Genetic sonogram and soft tissue markers

1. Genetic sonogram
&
Soft tissue markers
Dr. Mohit Satodia
GMCH 32
Chadigarh

2. Introduction to Genetic sonogram
•It’s a specific targeted examination for fetal aneuploidy,
most specific for Downs syndrome, that searches for the
presence of
1)Fetal structural anomalies
2)Aneuploidy markers and
3)Abnormal biometry. (Callen’s 5th)
• These aneuploidy markers are called as “soft” markers
and these are variations in normal anatomy that, except for
their relationship to aneuploidy, are unlikely to be
clinically significant. (Callen’s 5th)
• soft markers are often transient and nonspecific findings
which can also occur frequently in euploid fetuses.

3. Genetic Sonogram
•Sensitivity of genetic sonogram ranges from 84%
among women with advanced maternal age to 90%
among women younger than 35 years with abnormal
triple test.
• Performed between 18 to 20 weeks of gestation.
• Major advantage is, it reduces the invasive testing rate
and can optimize the selection of candidate for invasive
testing in order to minimize the procedure related losses
of normal fetuses without significantly decreasing
detection rate.
(Callen’s 5th)

4. Candidate for Genetic sonogram
Low risk vs. high risk population
• Inappropriate for LOW RISK population
1)High false positive rate of 12 to 15% in high risk
population (which is probably more in low risk).
2)Each marker by itself has only low to moderate
sensitivity for Downs, when found in isolation it not necessarily
increase the risk but increases cost and anxiety in LOW RISK.
3) In LOW RISK patient the prior risk may be so low that
Presence of one marker will not qualify a patient for
Amniocentesis.
4) Further the accuracy of soft markers has only been
studied in HIGH RISK population and generalizing the result in
low risk is not appropriate.

5. Prenatal sonographic features of trisomy 21
(Callen’s 5th)

6. Prenatal sonographic
features of trisomy 18
(Callen’s 5th)

7. Prenatal sonographic
features of trisomy 13
(Callen’s 5th)

8. Most investigated “Six Soft markers” of downs syndrome with
likelihood ratio
( Williams 23rd edi)

9. Second Trimester Ultrasound Markers Practice
Guidelines
Normal Ultrasound (No marker present)
Low Risk
Including
1)Age < 35 and
2)serum screen negative
High Risk
Including Age
1) Age≥ 35years
or 2) Serum screen positive
or Both
No testing required Downs syndrome risk
adjustment (80% reduction in a
priori risk)
From (Callen’s 5th)

10. Second Trimester Ultrasound Markers Practice
Guidelines
ONE ISOLATED SOFT MARKER PRESENT ( Except Nuchal
Fold or Absent nasal bone)
Low Risk
Including
1)Age < 35 and
2)serum screen negative
High Risk
Including Age
1) Age≥ 35years
or 2) Serum screen positive
or Both
No testing required Offer Genetic Amniocentesis
From (Callen’s 5th)

11. Second Trimester Ultrasound Markers Practice
Guidelines
≥ 2 SOFT MARKERS PRESENT OR Thick Nuchal fold OR
Absent nasal bone OR structural anomaly
Low Risk
Including
1)Age < 35 and
2)serum screen negative
High Risk
Including Age
1) Age≥ 35years
or 2) Serum screen positive
or Both
Offer Genetic AmniocentesisOffer Genetic Amniocentesis
From (Callen’s 5th)

12. Individual soft markers

13. Nuchal fold
• Most sensitive and specific single midtrimester marker
of downs syndrome.
Also seen in 1) trisomy 18
2) trisomy 13
3) Turners syndrome.
• Nuchal skin folds is excess soft tissue in posterior neck
area.
• Sensitivity of Downs detection in range of 42 to 43%
with cut off as 6mm, sensitivity increases to 77.8% with
5mm as cut off (with slight increase in false positive rate)
• Best obtained in trans axial plane through head, angled
posteriorly to include cerebellum and occipital bone.

14. Trans axial plane for
taking nuchal fold
It should include
following internal
structures.
1)cerebellum,
2)occipital bone
3)cavum septum
pellucidum
• The nuchal fold is
measured with
placement of calipers
from the outer edge of
occipital bone to the
outer edge of the skin
Nuchal fold

15. Increased Nuchal fold on USG

16. Significance of Nuchal fold
• Most sensitive and specific with likelihood ratio of 11
for down syndrome even as isolated marker.
• In low risk patients also its helpful in detecting cases.
• Amniocentesis is advised even in low risk patients with
abnormal nuchal fold thickness.

17. Nasal Bone
• Common feature of downs syndrome facies is flat face with
small nose, again there were evidences of absent, hypoplastic ,
short and agenesis of nasal bone in radiographs of downs
syndrome fetuses—this formed the basis of incorporating absent
nasal bone as soft marker.
• Ideal method for evaluating the facial profile for Nasal bone
include—midsagittal plane with angle of insonation close to 45º
or 135º.
As with angle <45º or >135º the nasal bone may appear
absent, further with angle approaching 90º it may appear large.

