ORIGINAL ARTICLE Diagnosis and Therapy for in Children With Down Syndrome

Ron B. Mitchell, MD; Ellen Call, MS, CFNP; James Kelly, PhD

Objectives: To document the causes of upper airway children had . Laryngomalacia was the obstruction in a population of children with Down syn- primary diagnosis in 10 children (43%), 8 of whom were drome and to highlight the role of associated comorbidi- younger than 1 month. Obstructive sleep apnea was the ties. primary diagnosis in 11 children (48%), 8 of whom were older than 2 years. All children with obstructive sleep ap- Design and Setting: Review of 23 cases involving chil- nea and 4 children with laryngomalacia had a second- dren with Down syndrome who were referred for upper ary ear, nose, and throat disorder. Gastroesophageal re- airway obstruction over a 21⁄2-year period to the Pediat- flux was a comorbidity in 14 children (61%). ric Otolaryngology Service of the University of New Mexico, Albuquerque. Conclusions: The causes, severity, and presentation of upper airway obstruction in children with Down syn- Methods: Data on the following variables were ob- drome are related to the age of the child and to associ- tained: reason for referral, demographics, diagnosis, sur- ated comorbidities. The treatment of comorbidities and gical procedures, complications, and comorbidities. secondary ear, nose, and throat disorders is an integral component of the surgical management of upper airway Results: The children ranged in age from 1 day to 10.2 obstruction in such cases. years (mean age, 1.8 years; median age, 6 months). Thir- teen children were male and 10 were female. None of the Arch Otolaryngol Head Surg. 2003;129:642-645

HE INTERPLAY between oto- METHODS laryngologic disease and systemic comorbidities in A retrospective review of cases involving chil- children with Down syn- dren with Down syndrome who were referred drome has been discussed for upper airway obstruction to the Pediatric inT a recent report.1 However, there are few Otolaryngology Service at the University of New reports that have specifically addressed up- Mexico Health Sciences Center, Albuquer- per airway obstruction and associated co- que, was undertaken. Approval (Human Re- morbidities in these children.2 Children search Review Committee Approval No. 01- with Down syndrome have midface hy- 301) was obtained from the institutional review poplasia, macroglossia, a narrow naso- board of the University of New Mexico School 3-5 of Medicine. All pediatric surgical procedures , and a shortened palate. These and inpatient consultations between July 1, anatomical abnormalities along with gen- 1999, and December 31, 2001, were entered eralized hypotonia, an immature im- into a spreadsheet (Excel; Microsoft Corp, Red- mune system, and a tendency to obesity mond, Wash). Children with Down syn- predispose children with Down syn- drome were identified from this database, and drome to upper airway obstruction. Fur- those with a primary diagnosis of upper air- thermore, gastroesophageal reflux dis- way obstruction were included in the study. Pri- ease (GERD)6 and chronic disease7 mary otolaryngologic diagnosis was defined as From the Departments of are also common in these children and may the primary disorder underlying the reason for Surgery (Drs Mitchell, Call, worsen airway problems. referral. Secondary otolaryngologic diagnosis and Kelly) and Pediatrics was defined as a disorder that was revealed by (Dr Mitchell), University of Our goal is to describe the causes of history and physical examination in addition New Mexico Health Sciences upper airway obstruction in a population of to the primary disorder. A single surgeon Center, Albuquerque. The children with Down syndrome, the surgi- (R.B.M.) was responsible for all otolaryngo- authors have no relevant cal therapy used to treat this obstruction, logic procedures performed on children in the financial interest in this article. and the role of associated comorbidities. study population. The following parameters

