Pediatric Radiology

, 38:1062

Relative rather than absolute macroglossia in patients with Down syndrome: implications for treatment of obstructive sleep apnea

Authors

  • Carolina V. A. Guimaraes
    • Department of RadiologyCincinnati Children’s Hospital Medical Center
    • Department of RadiologyCincinnati Children’s Hospital Medical Center
    • Department of PediatricsCincinnati Children’s Hospital Medical Center
  • Sally R. Shott
    • Division of OtolaryngologyCincinnati Children’s Hospital Medical Center
  • Raouf S. Amin
    • Department of PediatricsCincinnati Children’s Hospital Medical Center
  • Maninder Kalra
    • Department of PediatricsCincinnati Children’s Hospital Medical Center
Original Article

DOI: 10.1007/s00247-008-0941-7

Cite this article as:
Guimaraes, C.V.A., Donnelly, L.F., Shott, S.R. et al. Pediatr Radiol (2008) 38: 1062. doi:10.1007/s00247-008-0941-7

Abstract

Background

Children with Down syndrome are described as having macroglossia as well as midface hypoplasia. We reviewed anatomic parameters on MRI to determine whether adolescents with Down syndrome have true macroglossia or relatively large tongues compared to the small size of their oral cavity. This has implications for the treatment of obstructive sleep apnea, which occurs at a relatively high rate among patients with Down syndrome.

Objective

To determine whether adolescents with Down syndrome have relative rather than true macroglossia.

Materials and methods

On sagittal and axial MR images, parameters for tongue size (area in sagittal midline), the bony craniofacial confines of the retroglossal pharynx (distance between the mandibular rami and distance between the posterior aspect of the mental mandible and the anterior aspect of the spine), and the size of the tongue relative to the craniofacial bony parameters [tongue area/(transverse diameter × anterior-to-posterior diameter)] were compared between 16 patients with Down syndrome and 16 age- and gender-matched controls.

Results

The tongue area was significantly smaller in patients with Down syndrome (2,432 mm2) than in the control patients (2,767 mm2; P=0.02). The craniofacial bony parameters were also smaller in patients with Down syndrome than in the controls (left–right 69.8 vs. 80.1 mm, P<0.001; anterior–posterior 64.2 vs. 74.9 mm, P<0.001). However, the size of the tongue relative to the craniofacial parameters was larger in the patients with Down syndrome (0.54) than in the controls (0.46; P<0.001).

Conclusion

Children with Down syndrome do not have true macroglossia but have relatively large tongues compared to the bony confines of the oral cavity.

Keywords

MR sleep studySleep apneaMacroglossiaDown syndrome

Introduction

Down syndrome (trisomy 21) is the most common genetic cause of developmental disability, with an incidence of 1 per 660 live births [1, 2]. In patients with Down syndrome, obstructive sleep apnea is common, occurring in 30–60% of patients [16]. The first line of surgical treatment is often palatine tonsillectomy and adenoidectomy. However, in 30–50% of children with Down syndrome, obstructive sleep apnea will recur despite such interventions [1, 711]. The anatomic causes of persistent obstructive sleep apnea as demonstrated on MR sleep studies include glossoptosis (tongue moving retrograde and obstructing the retroglossal airway during sleep) (63%), hypopharyngeal collapse (22%), recurrent and enlarged adenoid tonsils (63%), enlarged lingual tonsils (30%), and macroglossia (enlarged tongue) (74%). In such patients, MR sleep studies that utilize both anatomic and dynamic images show persistent anatomic causes and patterns of airway collapse [1, 12].

In patients with Down syndrome, both macroglossia and midface and mandibular hypoplasia (micrognathia) are described [2, 9]. This raises the question as to whether patients with Down syndrome have true macroglossia or a relative macroglossia related to their midface and mandibular hypoplasia. We define “true” or “absolute” macroglossia as a tongue with an absolute volume greater than that of the normal tongue. We define “relative” macroglossia as a tongue that is large relative to the bony confines of the oral cavity but with an absolute volume not greater than that of the normal tongue. We reviewed anatomic parameters on MRI to determine whether children with Down syndrome have true macroglossia or just relative macroglossia because of the small size of their oral cavity.

Materials and methods

The study was reviewed and approved by our Institutional Review Board (IRB). Data were stored in a secure and HIPAA-compliant fashion. Tongue size and craniofacial dimensions were measured by MR imaging in 16 children with Down syndrome and 16 age- and gender-matched controls.

Subjects

Sixteen subjects with Down syndrome were identified who had undergone clinically indicated MR sleep studies for the work-up of obstructive sleep apnea [12]. All subjects had obstructive sleep apnea documented by polysomnography with an apneic hypoxic index (AHI) of more than 5. All children were evaluated with MR sleep studies because of recurrent obstructive sleep apnea despite previous palatine tonsillectomy and adenoidectomy, to help guide potential additional surgical management. These MR sleep studies were performed under sedation (dexmedetomidine), per clinical protocol. The data were retrospectively reviewed and children and parents were not contacted as part of the study.

