Pharyngeal Hypoplasia in Treacher Collins Syndrome Robert J. Shprintzen, PhD; Charles Croft, MD; Milton D. Berkman, DMD; Saul J. Rakoff, MD
\s=b\Examination of 11 patients with Treacher Collins syndrome (TCS), with the use of multiple-view videofluoroscopy and nasopharyngoscopy of the pharynx, disclosed marked narrowing of the airway. In several patients, the pharynx was less than 1 cm in width at its most narrow point. It is- thought that reduced airway in TCS may help to explain the frequent reports of neonatal death associated with the syndrome. Pharyngeal narrowing was found throughout the entire vertical height of the pharynx in all 11 patients. Pharyngeal hypoplasia is probably responsible for reported difficulties in intubating patients with TCS for endotracheal anesthesia and for respiratory complications after palatoplasty and pharyngoplasty. Pharyngeal hypoplasia is considered to be a primary feature of the syndrome and may aid in its diagnosis.
(Arch Otolaryngol 105:127-131, 1979) purpose of this communication is to report on a series of patients with the Treacher Collins syndrome (TCS), with special reference to the
The
pharyngeal airway. Though previous
reports have not included airway restriction as a feature of TCS, preliminary observations have led us to believe that pharyngeal dimensions may be important in the diagnosis and treatment of the syndrome. Treacher Collins syndrome has been extensively described in the litera¬ ture. Several comprehensive reports have catalogued the features of this well-recognized congenital malforma¬ tion syndrome.1"' Many studies, have for publication May 19, 1978. From the Departments of Plastic Surgery (Dr Shprintzen), Otolaryngology (Drs Shprintzen and Croft), Dentistry (Dr Berkman), and Radiology (Dr Rakoff), Center for Craniofacial Disorders, Montefiore Hospital and Medical Center, and the Albert Einstein College of Medicine (Drs Shprintzen, Croft, Berkman, and Rakoff), Bronx, NY. Reprint requests to Center for Craniofacial Disorders, Montefiore Hospital and Medical Center, 111 E 210th St, Bronx, NY 10467 (Dr
Accepted
Shprintzen).
cited the frequent occurrence of neonatal death in the syndrome (R. J. Gorlin, DDS, oral communication, No¬ vember 1977).''61- These neonatal deaths have typically been attributed to presumed homozygosity, "constitu¬ tional weakness," "decrease of vitali¬ ty," and "presumed" cardiac malfor¬ mations. Several authors have noted
"apparent respiratory distress,"10 "possible upper airway obstruction,"12 "asphyxia,"3 and "stridorous breath¬ ing"6 as contributory to infant mortal¬ ity. There have been two reports in the anesthesiology literature of diffi¬ culty with endotracheal intubation in patients with TCS.1'14 In a recent report, Falzone and Pruzansky1"' re¬ ferred to "constriction of the airway" in patients with TCS in relation to
increased anesthesia risk and difficul¬ ty in the implementation of pharyngo¬ plasty or speech bulb prosthetics. They indicated that airway compro¬ mise in TCS is the result of maxillary and mandibular hypoplasia (mandibulofacial dysostosis). The authors did not mention which portion of the airway was constricted. PATIENTS AND METHODS The findings in 11 patients with TCS, referred to the Center for Craniofacial Disorders (CCFD) of Montefiore Hospital and Medical Center, Bronx, NY in 1976, are catalogued in Table 1. The patients ranged in age from 2 to 34 years, with a mean age of 18.3 years. The facial expression of TCS varied from mild to severe (Fig 1). Two of the patients (Table 1, cases 1 and 2) were brother and sister. Pedigree analysis showed the first documented case in the family to be the paternal grandmother of these patients. The father was affected, as were numerous other relatives. Another two patients were mother and daughter (cases 5 and 6).
Examination Each patient received an extensive examination from the multidisciplinary
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During the course of the examination, each patient had multiview videofluoroscopy and flexible fiberoptic nasopharyngoscopy to assess the compe¬
team at CCFD.
tence of the
velopharyngeal sphincter.
