Pediatr Radiol (2014) 44:506–521 DOI 10.1007/s00247-013-2859-y
REVIEW
Imaging findings in Down syndrome Rupa Radhakrishnan & Alexander J. Towbin
Received: 1 August 2013 / Revised: 18 November 2013 / Accepted: 11 December 2013 # Springer-Verlag Berlin Heidelberg 2014
Abstract Down syndrome, or trisomy 21, is the most common chromosomal anomaly and is characterized by intellectual disability and a typical facies. People with Down syndrome can have abnormalities of multiple organ systems. Cardiac and respiratory system involvement is the most common cause of morbidity and mortality, although every organ system can be affected. Patients may present prenatally with findings on screening sonography. If the diagnosis is not made prenatally, it is apparent at birth because of the characteristic facial features and musculoskeletal findings. Children with Down syndrome present to the radiology department at various ages depending on the severity of the specific finding. The purpose of this paper is to review the most common antenatal and postnatal imaging findings of Down syndrome as they manifest throughout the body. Keywords Down syndrome . Trisomy 21 . Imaging findings . Ultrasonography . Magnetic resonance imaging . Children
Introduction Down syndrome is the most common chromosomal cause of intellectual disability, affecting one in 600–800 pregnancies worldwide [1, 2]. It is typically caused by a trisomy of chromosome 21, although other chromosomal abnormalities such
CME activity This article has been selected as the CME activity for the current month. Please visit the SPR Web site at www.pedrad.org on the Education page and follow the instructions to complete this CME activity. R. Radhakrishnan : A. J. Towbin (*) Department of Radiology, Cincinnati Children’s Hospital Medical Center, MLC 5031, 3333 Burnet Ave., Cincinnati, OH 45229-3039, USA e-mail: [email protected]
as a Robertsonian translocation, partial trisomy, isochromosomes and ring chromosomes can occur [3]. Even though advanced maternal age is a major risk factor for Down syndrome, most children with Down syndrome are born to women younger than 30 years [4, 5]. This, along with improved screening techniques, led the American College of Obstetricians and Gynecologists (ACOG) to recommend that all pregnant women be offered screening for Down syndrome before 20 weeks of gestation [6]. Prenatal screening includes sonogram, serum markers and maternal age. Postnatally, the diagnosis of Down syndrome is rarely in question because of the characteristic physical features present at birth, which include an epicanthic fold, brachycephaly, flat nasal bridge, upward angle of the eyes, a wide gap between the first and second toes, clinodactyly, small nose, single palmar crease and increased nuchal skin. In addition to affecting the outward appearance, Down syndrome can affect every organ system. Imaging plays a particularly important role in the diagnosis and management of cardiovascular, pulmonary, gastrointestinal, neurological and musculoskeletal complications.
Cardiovascular findings Congenital heart disease Congenital heart disease is commonly associated with Down syndrome, affecting 40–45% of patients [7]. Researchers have reported varying incidences of congenital heart diseases. Ventricular septal defect, atrioventricular septal defect (AVSD), tetralogy of Fallot (TOF), atrial septal defect, patent ductus arteriosus and aortic coarctation are described associations. Ventricular septal defects occur in 43% of children with Down syndrome and congenital heart disease. The ventricular
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septal defect can be isolated or associated with other cardiac anomalies. Atrial septal defects occur in 42% of children with Down syndrome and congenital heart disease [7]. An AVSD, also known as an endocardial cushion defect, is the most common complex congenital heart defect in children with Down syndrome, affecting approximately 39% of infants with Down syndrome and congenital heart disease [7]. An AVSD is more common in girls and African Americans and less common in the Hispanic population [7]. It is caused by abnormal development of the lower atrial and upper ventricular septum leading to a common channel that communicates with the atria and the ventricles. The tricuspid and mitral valves are affected as well. Children with an AVSD usually present in the neonatal period with congestive cardiac failure caused by a left-to-right shunt. However if the pulmonary vascular resistance is increased, as can happen in children with Down syndrome, there can be reversal of the shunt, leading to cyanosis and tachypnea. Radiographs show cardiomegaly and increased pulmonary vascularity. Echocardiography is used to diagnose an AVSD and define its severity. Echocardiogram and cardiac MRI show the defect in the atrioventricular septum, a left-to-right shunt, and the amount of mitral or tricuspid valve regurgitation (Fig. 1). Although a cardiac catheterization is not usually performed to diagnose an AVSD, it can be used to measure pulmonary vascular resistance. When cardiac catheterization is performed, shortening of the left ventricular inflow tract and elongation and narrowing of the left ventricular outflow tract combine to produce the classic “gooseneck deformity” of the left ventricular outflow tract view (Fig. 2) [8]. Tetralogy of Fallot affects 6% of children with Down syndrome who have congenital heart disease [7]. Classically,
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Fig. 2 Gooseneck deformity. Cardiac catheterization in a 22-day-old girl with an endocardial cushion defect. A catheter in the left ventricle with contrast agent shows a narrow gooseneck deformity of the medial margin of the left-ventricular outflow tract (arrows)
children with tetralogy of Fallot become symptomatic with cyanosis and failure to thrive in later infancy as the pulmonary vascular resistance increases, exceeding that of the systemic circulation. The four components of tetralogy of Fallot (pulmonary outflow obstruction, ventricular septal defect, an over-riding aorta, and right ventricular hypertrophy) can be easily visualized with echocardiography, cardiac CT or cardiac MRI. However the presence of associated peripheral pulmonary arterial anomalies and patent ductus arteriosus or collaterals is not adequately imaged by echocardiogram and requires cross-sectional imaging or cardiac catheterization to diagnose. Radiographs in children with tetralogy of Fallot might demonstrate decreased pulmonary vascularity and a characteristic boot-shaped heart (Fig. 3). The cardiac contour abnormality is caused by a narrow mediastinum from small pulmonary arteries and an upturned apex from right ventricular hypertrophy; however this is not always present. Cardiac CT and MR imaging are used to assess the heart between staged surgeries or after surgery, especially in adolescents and adults. Specifically, cardiac MRI can be used to assess the ventricular dimensions, degree of pulmonary regurgitation, and presence of right ventricular outflow tract aneurysm [9]. Antenatal imaging, including fetal sonography and fetal MR imaging, can be used to screen for and assess the severity of cardiovascular abnormalities [10]. Pulmonary arterial hypertension
Fig. 1 Atrioventricular defect. Four-chamber view on white-blood gradient echo cardiac MRI in an 11-week-old girl with Down syndrome shows a left-ventricular dominant atrioventricular canal defect (arrow) with a moderate to severely hypoplastic, nonapex-forming right ventricle (*). RA right atrium, LA left atrium, LV left ventricle
Neonates with Down syndrome are at an inherently higher risk of having pulmonary hypertension. This is at least partially explained by pulmonary alveolar hypoplasia, structural
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Vascular anomalies An aberrant right subclavian artery is a common anatomical variant in children with Down syndrome, occurring in 16– 39% of patients [8]. Although this is often an incidental finding, children with an aberrant right subclavian artery can rarely present with dysphagia and feeding problems if the aberrant right subclavian artery is part of a vascular ring encircling the esophagus and trachea [11, 12]. If other mechanical causes of feeding intolerance have been excluded, a contrast esophagram is a sensitive method of identifying an aberrant right subclavian artery. If positive, the test shows a posterior impression on the esophagus [13]. CT angiography or MR angiography can be used to show the right subclavian artery arising as the most distal branch from the aortic arch and traversing posteriorly behind the esophagus before continuing on its normal course (Fig. 4) [11]. Fig. 3 Tetralogy of Fallot and esophageal atresia/tracheoesophageal fistula. Anteroposterior chest radiograph in a newborn boy shows that the heart has a boot-shaped contour with an upturned apex compatible with a diagnosis of tetralogy of Fallot. A nasoenteric tube is coiled in the upper esophageal pouch (arrow), consistent with esophageal atresia. The presence of bowel gas (arrowhead) in the upper abdomen confirms the presence of a tracheoesophageal fistula. There are also 13 pairs of ribs
abnormalities in the arterial wall, and disturbances in the regulation of pulmonary vascular resistance [2]. In these children, increased pulmonary arterial blood flow caused by concomitant congenital heart disease containing a left-to-right shunt (especially AVSD) exacerbates the risk of pulmonary arterial hypertension [2]. The main strategy to prevent pulmonary arterial hypertension is to identify and manage the cardiac defect in a timely manner. Fig. 4 Aberrant right subclavian artery. Sequential axial contrastenhanced CT images in a 19-yearold woman with Down syndrome demonstrate an aberrant right subclavian artery (arrows) extending from the aortic arch (a) and coursing to the right posterior to the esophagus (* in d)
Respiratory findings Respiratory problems are the most common reason for children with Down syndrome to be admitted to the hospital and are the most common cause of excess mortality [2]. Multiple abnormalities in Down syndrome contribute to the severity of respiratory disease, including immune defects, hypotonia, developmental delay, craniofacial anomalies and chronic aspiration. Pneumonia Pneumonia is the most common respiratory disorder in children with Down syndrome, accounting for nearly 80% of
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hospitalizations and intensive care unit admissions [1]. Compared to unaffected children, children with Down syndrome have a more severe course of disease, longer length of admission, higher cost per admission and increased incidence and severity of respiratory syncytial virus (RSV) bronchiolitis [14]. The findings on radiographs in children with Down syndrome and RSV bronchiolitis are similar to those in other children and include hyperinflated lungs, streaky parahilar opacities and bronchial cuffing. One difference is that children with Down syndrome are more likely to have radiographic consolidation (Fig. 5) [11].
