Download Prenatal Sonographic Findings in Trisomy 21

Junne Kamihara, HMS III
Gillian Lieberman, MD
Prenatal Sonographic Findings
in Trisomy 21
Junne Kamihara, HMS Year III
Gillian Lieberman, MD
March 2007
Junne Kamihara, HMS III
Gillian Lieberman, MD
Prenatal imaging: Menu of tests
Ultrasound
Advantages
• Non-invasive
• Not harmful to fetus,
even in first trimester
• Cost-effective
• Main modality for
screening
Disadvantages
• Operator-dependent
• Unable to detect many
anomalies in fetus
Estroff, JA Semin Roentgenol. 2004, 39:2
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Prenatal imaging: Menu of tests
MRI and Maternal Radiography
MRI
• Better characterization of
anatomic details (e.g.
brain)
• Better tissue contrast
• Large field of view
• Safety for fetus still not
well characterized (avoid
first trimester)
Maternal Radiography
• Used historically for
limited survey of
structural anomalies
• Currently investigated for
use in additional studies
(e.g. to evaluate fetal
bone)
Shinmoto H, et. al. Radiographics 2000, 20
Estroff, JA Semin Roentgenol. 2004, 39:2
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Prenatal Ultrasound
• Full fetal survey: ~18 weeks gestation
(structural anomalies can be detected)
• Early ultrasound: 10-14 weeks gestation
– Nuchal translucency measurements
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Down Syndrome
• Common: overall incidence
about 1 in 700
• Trisomy 21 (47XX or 47XY)
• Most Trisomy 21 caused by
non-disjunction event in
maternal meiosis
• Strong association with
advancing maternal age
Karyotype with 3 copies of Chromosome 21
http://www.biotechnologyonline.gov.au
Emery’s Elements of Medical Genetics , 1995
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Down syndrome: Clinical features
• Characteristic facies, transverse
palmer crease
• Newborn: excess nuchal skin
• Atrial and ventricular septal
defects
• Small middle phalanx of 5th
finger
• Duodenal atresia
Photo demonstrating
transverse palmer crease
http://utdol.com
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Ultrasound detection of Down syndrome
Structural anomalies
NB: found in less than 20%
fetuses with Trisomy 21
• Cardiac defects: e.g. VSD,
ASD
• Duodenal atresia
• Ventriculomegaly
Sonographic markers
• Shortened proximal long
bones (humerus/femur)
• Echogenic intracardiac
focus
• Echogenic bowel
• Absent nasal bone
• Nuchal thickening
• Pyelectasis (renal pelvis
dilation)
Adapted from Table 1: Estroff, JA Semin
Roentgenol. 2004, 39:2
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Our Patient 1: JM
11 wks 2 days
• 36 yo G1P0 female who presents for her initial
visit to the OB
• 11 weeks and 2 days pregnant and otherwise
healthy
• No known history of inherited genetic or
chromosomal disorders
• Expresses a desire to have first trimester
screening.
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Our Patient JM: Early OB ultrasound
12 wks 4 days
• Transabdominal ultrasound
• Crown rump length corresponding to
appropriate gestational age
• Significant abnormal finding:
Thickened nuchal translucency (NT)
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Our Patient JM fetus: Sagittal Ultrasound
Demonstrating Thickened NT of 4.2 mm
http://www.mums.me.uk
Thickened NT
Landmark:
*: Skin
*
PACS, BIDMC
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Junne Kamihara, HMS III
Gillian Lieberman, MD
The following images show another example of
thickened nuchal translucency in a 12-week fetus
with Trisomy 21 (right), as well as an example of
the corresponding subcutaneous fluid collection
which can be seen behind the neck (left)
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Companion Images of Nuchal Translucency:
image of embryo & 12-week sagittal ultrasound
Thickened Nuchal Translucency
http://www.centrus.com.br
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Nuchal translucency
• Normal subcutaneous fluid-filled space found between
the back of the fetal neck/upper trunk and overlying
skin
• Measurements must be made between 10 wks 3 days
and 13 wks 6 days
• With maternal age and biochemical markers, can
detect Trisomy 21 to 90% with false positive rate of
~1%
• Possible pathophysiology of enlarged NT:
abnormalities in extracellular matrix, delayed
development of lymphatics, cardiac abnormalities.