Multiview videofluoroscopy in lateral, frontal, and base projections has been described in detail elsewhere16'8 and will not be repeated. Nasopharyngoscopy was performed under 2% topical tetracaine (Pontocaine) hydrochloride anesthesia with a forward-looking, flexible fiberoptic endo¬ scope (Machida), which had a high-intensi¬
ty,
xenon,
cold-light
source
(Machida)
as
described by Croft et al" (Fig 2). Endoscop¬ ie examinations (Fig 3) were recorded with a
motion-picture
camera
(GAF 250XL)
with simultaneous sound (Fig 4) and in still frames with an endoscopie camera (Kowa) (Fig 5). Both fluoroscopic and endoscopie examinations included views of the naso¬ pharynx, oropharynx, and hypopharynx. In addition, posteroanterior and lateral ceph¬ alometric roentgenograms were performed and analyzed for each patient. Pharyngeal area was assessed by multiview videofluoroscopy and nasopharyngos¬ copy. Multiview Videofluoroscopy.-During all videofluoroscopic examinations, a lead marker of known diameter was inserted into the mouth and placed against the posterior pharyngeal wall, just below the velopharyngeal sphincter (Fig 6). The marker was measured from the video screen, as was the resting distance between the lateral pharyngeal walls in frontal view over the full vertical height of the pharynx as described by Shprintzen et al,2" the resting distance between the velum and posterior pharyngeal wall in lateral view, and the total sphincter area in base view at rest. To have a baseline for comparison, this procedure was also implemented for 40 normal subjects (data obtained for a previous study) who ranged in age from 6 to 45 years and for 40 subjects with cleft palate (clinical examinations selected from approximately 1,300 cases) who were matched for age and sex with the normal
subjects. Nasopharyngoscopy.—The flexible fiberscope was passed through the entire length
Table
Patient/
Age, yr/Sex 1/28/M 2/26/F 3/5/M 4/22/M 5/12/F
Down-slanting Palpebrai Fissures + Severe + Mild + Severe Severe + Moderate -
Lower Lid Coloboma + Severe + +
+
Zygoma-Malar Hypoplasia
1.—Summary Cleft Palate
Severe + Mild + Severe + Severe + Moderate +
Severe Severe Mild
of
Findings*
Microtia Moderate + Mild + Severe Moderate
Face Hair
Absent Frontonasal
Mandibular
Angle
Hypoplasia
-
-
Other
Moderate -Mild -
Severe Severe + Severe
Bilateral cleft lip and Sister of patient 1
+
+
Moderate
Mental retardation, micro¬
cephaly
-
6/34/F 7/22/M
+ Mild
Mild -Mild
+
-f-
Moderate
Mild
Mother of patient 5 Mental retardation, micro¬
+
Mild
+
Moderate
cephaly
-
8/18/F
+
Mild
palate
-Mild
Mental retardation, cardiac and renal anomalies, mi¬
+
Mild
+
Mild
+
Mild
+ Mild
+
Mild
+
Mild
+
Mild
Mental retardation, cardiac
-Mild
+
Moderate
+
Moderate
anomalies, microcephaly Microcephaly, mental retar¬
crocephaly 9/11/F
Moderate
+ Mild
Mental retardation, cho¬ anal atresia, small stature, sleep apnea, microceph¬
-
aly 10/21/F
+
Mild
11/2/M
dation '•"Plus
not
sign indicates feature present; minus sign, feature
present.
sions of the pharynx and the optical limita¬ tion of the endoscope (Fig 8). For each patient with TCS, the percentage of the visual field occupied by the pharyngeal lumen was judged to be normal or mildly,
moderately,
or
severely
narrow.
Data Reduction
Fig 1 .—Left, Frontal view of 22-year-old patient 4). Right, Side view.
man
with
severe
expression
of TCS
(Table 1,
nasopharynx, oropharynx, and hypo¬ pharynx. Filming of the pharynx, at rest, was accomplished at numerous levels from the larynx to the palate. It became subjec¬ tively evident in several of the earlier patients that the pharynx was narrow, since both lateral walls of the pharynx could be seen in the endoscope's field of vision (Fig 7). In a recent investigation of
of the
than 40 normal subjects who were examined by two of us (R.J.S. and C.C.), only one lateral wall could be seen at a time due to the normally wider lateral dimenmore
Fig 2.—Flexible fiberscope (Machida) used in study.
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Data on pharyngeal width, from lateral wall to lateral wall at the most narrow point, were tabulated, and measurements of patients with TCS were compared with those made for normal patients and patients with cleft palate but no other associated anomalies. To correlate pharyn¬ geal width with the severity of expression of the facial features of the syndrome, pharyngeal width measurements were rank ordered for fluoroscopic and endo¬ scopie studies. Pharyngeal width was assigned to normal or mildly, moderately, and severely narrow categories, depending on comparison with the data on normal subjects. Judgments of the degree of sever¬ ity of the facial features of TCS were made by two of us (R.J.S. and M.D.B.) indepen¬ dently on a mild, moderate, and severe scale. Interjudge agreement was excellent. A Cramer correlation coefficient for the ordinal ranking of severity of expression of the syndrome and pharyngeal narrowing was
computed.
RESULTS found that narrowing of the uniform feature of all pharynx 11 patients with TCS. The pharyngeal lumen size was reduced most evidentIt
was
was a
ly in the coronal plane, ie, from later¬ al pharyngeal wall to lateral pharyn¬ geal wall. Observations from lateralview roentgenograms and nasophar¬
yngoscopy showed some reduction of the pharynx in the anteroposterior
dimensions, but
a more remarkable reduction was seen in the lateral aspects of the pharynx. The extent of pharyngeal narrow¬ ing in several of the patients was striking. While the range of pharyn¬ geal width, as measured from frontalview fluoroscopy at the most narrow point (generally near the base of the tongue), was 22 to 44 mm for the normal subjects and 19 to 48 mm for the subjects with cleft palate, for the patients with TCS, the range was 5 to 22 mm (Fig 9). Mean pharyngeal width for the normal subjects was 32 mm, and 36 mm for the subjects with cleft palate, but only 14 mm for the patients with TCS (Table 2). For most of the patients with TCS,
Fig 3.—Endoscopie examination of 5-year-old boy.
pharyngeal narrowing was present along the entire vertical height of the pharynx, though for several patients (Table 2, cases 3, 8, and 9), there was one particular area of more severe constriction, generally at the junction of the oropharynx and hypopharynx near
Fig 4—Motion-picture recording of endos¬
Fig 5.—Still-picture recording
copy.
py·
of endosco¬
the base of the tongue. For
example, case 9 (Table 2) had a pharyngeal lumen breadth of 5 mm at its most narrow point, though at several points in the oropharynx and nasopharynx, the pharyngeal walls were separated by as much as 12 mm.