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58% to 83% of the predicated number [11]. These children are categorized as having an alveolar growth abnormality per the Children’s Interstitial Lung Disease (ChILD) classification [15]. This alveolar growth abnormality is most pronounced in the subpleural region, giving the appearance of subpleural cysts (Fig. 6). These cysts are present in 20%–-36% of children with Down syndrome [15, 16]. On CT there are numerous small subpleural cysts, measuring 1–4 mm in the periphery of the anteromedial lung. The cysts have been shown to communicate with more proximal airspaces [17]. No particular management has been suggested because most people are asymptomatic [1].
Chronic lung disease Upper airway obstruction Chest radiographs in children with Down syndrome can demonstrate chronic changes of diffuse parenchymal lung disease, which are sometimes symptomatic. These changes can occur from a primary process such as pulmonary hypoplasia, pulmonary lymphangectasia or lymphoid interstitial pneumonitis or they can occur secondary to bronchopulmonary dysplasia, infection or post-infectious complications, pulmonary hemosiderosis, cardiac and pulmonary vascular disease or chronic aspiration [2]. Several of these entities are described below. Pulmonary hypoplasia and subpleural cysts Autopsy studies in people with Down syndrome have shown a difference in the histological appearance of the lungs compared to unaffected people. In people with Down syndrome, the alveolar size is increased while the total number of alveoli is decreased [11]. Overall, the number of alveoli ranges from
Fig. 5 Respiratory syncytial virus bronchiolitis. Anteroposterior radiograph of the chest in a 14-month-old girl with Down syndrome shows symmetrical hyperinflation of the lungs, streaky perihilar opacities and other focal right upper lobe opacities. The girl was diagnosed with respiratory syncytial virus (RSV) bronchiolitis
Airway obstruction is often multifactorial in children with Down syndrome. In children with the most severe symptoms, multiple obstructive lesions are found nearly 40% of the time at bronchoscopy [1]. Upper airway obstruction occurs in 14% of children with Down syndrome [1]. Some of the more common causes include adenoid and tonsillar hypertrophy, laryngomalacia and macroglossia. Obstructive sleep apnea is the second most common respiratory disorder in children with Down syndrome, affecting 30–75% [1]. Affected patients are identified through a history of snoring and restless sleep. Nearly all children with Down syndrome who snore have obstructive sleep apnea [1]. Several characteristics of the upper airway predispose children with Down syndrome to develop obstructive sleep apnea, including a small mid-face, narrow nasal airways, micrognathia, macroglossia, glossoptosis, increased frequency of tonsil and adenoid hypertrophy, and increased collapsibility of the upper airway. Although the risk of obstructive sleep apnea increases with a larger body mass index, 91% of children with Down syndrome who have obstructive sleep apnea have a normal body mass index [1].
Fig. 6 Subpleural cysts. Axial CT of the chest in 1-year-old girl with Down syndrome demonstrates multiple small subpleural cysts (arrows) along the pleural surface of the mediastinum and chest wall in both upper lungs. Note the median sternotomy wires from previous repair of atrioventricular septal defect
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Fig. 7 Obstructive sleep apnea. Sequential images from a dynamic axial cine MRI sequence through the hypopharynx in a 12-year-old girl with Down syndrome and obstructive sleep apnea. a, b Images show anteroposterior collapse of the airway (arrows) during respiration
Lateral airway radiographs can demonstrate narrowing of the nasopharyngeal and oropharyngeal airway caused by enlargement of the adenoids, soft palate, and palatine and lingual tonsils as well as relative macroglossia. The initial therapy for obstructive sleep apnea in children with Down syndrome is often tonsillectomy and adenoidectomy; however, 30–50% of these children have persistent or recurrent symptoms. Dynamic cine MRI can provide functional assessment of the upper airway in these children. The most common findings are recurrent and enlarged adenoids, glossoptosis, hypopharyngeal collapse, enlarged lingual tonsils and macroglossia [18]. The enlarged adenoids and lingual tonsils are best seen on short tau inversion recovery images, where they appear as areas of increased signal in the posterior nasopharynx and at the base of the tongue, respectively. On the cine images, glossoptosis appears as posterior motion of the tongue, narrowing the hypopharynx. Hypopharyngeal collapse can also be seen on cine images and is defined as intermittent cylindrical collapse of the hypopharynx (Fig. 7) [18]. Lower airway obstruction and other abnormalities Lower airway obstruction, caused by entities such as subglottic stenosis and tracheobronchomalacia, occurs in 25% of children with Down syndrome [2]. Children with
Fig. 8 Tracheal bronchus. a Frontal radiograph and (b) coronal CT image of the chest in a 3-year-old boy show a right upper lobe tracheal bronchus (arrows). On the CT image there is associated atelectasis (arrowheads) of the right upper lobe
Down syndrome and subglottic stenosis account for 4% of all patients undergoing laryngotracheal reconstruction [1]. On imaging, the trachea is focally narrowed below the level of the vocal cords. A tracheal bronchus, commonly a right upper lobe bronchus that originates from the trachea (bronchus suis/pig bronchus), is seen in 21% of children with Down syndrome who undergo bronchoscopy [1]. These children can present with recurrent right upper lobe pneumonia or collapse. It is important to recognize this malformation, especially in intubated patients, because the tip of the endotracheal tube should be positioned above the anomalous bronchus in order to prevent occlusion. A tracheal bronchus is often not easily identified on chest radiograph and can be better seen on CT (Fig. 8). Another airway malformation more common in children with Down syndrome is complete cartilaginous tracheal rings [19]. The degree and length of tracheal narrowing determines the clinical symptoms, which can range from severe respiratory distress to intermittent symptoms associated with upper respiratory infections. Both CT and bronchoscopy can demonstrate complete cartilaginous tracheal rings with luminal narrowing. Complete tracheal rings can be distinguished from normal tracheal cartilage by their circular appearance (Fig. 9). Vascular abnormalities such as pulmonary sling are associated with complete tracheal rings; however, the exact prevalence of
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Fig. 9 Tracheal rings. Axial CT of the chest in a 23-month-old boy with Down syndrome shows a circular configuration of the trachea (arrow). This along with the small caliber of the trachea is consistent with a diagnosis of complete tracheal rings
this association in children with Down syndrome is unclear. Treatment is based on symptoms and can range from observation to tracheoplasty [20].
Gastrointestinal findings Congenital gastrointestinal anomalies are present in 4–10% of children with Down syndrome and can involve most portions of the gastrointestinal tract [21, 22]. Foregut anomalies
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Annular pancreas is more common in children with Down syndrome. One study showed that the risk of having annular pancreas is 430 times higher in children with Down syndrome compared to children without Down syndrome [23]. On radiograph an annular pancreas can be a cause of a double bubble; however, with isolated annular pancreas there is usually distal small bowel gas, unlike the typical findings of duodenal atresia. On fluoroscopy there is circumferential narrowing of the second portion of the duodenum. At endoscopic retrograde cholangiopancreatography, the pancreatic duct encircles the duodenum, and on cross-sectional imaging, the pancreatic tissue surrounds the second portion of the duodenum. Oral contrast agent can be used to help identify the duodenum on CT images. Esophageal atresia with tracheoesophageal fistula is more prevalent in Down syndrome than in the general population, occurring with a frequency of 0.3–0.8% [22]. Children present with difficulty feeding and increased oral secretions. Chest radiograph shows a dilated, air-filled esophageal pouch. An enteric tube, if placed, is coiled within the esophageal pouch (Fig. 3). Air in the stomach confirms presence of a tracheoesophageal fistula (Fig. 3). Additional imaging is rarely required to confirm the diagnosis of esophageal atresia. Midgut anomalies
The most common gastrointestinal anomaly in Down syndrome is duodenal atresia, occurring in 1–5% [22]. Thirty percent of infants with duodenal atresia have Down syndrome [22]. On fetal sonography or MRI there is a characteristic double-bubble appearance with an enlarged, fluid-filled stomach and proximal duodenum (Fig. 10). Polyhydramnios is often present. Postnatal radiograph shows an air-filled double bubble and a lack of distal bowel gas (Fig. 10).
The most common midgut anomaly associated with Down syndrome is malrotation, with an estimated incidence 45 times higher than that in children without Down syndrome [23]. Children with malrotation and midgut volvulus usually present with bilious emesis in the first week after birth. Abdominal radiograph can be normal or have findings of a proximal obstruction. Upper gastrointestinal study is typically the next study performed and shows an abnormal location of the duodenojejunal junction, with the duodenum remaining to the right of the spine and coursing inferiorly (Fig. 11).
