Postnatal Down Syndrome (Trisomy 21) Imaging

Updated: Mar 24, 2022
  • Author: Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR; Chief Editor: Eugene C Lin, MD  more...
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Practice Essentials

Imaging plays an important role in the prenatal and postnatal diagnosis of anomalies associated with Down syndrome. Most attention in Down syndrome (trisomy 21)is directed toward imaging to detect gastrointestinal anomalies in the early postnatal period and toward imaging congenital heart disease, which may be present at birth and may remain throughout the patient's lifetime. [1, 2, 3, 4, 5, 6]

Approximately 50% of infants with Down syndrome have congenital heart disease, most commonly atrioventricular septal defect and ventricular septal defect.  Less common are secundum atrial septal defect and tetralogy of Fallot. [7]  Approximately 25-30% of patients with Down syndrome die during the first year of life. Congenital heart disease is the second leading cause of death among these patients, and early diagnosis is essential to improve outcomes. [8]

Because Down syndrome is associated with a high risk of congenital heart disease,  there is an increased risk of cardioembolic events, such as moyamoya disease, which has been found to occur in patients with Down syndrome at a rate 3 times that of the general population. CT angiography of the head and neck with contrast has demonstrated severe narrowing of the bilateral supraclinoid internal carotid arteries, which suggests moyamoya disease. [9, 10, 11, 12, 13]

Adults with Down syndrome are at increased risk for Alzheimer disease, especially by their 5th decade. [14, 15, 16, 17, 18] The Biomarkers of Alzheimer’s Disease in Down Syndrome study identified MRI-based biomarkers of cerebrovascular pathology, including white matter hyperintensities, infarcts, cerebral microbleeds, and enlarged perivascular spaces, as well as PET-based biomarkers of amyloid burden. [19]

Skeletal abnormalities in persons with Down syndrome have been confirmed by a number of studies. Lateral cephalometric radiography studies have shown that patients with Down syndrome have a characteristic craniofacial morphology. [20] Measurements of bone mineral density (BMD) in individuals with Down syndrome have found abnormalities of the lumbar spine and femoral neck from osteoporosis. [21]  In addition, people with Down syndrome, particularly men, have been found to have a lower hip volumetric bone mineral density than the general population, and a lower areal bone mineral density as measured by dual-energy X-ray absorptiometry has also been identified. [22]

Conventional radiography

Conventional radiography remains the mainstay of imaging in the immediate postnatal period and in the older child with suspected congenital heart disease, infection, GI anomalies, or skeletal anomalies (see the images below). Contrast-enhanced studies can be added if and when they are required, as in an evaluation for GI and urinary abnormalities. Moreover, conventional radiography is an essential part of dental practice.

Lateral inverted abdominal radiograph in a baby wi Lateral inverted abdominal radiograph in a baby with Down syndrome who presented with clinical features of intestinal obstruction. A radio-opaque marker was placed on the anal dimple. Image shows an air-fluid level with a short distance between the air-filled rectum and the marker. The features are those of a low, imperforate anus. However, note that that the distance between the rectal air and the marker do not accurately outline the atretic rectum and the anus due to variations in the length of the air column during crying. Crying increases abdominal pressure and causes contraction of the levator ani muscle.
Chest radiograph in a 3-year-old with Down syndrom Chest radiograph in a 3-year-old with Down syndrome and a ventricular septal defect. Image shows features of such a defect, namely, cardiomegaly and prominent pulmonary arteries associated with pulmonary plethora.
Small-bowel study in a 2-month-old infant with Dow Small-bowel study in a 2-month-old infant with Down syndrome shows features of small bowel malrotation, with the ligament of Treitz in the right upper quadrant and the cecum in the left iliac fossa.

Conventional radiographic findings are nonspecific but can demonstrate chamber enlargement, an abnormal cardiac configuration, and signs of heart failure. However, the results do not permit a specific diagnosis of congenital heart disease.

The transverse ligaments between the atlas and the odontoid processes have increased laxity in 20% of patients with Down syndrome, and this laxity results in atlantoaxial instability. The diagnosis is suggested when radiographs of the lateral cervical spine obtained in flexion and extension show a distance of more than 4.5 mm between the odontoid process of the axis and the anterior arch of the atlas or when atlanto-occipital and rotational instability are present.


In patients who require surgical or catheter-based cardiac intervention, angiography is usually considered an essential component of patient assessment. Angiography and/or cardiac catheterization allows clinicians to accurately assess pressure, blood flow, the hemodynamics of any defects, and the anatomy of the pulmonary artery.

