Clinical Review Laryngotracheal Anomalies in Children With Craniofacial Syndromes Frank A. Papay, MD, FACS* Vincent P. McCarthy, MD† Isaac Eliachar, MD‡ James Arnold, MD§ Cleveland, Ohio INTRODUCTION sleep apnea. Recent literature reviews have ad- dressed the causes of sleep apnea in various cranio- he formation of the nasal oropharyngeal airway facial syndromes and will not be discussed in detail in conjunction with the laryngotracheal airway T herein.1,2 Craniofacial syndromes that involve an ab- and its related structures is a complex process de- normal anterior and middle cranial base in associa- pendent on the separate yet interrelated ontologic tion with mid-facial maxillary hypoplasia often have development of the mouth, nose, pharynx, larynx, narrow nasopharyngeal channels causing nasopha- and the tracheo-bronchial tree. These relationships ryngeal airway constriction. In neonates who are ob- are also influenced by the adjacent formation of the ligate nasal breathers, this may pose difficulties such posterior cranial base, anterior craniofacial skeleton, as a physiologic choanal atresia type of nasopharyn- neck, and adjacent thoracic structures. Not surpris- geal obstruction. In addition, the mid to lower cranial ingly, a vast array of airway anomalies can occur base in close association with the oropharyngeal cav- when each interrelated adjacent structure is abnor- ity, may cause respiratory comprise with the base of mal. Because of its vital nature, life-threatening air- the tongue and the glottic opening. Patients having way anomalies are apparent at birth or soon after. cranial base, maxillary midfacial hypoplasia with an Respiratory distress, cyanosis, difficulty feeding, and additional mandibular hypoplasia, will in essence visually observed abnormalities can lead to an early have partial obstruction in all zones of the upper diagnosis. However, less severe airway anomalies supraglottic airway. can be occult and take months or years to be diag- The etiologies of craniofacial syndromal upper nosed. These patients’ symptoms express only when airway obstruction and restriction are not based only the respiratory system is stressed during the de- on anatomic deformity. Ruckstein summarized the mands of increased respiratory function that can oc- impact of mucopolysaccharide infiltration into the cur with infection or postoperative. soft tissue of the upper airway in patients with the Of further note is the fact that while breathing mucopolysaccharidoses.3 Of interest is the fact that may be normal and asymptomatic while a patient is such infiltration and its consequent obstruction re- awake, significant difficulty may occur when the pa- solves with successful bone marrow transplantation. tient goes to sleep. Physicians and parents may be Solomon discussed a similar significance of muco- totally unaware of ongoing nocturnal symptoms. Of polysaccharide soft tissue infiltration in Apert’s syn- those patients with craniofacial syndromes, the ma- drome.4 Recently, mutations in human growth factor jority of respiratory difficulties are due to obstructive receptors (FGFR1, FGFR2, and FGFR3) have been as- sociated with the phenotypic expression of the Ap- *Head, Section of Craniofacial Surgery, Department of Plastic ert, Crouzon, Pfeiffer, and Jackson-Weiss syndromes and Reconstructive Surgery, Cleveland Clinic Foundation, Cleve- as well as thanatophoric dysplasia, with or without a land, Ohio, USA; †Fellow, Section of Sleep Medicine, Department cloverleaf deformity.5 of Neurology, Cleveland Clinic Foundation, Cleveland, Ohio, USA; ‡Head, Section of Laryngotracheal Reconstruction, Depart- Neither craniofacial syndromes nor congenital ment of Otolaryngology and Communicative Disorders, Cleve- anomalies of the pediatric airway are common. Mal- land Clinic Foundation, Cleveland, Ohio, USA; §Head Section of formations in general occur in 0.47% of live births Pediatric Otolaryngology, Department of Otolaryngology, Univer- and respiratory tract malformations account for 0.3% sity Hospitals, Cleveland, Ohio, USA. of these.6 Significant craniofacial syndromes with Correspondence to Frank A. Papay, MD, FACS, Cleveland Clinic Foundation, 9500 Euclid Avenue—Desk A60, Cleveland, craniosynostosis have an occurrence of 0.4 in 1,000 OH 44195, USA births.7 Case reports have documented marked 351 THE JOURNAL OF CRANIOFACIAL SURGERY / VOLUME 13, NUMBER 2 March 2002 lower airway pathology in craniofacial syndromes Laryngeal Atresia with mid-facial maxillary hypoplasia, i.e. Apert’s Severe laryngeal atresia was reported in a case report and Crouzons’s syndromes, but such reports have of a term infant with 47XXX Syndrome (hypertelor- been sporadic and based primarily on autopsy find- 8 ism, short philtrum, beaked nasal tip, rudimentary ings. There have been no comprehensive attempts to helices) who died at birth. The vocal cords were hy- broadly define the coincidental occurrence of airway poplastic and the larynx was totally occluded with a anomalies in craniofacial syndromes and their im- band of cartilage and connective tissue (Table 1) (Fig pact on one another. 