Fig. 10 Duodenal atresia. a Prenatal sonogram and (b) prenatal FIESTA (fast imaging employing steady-state acquisition) MR image in a 33week fetus with Down syndrome show a dilated stomach (arrow) and proximal duodenum (arrowhead), typical of the double-bubble sign of
duodenal atresia. Polyhydramnios was present (not shown). c Abdominal radiograph in a different neonate with Down syndrome also shows the double-bubble appearance with dilated stomach (arrow) and proximal duodenum (arrowhead)
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Fig. 11 Malrotation. Anteroposterior image in a 5‐month‐old girl with Down Syndrome who presented with emesis shows an abnormal position of the duodenojejunal junction (arrow), which is positioned closer to midline and lower than the pylorus, indicating malrotation. At surgery, there was no volvulus
Hindgut anomalies The most common hindgut disorders in children with Down syndrome are constipation, Hirschsprung disease and anorectal malformations. Constipation is a common functional gastrointestinal symptom, occurring in 30–50% of children with Down syndrome [1]. Children present with abdominal pain, decreased appetite, vomiting and behavioral changes. Although it is usually idiopathic, constipation can be caused by hypothyroidism or medications. Abdominal radiographs can identify fecal impaction and evaluate the effectiveness of bowel management programs. Hirschsprung disease, or congenital aganglionic megacolon, is a disorder characterized by the lack of ganglion cells innervating the affected portion of colon or rectum. It occurs in 1–3% of infants with Down syndrome; approximately 3–11% of patients with Hirschsprung disease have Down syndrome [22]. Children present with failure to pass meconium or long-term constipation. The length of the aganglionic colon is variable and can range from the distal rectum to the entire colon. Contrast enemas are used to help diagnose Hirschsprung disease. Normally the diameter of the rectum is larger than the diameter of the sigmoid colon, making the rectosigmoid ratio greater than one. In Hirschsprung disease, the diameter of the rectum is smaller than the sigmoid colon and the rectosigmoid ratio is less than one (Fig. 12). The other common finding of Hirschsprung disease is a transition zone from narrowed, affected bowel to dilated, unaffected bowel. Definitive diagnosis is made by rectal suction biopsy.
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Fig. 12 Hirschsprung disease. Lateral view after a contrast enema in an 11-day-old boy with Down syndrome shows an abnormal rectosigmoid ratio and irregular contractions of the rectum (arrow), compatible with Hirschsprung disease
Anorectal malformations occur in 1–3% of children with Down syndrome [24]. Anal atresia without a fistula is the characteristic anorectal malformation, accounting for 95% of anorectal malformations in children with Down syndrome [22, 24]. In this defect, the rectum ends blindly about 2 cm above the perianal skin. Examination of the perineum reveals imperforate anus, and imaging can be used to help define the defect and identify presence of a fistula. Often the first imaging study performed is an abdominal radiograph. The anteroposterior radiograph shows dilated, air-filled loops of bowel extending toward the rectum. The type of anorectal malformation and presence of a fistula can often be determined by the neonatologist/surgeon based on a good physical examination. If the physical exam is indeterminate, imaging with prone radiograph or transperineal sonography can help with the distinction. We typically perform a cross-table lateral view with the child in the prone position, with a bolster under his or her pelvis to cause the air to rise to the anti-dependent rectum and show the level of atresia. The length of atresia can be estimated if a metallic BB is placed on the anal dimple prior to imaging. Prone imaging, if indicated, should be done in a neonate who is at least 24 h old to allow sufficient gas to accumulate within the rectum. Transperineal sonography has been reported to be useful in evaluation of the level of atresia and presence of a fistula [25, 26]. A greater than 1.5-cm depth of the blind-ending rectal pouch from the perineal skin is considered a high atresia and would need a diverting colostomy; a depth of less than 1.5 cm is considered a low atresia and would be eligible for primary repair [25, 26]. This technique is limited
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demonstrate the characteristic absence of fistula to the genital or urinary tract (Fig. 13). Pelvic MRI is useful in evaluation of complex anorectal malformations where fluoroscopic and US findings are inconclusive [27]. Intraoperative or preoperative MR genitography and cloacography is an emerging technique for the evaluation of the pelvis in these children [27]. In this technique dilute gadolinium is instilled in the bladder, vagina and distal colon and rectum through the mucus fistula to better depict the complex anatomy [27]. MRI also provides adequate information of the pelvic floor musculature, which is useful in future continence post-repair [27].
Musculoskeletal findings Craniovertebral junction
by the skill of the sonographer. Crying or straining by the infant could displace the rectum and affect the accuracy of both the prone radiograph and transperineal US exam [25]. In children with high anal atresia who are treated with initial colostomy followed by definitive repair, a high-pressure distal colostogram is performed to evaluate the level of atresia and
In children with Down syndrome dysfunction at the atlantooccipital joint and the atlanto-axial joint contribute to upper cervical instability. Ligamentous laxity plays a major role in craniovertebral instability; however, associated bony abnormalities in this region and hypotonia are also contributory. Atlanto-occipital instability is reported in 8–63% of children with Down syndrome and atlanto-axial instability is found in 10–30% of children with Down syndrome [28]. Most children with craniovertebral junction instability are asymptomatic, with symptomatic disease occurring in 1–2% [28]. Instability of the upper cervical spine is diagnosed using lateral radiographs of the cervical spine obtained in the neutral position as well as during flexion and extension. Measures used to assess the craniovertebral junction include the Powers ratio, Wackenheim clivus/canal line and the dens–basion distance (Figs. 14 and 15). On lateral cervical spine radiographs and sagittal craniocervical CT, the upper limit for normal
Fig. 14 Craniovertebral instability. Diagram shows the lines used in the assessment of craniovertebral instability. a Powers’ ratio is a measure of the anterior atlanto-occipital subluxation. It is the ratio between the distance from the basion (B) to the mid-vertical portion of the posterior laminar line of the atlas (P) and the distance from the opisthion (O) to mid-vertical portion of posterior surface of the anterior ring of the atlas (A). If this ratio (BP/OA) is
greater than one, anterior craniocervical subluxation is present. b The Wackenheim clivus line is a line drawn down the posterior surface of the clivus (C); its inferior extension should barely touch the posterior aspect of the odontoid (D) tip, a relationship that does not change with flexion and extension. If this line is posterior to the odontoid, it is considered posterior subluxation, and if the line is anterior to the odontoid, it is anterior subluxation
Fig. 13 Anorectal malformation. Lateral image from a high-pressure distal colostogram in a 3-month-old boy with Down syndrome shows a blind-ending rectum (arrow). A BB (arrowhead) identifies the expected location of the anus. No fistula is present, a typical finding in children with anorectal malformation and Down syndrome
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Fig. 15 Craniocervical subluxation. Lateral cervical radiograph in a 4year-old boy with Down syndrome in neutral neck position shows the Wackenheim clivus line (an inferior extrapolation of the posterior margin of the clivus) in abnormal position anterior to the tip of the dens (D), which indicates anterior craniocervical subluxation. There is also reversal of normal cervical lordotic curvature
distance from the tip of the dens to the basion is 12 mm. The upper limit of this value can be lower in children, with the vast majority below 10.5 mm [29]. A greater distance would indicate craniocervical dissociation [29]. A normal atlanto– dens interval is less than 3 mm in adults and could be as wide as 5 mm in children. Atlanto-axial instability is diagnosed in children if the atlanto–dens interval is greater than 4.5 mm (Fig. 16) [28]. Because the atlanto–dens interval is an indirect measure of the neural canal width at C1, some have proposed measuring the neural canal directly from the posterior aspect of the dens to the anterior aspect of the posterior arch of C1. A neural canal width of less than 14 mm from the posterior margin of the dens to the anterior margin of the
Fig. 16 Atlanto-axial instability. Lateral cervical radiographs on a 15-year-old girl with Down syndrome. a On extension there is normal anterior atlanto–dens distance of 1.5 mm, and the neural canal width at C1 from the posterior margin of the dens (D) to the posterior arch of C1 is 24.2 mm. b On flexion there is abnormal increased atlanto–dens distance of 7.2 mm and the neural canal width at C1 is mildly decreased at 19.3 mm
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posterior arch of C1 is abnormal and concerning for spinal cord compression. The presence of osseous anomalies such as an unfused anterior and posterior arch of the atlas, atlanto-occipital assimilation, odontoid hypoplasia and an ossiculum terminale or os odontoideum in addition to spinal ligamentous laxity can accentuate craniovertebral junction instability [28, 30]. Although os odontoideum can occur secondary to trauma in normal children, studies suggest there is a congenital etiology for os odontoideum in children with Down syndrome, possibly occurring as a result of ligamentous laxity [31]. These abnormalities prevent the dens from being adequately secured against the anterior arch of C1 during flexion and extension, leading to narrowing of the neural canal [28]. The superior endplate of the lateral mass of C1 is flat in children with Down syndrome rather than curved (Fig. 17) [32]. Compared to radiographs, CT can better demonstrate the bony abnormalities at the craniovertebral junction. If children are symptomatic as a result of the craniovertebral instability, or if there is suspicion of neural canal narrowing, MRI is performed to assess the cervical spinal cord. There is some controversy about intervention in children with craniovertebral instability. Generally surgical fixation of the spine is performed if the child is symptomatic, if there is spinal cord compression on MRI or if atlanto-occipital subluxation is more than 7 mm [28, 33–35]. Screening for craniovertebral junction abnormalities in asymptomatic children is also controversial. The most recent American Academy of Pediatrics guideline no longer recommends general screening because “radiographs do not predict well which children are at increased risk of developing spine problems and do not provide assurance of not having a future problem” [36]. The American Academy of Pediatrics instead recommends screening symptomatic children. Some researchers have found that children with bony craniocervical
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Fig. 17 Flat superior endplate of C1 (arrow). a Parasagittal CT image of the cervical spine in a 16-year-old boy with Down syndrome shows a flat superior endplate of C1 (arrow). b Comparative parasagittal CT shows a normal C1 (arrowhead) in an 11-year-old without Down syndrome
junction abnormalities are at a higher risk of progression and they recommend radiographic follow-up [28]. Children with os odontoideum are at increased risk of atlanto-axial instability causing neural canal narrowing and should be considered for surgical fixation [28]. The Special Olympics continues to require cervical spine screening for participation in certain sports that place undue stress on the head and neck such as swimming the butterfly stroke, diving, certain track and field events, soccer, skiing, gymnastics and equestrian events. If there is evidence of atlanto-axial instability on radiographs, the Special Olympics restricts participation (http://sports.specialolympics.org/specialo.org/Special_/English/ Coach/Coaching/Basics_o/Down_Syn.htm) [37].