Pharyngeal width was rank ordered for the patients with TCS to compute a Cramer correlation coefficient be¬ tween pharyngeal narrowing and fa¬ cial expression. The ranking was based on the measurements between the lateral pharyngeal walls and the nasopharyngoscopic studies. For ex¬ ample, for the frontal-view fluorosco¬
Fig 6.—Radiopaque bead (arrow) between outlined lateral pharyngeal walls in frontalview videofluoroscopy of subject with cleft palate.
Fig 7.—Excessively narrow airspace in patient with TCS. Arrows show rest posi¬ tion of lateral pharyngeal walls at level of velopharyngeal orifice.
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py, narrowing was judged as severe when the lateral walls were separated by 5 to 10 mm, moderate from 11 to 16 mm, mild from 17 to 22 mm, and normal from 23 mm and above. Table 2 shows the relationship between facial and pharyngeal factors with a weak correlation of .27.
Cephalometric analysis antegonial notching
marked
showed of the
Fig 8.—Left, Normal pharynx at level of velopharyngeal portal. Note musculus uvulae bulge (at right), which marks center of velum. Right, Velopharyngeal orifice in two normal subjects with lateral pharyngeal wall (arrow) and posterior border of velum (arrow¬ head). Table 2.—Relationship of Facies to Pharynx
Pharyngeal Patient 1 2 3 4 5 6 7 8 9 10 11
Width, mm* 22 (mild) 20 (mild) 10 (severe) 10 (severe) 16 (moderate) 22 (mild) 16 (moderate) 9 (severe) 5 (severe) 15 (moderate) 8 (severe)
Facial
Severity Severe Mild Severe Severe Moderate Mild Mild Mild Moderate Mild Mild
indicates pharyngeal width at most
narrow
point.
mandible for eight of the patients, with a mild antegonial depression in three patients (Fig 10). The hyoid bone was typically displaced anteroinferiorly. Another finding was acuteness of the cranial base angle.
Fig 10.—Cephalometric roentgenogram of patient 4 (Table 1) showing position of hyoid (arrowhead), antegonial notch of mandible (outline arrow), and acute crani¬ al base (black arrow).
COMMENT
Narrowing of the airway would
appear to be a common feature of TCS and may be responsible for the frequent occurrence of neonatal death in the syndrome.14"1- R. J. Gorlin, DDS (oral communication, November 1977) has indicated that he has seen several patients with mandibulofacial
dysostosis of both the TCS and Nager type who have required tracheostomy to maintain respiration. In short, though numerous instances of appar¬ ent respiratory failure have occurred, these have probably been attributed to glossoptosis, as seen in the Robin malformation complex or to lethality
of the gene, rather than to an actual restriction of the entire pharyngeal airway (R. J. Gorlin, DDS, oral communication, November 1977). It is also speculated that some of the neonatal deaths attributed to "sup¬ posed" or "presumed" cardiac malfor¬ mations may have actually been a result of airway compromise. It has been reported that individuals with airway restriction have a substantial risk of polycythemia, pulmonary hy¬
pertension,
pulmonale, congestive heart failure, and cardiac arrhyth¬ mias.-1-3- These are common findings in patients with sleep apnea, a condìcor
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Fig 9.—Pharyngeal lumen in patient with showing severe airway restriction.