Control children were selected from a cohort who underwent MR imaging as part of a research protocol. The controls did not have underlying medical conditions. All controls underwent polysomnography and did not have evidence of obstructive sleep apnea (AHI <5). These studies were performed with the control subjects awake. Informed consent was obtained. Controls were chosen to create an age- and gender-matched control group.

The Down syndrome and control groups were matched by age and gender. The mean (±SD) age of the Down syndrome group was 14.9±3.7 years. The mean age of the control group was 15.8±3.3 years (P-value not significant). In both the Down syndrome group and the control group 19% of the children were female (P-value not significant).

MR imaging sequence

Subjects underwent an MR sleep study protocol. For the purposes of measuring the tongue size and craniofacial dimensions, axial proton density spin echo and sagittal fast spin-echo inversion recovery (FSEIR) images of the supraglottic airway were utilized. All imaging studies were obtained on a 1.5-T MRI unit (GE Signa Excite HD; General Electric Medical Systems, Milwaukee, WI) with subjects positioned supine within a head and neck vascular coil. Technical parameters for the FSEIR images included TR 5,000 ms, TE 34 ms, echo train length 12, field-of-view 22 cm, slice thickness 6 mm, gap 2 mm, matrix 256×192, and two signal acquisitions. Technical parameters for the axial proton density images included TR 4,000 ms, TE 10 ms, field-of-view 22 cm, slice thickness 3 mm, gap 3 mm, matrix 256×192, and two signal acquisitions (for the controls the slice thickness was 5 mm, zero gap).

Tongue measurements

In each case, three measurements were made of tongue size: maximum anterior-to-posterior diameter, midline sagittal area, and total tongue volume. All measurements were performed on a PACS workstation.

The maximum anterior-to-posterior diameter of the tongue was measured on the sagittal midline image. To calculate the distance, a line was drawn from the posterior aspect of the posterior cortex of the mental portion of the mandible to the posterior aspect of the tongue between the inferior tip of the soft palate superiorly and the superior tip of the epiglottis superiorly (Fig. 1).
https://static-content.springer.com/image/art%3A10.1007%2Fs00247-008-0941-7/MediaObjects/247_2008_941_Fig1_HTML.gif
Fig. 1

Method for measuring anterior-to-posterior tongue diameter. The length of a line (white line) from the posterior cortex of the mental portion of the mandible to the posterior aspect of the tongue was measured on the midline sagittal FSEIR image

The midline sagittal area was calculated by drawing a region of interest overlying the tongue on the midline sagittal image (Fig. 2). The region of interest was used to calculate the area.
https://static-content.springer.com/image/art%3A10.1007%2Fs00247-008-0941-7/MediaObjects/247_2008_941_Fig2_HTML.jpg
Fig. 2

Method for measuring the area of the tongue. A region of interest (gray area) was drawn about the borders of the tongue musculature on the midline sagittal FSEIR image. The area is calculated automatically

Tongue volume was determined by calculating the area of the tongue on each sagittal image in which the tongue was visualized. Each individual calculated tongue area was then multiplied by the sum (8 mm) of the slice thickness (6 mm) and the gap (2 mm). The resulting individual volumes were then added together to calculate the total volume of the tongue.

All measurements were made by a pediatric radiology fellow and faculty and any disagreements resolved by consensus.

Measurements of the bony confines of the oral pharynx

In each patient, measurements of the bony confines of the retroglossal pharynx (craniofacial dimensions) were made. On the axial proton density images, the distance between the intermandibular rami was measured by drawing a line from the internal cortex of the right mandibular ramus to the internal cortex of the left mandibular ramus at the posterior aspect of the ramus near the angle of the mandible (Fig. 3). This was a measurement of the left-to-right bony confines of the retroglossal airway.
https://static-content.springer.com/image/art%3A10.1007%2Fs00247-008-0941-7/MediaObjects/247_2008_941_Fig3_HTML.gif
Fig. 3

Method for measuring the intermandibular distance. On axial proton density images the length of a line (white line) drawn from the internal cortex of the right mandibular ramus to the internal cortex of the left mandibular ramus is measured

Measurements of the anterior-to-posterior bony confines of the retroglossal airway included the mental–spine distance and the mental–clivus distance. Two types of anterior-to-posterior measurements were chosen, as it was not clear which would be the superior method. Both these measurements were calculated on the midline sagittal FSEIR images. The mental–spine distance was calculated by measuring the distance of a line extending from the posterior cortex of the mental portion of the mandible to the anterior cortex of the vertebral bodies with the line drawn parallel to the long axis of the tongue (Fig. 4). The mental–clivus distance was calculated by measuring the distance of a line extending from the posterior cortex of the mental portion of the mandible to the anterior cortex of the mid-portion of the clivus (Fig. 5).
https://static-content.springer.com/image/art%3A10.1007%2Fs00247-008-0941-7/MediaObjects/247_2008_941_Fig4_HTML.gif
Fig. 4