Thoracic cage
Fig. 18 Hypersegmented manubrium. Midline sagittal chest CT in a 17-month-old boy with Down syndrome shows more than five sternal segments, with three ossification centers of the manubrium (arrows)
Fig. 19 Characteristic appearance of the pelvis in Down syndrome. Frontal radiograph of the pelvis in a 6-year-old girl with Down syndrome demonstrates characteristic short, divergent iliac wings that are more coronally oriented than normal and small acetabular angles
A hypersegmented sternum with two or more manubrial ossification centers is more prevalent in children with Down syndrome [38–40] (Fig. 18). Presence of a bell-shaped thorax on neonatal radiograph is described in children with Down syndrome [39]. Either 11 or 13 pairs of ribs have been associated with Down syndrome (Fig. 3) [39]. Pelvis In children with Down syndrome the pelvis has a characteristic appearance: flared iliac wings, a flat acetabular roof and a small acetabular angle [41] (Fig. 19). Hip dislocation or dysplasia is the most common disorder of the hip in children with Down syndrome, occurring with a prevalence of 1.5–7% in institutionalized patients with Down syndrome compared to an incidence of less than 0.2% in the general population [42, 43]. Hip instability is related to capsular laxity and low muscle
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tone and is typically identified in children between 2 years and 10 years of age [42]. Other hip conditions that occur with increased frequency in children with Down syndrome include slipped capital femoral epiphysis and idiopathic osteonecrosis of the femoral head (Legg-Calve-Perthes disease). Slipped capital femoral epiphysis occurs in 1.3% of children with Down syndrome compared to 0.01% in the general population, while Legg-Calve-Perthes disease occurs in 2% of children with Down syndrome compared to less than 0.02% in the general population [42, 44, 45]. Children with both disorders might have a delayed diagnosis because of difficulty communicating.
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trimester [47]. Other common abnormalities of the foot in children with Down syndrome include metatarsus primus varus and pes planus [42]. Spine Scoliosis is a common disorder in Down syndrome affecting 9–52% of patients [42]. It can be idiopathic or caused by prior thoracotomy. It is recommended that school-age children with Down syndrome undergo screening via physical exam followed by radiograph if necessary [42].
Appendicular skeleton
Genitourinary findings
Short humeri and femurs are typical of Down syndrome and can be identified in utero.
Genital abnormalities
Hands and feet In the hands hypoplasia of the middle phalanx of the fifth digit is characteristic in Down syndrome [46]. Clinodactyly, or deviation of the distal phalanx of the fifth digit toward the fourth digit, is commonly encountered in Down syndrome, although it is not specific. In the feet there is often widening of the first metatarsal web space, also known as the sandal gap sign (Fig. 20). Although not specific for Down syndrome, this finding is present in 45% of children with Down syndrome and can be seen as early as the second
Cryptorchidism is seen in 14–27% of boys with Down syndrome [48]. The increased incidence of cryptorchidism leads to an increased risk of testicular malignancy, which occurs in 0.5–0.9% of children with Down syndrome [48]. Men with Down syndrome are almost always sterile and fertility is reduced in women [48]. Urinary tract abnormalities Although less frequently encountered, renal and urinary tract anomalies occur in 3.2% of children with Down syndrome, a prevalence that is almost five times greater than that of the general population [49]. Urinary obstruction is the most common finding and presents with varying degrees of hydronephrosis and hydroureter [23]. Urinary obstruction can occur at any level, including the urethra, ureterovesical junction or ureteropelvic junction. The prevalence of posterior urethral valves in children with Down syndrome is reported to be higher than that of the general population [49]. Other associated urinary anomalies include megaureter, vesicoureteral reflux, hypospadias, renal agenesis, renal dysplasia, horseshoe kidney and glomerular microcysts [23, 48–50]. In addition to congenital urinary tract anomalies, children with Down syndrome are at increased risk for medical renal disease including glomerulopathies [51]. Because these conditions are potentially correctable, there are many advocates for early screening for anatomical renal and urological abnormalities in infants with Down syndrome [49, 51].
Neurological findings Fig. 20 Sandal gap sign. Anteroposterior radiograph of the foot in a 5day-old boy with Down syndrome shows a widened first inter-metatarsal space (arrow) known as the sandal gap sign
Children with Down syndrome have varying degrees of intellectual ability. MRI evaluation of the brain in children and
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younger and are more likely to be Caucasian and male [53]. CT angiography, MR angiography and traditional angiography show occlusion of the internal carotid artery distal to the posterior communicating artery and extensive parenchymal collaterals (Fig. 21) [54]. The collateral vessels can appear as flow voids within the basal ganglia on T2-weighted MR images. MRI and CT can also show signs of stroke. Delayed myelination
Fig. 21 Moyamoya disease. Time-of-flight maximum-intensity projection MRA image in an 18-year-old man with Down syndrome shows abrupt termination of the left internal carotid artery (arrow) with blush of deep perforating collateral vessels indicative of moyamoya disease. There is also narrowing of the right proximal middle cerebral artery (arrowhead)
adults with Down syndrome has demonstrated overall smaller brain volumes because of a decrease in cerebral gray and white matter, with relative preservation of the parietal gray matter. There is disproportionate decrease in cerebellar volumes compared to individuals without Down syndrome. The thalami and basal ganglia volumes are not affected [52]. Brain imaging is only performed when neurological signs and symptoms are present. Moyamoya disease Moyamoya disease is associated with Down syndrome. People with Down syndrome account for nearly 4% of all patients with moyamoya disease and 9.5% of those younger than age 15 [53]. Patients with moyamoya disease are most likely to present with ischemic stroke. Compared to other patients with moyamoya disease, those with Down syndrome tend to be
Fig. 22 Sensorineural hearing loss. Axial temporal bone CT in a 19-year-old man with Down syndrome and hearing difficulties. a The left cochlea is hypoplastic with poorly differentiated apical and middle turns (arrow). The vestibular aqueduct was normal. b The right lateral semicircular canal is hypoplastic (arrow), with the bone island measuring less than 3 mm
The normal predicted pattern of myelination of the white matter recognized on MRI, which proceeds from central to peripheral, inferior to superior, and posterior to anterior, can be delayed in children with Down syndrome [55, 56]. This delay in myelination is also demonstrated microscopically [57]. Dementia People older than 40 years who have Down syndrome can develop progressive cognitive impairment resembling Alzheimer dementia. The prevalence of dementia in people with Down syndrome increases with age, rising to nearly 55% by the sixth decade of life [58]. Patients with Down syndrome and dementia have similar MRI findings as patients with Alzheimer dementia, including marked brain atrophy, temporal lobe and hippocampal volume loss, and enlargement of the lateral ventricles [59, 60]. Some of these changes, especially temporal lobe and hippocampal volume loss, can also be seen with aging in people who have Down syndrome without dementia [60]. Hearing loss Hearing loss is common in patients with Down syndrome, occurring in 38–78% [61]. Conductive hearing loss, often as a result of middle ear pathology, is the most common cause of hearing loss and is seen in 53–88% of patients [61]. It most
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commonly occurs as a sequela of chronic otitis media with effusion but can also occur as a result of impacted cerumen, stenotic auditory canals or ossicular chain abnormalities [61]. Sensorineural hearing loss is less common in children with Down syndrome. In these children inner ear dysplasia is present on temporal bone CT in 75% [61]. The most common inner ear anomalies include a maldeveloped bone island of the lateral semicircular canal (defined as measuring ≤3 mm), cochlear nerve canal stenosis (
REVIEW
Imaging findings in Down syndrome Rupa Radhakrishnan & Alexander J. Towbin
Received: 1 August 2013 / Revised: 18 November 2013 / Accepted: 11 December 2013 # Springer-Verlag Berlin Heidelberg 2014
Abstract Down syndrome, or trisomy 21, is the most common chromosomal anomaly and is characterized by intellectual disability and a typical facies. People with Down syndrome can have abnormalities of multiple organ systems. Cardiac and respiratory system involvement is the most common cause of morbidity and mortality, although every organ system can be affected. Patients may present prenatally with findings on screening sonography. If the diagnosis is not made prenatally, it is apparent at birth because of the characteristic facial features and musculoskeletal findings. Children with Down syndrome present to the radiology department at various ages depending on the severity of the specific finding. The purpose of this paper is to review the most common antenatal and postnatal imaging findings of Down syndrome as they manifest throughout the body. Keywords Down syndrome . Trisomy 21 . Imaging findings . Ultrasonography . Magnetic resonance imaging . Children
Introduction Down syndrome is the most common chromosomal cause of intellectual disability, affecting one in 600–800 pregnancies worldwide [1, 2]. It is typically caused by a trisomy of chromosome 21, although other chromosomal abnormalities such
CME activity This article has been selected as the CME activity for the current month. Please visit the SPR Web site at www.pedrad.org on the Education page and follow the instructions to complete this CME activity. R. Radhakrishnan : A. J. Towbin (*) Department of Radiology, Cincinnati Children’s Hospital Medical Center, MLC 5031, 3333 Burnet Ave., Cincinnati, OH 45229-3039, USA e-mail: [email protected]
as a Robertsonian translocation, partial trisomy, isochromosomes and ring chromosomes can occur [3]. Even though advanced maternal age is a major risk factor for Down syndrome, most children with Down syndrome are born to women younger than 30 years [4, 5]. This, along with improved screening techniques, led the American College of Obstetricians and Gynecologists (ACOG) to recommend that all pregnant women be offered screening for Down syndrome before 20 weeks of gestation [6]. Prenatal screening includes sonogram, serum markers and maternal age. Postnatally, the diagnosis of Down syndrome is rarely in question because of the characteristic physical features present at birth, which include an epicanthic fold, brachycephaly, flat nasal bridge, upward angle of the eyes, a wide gap between the first and second toes, clinodactyly, small nose, single palmar crease and increased nuchal skin. In addition to affecting the outward appearance, Down syndrome can affect every organ system. Imaging plays a particularly important role in the diagnosis and management of cardiovascular, pulmonary, gastrointestinal, neurological and musculoskeletal complications.