Malone FD and D’Alton ME, Obstets and Gynecol 2003, 102:5
Estroff JA, Semin Roentgenol. 2004, 39:2
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Differential diagnosis for increased NT
•
•
•
•
•
•
Trisomy 21
Trisomy 13, trisomy 18
Turner Syndrome (XO)
Triploidy
Structural heart disease
Other anomalies
Estroff, JA Semin Roentgenol. 2004, 39:2
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Our Patient JM: Plan for further studies to
confirm risk of Down syndrome in fetus
• First-trimester screen positive for Down
syndrome, risk of 1 in 5
• Too late for CVS diagnosis- Amniocentesis
planned
• Full fetal ultrasound scheduled
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Our Patient JM: Full fetal Ultrasound
demonstrated 3 additional findings in fetus
15 wks 2 days
• Short femur
• Echogenic focus in heart
• Ventricular septal defect
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Our Pt JM fetus: Femur length measurementAnatomic orientation
Landmarks:
1 & 2: Inner thighs
3: Posterior
1
3
2
Femurs
PACS, BIDMC
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Two fetal length measurements were made for
our Patient JM fetus as shown in the following
two slides
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Our Pt JM fetus: Femur length measurement 1Short for gestational age
Femur length
PACS, BIDMC
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Our Pt JM fetus: Femur length measurement 2Short for gestational age
Femur length
PACS, BIDMC
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Junne Kamihara, HMS III
Gillian Lieberman, MD
The second finding in our Patient JM fetus was
an Echogenic Intracardic focus (EIF). In
Trisomy 21, this is thought to be due to
calcification of the papillary muscle
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Our Pt JM fetus: 4 chamber view of heart
demonstrating echogenic intracardiac focus
Echogenic focus
4
Landmarks:
1: Spine
2: Ribs
3: Left Atrium
4: Left Ventricle
3
1
2
PACS, BIDMC
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Junne Kamihara, HMS III
Gillian Lieberman, MD
The following companion images show two other
examples of echogenic intracardiac foci and a
normal 4-chamber heart for comparison
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Companion images: Echogenic intracardiac foci
and normal 4-chamber heart view
EIF
Landmarks:
1: Spine
2: Ribs
3: Left Atrium
4: Left Ventricle
http://www.fetal.com
http://www.centrus.com.br
4
3
1
2
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Junne Kamihara, HMS III
Gillian Lieberman, MD
The third finding in our Patient JM fetus was a
suspected endocardial cushion defect. No
normal 4-chamber views of the hearts could be
obtained
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Our Pt JM fetus: 4-chamber views of the heart
demonstrate a probable endocardial cushion defect
Ventricular septal defect
PACS, BIDMC
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Junne Kamihara, HMS III
Gillian Lieberman, MD
The following companion image shows an
example outlining a full endocardial cushion
defect
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Companion image: Full endocardial cushion
defect
http://www.fetal.com
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Differential diagnosis for each finding
Short Femur: Nonlethal osteogenesis imperfecta,
Diabetic embryopathy, trisomy 21, fetal hypoplasiaunusual facies syndrome, ethnic variation
Echogenic intracardiac focus: Fetal cardiac tumors,
endocardial fibroelastosis, trisomy 21, trisomy 13
Ventricular septal defect: Trisomy 21, trisomy 13,
trisomy 18, prematurity, other chromosomal
abnormalities and syndromes
http://www.acsu.buffalo.edu
Reeder and Felson’s Gamuts in Radiology, 3rd ed.
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Our Patient JM: Summary of findings
• U/S 12 wks 4 d: Thickened NT in fetus
• U/S 15 wks 3 d: Short femur, echogenic
intracardiac focus, probable endocardial
cushion defect in fetus
• Amniocentesis performed and confirmed
Trisomy 21 in fetus
• Pt. elected to have pregnancy termination
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Our Patient 2: LG
16 weeks 6 days
• 40 yo who is 16 weeks 6 days pregnant and
otherwise healthy
• Presents for full fetal ultrasound and
amniocentesis
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Our Patient LG: Full fetal ultrasound
demonstrated 2 significant findings in fetus
16 wks 6 days
• Echogenic bowel
• Short femur
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Junne Kamihara, HMS III
Gillian Lieberman, MD
The following image demonstrates the echogenic
bowel seen in our Pt LG fetus. Note the
echogenicity of bowel compared to bone
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Our Pt LG fetus: Sagittal ultrasound
demonstrating Echogenic bowel
Echogenic bowel
Spine
PACS, BIDMC
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Junne Kamihara, HMS III
Gillian Lieberman, MD
The second finding for our Pt LG fetus was a
short femur, shown on the next slide
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Our Pt LG fetus: Short femur
Short femur
PACS, BIDMC
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Differential Diagnosis for each finding
Echogenic Bowel: Normal variant, Trisomy 21, Meconium
ileus (cystic fibrosis), CMV infection
Short Femur: Nonlethal osteogenesis imperfecta, Diabetic
embryopathy, Trisomy 21, fetal hypoplasia-unusual facies
syndrome, ethnic variation
Sickler GK et. al. J Ultrasound Med 1998, 17
Reeder and Felson’s Gamuts in Radiology, 3rd ed.