Method for measuring mental–spine distance. The length of a line (white line) drawn parallel to the long axis of the tongue from the posterior cortex of the mental portion of the mandible to the anterior cortex of the vertebral bodies is measured on the midline sagittal FSEIR image

https://static-content.springer.com/image/art%3A10.1007%2Fs00247-008-0941-7/MediaObjects/247_2008_941_Fig5_HTML.gif
Fig. 5

Method for measuring mental–clivus distance. The length of a line (white line) drawn from the posterior cortex of the mental portion of the mandible to the anterior cortex of the mid-portion of the clivus is measured on the midline sagittal FSEIR image

Ratio of tongue area to bony confines of retroglossal pharynx (relative tongue size)

The size of the tongue relative to the bony confines of the retroglossal area was calculated using two formulas:
  1. 1.

    Tongue area/(intermandibular distance × mental–spine distance)

     
  2. 2.

    Tongue area/(intermandibular distance × mental–clivus distance)

     

Statistical evaluation

The significance of differences in tongue size, bony craniofacial confines of the retroglossal pharynx, and tongue size relative to the craniofacial bony confines between the Down syndrome and control groups were determined using Student’s t-test. P values less than 0.05 were considered statistically significant.

Results

The results are presented in Tables 1, 2 and 3. The tongues in the Down syndrome group were significantly smaller than those in the control group. The craniofacial bony parameters were also smaller in the Down syndrome group than in the control group. However, the size of the tongue relative to the craniofacial parameters was larger in the Down syndrome group than in the control group.
Table 1

Measurements of tongue size on MRI in the Down syndrome and control groups.

Tongue parameter

Down syndrome group (n=16)

Control group (n=16)

P value

Area (mm2)

2,431.9±432.3

2,767.4±326.6

0.02

Volume (mm3)

81.1±20.3

96.2±11.8

0.02

AP diameter (mm)

48.2±6.2

54.4±4.8

<0.001

Table 2

Measurements of the bony confines of the pharynx on MRI in the Down syndrome and control groups.

Craniofacial parameter

Down syndrome group (n=16)

Control group (n=16)

P value

Intermandibular distance (mm)

69.8±4.3

80.15±1.5

<0.001

Mental–spine distance (mm)

64.2±7.6

74.9±5.4

<0.001

Mental–clivus distance (mm)

82.1±4.5

98.1±4.6

<0.001

Table 3

Ratios of tongue area to the bony confines of the retroglossal pharynx (relative tongue size) on MRI in the Down syndrome and control groups.

Relative tongue size

Down syndrome group (n=16)

Control group (n=16)

P value

Tongue area/(intermandibular distance × mental–spine distance)

0.54±0.06

0.46±0.05

<0.001

Tongue area/(intermandibular distance × mental–clivus distance)

0.42±0.05

0.35±0.04

<0.001

Discussion

The findings in this study indicate that adolescents with Down syndrome do not have absolute macroglossia. For all parameters of tongue size evaluated including anterior-to-posterior diameter, midline area, and volume, the tongues of control subjects were larger than those of the Down syndrome patients. This differs from the conventional teaching that children with Down syndrome have macroglossia and with a previous study that showed no significant difference in tongue size between 11 Down syndrome patients and 14 controls [2].

Multiple aspects of the design of this study might limit how broadly the conclusions about relative macroglossia can be applied. First, the study group was confined to adolescents with Down syndrome, previous palatine tonsillectomy and adenoidectomy, and persistent obstructive sleep apnea. Whether the conclusions also apply to Down syndrome patients of other ages or those without obstructive sleep apnea is somewhat speculative. A previous study of young patients with Down syndrome (mean age 3.3 years) [2] showed that the tongue size was not different between Down syndrome patients and normal controls, but the airway volume was smaller in the Down syndrome subjects. This suggests that the finding of relative macroglossia might also apply to other ages and groups of patients with Down syndrome.

In addition, it has been shown that obstructive sleep apnea can have an effect on tongue size in adults with obstructive sleep apnea, as compared to controls [13]. This raises the question as to whether the conclusions of this study apply to Down syndrome patients without obstructive sleep apnea and whether it is a limitation to compare subjects with Down syndrome and obstructive sleep apnea to normal controls without obstructive sleep apnea. We chose controls without obstructive sleep apnea because we wanted to see whether the patients with Down syndrome had true or relative macroglossia as compared to normal subjects. We picked subjects with Down syndrome with, as opposed to without, obstructive sleep apnea as the study group for two reasons: (1) the imaging data were readily available for retrospective review, as they were obtained because of the presence of obstructive sleep apnea clinically; and (2) the presence of macroglossia (relative or true) and glossoptosis are clinical issues in patients with obstructive sleep apnea but not in those without obstructive sleep apnea. Finally, our results are the opposite of what one would expect if the presence of obstructive sleep apnea had the effect of making the tongue larger over time, as has been suggested in the literature [13]. In our study, the patients with Down syndrome and obstructive sleep apnea had smaller tongues than did the controls without obstructive sleep apnea.