Cardiovascular findings Congenital heart disease Congenital heart disease is commonly associated with Down syndrome, affecting 40–45% of patients [7]. Researchers have reported varying incidences of congenital heart diseases. Ventricular septal defect, atrioventricular septal defect (AVSD), tetralogy of Fallot (TOF), atrial septal defect, patent ductus arteriosus and aortic coarctation are described associations. Ventricular septal defects occur in 43% of children with Down syndrome and congenital heart disease. The ventricular
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septal defect can be isolated or associated with other cardiac anomalies. Atrial septal defects occur in 42% of children with Down syndrome and congenital heart disease [7]. An AVSD, also known as an endocardial cushion defect, is the most common complex congenital heart defect in children with Down syndrome, affecting approximately 39% of infants with Down syndrome and congenital heart disease [7]. An AVSD is more common in girls and African Americans and less common in the Hispanic population [7]. It is caused by abnormal development of the lower atrial and upper ventricular septum leading to a common channel that communicates with the atria and the ventricles. The tricuspid and mitral valves are affected as well. Children with an AVSD usually present in the neonatal period with congestive cardiac failure caused by a left-to-right shunt. However if the pulmonary vascular resistance is increased, as can happen in children with Down syndrome, there can be reversal of the shunt, leading to cyanosis and tachypnea. Radiographs show cardiomegaly and increased pulmonary vascularity. Echocardiography is used to diagnose an AVSD and define its severity. Echocardiogram and cardiac MRI show the defect in the atrioventricular septum, a left-to-right shunt, and the amount of mitral or tricuspid valve regurgitation (Fig. 1). Although a cardiac catheterization is not usually performed to diagnose an AVSD, it can be used to measure pulmonary vascular resistance. When cardiac catheterization is performed, shortening of the left ventricular inflow tract and elongation and narrowing of the left ventricular outflow tract combine to produce the classic “gooseneck deformity” of the left ventricular outflow tract view (Fig. 2) [8]. Tetralogy of Fallot affects 6% of children with Down syndrome who have congenital heart disease [7]. Classically,
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Fig. 2 Gooseneck deformity. Cardiac catheterization in a 22-day-old girl with an endocardial cushion defect. A catheter in the left ventricle with contrast agent shows a narrow gooseneck deformity of the medial margin of the left-ventricular outflow tract (arrows)
children with tetralogy of Fallot become symptomatic with cyanosis and failure to thrive in later infancy as the pulmonary vascular resistance increases, exceeding that of the systemic circulation. The four components of tetralogy of Fallot (pulmonary outflow obstruction, ventricular septal defect, an over-riding aorta, and right ventricular hypertrophy) can be easily visualized with echocardiography, cardiac CT or cardiac MRI. However the presence of associated peripheral pulmonary arterial anomalies and patent ductus arteriosus or collaterals is not adequately imaged by echocardiogram and requires cross-sectional imaging or cardiac catheterization to diagnose. Radiographs in children with tetralogy of Fallot might demonstrate decreased pulmonary vascularity and a characteristic boot-shaped heart (Fig. 3). The cardiac contour abnormality is caused by a narrow mediastinum from small pulmonary arteries and an upturned apex from right ventricular hypertrophy; however this is not always present. Cardiac CT and MR imaging are used to assess the heart between staged surgeries or after surgery, especially in adolescents and adults. Specifically, cardiac MRI can be used to assess the ventricular dimensions, degree of pulmonary regurgitation, and presence of right ventricular outflow tract aneurysm [9]. Antenatal imaging, including fetal sonography and fetal MR imaging, can be used to screen for and assess the severity of cardiovascular abnormalities [10]. Pulmonary arterial hypertension
Fig. 1 Atrioventricular defect. Four-chamber view on white-blood gradient echo cardiac MRI in an 11-week-old girl with Down syndrome shows a left-ventricular dominant atrioventricular canal defect (arrow) with a moderate to severely hypoplastic, nonapex-forming right ventricle (*). RA right atrium, LA left atrium, LV left ventricle
Neonates with Down syndrome are at an inherently higher risk of having pulmonary hypertension. This is at least partially explained by pulmonary alveolar hypoplasia, structural
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Vascular anomalies An aberrant right subclavian artery is a common anatomical variant in children with Down syndrome, occurring in 16– 39% of patients [8]. Although this is often an incidental finding, children with an aberrant right subclavian artery can rarely present with dysphagia and feeding problems if the aberrant right subclavian artery is part of a vascular ring encircling the esophagus and trachea [11, 12]. If other mechanical causes of feeding intolerance have been excluded, a contrast esophagram is a sensitive method of identifying an aberrant right subclavian artery. If positive, the test shows a posterior impression on the esophagus [13]. CT angiography or MR angiography can be used to show the right subclavian artery arising as the most distal branch from the aortic arch and traversing posteriorly behind the esophagus before continuing on its normal course (Fig. 4) [11]. Fig. 3 Tetralogy of Fallot and esophageal atresia/tracheoesophageal fistula. Anteroposterior chest radiograph in a newborn boy shows that the heart has a boot-shaped contour with an upturned apex compatible with a diagnosis of tetralogy of Fallot. A nasoenteric tube is coiled in the upper esophageal pouch (arrow), consistent with esophageal atresia. The presence of bowel gas (arrowhead) in the upper abdomen confirms the presence of a tracheoesophageal fistula. There are also 13 pairs of ribs
abnormalities in the arterial wall, and disturbances in the regulation of pulmonary vascular resistance [2]. In these children, increased pulmonary arterial blood flow caused by concomitant congenital heart disease containing a left-to-right shunt (especially AVSD) exacerbates the risk of pulmonary arterial hypertension [2]. The main strategy to prevent pulmonary arterial hypertension is to identify and manage the cardiac defect in a timely manner. Fig. 4 Aberrant right subclavian artery. Sequential axial contrastenhanced CT images in a 19-yearold woman with Down syndrome demonstrate an aberrant right subclavian artery (arrows) extending from the aortic arch (a) and coursing to the right posterior to the esophagus (* in d)
Respiratory findings Respiratory problems are the most common reason for children with Down syndrome to be admitted to the hospital and are the most common cause of excess mortality [2]. Multiple abnormalities in Down syndrome contribute to the severity of respiratory disease, including immune defects, hypotonia, developmental delay, craniofacial anomalies and chronic aspiration. Pneumonia Pneumonia is the most common respiratory disorder in children with Down syndrome, accounting for nearly 80% of
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hospitalizations and intensive care unit admissions [1]. Compared to unaffected children, children with Down syndrome have a more severe course of disease, longer length of admission, higher cost per admission and increased incidence and severity of respiratory syncytial virus (RSV) bronchiolitis [14]. The findings on radiographs in children with Down syndrome and RSV bronchiolitis are similar to those in other children and include hyperinflated lungs, streaky parahilar opacities and bronchial cuffing. One difference is that children with Down syndrome are more likely to have radiographic consolidation (Fig. 5) [11].