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Our Patient LG: summary
• U/S 16 wks 6 d: Short femur, echogenic bowel
in fetus
• Amniocentesis performed and confirmed
Trisomy 21 in fetus
• Pt. elected to have pregnancy termination at 19
wks
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Pathology report from our Pt LG fetus included
findings of GI tract with calcifications and small
ventricular septal defect.
Note that one hypothesis for echogenic bowel in
Trisomy 21 includes calcified meconium due to
hypomotility of bowel leading to increased water
absorption, thickening, and subsequent calcification.
Also note that ventricular septal defect was not seen
in ultrasound performed earlier.
Sickler GK et. al. J Ultrasound med 1998
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Main Summary
• Thickened nuchal translucency, (10-14 wks), when
combined with maternal age and biochemical
markers, can detect Trisomy 21 to 90%.
• Structural anomalies, e.g. endocardial cushion
defects, found in less than 20% of fetuses with
Trisomy 21, may be seen in the full fetal scan.
• Sonographic markers, e.g. shortened femur,
echogenic intracardiac focus, and echogenic bowel
can be normal variants but also seen frequently in
Trisomy 21 fetuses.
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Junne Kamihara, HMS III
Gillian Lieberman, MD
References
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Estroff JA. Prenatal Diagnosis and Imaging of Genetic Syndromes, Seminars in Roentgenology
2004; 39: 323-335.
Malone FD, D’Alton MR. First-Trimester Sonographic Screening for own Syndrome, Obstet
Gynecol. 2003; 102: 1066-1079.
Mueller RF, Young ID. Emery’s Elements of Medical Genetics 1995 Pearson Professional Ltd. New
York.
Nyberg DA, Souter VL. Sonographic Markers of Fetal Trisomies: Second Trimester, J Ultrasound in
Medicine 2001; 20:655-674.
Oh KY, Frias AE, Byrne JLB, Kennedy AM. Isolated short femur-what does this mean? 16th World
Congress on Ultrasound in Obstetrics and Gynecology, poster abstract P02.12. Ultrasound in
Obstetrics and Gynecology 2006; 28: 525.
Reeder MM, Bradley WG. Reeder and Felson’s Gamuts in Radiology: Comprehensive Lists of
Roenten Differential Diagnosis, 3rd ed. 1993 Springer-Verlag Telos, New York.
Sadler TW. Langman’s Medical Embryology, 7th ed. 1995 Williams and Wilkins, Baltimore.
Shinmoto HS, Kashima K, et. al. MR Imaging of Non-CNS Fetal Abnormalities: A Pictorial Essay,
Radiographics 2000; 20:1227-1243.
Sickler GK, Vang R, Maklad N. Echogenic Fetal Bowel and Calcified Meconium in a Fetus with
Trisomy 21, J Ultrasound Med 1998; 17: 591-593.
http://www.acsu.buffalo.edu/~brodger/foci.doc
http://www.biotechnologyonline.gov.au/popups/img_trisomy21.cfm
http://www.centrus.com.br/DiplomaFMF/SeriesFMF/11-14weeks/chapter-01/chapter-01-final.htm
http://familymed.uthscsa.edu/residency/maternityguide/ultrasound.htm
http://www.mums.me.uk/nuchal.htm
http://utdol.com/utd/content/topic.do?topicKey=dis_chld/13798
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Junne Kamihara, HMS III
Gillian Lieberman, MD
Acknowledgements
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Shambhavi Venkataraman, MD
David Graham, MD
Maryellen Sun, MD
Gillian Lieberman, MD
Larry Barbaras
Pamela Lepkowski
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