Another potential limitation is that the controls were matched by age and gender in this study but were not matched by height or weight. Growth curves for children with Down syndrome are significantly different from those for normal children, particularly for height but also for weight [14]. As it would be nearly impossible to match Down syndrome patients and normal controls by age, gender, and size, we chose to use age and gender. We wanted to compare the parameters of Down syndrome to truly normal controls. In addition, because of the propensity for obesity in Down syndrome, normal subjects matched only for height or weight might not be ideal controls in this situation.

It is important to point out that subjects with Down syndrome were imaged under sedation and those in the control group were imaged awake. This is a limitation, but was probably unavoidable. The study group was evaluated as part of a clinical protocol that required sedation for the MR sleep study. In addition, most of these patients with Down syndrome were not able to cooperate with an MRI scan without sedation, even if it were not required as part of the MR sleep study. For the control subjects, many would consider it unethical to sedate them for the research purposes in this study. Previous groups have reported a lack of difference in tongue volume between asleep and awake states in subjects without sleep apnea [15]; therefore, we believe that this did not distort the tongue size data in the observed group.

This study also showed that the bony confines influencing the retroglossal airway were significantly smaller in the Down syndrome group than in controls. This is consistent with previous reports of midface and mandibular hypoplasia in patients with Down syndrome [2, 6, 11]. Unlike most previous studies that were based on radiographic findings and MR data, we used parameters of bony confines that took into consideration bony restriction in multiple planes. This allowed a two-dimensional index for tongue size that captured the restrictions on the retroglossal airway better than measurements in a single plane. These data showed that there was relative macroglossia in Down syndrome patients as compared to controls. The relative size of the tongue as compared to the bony confines was larger in the Down syndrome patients than in controls utilizing either of the anterior-to-posterior parameters for bony confines. One question that might arise is why we chose to measure the bony confines of the airway rather than taking into account the retropharyngeal soft tissues (size of the retroglossal airway). We chose bony confines for several reasons. First, our experience with cine images of the airway shows that the width of the retropharyngeal soft tissues is a parameter that varies dynamically with the respiratory cycle, particularly in subjects with obstructive sleep apnea. Therefore, making a measurement of this area of soft tissue on static images would not be ideal. Second, most of the comparable previously published data are based on measurements of the bony confines.

The relative rather than absolute macroglossia in adolescents with Down syndrome might have implications for both imaging and clinical management, as discussed below. One question that often comes up around the interpretation of MR sleep studies is whether there is a quantitative means for determining whether a patient’s tongue is enlarged. This determination currently is typically achieved by subjective gestalt. Because children with Down syndrome actually have relative rather than absolute macroglossia, the absolute measurement of tongue size is likely not as important as the relative size of the tongue compared to the size of the oral cavity. Those interpreting MR sleep studies need not be concerned about an absolute measurement of the tongue. How much the tongue encroaches upon and intermittently obstructs the retroglossal airway or displaces the soft palate posteriorly and obstructs the posterior nasopharynx is likely the key parameter [1, 11].

In patients with Down syndrome and persistent obstructive sleep apnea related to glossoptosis, there are multiple surgical options involving either reduction in tongue volume or pulling the tongue forward from the posterior pharyngeal wall [1, 36, 10, 16]. Options include midline posterior wedge resection of the tongue, radiofrequency reduction (of the submucosal tissues of the posterior tongue to scar and shrink this area), genoglossius advancement (where a lasso suture is placed and anchored into the mental portion of the mandible by a screw), or mandibular distraction [1, 36, 10, 16]. The knowledge that children with Down syndrome have relative macroglossia will not affect the surgical treatment goal of increasing the size of the retroglossal airway by either reducing the size of the posterior tongue or moving the tongue more anteriorly, but it could affect thinking on the relative uses of mandibular distraction and tongue volume-reduction surgery. In patients with relative macroglossia, mandibular distraction or other means of increasing the bony confines of the oral cavity might be more effective than efforts to reduce the volume of the tongue.

Conclusion

This study suggests that adolescents with Down syndrome and obstructive sleep apnea have smaller tongues and bony confines of the retroglossal airway than normal controls. However, it also shows that adolescents with Down syndrome have relative macroglossia as compared to the size of the bony confines of the oral cavity.

Copyright information

© Springer-Verlag 2008