In patients older than 30 years and in those in whom past or future surgery involved or will involve the coronary arteries, selective coronary angiography is an essential component of the overall assessment.

Angiocardiography is an invasive procedure. Children undergoing angiocardiography may need a general anesthetic. Cardiac angiography and interventional cardiac catheterization in patients with congenital heart disease pose specific technical challenges, which include the need for a well-equipped cardiac laboratory, experienced operators, biplanar angiographic equipment, and unrestricted procedure time. Moreover, because of the high incidence of cardiac arrhythmias that occur during and after the procedure, facilities and experienced staff should be available to conduct concomitant electrophysiologic studies and radiofrequency ablation as needed. These requirements are met in only few selected centers.


Other noninvasive studies, such as ultrasonography, are instrumental not only in the prenatal detection of Down syndrome but also in the antenatal diagnosis of anomalies, which may have a major effect on postnatal care. Transesophageal ultrasonography is becoming an essential tool in cardiac surgery. [23, 24, 25, 2]

Ultrasonography is operator dependent, and acoustic windows may be difficult to obtain in patients who are obese or who have chest wall abnormalities. In addition, the lung may be in the way of the ultrasound beam. Clinicians should not rely on ultrasonography as the primary method of diagnosing Down syndrome because the results can cause the diagnosis to be missed in affected families.

Like transesophageal ultrasonography, intracardiac echocardiography is becoming an important study in cardiac surgery. With advances in echocardiography, the need for conventional cardiac angiography is declining. Current limitations of intracardiac echocardiography include monoplanar imaging and a narrow field of view. [26, 27, 28, 3]

MRI and CT

Cardiac MRI may limit the need for but not obviate standard ventriculography. The nonspecific indications for MRI or CT have been established, though either imaging study could be applied to evaluate suspected atlantoaxial subluxation. Cardiac CT and MRI are also contributing to the diagnosis and classification of congenital heart disease. MRI can also provide functional information regarding the heart.

CT and MRI may be difficult to perform in children without sedation or general anesthesia. Similar principles apply to the occasional adult who may be obstinate. MRI is an expensive tool, and cardiac expertise is not widely available. Furthermore, the presence of ferromagnetic foreign bodies and certain cardiac pacemakers are incompatible with MRI.

Radionuclide studies

Radionuclide studies may be used to measure ejection fractions and to investigate cardiac shunts, although investigating shunts is now most reliably studied by using echocardiography with contrast media. Radionuclide studies have a high sensitivity but low specificity, and they provide limited anatomic information. [29]


Tonni et al describe fetal gastroschisis at 12 weeks’ gestation associated with Down syndrome, to report a clinical antenatal management strategy based on integrating ultrasound and MRI in the evaluation of herniated bowel following early prenatal diagnosis of gastroschisis. [4] Fetal gastroschisis was documented at 12 weeks at the time of first-trimester screening for Down syndrome. Fetal karyotype was performed at 16 weeks and showed a 46,XY karyotype. Ultrasound at 20 weeks diagnosed gastroschisis as an isolated finding. Follow-up scans were planned monthly.

The case report has shown the integrating approach to be clinically useful in planning the timing of delivery (cesarean delivery) and, in turn, has been associated with an easy surgical repair and led to a favorable postnatal outcome. The result of amniocentesis was crucial for the parent's decision-making process whether to continue the pregnancy. Moreover, amniotic fluid alpha-fetoprotein levels may be used as an index of small bowel damage when loops of small bowel are uncovered within the amniotic cavity.



Conventional radiographs are seldom diagnostic of congenital heart disease, but cardiac-contour abnormalities and particular chamber enlargements may guide the next appropriate imaging test. Chest radiography is an initial workup study in the differential diagnosis of pneumonia, heart failure, and pulmonary embolism.

Conventional radiography is the initial, and sometimes only, investigation for diagnosing craniofacial anomalies (eg, brachycephaly microcephaly, hypoplastic facial bones). Radiographs of the cervical spine may be required if atlantoaxial subluxation is suspected. Lateral radiographs of the cervical spine are obtained in flexion and extension to measure the atlantodens distance and to rule out atlantoaxial instability at the age of 3 years. If the patient has signs of spinal cord compression, radiography of the cervical spine may also be performed before an anesthetic is given.

Other radiographically observed musculoskeletal abnormalities in Down syndrome include a reduced iliac and acetabular angle in infants, short hands with shortened digits, and clinodactyly due to a hypoplastic middle phalanx of the fifth finger.

In patients with suspected duodenal atresia, plain abdominal radiographs may show the double-bubble sign.