TCS
tion shown by patient 9 (Table 1). While glossoptosis may be likely to in individuals with severe occur micrognathia, it is apparent from our observations that the narrowing of the pharynx occurs more noticeably in the lateral dimensions, generally throughout the entire vertical length of the pharynx. It is probable that pharyngeal hypoplasia, rather than glossoptosis, is primarily responsible for episodes of respiratory distress in individuals with TCS by causing approximation of the lateral pharyn¬ geal walls. This has been demon¬ strated in patients with sleep apnea and resultant respiratory arrest.33 Respiratory arrest developed in two of our patients with TCS after endotra¬ cheal intubation for palatoplasty (Ta¬ ble 1, patient 11) and pharyngeal flap surgery (Table 1, patient 7) at other institutions prior to referral to CCFD. These patients had extremely narrow pharyngeal airways with the lateral pharyngeal walls separated by less than 1 cm at the most narrow point in both cases. Respiratory arrest after intubation was probably caused by the following: (1) surgical reduction of the airspace, which triggered apneic epi¬ sodes; and (2) postintubation pharyn¬ geal edema in an already narrow pharynx, which causes the lateral pharyngeal walls to approximate, thus
triggering apneic episodes.33 It is our impression that pharyngeal hypoplasia is a primary feature of TCS. The following observations have led to this conclusion:
1. There is a relatively weak corre¬ lation between the facial features of TCS (mandibulofacial dysostosis) and the degree of pharyngeal narrowing. 2. The narrowing of the pharynx typically occurs at all levels between the base of the cranium and the larynx and not just in the area that is surrounded by the mandible. 3. The syndrome is marked by numerous areas of hypoplastic mesodermal elements (zygomas, malar
bones, eyelids, maxilla, mandible, pal¬ ate, auricles, middle ear). Other
in patients with TCS are known to be deficient, ie, hypoplastic, such as the nose (choanal atresia4·3), sinuses,4 and middle ear.*·' Therefore, there may be a generalized hypoplasia of the head and neck airspaces in TCS. The high frequency of pnaryngeal hypoplasia in our sample of 11 patients with TCS leads us to believe that pharyngeal hypoplasia is diag¬ nostic of the syndrome. Gorlin et al4 stated that TCS is one of the few craniofacial syndromes that is readily diagnosed by the appearance of the facies. However, quite a few patients with TCS have such minimal expres¬ sion of the syndrome that diagnosis by sight becomes extremely difficult. In several instances at CCFD, the diagnosis was made based on tracing the effects of the dominant gene through the family pedigree. There¬ fore, for patients who have a mild facial expression, such as down-slant¬ ing palpebrai fissures with minimal mandibular hypoplasia, pharyngeal hypoplasia as viewed by nasopharyn¬
airspaces
or anteroposterior roentgen¬ ography may be a valuable aid in diagnosing TCS. The implications of airway hypopla¬ sia in TCS for proposed treatment requires in-depth investigation. How¬
goscopy
have had several of personal reports serious postsurgical complications and mortalities due to respiratory failure, as well as reports in the literature of neonatal death and anesthesia risk, we think that those who plan treatments of patients with TCS must be sensitive to airway problems. For example, pharyngoplasties should not be planned if they would compromise the ever,
since
we
airway to the point of inducing apneic episodes. In planning anesthesia for any surgical procedure, great care must be exercised in determining airway size and potential edema, which might compromise the pharynx. Tracheostomy must be considered as a
viable alternative to endotracheal intubation for the administration of general anesthesia. It is interesting to note that the mean pharyngeal width was greatest for the subjects with cleft palate who were used in this study for comparison with the normal subjects and patients with TCS. This finding is consistent with reports by Maue-Dickson et al34 of increased pharyngeal width in cleft palate fetal heads. It should be noted that nine of the sample population of patients with TCS had cleft palate with pharyngeal narrowing. This may suggest a different mechanism for clefting in TCS than in the isolated cleft palate. This study was supported in part by grants from the Max and Victoria Dreyfus Foundation and the Rosenhirsch Foundation.
1. Axellson
References A, Brolin I, Engstrom H, et al:
Dysostosis mandibulofacialis.
J
Laryngol
Otol
87:575-592, 1963. 2. Behrents RG, McNamara JA, Avery JK: Prenatal mandibulofacial dysostosis (Treacher Collins syndrome). Cleft Palate J 14:13-34, 1977. 3. Franceschetti A, Klein D: The mandibulofacial
dysostosis,
a new
hereditary syndrome.
Acta Ophthalmol 27:141-224, 1949. 4. Gorlin RJ, Pindborg JJ, Cohen MM Jr: Syndromes of the Head and Neck, ed 2. New York, McGraw-Hill Book Co Inc, 1976. 5. Smith DW: Recognizable Patterns of Human Malformation, ed 2. Philadelphia, WB Saunders Co, 1976. 6. Book JA, Fraccaro M: Genetical investigations in a North-Swedish population with mandibulo-facial dysostosis. Acta Genet Med Gemellol 5:327-333, 1955. Famili\l=a"\re kombinierte 7. Debussman: Gesichts-missbildung im Bereich des ersten Visceralbogens. Arch Kinderheilkd 120:133-139, 1940. 8. Fagen LE, Elmore J, Nadler HL: Mandibulo-facial dysostosis. Am J Dis Child 113:405-410, 1967. 9. Francois J: Heredity in Ophthalmology. St Louis, CV Mosby Co, 1961. 10. Hall JG: Case report D\p=m-\mandibulo-facial dysostosis. Birth Defects 2:215, 1969. 11. Rogers BO: Berry-Treacher Collins syndrome: A review of 200 cases. Br J Plast Surg 17:109-137, 1964. 12. Sando I, Hemenway WG, Morgan WR: Histopathology of the temporal bones in mandibulofacial dysostosis. Trans Am Acad Ophthalmol Otolaryngol 72:913-924, 1968. 13. Divekar VM, Sircar BN: Anesthetic management in Treacher-Collins syndrome. Anesthesiology 26:692-693, 1965.
