Antenatal Sonographic findings in Trisomy 21eradiology.bidmc.harvard.edu/LearningLab/genito/Kamihara.pdf · Junne Kamihara, HMS III Gillian Lieberman, MD Prenatal Sonographic Findings

Junne Kamihara, HMS IIIGillian Lieberman, MD

Prenatal Sonographic Findings in Trisomy 21

Junne Kamihara, HMS Year IIIGillian Lieberman, MD

March 2007

Estroff, JA Semin Roentgenol. 2004, 39:2 2

Junne Kamihara, HMS IIIGillian 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 3

Junne Kamihara, HMS IIIGillian 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

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Junne Kamihara, HMS IIIGillian Lieberman, MD

Prenatal Ultrasound

• Full fetal survey: ~18 weeks gestation (structural anomalies can be detected)

• Early ultrasound: 10-14 weeks gestation– Nuchal translucency measurements

Emery’s Elements of Medical Genetics , 1995 5

Junne Kamihara, HMS IIIGillian 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

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Junne Kamihara, HMS IIIGillian 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 demonstratingtransverse palmer crease

http://utdol.com

Adapted from Table 1: Estroff, JA Semin Roentgenol. 2004, 39:2

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Junne Kamihara, HMS IIIGillian Lieberman, MD

Ultrasound detection of Down syndrome

Structural anomaliesNB: 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)

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Junne Kamihara, HMS IIIGillian 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 IIIGillian 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 IIIGillian Lieberman, MD

Our Patient JM fetus: Sagittal Ultrasound Demonstrating Thickened NT of 4.2 mm

http://www.mums.me.uk

Thickened NT

*Landmark:*: Skin

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Junne Kamihara, HMS IIIGillian 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)

http://www.centrus.com.br 12

Junne Kamihara, HMS IIIGillian Lieberman, MD

Companion Images of Nuchal Translucency: image of embryo & 12-week sagittal ultrasound

Thickened Nuchal Translucency

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Junne Kamihara, HMS IIIGillian 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, 102:5Estroff JA, Semin Roentgenol. 2004, 39:2

Estroff, JA Semin Roentgenol. 2004, 39:2 14

Junne Kamihara, HMS IIIGillian Lieberman, MD

Differential diagnosis for increased NT

• Trisomy 21• Trisomy 13, trisomy 18• Turner Syndrome (XO)• Triploidy• Structural heart disease• Other anomalies

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Junne Kamihara, HMS IIIGillian 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 IIIGillian 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 IIIGillian Lieberman, MD

Our Pt JM fetus: Femur length measurement- Anatomic orientation

1

23

Femurs

Landmarks:1 & 2: Inner thighs 3: Posterior

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Junne Kamihara, HMS IIIGillian 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 IIIGillian Lieberman, MD

Our Pt JM fetus: Femur length measurement 1- Short for gestational age

Femur length

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Junne Kamihara, HMS IIIGillian Lieberman, MD

Femur length

Our Pt JM fetus: Femur length measurement 2- Short for gestational age

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Junne Kamihara, HMS IIIGillian 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 IIIGillian Lieberman, MD

Our Pt JM fetus: 4 chamber view of heart demonstrating echogenic intracardiac focus

Echogenic focus

Landmarks:1: Spine2: Ribs3: Left Atrium4: Left Ventricle

3

21

4

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Junne Kamihara, HMS IIIGillian 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 IIIGillian Lieberman, MD

Companion images: Echogenic intracardiac foci and normal 4-chamber heart view

http://www.centrus.com.brhttp://www.fetal.com

EIF

Landmarks:1: Spine2: Ribs3: Left Atrium4: Left Ventricle

1

2

3

4

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Junne Kamihara, HMS IIIGillian 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 IIIGillian Lieberman, MD

Our Pt JM fetus: 4-chamber views of the heart demonstrate a probable endocardial cushion defect

Ventricular septal defect

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Junne Kamihara, HMS IIIGillian Lieberman, MD

The following companion image shows an example outlining a full endocardial cushion

defect

http://www.fetal.com 28

Junne Kamihara, HMS IIIGillian Lieberman, MD

Companion image: Full endocardial cushion defect

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Junne Kamihara, HMS IIIGillian Lieberman, MD

Differential diagnosis for each finding

Short Femur: Nonlethal osteogenesis imperfecta, Diabetic embryopathy, trisomy 21, fetal hypoplasia- unusual 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.eduReeder and Felson’s Gamuts in Radiology, 3rd ed.

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Junne Kamihara, HMS IIIGillian Lieberman, MD

Our Patient JM: Summary of findings

• Amniocentesis performed and confirmed Trisomy 21 in fetus

• Pt. elected to have pregnancy termination

• 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

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Junne Kamihara, HMS IIIGillian 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 IIIGillian 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 IIIGillian 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 IIIGillian Lieberman, MD

Our Pt LG fetus: Sagittal ultrasound demonstrating Echogenic bowel

Spine

Echogenic bowel

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Junne Kamihara, HMS IIIGillian 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 IIIGillian Lieberman, MD

Our Pt LG fetus: Short femur

Short femur

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Junne Kamihara, HMS IIIGillian 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, 17Reeder and Felson’s Gamuts in Radiology, 3rd ed.

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Junne Kamihara, HMS IIIGillian Lieberman, MD

• U/S 16 wks 6 d: Short femur, echogenic bowel in fetus

• Amniocentesis performed and confirmed Trisomy 21 in fetus

Our Patient LG: summary

• Pt. elected to have pregnancy termination at 19 wks

Sickler GK et. al. J Ultrasound med 1998 39

Junne Kamihara, HMS IIIGillian 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.

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Junne Kamihara, HMS IIIGillian Lieberman, MD

• Sonographic markers, e.g. shortened femur, echogenic intracardiac focus, and echogenic bowel can be normal variants but also seen frequently in Trisomy 21 fetuses.

• Thickened nuchal translucency, (10-14 wks), when combined with maternal age and biochemical markers, can detect Trisomy 21 to 90%.

Main Summary

• 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.

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Junne Kamihara, HMS IIIGillian Lieberman, MD

References• 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 IIIGillian Lieberman, MD

Acknowledgements

• Shambhavi Venkataraman, MD• David Graham, MD• Maryellen Sun, MD• Gillian Lieberman, MD• Larry Barbaras• Pamela Lepkowski