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©2003 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 were obtained from the medical records of children included in the study: gestational age; birth weight; reason for referral; Table 1. Primary and Secondary Diagnoses for Children number and types of previous surgical procedures; complica- With Down Syndrome Presenting With Upper Airway tions; presence and nature of cardiac disease; and presence of Obstruction other comorbidities, such as GERD and chronic lung disease. The diagnosis of GERD was based on the results of a radio- Secondary logic contrast study and clinical findings. Reflux was identified Primary Diagnosis No. Diagnosis No. by the presence of contrast medium above the lower esophageal Obstructive sleep apnea 11 Ear canal atresia 2 sphincter. In children younger than 6 months, 3 or more epi- Laryngomalacia 10 Chronic 1 sodes of reflux were considered a positive finding. In children 1 Laryngomalacia 1 older than 6 months, a positive finding was 1 or more episodes Inhaled foreign body 1 Recurrent otitis media 11 of reflux. The severity was defined according to the following Recurrent 1 classification: mild, the presence of contrast medium confined Vocal cord palsy 1 to the lower third of the esophagus; moderate, up to the middle third of the esophagus; and severe, up to the level of the crico- pharyngeus muscle, with dilatation of the esophagus. The clini- cal findings relevant to GERD included the number of respira- tory tract infections, posturing, weight loss, and failure to thrive. laryngomalacia, 3 had obstructive sleep apnea, and 1 had A total of 23 children were included in the study. Ethnic- tracheomalacia. All 11 children who had a diagnosis of ity was classified as Hispanic or Latino, Caucasian, African obstructive sleep apnea underwent full-night polysom- American, Native American, Asian, or other. The gestational nography (Table 2). age of the infant at birth was recorded as follows: term, 40 ±2 Eight children underwent bronchoscopy (Table 2). weeks (mean±SE); nonterm, younger than 38 weeks; or un- Four of these children had laryngomalacia and episodes known. Both diagnostic and therapeutic surgical interven- of cyanosis. Two children had obstructive sleep apnea tions were recorded. Comorbidities were recorded to include and . One child with stridor had no evidence of the nature of comorbidity, surgical intervention, and out- laryngomalacia but had tracheomalacia diagnosed on come. Therefore, a total of 55 fields were maintained for each child. A unique identifier was used for each record so that medi- bronchoscopy. One child underwent bronchoscopy to cal record numbers and names of patients could be deleted from remove a foreign body. Nine children had obstructive the database to protect the privacy of the patients. sleep apnea and no evidence of stridor. These children did not undergo bronchoscopy. The remaining 6 chil- dren of the total study population of 23 children had RESULTS mild symptoms that did not justify bronchoscopy. A was performed in 6 children, 2 of whom Twenty-three children with Down syndrome and upper air- had laryngomalacia that had been treated unsuccess- way obstruction were included in the study. The children fully with laser aryepiglottoplasty. Two other children ranged in age from 1 day to 10.2 years (mean age, 1.8 years; had GERD and severe aspiration in addition to laryngo- median age, 6 months). Thirteen children were male and malacia. One child had tracheomalacia, and 1 child had 10 were female. The caregivers for 15 children identified obstructive sleep apnea that did not improve after themselves as Hispanic or Latino, 5 as Native Americans, adenotonsillectomy. 2 as non-Hispanic whites, and 1 as Asian. Fourteen chil- Nineteen (83%) of the children in the study popu- dren were full-term neonates and 9 were preterm. lation had systemic comorbidities. Gastroesophageal re- Eleven children (48%) had obstructive sleep ap- flux, which was the most common systemic comorbid- nea, 10 (43%) had laryngomalacia, 1 had tracheomala- ity, was present in 14 children (61%). Chronic lung disease cia, and 1 had inhaled a foreign body (Table 1). The was present in 13 children (56%), 6 of whom were pre- age range for children with obstructive sleep apnea was term. Congenital cardiac disease was present in 11 chil- 3 months to 10 years. The majority of these children (73%) dren (48%). was diagnosed in were older than 2 years. The age range for children with 7 children (30%). Seventeen children (74%) had 2 or more laryngomalacia was 1 day to 2 years. Eight of these chil- systemic comorbidities. Four children (17%) had 3 co- dren were 1 month or younger. morbidities, which included GERD, chronic lung dis- All children with a primary diagnosis of obstruc- ease, and congenital heart disease. tive sleep apnea had a secondary ear, nose, and throat disorder, most commonly recurrent otitis media (73%). COMMENT One child with obstructive sleep apnea also had laryn- gomalacia. A secondary ear, nose, and throat disorder was In children with Down syndrome who are younger than present in 4 children with laryngomalacia. One child with 1 month, the combination of laryngomalacia and GERD laryngomalacia also had a unilateral vocal cord palsy. Sec- may lead to upper airway obstruction that presents as stri- ondary ear, nose, and throat disorders were present in dor. In the present study, this was the most common rea- all children 2 years or older and in 7 (54%) of the chil- son for a neonate with Down syndrome to require a tra- dren younger than 2 years. cheotomy. In children 2 years and older, obstructive sleep All children in the study population underwent at apnea is the major cause of upper airway obstruction that least 1 diagnostic or therapeutic procedure for upper air- presents as sleep-disordered breathing. Gastroesopha- way obstruction. The most common diagnostic proce- geal reflux disease was the most common comorbidity dure was flexible (Table 2). Ten chil- in all age groups and in many instances required addi- dren who underwent flexible laryngoscopy had tional surgical therapy.