18. Face profile with angle of insonation as 45º showing Nasal Bone

19. Nasal Bone
• Sensitivity for absent nasal bone have ranged from 28
to 66%, with likelihood ratio of 83 for Downs.
(this approximates that of nuchal fold thickening).
• After addition of absent nasal bone as soft marker, the
sensitivity of genetic sonogram has increased from 87%
to 92.8% without increasing false +ve rate.
• Short or hypoplastic nasal bone as soft marker requires
sonographic normograms which are specific to local
population and based on it cutoff are decided for better
results.
•Further BPD/NBL ratio >10 can also be used, with
81% sensitivity for downs syndrome.

20. Echogenic Intracardiac Focus (EIF)
• Echogenic cardiac foci (EIF) is commonly seen on 2nd
trimester USG –in 3 to 4% of normal fetuses.
• EIF-its discrete brightly echogenic spot with brightness
similar to bone, due to reflection from coarse intra
myocardial calcification of papillary muscles and chordae
tendinae surrounded by myocardial fibrosis.
• Best visualized in apical 4 chamber view with apex
towards or away from transducer.
• Resolves by 3rd trimester
•Most frequently seen in the left ventricle, but also can be
seen in right ventricle or bilaterally.
•Likelihood ratio of EIF for Downs syndrome ranges
between 1.8 to 4.2.

21. Echogenic Intracardiac Focus

22. Significance of EIF
• EIF is associated with aneuploidy trisomy 21 and 13.
• In high risk populations EIF increases the risk of
downs syndrome, but in low risk EIF is considered a
normal variant with absence of other major or minor
USG anomalies.
• M/C in left ventricle but right side or bilateral EIF-
higher risk of aneuploidy.
• Multiple(67%) and large in size-higher risk of
aneuploidy.
• Right vs. Left EIF-higher risk of aneuploidy in right
side EIF.

23. Echogenic Intracardiac Focus

24. Choroid plexus Cysts (CPCs)
• Lateral ventricles contain sonolucent CSF and with in this
lies brightly echogenic choroid plexus that normally fills the
atrium and may contains cyst.
• Prevalence among normal is variable from 0.3% to 3.6%.
• CPCs seen between 16 to 21 weeks of GA and are transient,
by 23rd weeks undergo resolutions and uncommon after 25 to
26 weeks.
• CPCs can be unilateral/bilateral/ unilocular or multilocular.
•Commonly they are multilocular and range from 0.5 to 2cm,
occasionally large as to fill almost entire lateral ventricle.

25. Significance of Choroid plexus Cysts
•CPCs always resolve, Larger cysts may take longer time.
•CPCs are associated with fetal aneuploidy- Trisomy 18.
•Prevalence of CPCs in trisomy 18 is 53% when other soft tissue
marker is also present, isolated CPCs are not associated with
trisomy 18.
• Larger cyst (>1cm) compared to smaller increases the risk of
trisomy 18.
• Isolated presence of CPCs in low risk patient is not considered
clinically significant, does not change risk category.
• CPCs in absence of other minor or major soft markers & in
absence of other risk factors considered to be a “normal variant”
and no further evaluation is needed.
• Recommendations are if CPCs is present detailed USG for other
soft markers to be done, and if isolated and they always resolve
repeat scan add no value to decision making.

26. Choroid plexus Cysts
Choroid plexus cyst single
unilateral with normal
chromosomes

27. Choroid plexus Cysts
Multiple Unilateral Cysts
with normal
chromosomes

28. Choroid plexus Cysts
Bilateral cysts with
trisomy 18

29. Hyper echogenic bowel
• Non specific and can be seen in normal fetuses (0.5%).
• Normally in 2nd trimester bowel is homogenous with
same echogenicity as rest of abdomen, if it has
echogenicity similar to iliac bones-
HYPERECHOGENIC.
• Hyper echogenic bowel is seen with increased
frequency in trisomy 21, it increases risk by six to
sevenfold ( with other risk factors like age, other soft
markers).
•Risk of trisomy 21 with isolated Hyper echogenic bowel
is 1.4%.

30. Significance of Hyper echogenic bowel
• Other conditions were Hyper echogenic bowel is seen
1) congenital infections- Cytomegalovirus, herpes
simplex, parvo virus.
2) meconium ileus (due to cystic fibrosis).
3) Bowel obstructions/ Atresia / malformations.
4) Prenatal vaginal bleeding and fetal swallowing
of blood from inatraamniotic hemorrhage.
• There is also increases risk of fetal demise, IUGR and
placenta related complications.
• Risk of both cystic fibrosis and aneuploidy increases
with degree of echogenicity.

31. Hyper echogenic bowel
Recommendations-
1)consider maternal
studies for congenital
infection, cystic
fibrosis carrier status.
2)invasive testing for
fetal karyotype.
3)serial scan for
IUGR and to rule out
bowel malformations
( evident mostly in
3rd trimester).