1).9 Below the occlusion was a patent trachea. De- This presentation attempts to provide an over- spite visualization of the vocal cords, an endotrache- view of congenital anomalies of the pediatric airway al tube could not be passed and the patient failed proximal to the bronchioles that are likely to confront tracheostomy. Schimke et al reported a 35-week-old the craniofacial surgeon, otolaryngologist, anesthesi- infant with hypomandibular cranial dysostosis (max- ologist, and pediatric pulmonologist in patients with illary and zygomatic hypoplasia, coronal synostosis craniofacial anomalies. The advent of the pediatric and absent mandible). The patient had bilateral choa- flexible fiberoptic bronchoscope, and standards for nal stenosis and optic nerve hypoplasia, in addition pediatric polysomnography allow direct evaluation to a rudimentary epiglottis, a slit-like larynx with of infants and children with preoperative symptoms. absence of laryngeal cartilage, and an atretic trachea, The pediatric flexible bronchoscope allows both a which ended blindly 1 cm below the larynx. No tra- static and dynamic evaluation of the upper and cheal cartilage was present in the trachea or primary lower airways. Preoperatively, all symptomatic pa- bronchi.10 In such instances where it is apparent that tients with craniofacial anomalies should be exam- ventilation can be maintained despite inability to in- ined for obstructive sleep apnea and the possibility tubate the trachea by the laryngeal route, a tracheo- of occult airway anomalies that may affect the peri esophageal fistula must exist, and the esophago- and/or postoperative course of these patients. Indi- tracheal communication needs to be cannulated and vidual patients with any given craniofacial syn- isolated from the gastrointestinal tract. A cervical dromes may have single or multiple anomalies. At esophagostomy also needs to be established to con- the same time more than one anomaly may be asso- trol oral secretions. These emergent measures will ciated with a specific syndrome. Thirty-six syn- allow time to better assess the overall viability of the dromes with craniofacial anomalies were found that patient and make the correct individual ethical deci- were associated with one or more of 14 airway mal- sions pertinent to the situation.11 Two patients with formations or anomalies. To simplify this issue, in- Fraser’s Syndrome (cryptophalmos, dyscephaly, syn- dividual anomalies will be presented with the syn- dactyly, and urogenital anomalies) have been de- dromes that have been described to have an scribed with laryngeal atresia, having a poorly de- association. Appendix 1, however, will alphabeti- veloped larynx, small vocal cords, and an anterior cally list all syndromes and their associated anoma- membranous fusion.12,13 lies. Laryngeal Hypoplasia LARYNGEAL ANOMALIES Small, malformed larynxes with laryngeal stenosis have also been described in several craniofacial syn- he larynx begins development from the laryn- dromes (Fig 2) (Table 2). In some instances, the dif- Tgotracheal groove in the fourth week and is a ference between hypoplasia and atresia is arbitrary, well-formed organ by the eighth week. A wide spec- and the degree site of stenosis often creates a con- trum of laryngeal anomalies has been described in tinuum rather than a well-defined anatomical diag- association with craniofacial syndromes. The symp- nosis. Two infants with Marshall-Smith Syndrome toms of a laryngeal abnormality are usually stridor, (accelerated skeletal maturation, failure to thrive, respiratory distress, or abnormal phonation. Emer- and dysmorphic features), ages 3 to 16 months re- gent laryngoscopy is indicated when life-threatening laryngeal anomaly is suspected. In the face of a se- Table 1. Craniofacial Anomalies Associated with vere craniofacial anomaly however, laryngoscopy Laryngeal Atresia may be difficult to perform, even with a flexible fi- 1. Fraser syndrome beroptic laryngoscope. Antecedent radiologic or 2. Hypomandibular fasciocranial dysostosis computed tomographic evaluation of the airway 3. 47 XXX syndrome may help localize the pathology in these instances. 352 LARYNGOTRACHEAL ANOMALIES IN CHILDREN WITH CRANIOFACIAL SYNDROMES / Papay external compression due to an aberrant innominate artery.15 Camera et al described a 2-year-old female with Toriello-Carey Syndrome (craniofacial defects, congenital heart defects, agenesis of the corpus