Although the information obtained from conventional radiography is limited, it remains one of the most useful imaging techniques in the serial evaluation of heart size and pulmonary vascularity. The cardiothoracic ratio is still the most accurate predictor of exercise capacity after repair of tetralogy of Fallot. Conventional radiography is a noninvasive, universally available, and inexpensive method study that provides fairly accurate information. Its results guide further imaging, if required.


Computed Tomography

Multidetector-row CT (MDCT) is currently underused in the setting of congenital heart disease. MDCT can depict morphologic changes in many difficult congenital cardiac lesions seen. Technological advances have produced diagnostic images with increased speed, markedly decreased sedation times, and the ease of peripheral venous access.

MDCT is likely to enhance assessment of the aortic arch and the pulmonary vascular supply. It may become the imaging technique of choice for examining patients with complex forms of pulmonary atresia, ventricular septal defect, or major aortopulmonary collateral arteries.

Lee et al studied the technical and clinical feasibility of replacing diagnostic cardiac catheterization with MDCT and confirmed the technical and clinical feasibility of MDCT in the evaluation of complex congenital heart disease. Over 1 year, they prospectively enrolled 14 neonates with congenital heart disease who were referred for diagnostic cardiac catheterization after initial echocardiography. Imaging was performed with a 40-MDCT scanner with dual-syringe injection. The accuracy of MDCT in diagnosing separate cardiovascular anomalies was 98%. The authors concluded that after initial assessment with echocardiography, MDCT could probably replace diagnostic cardiac catheterization for further clarification of the anatomy in neonates. [30]

Contrast-enhanced ECG-gated MDCT and electron-beam CT provide morphologic information and may be used as a data set for off-line functional quantitation. [1, 31]


Magnetic Resonance Imaging

Initial experience with MRI indicated its effectiveness in defining the anatomy of the great vessels and internal structures of the heart in patients with congenital heart disease. This definition is accomplished without the use of contrast medium; therefore, MRI is a completely noninvasive technique for making a cardiovascular diagnosis. [32] With MRI, spin-echo acquisitions provide the imaging data for evaluating morphologic changes. Gradient-reversal techniques add functional and flow data to complement findings regarding morphologic changes.

MRI and contrast-enhanced MDCT noninvasively depict the underlying anatomic defects in congenital heart disease, as well as the physiologic changes caused by the underlying morphologic abnormalities. Experience with MRI is longer than that with MDCT, but the latter appears to provide more accurate and higher-quality images for diagnosis. Although CT provides exquisite images of the great vessels, intracardiac morphology is better defined with MRI than with CT. In adults with congenital heart disease, MRI and CT provide complementary images that are useful for depicting and quantifying physiologic changes when acquired cardiovascular disease is superimposed on the underlying congenital malformations.

Researchers from numerous comparative studies have defined its weaknesses and strengths compared with those of echocardiography, and they have documented its superiority in assessing ventricular anatomy, size, and function. In addition, MRI provides unparalleled assessment of the anatomy of pulmonary blood supply and of the aortic arch.

Pinter et al studied reported abnormalities of regional brain volumes in 19 patients (age range, 5-23 yr) with Down syndrome and in 15 healthy age- and sex-matched persons using high-resolution MRI. Their results largely confirmed previous findings with respect to overall patterns of brain volumes in Down syndrome and provided new evidence for abnormal volumes of specific regional tissue components. The presence of these abnormalities from an early age suggests that differences in fetal or early postnatal development may underlie the observed pattern of neuroanatomic abnormalities and contribute to the specific cognitive and developmental deficits seen in individuals with Down syndrome. [33, 34, 5]



Recommendations for infants with trisomy 21 include an echocardiogram in the first month of life. Echocardiography is the initial diagnostic modality of choice for patients with suspected congenital heart disease. It is noninvasive and universally available, and it provides detailed and quantifiable information about intracardiac morphology and function. Early detection may help prevent complications, such as pulmonary vascular disease, that may adversely affect the outcome of cardiac surgery. However, in some patients, this modality can be limited in its ability to delineate the great artery, intracardiac anomalies, pulmonary veins, and coronary arteries. [35, 36]

For examining a ventricular septal defect, echocardiography possesses an incomparable capability to depict all of the morphologic features of the defect. Doppler echocardiography has become an invaluable tool in the diagnosis and follow-up of ventricular septal defect, reducing the need for cardiac catheterization and helping in the management of these defects. [37] Improvements in defining transducers associated with conventional and color Doppler imaging has notably contributed to the reliability in detecting most of these defects. The great majority of associated lesions can easily be identified. Serial examination allows clinicians to predict which defect may shrink or even close spontaneously to ascertain which have resulted in deleterious changes in the heart.