Downloaded From: http://archotol.jamanetwork.com/ by a UQ Library User on 06/14/2015
14. Ross ED: Treacher Collins syndrome: An anesthetic hazard. Anaesthesia 18:350-354, 1963. 15. Falzone S, Pruzansky S: Cleft palate and congenital palatopharyngeal incompetency in mandibulofacial dysostosis: Frequency and problems in treatment. Cleft Palate J 13:354-360, 1976. 16. Shprintzen RJ, McCall GN, Skolnick ML: A new therapeutic technique for treatment of velopharyngeal incompetence. J Speech Hear Disord 40:70-83, 1975. 17. Skolnick ML: Videovelopharyngography in patients with nasal speech, with emphasis on lateral pharyngeal motion in velopharyngeal closure. Radiology 93:747-755, 1969. 18. Skolnick ML: Videofluoroscopic examination of the velopharyngeal portal during phonation in lateral and base projections: A new technique for studying the mechanics of closure. Cleft Palate J 7:803-816, 1970. 19. Croft C, Shprintzen RJ, Daniller AI, et al: The occult submucous cleft palate and the musculus uvulae. Cleft Palate J 15:150-154, 1978. 20. Shprintzen RJ, Lencione RM, McCall GN, et al: A three dimensional cinefluoroscopic analysis of velopharyngeal closure during speech and nonspeech activities in normals. Cleft Palate J 11:412-428, 1974. 21. Ainger LE: Large tonsils and adenoids in small children with cor pulmonale. Br Heart J 30:356-362, 1968. 22. Bland JW, Edwards FK, Brinsfield D: Pulmonary hypertension and congestive heart failure in children with chronic upper airway obstruction. Am J Cardiol 23:830-837, 1969. 23. Cayler GG, Johnson ED, Lewis BE, et al: Heart failure due to enlarged tonsils and adenoids. Am J Dis Child 118:708-717, 1969. 24. Cronje RE, Hurman GP, Simson JW: Hypoxaemic pulmonary hypertension in children. S Afr Med J 40:2-7, 1966. 25. Edison BD, Kerth JD: Tonsilloadenoid hypertrophy resulting in cor pulmonale. Arch Otolaryngol 98:205-207, 1973. 26. Gerald B, Dungan WT: Cor pulmonale from chronic nasopharyngeal obstruction. Surg Forum 18:493-495, 1967. 27. Gresham EL, Armstrong JG: Cardiac failure from tonsillar enlargement: A reminder. Clin Pediatr 10:236, 1971. 28. Kravath RE, Pollak CP, Borowiecki B: Hypoventilation during sleep in children who have lymphoid airway obstruction treated by nasopharyngeal tube and T and A. Pediatrics 59:865-872, 1977. 29. Levy AM, Tabakin BS, Hanson JS, et al: Hypertrophied adenoids causing pulmonary hypertension and severe congestive heart failure. N Engl J Med 277:506-510, 1967. 30. Menashe VD, Farrehi C, Miller M: Hypoventilation and cor pulmonale due to chronic upper airway obstruction. J Pediatr 67:198-203, 1965. 31. Talbot AR, Robertson LW: Cardiac failure with tonsil and adenoid hypertrophy. Arch Otolaryngol 98:277-281, 1973. 32. Thanopoulos B, Skkos DD, Milingos M, et al: Cardiorespiratory syndrome due to enlarged tonsils and adenoids. Acta Paediatr Scand 64:659-663, 1975. 33. Weitzman ED, Pollak CP, Borowiecki B, et al: The hypersomnia-sleep apnea syndrome: Site and mechanism of upper airway obstruction, in Guilleminault C, Dement WC (eds): Sleep Apnea Syndromes. New York, Alan R Liss Inc, 1978, chap 15, pp 235-248. 34. Maue-Dickson W, Dickson DR, Rood SR: Anatomy of the Eustachian tube and related structures in age-matched human fetuses with and without cleft palate. Trans Am Acad Ophthalmol Otolaryngol 82:159-163, 1976.
\s=b\Examination of 11 patients with Treacher Collins syndrome (TCS), with the use of multiple-view videofluoroscopy and nasopharyngoscopy of the pharynx, disclosed marked narrowing of the airway. In several patients, the pharynx was less than 1 cm in width at its most narrow point. It is- thought that reduced airway in TCS may help to explain the frequent reports of neonatal death associated with the syndrome. Pharyngeal narrowing was found throughout the entire vertical height of the pharynx in all 11 patients. Pharyngeal hypoplasia is probably responsible for reported difficulties in intubating patients with TCS for endotracheal anesthesia and for respiratory complications after palatoplasty and pharyngoplasty. Pharyngeal hypoplasia is considered to be a primary feature of the syndrome and may aid in its diagnosis.
(Arch Otolaryngol 105:127-131, 1979) purpose of this communication is to report on a series of patients with the Treacher Collins syndrome (TCS), with special reference to the
The
pharyngeal airway. Though previous
reports have not included airway restriction as a feature of TCS, preliminary observations have led us to believe that pharyngeal dimensions may be important in the diagnosis and treatment of the syndrome. Treacher Collins syndrome has been extensively described in the litera¬ ture. Several comprehensive reports have catalogued the features of this well-recognized congenital malforma¬ tion syndrome.1"' Many studies, have for publication May 19, 1978. From the Departments of Plastic Surgery (Dr Shprintzen), Otolaryngology (Drs Shprintzen and Croft), Dentistry (Dr Berkman), and Radiology (Dr Rakoff), Center for Craniofacial Disorders, Montefiore Hospital and Medical Center, and the Albert Einstein College of Medicine (Drs Shprintzen, Croft, Berkman, and Rakoff), Bronx, NY. Reprint requests to Center for Craniofacial Disorders, Montefiore Hospital and Medical Center, 111 E 210th St, Bronx, NY 10467 (Dr
Accepted
Shprintzen).