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58% to 83% of the predicated number [11]. These children are categorized as having an alveolar growth abnormality per the Children’s Interstitial Lung Disease (ChILD) classification [15]. This alveolar growth abnormality is most pronounced in the subpleural region, giving the appearance of subpleural cysts (Fig. 6). These cysts are present in 20%–-36% of children with Down syndrome [15, 16]. On CT there are numerous small subpleural cysts, measuring 1–4 mm in the periphery of the anteromedial lung. The cysts have been shown to communicate with more proximal airspaces [17]. No particular management has been suggested because most people are asymptomatic [1].
Chronic lung disease Upper airway obstruction Chest radiographs in children with Down syndrome can demonstrate chronic changes of diffuse parenchymal lung disease, which are sometimes symptomatic. These changes can occur from a primary process such as pulmonary hypoplasia, pulmonary lymphangectasia or lymphoid interstitial pneumonitis or they can occur secondary to bronchopulmonary dysplasia, infection or post-infectious complications, pulmonary hemosiderosis, cardiac and pulmonary vascular disease or chronic aspiration [2]. Several of these entities are described below. Pulmonary hypoplasia and subpleural cysts Autopsy studies in people with Down syndrome have shown a difference in the histological appearance of the lungs compared to unaffected people. In people with Down syndrome, the alveolar size is increased while the total number of alveoli is decreased [11]. Overall, the number of alveoli ranges from
Fig. 5 Respiratory syncytial virus bronchiolitis. Anteroposterior radiograph of the chest in a 14-month-old girl with Down syndrome shows symmetrical hyperinflation of the lungs, streaky perihilar opacities and other focal right upper lobe opacities. The girl was diagnosed with respiratory syncytial virus (RSV) bronchiolitis
Airway obstruction is often multifactorial in children with Down syndrome. In children with the most severe symptoms, multiple obstructive lesions are found nearly 40% of the time at bronchoscopy [1]. Upper airway obstruction occurs in 14% of children with Down syndrome [1]. Some of the more common causes include adenoid and tonsillar hypertrophy, laryngomalacia and macroglossia. Obstructive sleep apnea is the second most common respiratory disorder in children with Down syndrome, affecting 30–75% [1]. Affected patients are identified through a history of snoring and restless sleep. Nearly all children with Down syndrome who snore have obstructive sleep apnea [1]. Several characteristics of the upper airway predispose children with Down syndrome to develop obstructive sleep apnea, including a small mid-face, narrow nasal airways, micrognathia, macroglossia, glossoptosis, increased frequency of tonsil and adenoid hypertrophy, and increased collapsibility of the upper airway. Although the risk of obstructive sleep apnea increases with a larger body mass index, 91% of children with Down syndrome who have obstructive sleep apnea have a normal body mass index [1].
Fig. 6 Subpleural cysts. Axial CT of the chest in 1-year-old girl with Down syndrome demonstrates multiple small subpleural cysts (arrows) along the pleural surface of the mediastinum and chest wall in both upper lungs. Note the median sternotomy wires from previous repair of atrioventricular septal defect
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Fig. 7 Obstructive sleep apnea. Sequential images from a dynamic axial cine MRI sequence through the hypopharynx in a 12-year-old girl with Down syndrome and obstructive sleep apnea. a, b Images show anteroposterior collapse of the airway (arrows) during respiration
Lateral airway radiographs can demonstrate narrowing of the nasopharyngeal and oropharyngeal airway caused by enlargement of the adenoids, soft palate, and palatine and lingual tonsils as well as relative macroglossia. The initial therapy for obstructive sleep apnea in children with Down syndrome is often tonsillectomy and adenoidectomy; however, 30–50% of these children have persistent or recurrent symptoms. Dynamic cine MRI can provide functional assessment of the upper airway in these children. The most common findings are recurrent and enlarged adenoids, glossoptosis, hypopharyngeal collapse, enlarged lingual tonsils and macroglossia [18]. The enlarged adenoids and lingual tonsils are best seen on short tau inversion recovery images, where they appear as areas of increased signal in the posterior nasopharynx and at the base of the tongue, respectively. On the cine images, glossoptosis appears as posterior motion of the tongue, narrowing the hypopharynx. Hypopharyngeal collapse can also be seen on cine images and is defined as intermittent cylindrical collapse of the hypopharynx (Fig. 7) [18]. Lower airway obstruction and other abnormalities Lower airway obstruction, caused by entities such as subglottic stenosis and tracheobronchomalacia, occurs in 25% of children with Down syndrome [2]. Children with
Fig. 8 Tracheal bronchus. a Frontal radiograph and (b) coronal CT image of the chest in a 3-year-old boy show a right upper lobe tracheal bronchus (arrows). On the CT image there is associated atelectasis (arrowheads) of the right upper lobe
Down syndrome and subglottic stenosis account for 4% of all patients undergoing laryngotracheal reconstruction [1]. On imaging, the trachea is focally narrowed below the level of the vocal cords. A tracheal bronchus, commonly a right upper lobe bronchus that originates from the trachea (bronchus suis/pig bronchus), is seen in 21% of children with Down syndrome who undergo bronchoscopy [1]. These children can present with recurrent right upper lobe pneumonia or collapse. It is important to recognize this malformation, especially in intubated patients, because the tip of the endotracheal tube should be positioned above the anomalous bronchus in order to prevent occlusion. A tracheal bronchus is often not easily identified on chest radiograph and can be better seen on CT (Fig. 8). Another airway malformation more common in children with Down syndrome is complete cartilaginous tracheal rings [19]. The degree and length of tracheal narrowing determines the clinical symptoms, which can range from severe respiratory distress to intermittent symptoms associated with upper respiratory infections. Both CT and bronchoscopy can demonstrate complete cartilaginous tracheal rings with luminal narrowing. Complete tracheal rings can be distinguished from normal tracheal cartilage by their circular appearance (Fig. 9). Vascular abnormalities such as pulmonary sling are associated with complete tracheal rings; however, the exact prevalence of
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Fig. 9 Tracheal rings. Axial CT of the chest in a 23-month-old boy with Down syndrome shows a circular configuration of the trachea (arrow). This along with the small caliber of the trachea is consistent with a diagnosis of complete tracheal rings
this association in children with Down syndrome is unclear. Treatment is based on symptoms and can range from observation to tracheoplasty [20].
Gastrointestinal findings Congenital gastrointestinal anomalies are present in 4–10% of children with Down syndrome and can involve most portions of the gastrointestinal tract [21, 22]. Foregut anomalies
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Annular pancreas is more common in children with Down syndrome. One study showed that the risk of having annular pancreas is 430 times higher in children with Down syndrome compared to children without Down syndrome [23]. On radiograph an annular pancreas can be a cause of a double bubble; however, with isolated annular pancreas there is usually distal small bowel gas, unlike the typical findings of duodenal atresia. On fluoroscopy there is circumferential narrowing of the second portion of the duodenum. At endoscopic retrograde cholangiopancreatography, the pancreatic duct encircles the duodenum, and on cross-sectional imaging, the pancreatic tissue surrounds the second portion of the duodenum. Oral contrast agent can be used to help identify the duodenum on CT images. Esophageal atresia with tracheoesophageal fistula is more prevalent in Down syndrome than in the general population, occurring with a frequency of 0.3–0.8% [22]. Children present with difficulty feeding and increased oral secretions. Chest radiograph shows a dilated, air-filled esophageal pouch. An enteric tube, if placed, is coiled within the esophageal pouch (Fig. 3). Air in the stomach confirms presence of a tracheoesophageal fistula (Fig. 3). Additional imaging is rarely required to confirm the diagnosis of esophageal atresia. Midgut anomalies
The most common gastrointestinal anomaly in Down syndrome is duodenal atresia, occurring in 1–5% [22]. Thirty percent of infants with duodenal atresia have Down syndrome [22]. On fetal sonography or MRI there is a characteristic double-bubble appearance with an enlarged, fluid-filled stomach and proximal duodenum (Fig. 10). Polyhydramnios is often present. Postnatal radiograph shows an air-filled double bubble and a lack of distal bowel gas (Fig. 10).
The most common midgut anomaly associated with Down syndrome is malrotation, with an estimated incidence 45 times higher than that in children without Down syndrome [23]. Children with malrotation and midgut volvulus usually present with bilious emesis in the first week after birth. Abdominal radiograph can be normal or have findings of a proximal obstruction. Upper gastrointestinal study is typically the next study performed and shows an abnormal location of the duodenojejunal junction, with the duodenum remaining to the right of the spine and coursing inferiorly (Fig. 11).