Pediatric echocardiography has clearly become the primary tool for describing and characterizing diastolic function in infants and children with or without heart disease. It is becoming an important noninvasive diastolic monitoring tool that allows serial assessment of pathologic diastolic disease in both primary myocardial and systemic disease states. [38]

Ultrasonography may reveal a double-bubble sign due to distention of the stomach and of the first part of the duodenum, in association with hyperperistalsis of the stomach. Antenatal sonograms may demonstrate a double-bubble sign associated with polyhydramnios.

Bhatia et al evaluated the utility of echocardiography for assessing the frequency and nature of cardiac malformations in 50 children with chromosomally proven Down syndrome, and they found that 2-dimensional echocardiography was an excellent noninvasive tool for diagnosing cardiac malformations in Down syndrome. The prevalence and specific types of congenital heart disease were comparable to those reported from studies in which invasive means for diagnosis were used. These data further suggest that clinical examination of the cardiovascular system alone may be insufficient for detecting heart disease. [39]

Limitations of intracardiac echocardiography include monoplanar imaging and a narrow field of view. More than any other imaging techniques, ultrasonography is highly operator dependent. Although echocardiography is regarded as an accurate imaging modality in premature low-birth-weight infants with structural congenital heart disease, the incidence of clinically important diagnostic errors is higher in this group than it is in infants who weigh more than 2.5 kg. As the application of surgical transcatheter interventions are extended to this population, heightened awareness to the pitfalls of echocardiography in these patients is warranted. [40]

Ultrasonographic techniques are particularly prone to artifact due to gas, fat, or foreign bodies. In addition, scanning is difficult in patients who are obese or who have gas, as well as in patients with emphysema or those with a particular body habitus (eg, pectus excavatum). Cross-sectional image quality is often limited in adults, particularly those who have just undergone median sternotomy and patients with severe chest deformities or lung disease.


Nuclear Imaging

Radionuclide studies play an important role in the assessment of congenital heart disease, myocardial perfusion, and ventricular size and function. Lung perfusion scintigraphy is particularly helpful in assessing the pulmonary blood supply. Measurement of the cardiac ejection fraction by using radionuclide studies remains highly accurate.

Cerebral hypoperfusion can be demonstrated by using technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) to perform single-photon emission computed tomography (SPECT) in children with Down syndrome related to epilepsy and/or other coexisting conditions, congenital heart disease, and hypothyroidism. [6] When found, cerebral hypoperfusion further retards developmental levels, especially in terms of personal, social, and fine motor skills.

Radionuclide techniques tend to have low specificity and are seldom used as standalone imaging studies, remaining complementary methods for imaging.



In patients requiring surgical or catheter-based cardiac intervention, angiography is usually considered an essential component of their assessment. Angiography and/or cardiac catheterization allows for accurate assessment of the hemodynamics of defects, the anatomy of the pulmonary artery pressures, and blood flow. In patients older than 30 years and in those in whom previous surgery involved, or future surgery will involve, the coronary arteries, selective coronary angiography is considered an essential component of the overall assessment.

With the advent of noninvasive imaging, such as echocardiography, the role of angiography and cardiac catheterization in the pediatric population has declined steadily. At present, about 50% of all cardiac catheterization procedures done in children with congenital heart disease are interventional. The primary aim of diagnostic cardiac catheterization is shifting toward accurate assessment of the hemodynamics or pulmonary blood supply. This trend is mirrored in the practice of catheterization practice in adolescents and adults with congenital heart disease.

Invasive diagnostic studies should be undertaken only after noninvasive imaging techniques are exhausted and only after questions are clearly defined. Because patients with congenital heart disease undergo repeated cardiac catheterization procedures, the role of noninvasive imaging becomes especially important. Many patients will have received bilateral femoral cutdowns during cardiac catheterization in childhood that limit vascular access.

False-negative and false-positive results may occur as a result of poor quality or inadequate imaging. Cardiac angiography and interventional cardiac catheterization in patients with congenital heart disease pose specific technical challenges, which include a well-equipped cardiac lab, experienced operators, biplane angiographic equipment, and unrestricted procedure time. Moreover, because of the high incidence of cardiac arrhythmias during and after procedures, there should be experienced personnel and adequate facilities available to conduct concomitant electrophysiologic studies and radiofrequency ablations. These requirements can only be met in few selected centers.