cited the frequent occurrence of neonatal death in the syndrome (R. J. Gorlin, DDS, oral communication, No¬ vember 1977).''61- These neonatal deaths have typically been attributed to presumed homozygosity, "constitu¬ tional weakness," "decrease of vitali¬ ty," and "presumed" cardiac malfor¬ mations. Several authors have noted
"apparent respiratory distress,"10 "possible upper airway obstruction,"12 "asphyxia,"3 and "stridorous breath¬ ing"6 as contributory to infant mortal¬ ity. There have been two reports in the anesthesiology literature of diffi¬ culty with endotracheal intubation in patients with TCS.1'14 In a recent report, Falzone and Pruzansky1"' re¬ ferred to "constriction of the airway" in patients with TCS in relation to
increased anesthesia risk and difficul¬ ty in the implementation of pharyngo¬ plasty or speech bulb prosthetics. They indicated that airway compro¬ mise in TCS is the result of maxillary and mandibular hypoplasia (mandibulofacial dysostosis). The authors did not mention which portion of the airway was constricted. PATIENTS AND METHODS The findings in 11 patients with TCS, referred to the Center for Craniofacial Disorders (CCFD) of Montefiore Hospital and Medical Center, Bronx, NY in 1976, are catalogued in Table 1. The patients ranged in age from 2 to 34 years, with a mean age of 18.3 years. The facial expression of TCS varied from mild to severe (Fig 1). Two of the patients (Table 1, cases 1 and 2) were brother and sister. Pedigree analysis showed the first documented case in the family to be the paternal grandmother of these patients. The father was affected, as were numerous other relatives. Another two patients were mother and daughter (cases 5 and 6).
Examination Each patient received an extensive examination from the multidisciplinary
Downloaded From: http://archotol.jamanetwork.com/ by a UQ Library User on 06/14/2015
During the course of the examination, each patient had multiview videofluoroscopy and flexible fiberoptic nasopharyngoscopy to assess the compe¬
team at CCFD.
tence of the
velopharyngeal sphincter.
Multiview videofluoroscopy in lateral, frontal, and base projections has been described in detail elsewhere16'8 and will not be repeated. Nasopharyngoscopy was performed under 2% topical tetracaine (Pontocaine) hydrochloride anesthesia with a forward-looking, flexible fiberoptic endo¬ scope (Machida), which had a high-intensi¬
ty,
xenon,
cold-light
source
(Machida)
as
described by Croft et al" (Fig 2). Endoscop¬ ie examinations (Fig 3) were recorded with a
motion-picture
camera
(GAF 250XL)
with simultaneous sound (Fig 4) and in still frames with an endoscopie camera (Kowa) (Fig 5). Both fluoroscopic and endoscopie examinations included views of the naso¬ pharynx, oropharynx, and hypopharynx. In addition, posteroanterior and lateral ceph¬ alometric roentgenograms were performed and analyzed for each patient. Pharyngeal area was assessed by multiview videofluoroscopy and nasopharyngos¬ copy. Multiview Videofluoroscopy.-During all videofluoroscopic examinations, a lead marker of known diameter was inserted into the mouth and placed against the posterior pharyngeal wall, just below the velopharyngeal sphincter (Fig 6). The marker was measured from the video screen, as was the resting distance between the lateral pharyngeal walls in frontal view over the full vertical height of the pharynx as described by Shprintzen et al,2" the resting distance between the velum and posterior pharyngeal wall in lateral view, and the total sphincter area in base view at rest. To have a baseline for comparison, this procedure was also implemented for 40 normal subjects (data obtained for a previous study) who ranged in age from 6 to 45 years and for 40 subjects with cleft palate (clinical examinations selected from approximately 1,300 cases) who were matched for age and sex with the normal
subjects. Nasopharyngoscopy.—The flexible fiberscope was passed through the entire length
Table
Patient/
Age, yr/Sex 1/28/M 2/26/F 3/5/M 4/22/M 5/12/F
Down-slanting Palpebrai Fissures + Severe + Mild + Severe Severe + Moderate -
Lower Lid Coloboma + Severe + +
+
Zygoma-Malar Hypoplasia
1.—Summary Cleft Palate
Severe + Mild + Severe + Severe + Moderate +
Severe Severe Mild
of
Findings*
Microtia Moderate + Mild + Severe Moderate
Face Hair
Absent Frontonasal
Mandibular
Angle
Hypoplasia
-
-
Other
Moderate -Mild -
Severe Severe + Severe
Bilateral cleft lip and Sister of patient 1
+
+
Moderate
Mental retardation, micro¬
cephaly
-
6/34/F 7/22/M
+ Mild
Mild -Mild
+
-f-
Moderate
Mild
Mother of patient 5 Mental retardation, micro¬
+
Mild
+
Moderate
cephaly
-
8/18/F
+
Mild
palate
-Mild
Mental retardation, cardiac and renal anomalies, mi¬
+
Mild
+
Mild
+
Mild
+ Mild
+
Mild
+
Mild
+
Mild
Mental retardation, cardiac
-Mild
+
Moderate
+
Moderate
anomalies, microcephaly Microcephaly, mental retar¬
crocephaly 9/11/F
Moderate
+ Mild
Mental retardation, cho¬ anal atresia, small stature, sleep apnea, microceph¬
-
aly 10/21/F
+
Mild
11/2/M
dation '•"Plus
not
sign indicates feature present; minus sign, feature
present.