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©2003 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 Table 2. Diagnostic and Therapeutic Procedures for Upper Airway Obstruction in Children With Down Syndrome

Otolaryngologic Flexible Diagnosis No. Laryngoscopy Polysomnography Bronchoscopy Tracheotomy Obstructive sleep apnea 11 3 11 2 1 Laryngomalacia 10 10 ND 4 4 Tracheomalacia 1 1 ND 1 1 Inhaled foreign body 1 ND ND 1 ND Total 23 14 11 8 6

Abbreviation: ND, not done.

Laryngomalacia was described by Holinger8 as a con- structive sleep apnea among children in the general popu- dition that may lead to stridor in neonates. The disorder lation is approximately 3%.15 Because of macroglossia, is characterized by folding of the into an ⍀ shape, mandibular hypoplasia, adenotonsillar hypertrophy, and flaccidity of the aryepiglottic folds, and medial move- generalized hypotonia, children with Down syndrome are ment of the arytenoids on inspiration. Three factors ap- more likely to have constriction of the pharyngeal air- pear to determine whether laryngomalacia leads to stri- way during inspiration. Marcus et al16 found sleep- dor in neonates: (1) the extent of the morphological disordered breathing documented by full-night polysom- changes, such as the shape of the epiglottis and the de- nography in all 53 children with Down syndrome who gree of infolding of the aryepiglottic folds9; (2) the rela- were enrolled in their study. Levanon et al17 compared tive flaccidity and hypotonia of the muscles of the su- 23 children who had Down syndrome with 13 controls. praglottis; and (3) the presence and severity of GERD.10,11 They found that all children with Down syndrome whose It is likely that children with laryngomalacia who de- parents reported a sleep disturbance had obstructive sleep velop stridor represent a heterogeneous group in regard apnea that was confirmed by full-night polysomnogra- to the cause of the disorder. phy. Even children with Down syndrome but without ob- Laryngomalacia was present in 10 children (43%) structive sleep apnea had significant sleep fragmenta- in the present study. Previous studies have shown that tion that was manifested by frequent awakenings and laryngomalacia is more common in children with neu- arousals. This sleep fragmentation was not present in the rologic disorders, particularly hypotonia.12 Children with control group. Down syndrome have generalized hypotonia, leading to Pediatric obstructive sleep apnea may have several dif- flaccidity of the supraglottis; anatomical changes in the ferent clinical presentations, including daytime somno- epiglottis, arytenoids, and aryepiglottic folds; and a high lence, behavioral problems, poor school performance, and prevalence of GERD.13 It is not surprising that these chil- in younger children, developmental delay and enure- dren have a high prevalence of laryngomalacia that leads sis.18,19 Because many of these factors are also associated to upper airway obstruction and presents as stridor. with Down syndrome, a delay in diagnosis of obstructive Aryepiglottoplasty for laryngomalacia is a safe and ef- sleep apnea in children with Down syndrome is usually fective procedure for children without significant comor- the rule. Similarly, assessing improvement in behavior af- bidities.,14 Generalized hypotonia, the high incidence of ter surgery can be extremely complex. GERD, and the likelihood of multiple intubations for fur- In the present study, none of the children was di- ther surgical procedures make aryepiglottoplasty a ques- agnosed with subglottic stenosis. A relatively small tra- tionable procedure in children with Down syndrome. Out- chea as well as the need for multiple intubations for sur- come studies after aryepiglottoplasty in these children have gery put children with Down syndrome at risk for the not been reported, to our knowledge. development of subglottic stenosis.20 Shott13 showed that In the present study, 6 children underwent a trache- children with Down syndrome should be intubated ini- otomy. All 6 of them had multiple airway problems, and tially with an endotracheal tube at least 2 sizes smaller previous surgical therapy, including aryepiglottoplasty and than would be used in a child of the same age without adenotonsillectomy, had failed in 3 of them. Therefore, tra- Down syndrome. The present findings agree with pre- cheotomy was performed only in those children in the study vious reports that the incidence of subglottic stenosis is population either in whom previous surgical therapy had low in children with Down syndrome and may reflect in- failed or who had severe aspiration or tracheomalacia. These creasing awareness of the unique attributes of the air- children also had severe GERD in addition to the hypo- way in these children. tonia and craniofacial abnormalities that characterize Down In conclusion, the causes of upper airway obstruc- syndrome. As a consequence, a tracheotomy was the only tion in children with Down syndrome are age related. In effective mode of surgical therapy. In the present study, children younger than 2 years, the most common cause is treatment of laryngomalacia involved therapy for GERD laryngomalacia; in those older than 2 years, it is obstruc- and tracheotomy for severe cases. It remains is unclear what tive sleep apnea. The incidence of subglottic stenosis is low. the role of aryepiglottoplasty for laryngomalacia may be Airway problems in children with Down syndrome rarely in such cases. occur in isolation. The most common comorbidity in these Obstructive sleep apnea was the most common cause children is GERD, but both anatomical abnormalities and of upper airway obstruction in children with Down syn- systemic disease may exacerbate upper airway obstruc- drome who were older than 2 years. The incidence of ob- tion. It is not known whether neonates with Down syn-

