling (CVS)

performed between the 9th and 14th week.

Percutaneous umbilical blood sampling (PUBS)

performed after week 18.

Prenatal Risk Factor Assessment

Advanced Maternal Age

Maternal Serum Screening

First Trimester Screen Second Trimester Screen

Ultrasound Assessment

Quad Marker Screen

Triple Screen

Ultrasound Assessment
An estimate of gestational age by ultrasound examination improves the performance of the triple test. The use of ultrasound was found to raise the sensitivity of the triple test from 60 percent to 74 percent and to decrease the initial false-positive rate from 9 percent to 5 percent The biparietal diameter provides the best gestational age estimate for this purpose. Femur length and composite estimates derived from it should not be used, because underestimates the gestational age of fetuses with trisomy 21 Second-trimester ultrasound assessment may be helpful for predicting the likelihood of trisomy 21 in pregnancies at increased risk

Ultrasonographic Findings Associated with Fetal Down Syndrome

Intrauterine growth restriction Mild cerebral ventriculomegaly Choroid plexus cysts Increased nuchal fold thickness

Cystic hygromas

Echogenic intracardiac foci

Congenital heart defects

Increased intestinal echogenicity

Duodenal atresia (double-bubble sign)

Renal pelvis dilation

Shortened humerus and femur

Increased iliac wing angle

Incurving (clinodactyly) and hypoplasia of the fifth finger

Increased space between first and second toes

Two-vessel umbilical cord

Nuchal Translucency
The measurement is gestationalage dependent; on average, it increases 15 to 20 percent per week Setection rate approximately 70 to 71 percent for Down syndrome, with a 3.5 to 5 percent false-positive rate Increased nuchal translucency of greater than 3.5 mm is associated with:
major congenital heart defects and defects of the great vessels fetal malformations, dysplasias, deformations, and disruptions genetic syndromes

Nuchal Translucency
Nuchal translucency refers to an ultrasonographic sonolucency in the posterior fetal neck (nuchal) The most common ultrasonographic finding associated with trisomy 21 is increased nuchal fold thickness which is caused by subcutaneous edema at the base of the occiput

Advanced Maternal Age

Estimated risk of Down syndrome according to maternal age

FIRST-TRIMESTER SCREENING
Ultrasound measurement of nuchal translucency has been studied alone and in combination with new biochemical markers as a potentially useful first-trimester screening test for trisomy 21 maternal age and measurement of nuchal translucency could provide a trisomy 21 detection rate of 63 percent, with a 5 percent false-positive rate Pregnancy-associated plasma protein A (PAPP A) could increase the detection rate to 80 percent

Second-Trimester Screening Serum Screening Combined First- and Second-Trimester S creening Integrated Screeing Stepwise Sequential Screening

triple screen

quadruple screen

Integrated screening involves PAPP-A and nuchal translucency testing in the first trimester and the quadruplet screen in the second trimester

Ultrasonography

Triple Screening
Alpha-fetoprotein (AFP), unconjugated estriol and human chorionic gonadotropin (hCG) are the serum markers most widely used to screen for Down syndrome. With trisomy 21, second-trimester maternal serum levels of AFP and unconjugated estriol are about 25 percent lower than normal levels and maternal serum hCG is approximately two times higher than the normal hCG level The triple test is usually performed at 15 to 18 weeks of gestation

Procedures for Prenatal Genetic Diagnosis

Gestational age when test is done (weeks) 10 to 12 12 to 15 15 to 20

Diagnostic procedure Chorionic villus sampling Early amniocentesis Second-trimester amniocentesis

Risk of fetal loss (%) 0.5 to 1.5 1.0 to 2.0 0.5 to 1.0

Chorionic Villus Sampling

It entails sampling of the chorionic villus (placental tissue) and testing it for chromosomal abnormalities, usually with FISH or PCR. CVS usually takes place at 1012 weeks' gestation, earlier than amniocentesis (1416 weeks). It is the preferred technique before 15 weeks There are two approaches to CVS: transabdominal and transcervical

Chorionic Villus Sampling

Amniocentesis
a needle is inserted into the amniotic sac using ultrasound guidance, and amniotic fluid is aspirated The fetal loss rate associated with amniocentesis is often reported to be 1 percent Complications are uncommon, but may include vaginal spotting, amniotic fluid leakage, chorioamnionitis, failure of fetal cells to grow in culture, fetal needle injury, and fetal loss

Percutaneous umbilical blood sampling

a needle is inserted into the umbilical cord using ultrasound guidance, and fetal blood is aspirated Percutaneous umbilical blood sampling also called Cordocentesis performed after week 18.

Treatment
There is no medical cure for Down syndrome. However, children with Down syndrome would benefit from early medical assistance and developmental interventions beginning during infancy. Children with Down syndrome may benefit from:
speech therapy physical therapy occupational therapy. special education and assistance in school.

Treatment

Treatment
Discovering that child has Down syndrome can be scary and difficult. Three actions can be helpful in coping with this new situation:
Assemble a team of professionals Find a team of health care providers, teachers and therapists that you trust to work with you in providing the best care. Seek out other families - Support from those who have had similar experiences with a Down syndrome child can be very beneficial. These support groups can be found through local hospitals, physicians, schools and the Internet. Dont believe the myths about Down syndrome Immense strides have been made in recent years with people who have Down syndrome. Most live with their families, go to mainstream schools and have various jobs as adults. People with Down syndrome can lead fulfilling lives.

The reasons to test or not test

BENEFIT Begin planning for a child with special needs Start addressing anticipated lifestyle changes Identify support groups and resources Make a decision about carrying the child to term WEAKNESS They are comfortable with the results no matter what the outcome is Because of personal, moral, or religious reasons, making a decision about carrying the child to term is not an option Risk of harming the developing baby

They can make it

Picture of Paula Sage, a Scottish film and TV actress receiving her BAFTA award

They can make it

International Down's Syndrome swimmer Andy Banks takes the Olympic Torch through Melton

THANKYOU