sions of the pharynx and the optical limita¬ tion of the endoscope (Fig 8). For each patient with TCS, the percentage of the visual field occupied by the pharyngeal lumen was judged to be normal or mildly,
moderately,
or
severely
narrow.
Data Reduction
Fig 1 .—Left, Frontal view of 22-year-old patient 4). Right, Side view.
man
with
severe
expression
of TCS
(Table 1,
nasopharynx, oropharynx, and hypo¬ pharynx. Filming of the pharynx, at rest, was accomplished at numerous levels from the larynx to the palate. It became subjec¬ tively evident in several of the earlier patients that the pharynx was narrow, since both lateral walls of the pharynx could be seen in the endoscope's field of vision (Fig 7). In a recent investigation of
of the
than 40 normal subjects who were examined by two of us (R.J.S. and C.C.), only one lateral wall could be seen at a time due to the normally wider lateral dimenmore
Fig 2.—Flexible fiberscope (Machida) used in study.
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Data on pharyngeal width, from lateral wall to lateral wall at the most narrow point, were tabulated, and measurements of patients with TCS were compared with those made for normal patients and patients with cleft palate but no other associated anomalies. To correlate pharyn¬ geal width with the severity of expression of the facial features of the syndrome, pharyngeal width measurements were rank ordered for fluoroscopic and endo¬ scopie studies. Pharyngeal width was assigned to normal or mildly, moderately, and severely narrow categories, depending on comparison with the data on normal subjects. Judgments of the degree of sever¬ ity of the facial features of TCS were made by two of us (R.J.S. and M.D.B.) indepen¬ dently on a mild, moderate, and severe scale. Interjudge agreement was excellent. A Cramer correlation coefficient for the ordinal ranking of severity of expression of the syndrome and pharyngeal narrowing was
computed.
RESULTS found that narrowing of the uniform feature of all pharynx 11 patients with TCS. The pharyngeal lumen size was reduced most evidentIt
was
was a
ly in the coronal plane, ie, from later¬ al pharyngeal wall to lateral pharyn¬ geal wall. Observations from lateralview roentgenograms and nasophar¬
yngoscopy showed some reduction of the pharynx in the anteroposterior
dimensions, but
a more remarkable reduction was seen in the lateral aspects of the pharynx. The extent of pharyngeal narrow¬ ing in several of the patients was striking. While the range of pharyn¬ geal width, as measured from frontalview fluoroscopy at the most narrow point (generally near the base of the tongue), was 22 to 44 mm for the normal subjects and 19 to 48 mm for the subjects with cleft palate, for the patients with TCS, the range was 5 to 22 mm (Fig 9). Mean pharyngeal width for the normal subjects was 32 mm, and 36 mm for the subjects with cleft palate, but only 14 mm for the patients with TCS (Table 2). For most of the patients with TCS,
Fig 3.—Endoscopie examination of 5-year-old boy.
pharyngeal narrowing was present along the entire vertical height of the pharynx, though for several patients (Table 2, cases 3, 8, and 9), there was one particular area of more severe constriction, generally at the junction of the oropharynx and hypopharynx near
Fig 4—Motion-picture recording of endos¬
Fig 5.—Still-picture recording
copy.
py·
of endosco¬
the base of the tongue. For
example, case 9 (Table 2) had a pharyngeal lumen breadth of 5 mm at its most narrow point, though at several points in the oropharynx and nasopharynx, the pharyngeal walls were separated by as much as 12 mm.
Pharyngeal width was rank ordered for the patients with TCS to compute a Cramer correlation coefficient be¬ tween pharyngeal narrowing and fa¬ cial expression. The ranking was based on the measurements between the lateral pharyngeal walls and the nasopharyngoscopic studies. For ex¬ ample, for the frontal-view fluorosco¬
Fig 6.—Radiopaque bead (arrow) between outlined lateral pharyngeal walls in frontalview videofluoroscopy of subject with cleft palate.
Fig 7.—Excessively narrow airspace in patient with TCS. Arrows show rest posi¬ tion of lateral pharyngeal walls at level of velopharyngeal orifice.
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py, narrowing was judged as severe when the lateral walls were separated by 5 to 10 mm, moderate from 11 to 16 mm, mild from 17 to 22 mm, and normal from 23 mm and above. Table 2 shows the relationship between facial and pharyngeal factors with a weak correlation of .27.