Fig. 10 Duodenal atresia. a Prenatal sonogram and (b) prenatal FIESTA (fast imaging employing steady-state acquisition) MR image in a 33week fetus with Down syndrome show a dilated stomach (arrow) and proximal duodenum (arrowhead), typical of the double-bubble sign of
duodenal atresia. Polyhydramnios was present (not shown). c Abdominal radiograph in a different neonate with Down syndrome also shows the double-bubble appearance with dilated stomach (arrow) and proximal duodenum (arrowhead)
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Fig. 11 Malrotation. Anteroposterior image in a 5‐month‐old girl with Down Syndrome who presented with emesis shows an abnormal position of the duodenojejunal junction (arrow), which is positioned closer to midline and lower than the pylorus, indicating malrotation. At surgery, there was no volvulus
Hindgut anomalies The most common hindgut disorders in children with Down syndrome are constipation, Hirschsprung disease and anorectal malformations. Constipation is a common functional gastrointestinal symptom, occurring in 30–50% of children with Down syndrome [1]. Children present with abdominal pain, decreased appetite, vomiting and behavioral changes. Although it is usually idiopathic, constipation can be caused by hypothyroidism or medications. Abdominal radiographs can identify fecal impaction and evaluate the effectiveness of bowel management programs. Hirschsprung disease, or congenital aganglionic megacolon, is a disorder characterized by the lack of ganglion cells innervating the affected portion of colon or rectum. It occurs in 1–3% of infants with Down syndrome; approximately 3–11% of patients with Hirschsprung disease have Down syndrome [22]. Children present with failure to pass meconium or long-term constipation. The length of the aganglionic colon is variable and can range from the distal rectum to the entire colon. Contrast enemas are used to help diagnose Hirschsprung disease. Normally the diameter of the rectum is larger than the diameter of the sigmoid colon, making the rectosigmoid ratio greater than one. In Hirschsprung disease, the diameter of the rectum is smaller than the sigmoid colon and the rectosigmoid ratio is less than one (Fig. 12). The other common finding of Hirschsprung disease is a transition zone from narrowed, affected bowel to dilated, unaffected bowel. Definitive diagnosis is made by rectal suction biopsy.
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Fig. 12 Hirschsprung disease. Lateral view after a contrast enema in an 11-day-old boy with Down syndrome shows an abnormal rectosigmoid ratio and irregular contractions of the rectum (arrow), compatible with Hirschsprung disease
Anorectal malformations occur in 1–3% of children with Down syndrome [24]. Anal atresia without a fistula is the characteristic anorectal malformation, accounting for 95% of anorectal malformations in children with Down syndrome [22, 24]. In this defect, the rectum ends blindly about 2 cm above the perianal skin. Examination of the perineum reveals imperforate anus, and imaging can be used to help define the defect and identify presence of a fistula. Often the first imaging study performed is an abdominal radiograph. The anteroposterior radiograph shows dilated, air-filled loops of bowel extending toward the rectum. The type of anorectal malformation and presence of a fistula can often be determined by the neonatologist/surgeon based on a good physical examination. If the physical exam is indeterminate, imaging with prone radiograph or transperineal sonography can help with the distinction. We typically perform a cross-table lateral view with the child in the prone position, with a bolster under his or her pelvis to cause the air to rise to the anti-dependent rectum and show the level of atresia. The length of atresia can be estimated if a metallic BB is placed on the anal dimple prior to imaging. Prone imaging, if indicated, should be done in a neonate who is at least 24 h old to allow sufficient gas to accumulate within the rectum. Transperineal sonography has been reported to be useful in evaluation of the level of atresia and presence of a fistula [25, 26]. A greater than 1.5-cm depth of the blind-ending rectal pouch from the perineal skin is considered a high atresia and would need a diverting colostomy; a depth of less than 1.5 cm is considered a low atresia and would be eligible for primary repair [25, 26]. This technique is limited
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demonstrate the characteristic absence of fistula to the genital or urinary tract (Fig. 13). Pelvic MRI is useful in evaluation of complex anorectal malformations where fluoroscopic and US findings are inconclusive [27]. Intraoperative or preoperative MR genitography and cloacography is an emerging technique for the evaluation of the pelvis in these children [27]. In this technique dilute gadolinium is instilled in the bladder, vagina and distal colon and rectum through the mucus fistula to better depict the complex anatomy [27]. MRI also provides adequate information of the pelvic floor musculature, which is useful in future continence post-repair [27].
Musculoskeletal findings Craniovertebral junction
by the skill of the sonographer. Crying or straining by the infant could displace the rectum and affect the accuracy of both the prone radiograph and transperineal US exam [25]. In children with high anal atresia who are treated with initial colostomy followed by definitive repair, a high-pressure distal colostogram is performed to evaluate the level of atresia and
In children with Down syndrome dysfunction at the atlantooccipital joint and the atlanto-axial joint contribute to upper cervical instability. Ligamentous laxity plays a major role in craniovertebral instability; however, associated bony abnormalities in this region and hypotonia are also contributory. Atlanto-occipital instability is reported in 8–63% of children with Down syndrome and atlanto-axial instability is found in 10–30% of children with Down syndrome [28]. Most children with craniovertebral junction instability are asymptomatic, with symptomatic disease occurring in 1–2% [28]. Instability of the upper cervical spine is diagnosed using lateral radiographs of the cervical spine obtained in the neutral position as well as during flexion and extension. Measures used to assess the craniovertebral junction include the Powers ratio, Wackenheim clivus/canal line and the dens–basion distance (Figs. 14 and 15). On lateral cervical spine radiographs and sagittal craniocervical CT, the upper limit for normal
Fig. 14 Craniovertebral instability. Diagram shows the lines used in the assessment of craniovertebral instability. a Powers’ ratio is a measure of the anterior atlanto-occipital subluxation. It is the ratio between the distance from the basion (B) to the mid-vertical portion of the posterior laminar line of the atlas (P) and the distance from the opisthion (O) to mid-vertical portion of posterior surface of the anterior ring of the atlas (A). If this ratio (BP/OA) is
greater than one, anterior craniocervical subluxation is present. b The Wackenheim clivus line is a line drawn down the posterior surface of the clivus (C); its inferior extension should barely touch the posterior aspect of the odontoid (D) tip, a relationship that does not change with flexion and extension. If this line is posterior to the odontoid, it is considered posterior subluxation, and if the line is anterior to the odontoid, it is anterior subluxation
Fig. 13 Anorectal malformation. Lateral image from a high-pressure distal colostogram in a 3-month-old boy with Down syndrome shows a blind-ending rectum (arrow). A BB (arrowhead) identifies the expected location of the anus. No fistula is present, a typical finding in children with anorectal malformation and Down syndrome
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Fig. 15 Craniocervical subluxation. Lateral cervical radiograph in a 4year-old boy with Down syndrome in neutral neck position shows the Wackenheim clivus line (an inferior extrapolation of the posterior margin of the clivus) in abnormal position anterior to the tip of the dens (D), which indicates anterior craniocervical subluxation. There is also reversal of normal cervical lordotic curvature
distance from the tip of the dens to the basion is 12 mm. The upper limit of this value can be lower in children, with the vast majority below 10.5 mm [29]. A greater distance would indicate craniocervical dissociation [29]. A normal atlanto– dens interval is less than 3 mm in adults and could be as wide as 5 mm in children. Atlanto-axial instability is diagnosed in children if the atlanto–dens interval is greater than 4.5 mm (Fig. 16) [28]. Because the atlanto–dens interval is an indirect measure of the neural canal width at C1, some have proposed measuring the neural canal directly from the posterior aspect of the dens to the anterior aspect of the posterior arch of C1. A neural canal width of less than 14 mm from the posterior margin of the dens to the anterior margin of the
Fig. 16 Atlanto-axial instability. Lateral cervical radiographs on a 15-year-old girl with Down syndrome. a On extension there is normal anterior atlanto–dens distance of 1.5 mm, and the neural canal width at C1 from the posterior margin of the dens (D) to the posterior arch of C1 is 24.2 mm. b On flexion there is abnormal increased atlanto–dens distance of 7.2 mm and the neural canal width at C1 is mildly decreased at 19.3 mm
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posterior arch of C1 is abnormal and concerning for spinal cord compression. The presence of osseous anomalies such as an unfused anterior and posterior arch of the atlas, atlanto-occipital assimilation, odontoid hypoplasia and an ossiculum terminale or os odontoideum in addition to spinal ligamentous laxity can accentuate craniovertebral junction instability [28, 30]. Although os odontoideum can occur secondary to trauma in normal children, studies suggest there is a congenital etiology for os odontoideum in children with Down syndrome, possibly occurring as a result of ligamentous laxity [31]. These abnormalities prevent the dens from being adequately secured against the anterior arch of C1 during flexion and extension, leading to narrowing of the neural canal [28]. The superior endplate of the lateral mass of C1 is flat in children with Down syndrome rather than curved (Fig. 17) [32]. Compared to radiographs, CT can better demonstrate the bony abnormalities at the craniovertebral junction. If children are symptomatic as a result of the craniovertebral instability, or if there is suspicion of neural canal narrowing, MRI is performed to assess the cervical spinal cord. There is some controversy about intervention in children with craniovertebral instability. Generally surgical fixation of the spine is performed if the child is symptomatic, if there is spinal cord compression on MRI or if atlanto-occipital subluxation is more than 7 mm [28, 33–35]. Screening for craniovertebral junction abnormalities in asymptomatic children is also controversial. The most recent American Academy of Pediatrics guideline no longer recommends general screening because “radiographs do not predict well which children are at increased risk of developing spine problems and do not provide assurance of not having a future problem” [36]. The American Academy of Pediatrics instead recommends screening symptomatic children. Some researchers have found that children with bony craniocervical
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Fig. 17 Flat superior endplate of C1 (arrow). a Parasagittal CT image of the cervical spine in a 16-year-old boy with Down syndrome shows a flat superior endplate of C1 (arrow). b Comparative parasagittal CT shows a normal C1 (arrowhead) in an 11-year-old without Down syndrome
junction abnormalities are at a higher risk of progression and they recommend radiographic follow-up [28]. Children with os odontoideum are at increased risk of atlanto-axial instability causing neural canal narrowing and should be considered for surgical fixation [28]. The Special Olympics continues to require cervical spine screening for participation in certain sports that place undue stress on the head and neck such as swimming the butterfly stroke, diving, certain track and field events, soccer, skiing, gymnastics and equestrian events. If there is evidence of atlanto-axial instability on radiographs, the Special Olympics restricts participation (http://sports.specialolympics.org/specialo.org/Special_/English/ Coach/Coaching/Basics_o/Down_Syn.htm) [37].