32. Short Long Bones
•Somatic and visceral growth profiles of midtrimester
trisomy 21 fetuses have shown short limbs which are
discordant with head circumference (HC).
• Short Femur length – BPD/Femur length ratio or
observed to expected FL ratio—associated with downs
syndrome.
•Assessed between 15 to 23 weeks, but most helpful in
detecting trisomy 21 between 17 to 19 weeks.
•Ideal method—FL measured with diaphysis located
horizontally in image ( as vertical measurement a/w
high false + rate).

33. Short Long Bones
• Different studies showing different sensitivity rates for trisomy
21 detection.
• Most accepted studies out of all is by Lockwood et al showing
sensitivity of 51% with BPD/FL ratio and by Benacerraf et al
showing sensitivity of 68%.

34. Short Long Bones
• Humeral length--short humeral length also associated
with trisomy 21.
• with measured to expected HL >0.90 as cutoff
sensitivity is 50%.
• Short HL is less useful then FL as screening marker.

35. Significance of Short Long Bones
• Isolated Short FL is not much sensitive rather
combining it with other USG markers.
•Combining both HL and FL assessments—it carry a 11
fold higher risk of having trisomy 21.
• Gender influences the long bones length, affected
male fetuses had more short FL and HL than affected
female fetuses.

36. Pyelectasis
• Renal pyelectasis ( pelvic dilation) is measured in AP
dimension as fluid filled renal pelvis.
• Common finding on USG seen in 2 to 2.8% of normal
fetuses.
• Measured in view with kidney and spine are positioned
directly toward or away from transducer.
• Cut off is >4mm.
• sensitivity is 25% with cut off > 4mm.
• Isolated pyelectasis carries slightly increased risk but not
enough to justify amniocentesis in low risks and to be used
with other USG markers.
• When present in high risk as isolated it increased priori
risk for fetal trisomy 21.
•

38. Lliac Wing angle
• Trisomy 21 fetuses have pelvic dysplasia and wider
lateral span of iliac wing as compared to normal thus
causing a widened iliac angle.
• Its measured in transverse view of fetal pelvis, the
iliac angle made by two iliac crests at pivot point of
sacral spine is measured.
•Mean iliac angle in downs is 80± 19.7 ºas compare to
63.1±0.3ºin normal, thus by taking 90º as cut off—
sensitivity is 36.8%.

40. Significance of Lliac Wing angle
• It is non reproducible due to variation in measurement
of angle.
Depending on 1) actual transverse level
2) intra and interobserver variation.
3) Orientation of spine, axial level
and GA.
• Not a useful marker of trisomy 21.

41. Ear Length
• Abnormally small ears is one of the consistent clinical
finding in newborns and infants with aneuploidy
including downs syndrome.
•Its always found sonographically in cases with trisomy
18 and 13, and in half of the cases of trisomy 21.
•As a result Short ear length on midtrimester USG, is
taken as one of the soft markers of aneuploidy.
• Sensitivity of short ear length (<10th percentile of GA)
in midtrimester is 71%. ( as per Lettieri et al).
• Measured to expected ear length ratio < 0.8 had
sensitivity of 75% for downs and 83.3% for trisomy 18.
(Callens 5th edi)

43. Ear Length
• Further studies has shown that sensitivity of ear length
for downs syndrome is 41%, for trisomy 18 is 96% and
for trisomy 13 its 100%.
•

44. Single umbilical artery
• Single Umbilical artery (SUA) is associated with
cytogenetic abnormality – with incidence of 17% with
SUA.
• Trisomy 18 is most common aneuploidy associated
with SUA, then trisomy 13, Turners syndrome and
triploidy, but Downs syndrome is not commonly
associated with SUA.
• In midtrimester USG transverse views of a free loop of
cord with adequate magnification is examined, In SUA
only two vessels one large (vein) and smaller (artery)
will be seen.

45. Single umbilical artery
• Single Umbilical artery (SUA) is associated with
cytogenetic abnormality – with incidence of 17% with
SUA.
• Trisomy 18 is most common aneuploidy associated
with SUA, then trisomy 13, Turners syndrome and
triploidy, but Downs syndrome is not commonly
associated with SUA.
• In midtrimester USG transverse views of a free loop of
cord with adequate magnification is examined, In SUA
only two vessels one large (vein) and smaller (artery)
will be seen.

47. Single umbilical artery
• Overall SUA has incidence of 11.3% among
cytogenetically abnormal pregnancies, it can be found in
10 to 50% of trisomy 18 and 13 fetuses.
• It has also been reported to be associated with
1) Congenital anomalies involving various organ
system.(most common system involved-CVS, GIT, CNS).
2) Genetic syndrome ( VATER, Meckel Gruber syndrome)
3) Fetal growth restriction.
4) Prematurity.
5) Increased perinatal mortality rate.

48. Significance of Single umbilical artery
• In fetuses with isolated SUA there is no increased
incidence for chromosomal abnormality.
• With isolated SUA a detailed sonogram by experience
personnel for other anomalies to be done, once
confirmed isolated and in absence of high risk factors
no need of invasive analysis.
• If other multiple malformations are detected with SUA
Patient should be offered prenatal karyotyping

49. Sandal Gap
• Sandal gap is separation of great toe from second toe
causing a wide gap between two phalanges.
•

50. Sandal Gap