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©2003 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 drome progress from laryngomalacia to obstructive sleep 7. Jacobs I, Teague W, Bland J. Pulmonary vascular complications of chronic air- apnea as they age. Equally, it is unknown to what extent way obstruction in children. Arch Otolaryngol Head Neck Surg. 1997;123:700- 704. airway problems worsen developmental delay or whether 8. Holinger LD. Etiology of stridor in the neonate, infant and child. Ann Otol Rhinol correction of these problems leads to behavioral improve- Laryngol. 1980;89:397-400. ments. Future research on the pathogenesis and treat- 9. Belmont J, Grundfast K. Congenital laryngeal stridor (laryngomalacia): etiologic ment of airway problems in children with Down syn- factors and associated disorders. Ann Otol Rhinol Laryngol. 1984;93:430-437. 10. Olney D, Greinwald J, Smith R, et al. Laryngomalacia and its treatment. Laryn- drome may resolve these issues. goscope. 1999;109:1770-1775. 11. Toynton SC, Saunders MW, Bailey CM. Aryepiglottoplasty for laryngomalacia: Accepted for publication December 4, 2002. 100 consecutive cases. J Laryngol Otol. 2001;115:35-38. Corresponding author and reprints: Ron B. Mitchell MD, 12. Matthews B, Little J, Mcguirt W, et al. Reflux in infants with laryngomalacia: re- Department of Surgery, University of New Mexico Health sults of 24-hour double-probe pH monitoring. Otolaryngol Head Neck Surg. 1999; 120:860-864. Sciences Center, 2211 Lomas Blvd NE, Albuquerque, NM 13. Shott S. Otolaryngologic manifestations of Down syndrome. In: Cotton R, Myer 87131 (e-mail: [email protected]). C, eds. Practical Pediatric Otolaryngology. Philadelphia, Pa: Lippincott Williams & Wilkins; 1998:839-850. 14. Roger G, Denoyelle F, Triglia J, et al. Severe laryngomalacia: surgical indica- REFERENCES tions and results in 115 patients. Laryngoscope. 1995;105:1111-1117. 15. Ali NJ, Pitson DJ, Stradling JR. Snoring, sleep disturbance, and behaviour in 4-5 1. Mitchell R, Call E, Kelly J. Ear, nose and throat disorders in children with Down year olds. Arch Dis Child. 1993;68:360-366. syndrome. Laryngoscope. 2003;113:259-263. 16. Marcus C, Keens T, Bautista D, von Pechmann W, Davidson-Ward S. Obstruc- 2. Jacobs I, Gray R, Todd W. Upper airway obstruction in children with Down syn- tive sleep apnea in children with Down syndrome. Pediatrics. 1991;88:132- drome. Arch Otolaryngol Head Neck Surg. 1996;122:945-950. 139. 3. Shapiro B, Gorlin R, Redman R, Bruhl H. The palate and Down’s syndrome. 17. Levanon A, Tarasiuk A, Tal A. Sleep characteristics in children with Down syn- N Engl J Med. 1967;276:1460-1463. drome. J Pediatr. 1999;134:755-760. 4. Miller JD, Capusten BM, Lampard R. Changes at the base of skull and cervical 18. Gozal D. Sleep-disordered breathing and school performance in children. Pedi- spine in Down syndrome. Can Assoc Radiol J. 1986;37:85-89. atrics. 1998;102:616-620. 5. Kanamori G, Witter M, Brown J, Williams-Smith L. Otolaryngologic manifesta- 19. Lefaivre JF, Cohen SR, Burstein FD, et al. Down syndrome: identification and sur- tions of Down syndrome. Otolaryngol Clin North Am. 2000;33:1285-1292. gical management of obstructive sleep apnea. Plast Reconstr Surg. 1997;99: 6. Thompson L, McElhinney D, Jue K, Hodge D. Gastroesophageal reflux after re- 629-637. pair of atrioventricular septal defect in infants with trisomy 21: a comparison of 20. de Jong A, Sulek M, Nihill M, et al. Tenuous airway in children with trisomy 21. medical and surgical therapy. J Pediatr Surg. 1999;34:1359-1363. Laryngoscope. 1997;107:345-350.

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