Thoracic cage
Fig. 18 Hypersegmented manubrium. Midline sagittal chest CT in a 17-month-old boy with Down syndrome shows more than five sternal segments, with three ossification centers of the manubrium (arrows)
Fig. 19 Characteristic appearance of the pelvis in Down syndrome. Frontal radiograph of the pelvis in a 6-year-old girl with Down syndrome demonstrates characteristic short, divergent iliac wings that are more coronally oriented than normal and small acetabular angles
A hypersegmented sternum with two or more manubrial ossification centers is more prevalent in children with Down syndrome [38–40] (Fig. 18). Presence of a bell-shaped thorax on neonatal radiograph is described in children with Down syndrome [39]. Either 11 or 13 pairs of ribs have been associated with Down syndrome (Fig. 3) [39]. Pelvis In children with Down syndrome the pelvis has a characteristic appearance: flared iliac wings, a flat acetabular roof and a small acetabular angle [41] (Fig. 19). Hip dislocation or dysplasia is the most common disorder of the hip in children with Down syndrome, occurring with a prevalence of 1.5–7% in institutionalized patients with Down syndrome compared to an incidence of less than 0.2% in the general population [42, 43]. Hip instability is related to capsular laxity and low muscle
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tone and is typically identified in children between 2 years and 10 years of age [42]. Other hip conditions that occur with increased frequency in children with Down syndrome include slipped capital femoral epiphysis and idiopathic osteonecrosis of the femoral head (Legg-Calve-Perthes disease). Slipped capital femoral epiphysis occurs in 1.3% of children with Down syndrome compared to 0.01% in the general population, while Legg-Calve-Perthes disease occurs in 2% of children with Down syndrome compared to less than 0.02% in the general population [42, 44, 45]. Children with both disorders might have a delayed diagnosis because of difficulty communicating.
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trimester [47]. Other common abnormalities of the foot in children with Down syndrome include metatarsus primus varus and pes planus [42]. Spine Scoliosis is a common disorder in Down syndrome affecting 9–52% of patients [42]. It can be idiopathic or caused by prior thoracotomy. It is recommended that school-age children with Down syndrome undergo screening via physical exam followed by radiograph if necessary [42].
Appendicular skeleton
Genitourinary findings
Short humeri and femurs are typical of Down syndrome and can be identified in utero.
Genital abnormalities
Hands and feet In the hands hypoplasia of the middle phalanx of the fifth digit is characteristic in Down syndrome [46]. Clinodactyly, or deviation of the distal phalanx of the fifth digit toward the fourth digit, is commonly encountered in Down syndrome, although it is not specific. In the feet there is often widening of the first metatarsal web space, also known as the sandal gap sign (Fig. 20). Although not specific for Down syndrome, this finding is present in 45% of children with Down syndrome and can be seen as early as the second
Cryptorchidism is seen in 14–27% of boys with Down syndrome [48]. The increased incidence of cryptorchidism leads to an increased risk of testicular malignancy, which occurs in 0.5–0.9% of children with Down syndrome [48]. Men with Down syndrome are almost always sterile and fertility is reduced in women [48]. Urinary tract abnormalities Although less frequently encountered, renal and urinary tract anomalies occur in 3.2% of children with Down syndrome, a prevalence that is almost five times greater than that of the general population [49]. Urinary obstruction is the most common finding and presents with varying degrees of hydronephrosis and hydroureter [23]. Urinary obstruction can occur at any level, including the urethra, ureterovesical junction or ureteropelvic junction. The prevalence of posterior urethral valves in children with Down syndrome is reported to be higher than that of the general population [49]. Other associated urinary anomalies include megaureter, vesicoureteral reflux, hypospadias, renal agenesis, renal dysplasia, horseshoe kidney and glomerular microcysts [23, 48–50]. In addition to congenital urinary tract anomalies, children with Down syndrome are at increased risk for medical renal disease including glomerulopathies [51]. Because these conditions are potentially correctable, there are many advocates for early screening for anatomical renal and urological abnormalities in infants with Down syndrome [49, 51].
Neurological findings Fig. 20 Sandal gap sign. Anteroposterior radiograph of the foot in a 5day-old boy with Down syndrome shows a widened first inter-metatarsal space (arrow) known as the sandal gap sign
Children with Down syndrome have varying degrees of intellectual ability. MRI evaluation of the brain in children and
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younger and are more likely to be Caucasian and male [53]. CT angiography, MR angiography and traditional angiography show occlusion of the internal carotid artery distal to the posterior communicating artery and extensive parenchymal collaterals (Fig. 21) [54]. The collateral vessels can appear as flow voids within the basal ganglia on T2-weighted MR images. MRI and CT can also show signs of stroke. Delayed myelination
Fig. 21 Moyamoya disease. Time-of-flight maximum-intensity projection MRA image in an 18-year-old man with Down syndrome shows abrupt termination of the left internal carotid artery (arrow) with blush of deep perforating collateral vessels indicative of moyamoya disease. There is also narrowing of the right proximal middle cerebral artery (arrowhead)
adults with Down syndrome has demonstrated overall smaller brain volumes because of a decrease in cerebral gray and white matter, with relative preservation of the parietal gray matter. There is disproportionate decrease in cerebellar volumes compared to individuals without Down syndrome. The thalami and basal ganglia volumes are not affected [52]. Brain imaging is only performed when neurological signs and symptoms are present. Moyamoya disease Moyamoya disease is associated with Down syndrome. People with Down syndrome account for nearly 4% of all patients with moyamoya disease and 9.5% of those younger than age 15 [53]. Patients with moyamoya disease are most likely to present with ischemic stroke. Compared to other patients with moyamoya disease, those with Down syndrome tend to be
Fig. 22 Sensorineural hearing loss. Axial temporal bone CT in a 19-year-old man with Down syndrome and hearing difficulties. a The left cochlea is hypoplastic with poorly differentiated apical and middle turns (arrow). The vestibular aqueduct was normal. b The right lateral semicircular canal is hypoplastic (arrow), with the bone island measuring less than 3 mm
The normal predicted pattern of myelination of the white matter recognized on MRI, which proceeds from central to peripheral, inferior to superior, and posterior to anterior, can be delayed in children with Down syndrome [55, 56]. This delay in myelination is also demonstrated microscopically [57]. Dementia People older than 40 years who have Down syndrome can develop progressive cognitive impairment resembling Alzheimer dementia. The prevalence of dementia in people with Down syndrome increases with age, rising to nearly 55% by the sixth decade of life [58]. Patients with Down syndrome and dementia have similar MRI findings as patients with Alzheimer dementia, including marked brain atrophy, temporal lobe and hippocampal volume loss, and enlargement of the lateral ventricles [59, 60]. Some of these changes, especially temporal lobe and hippocampal volume loss, can also be seen with aging in people who have Down syndrome without dementia [60]. Hearing loss Hearing loss is common in patients with Down syndrome, occurring in 38–78% [61]. Conductive hearing loss, often as a result of middle ear pathology, is the most common cause of hearing loss and is seen in 53–88% of patients [61]. It most
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commonly occurs as a sequela of chronic otitis media with effusion but can also occur as a result of impacted cerumen, stenotic auditory canals or ossicular chain abnormalities [61]. Sensorineural hearing loss is less common in children with Down syndrome. In these children inner ear dysplasia is present on temporal bone CT in 75% [61]. The most common inner ear anomalies include a maldeveloped bone island of the lateral semicircular canal (defined as measuring ≤3 mm), cochlear nerve canal stenosis (