Cephalometric analysis antegonial notching
marked
showed of the
Fig 8.—Left, Normal pharynx at level of velopharyngeal portal. Note musculus uvulae bulge (at right), which marks center of velum. Right, Velopharyngeal orifice in two normal subjects with lateral pharyngeal wall (arrow) and posterior border of velum (arrow¬ head). Table 2.—Relationship of Facies to Pharynx
Pharyngeal Patient 1 2 3 4 5 6 7 8 9 10 11
Width, mm* 22 (mild) 20 (mild) 10 (severe) 10 (severe) 16 (moderate) 22 (mild) 16 (moderate) 9 (severe) 5 (severe) 15 (moderate) 8 (severe)
Facial
Severity Severe Mild Severe Severe Moderate Mild Mild Mild Moderate Mild Mild
indicates pharyngeal width at most
narrow
point.
mandible for eight of the patients, with a mild antegonial depression in three patients (Fig 10). The hyoid bone was typically displaced anteroinferiorly. Another finding was acuteness of the cranial base angle.
Fig 10.—Cephalometric roentgenogram of patient 4 (Table 1) showing position of hyoid (arrowhead), antegonial notch of mandible (outline arrow), and acute crani¬ al base (black arrow).
COMMENT
Narrowing of the airway would
appear to be a common feature of TCS and may be responsible for the frequent occurrence of neonatal death in the syndrome.14"1- R. J. Gorlin, DDS (oral communication, November 1977) has indicated that he has seen several patients with mandibulofacial
dysostosis of both the TCS and Nager type who have required tracheostomy to maintain respiration. In short, though numerous instances of appar¬ ent respiratory failure have occurred, these have probably been attributed to glossoptosis, as seen in the Robin malformation complex or to lethality
of the gene, rather than to an actual restriction of the entire pharyngeal airway (R. J. Gorlin, DDS, oral communication, November 1977). It is also speculated that some of the neonatal deaths attributed to "sup¬ posed" or "presumed" cardiac malfor¬ mations may have actually been a result of airway compromise. It has been reported that individuals with airway restriction have a substantial risk of polycythemia, pulmonary hy¬
pertension,
pulmonale, congestive heart failure, and cardiac arrhyth¬ mias.-1-3- These are common findings in patients with sleep apnea, a condìcor
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Fig 9.—Pharyngeal lumen in patient with showing severe airway restriction.
TCS
tion shown by patient 9 (Table 1). While glossoptosis may be likely to in individuals with severe occur micrognathia, it is apparent from our observations that the narrowing of the pharynx occurs more noticeably in the lateral dimensions, generally throughout the entire vertical length of the pharynx. It is probable that pharyngeal hypoplasia, rather than glossoptosis, is primarily responsible for episodes of respiratory distress in individuals with TCS by causing approximation of the lateral pharyn¬ geal walls. This has been demon¬ strated in patients with sleep apnea and resultant respiratory arrest.33 Respiratory arrest developed in two of our patients with TCS after endotra¬ cheal intubation for palatoplasty (Ta¬ ble 1, patient 11) and pharyngeal flap surgery (Table 1, patient 7) at other institutions prior to referral to CCFD. These patients had extremely narrow pharyngeal airways with the lateral pharyngeal walls separated by less than 1 cm at the most narrow point in both cases. Respiratory arrest after intubation was probably caused by the following: (1) surgical reduction of the airspace, which triggered apneic epi¬ sodes; and (2) postintubation pharyn¬ geal edema in an already narrow pharynx, which causes the lateral pharyngeal walls to approximate, thus
triggering apneic episodes.33 It is our impression that pharyngeal hypoplasia is a primary feature of TCS. The following observations have led to this conclusion:
1. There is a relatively weak corre¬ lation between the facial features of TCS (mandibulofacial dysostosis) and the degree of pharyngeal narrowing. 2. The narrowing of the pharynx typically occurs at all levels between the base of the cranium and the larynx and not just in the area that is surrounded by the mandible. 3. The syndrome is marked by numerous areas of hypoplastic mesodermal elements (zygomas, malar
bones, eyelids, maxilla, mandible, pal¬ ate, auricles, middle ear). Other
in patients with TCS are known to be deficient, ie, hypoplastic, such as the nose (choanal atresia4·3), sinuses,4 and middle ear.*·' Therefore, there may be a generalized hypoplasia of the head and neck airspaces in TCS. The high frequency of pnaryngeal hypoplasia in our sample of 11 patients with TCS leads us to believe that pharyngeal hypoplasia is diag¬ nostic of the syndrome. Gorlin et al4 stated that TCS is one of the few craniofacial syndromes that is readily diagnosed by the appearance of the facies. However, quite a few patients with TCS have such minimal expres¬ sion of the syndrome that diagnosis by sight becomes extremely difficult. In several instances at CCFD, the diagnosis was made based on tracing the effects of the dominant gene through the family pedigree. There¬ fore, for patients who have a mild facial expression, such as down-slant¬ ing palpebrai fissures with minimal mandibular hypoplasia, pharyngeal hypoplasia as viewed by nasopharyn¬
airspaces
or anteroposterior roentgen¬ ography may be a valuable aid in diagnosing TCS. The implications of airway hypopla¬ sia in TCS for proposed treatment requires in-depth investigation. How¬
goscopy
have had several of personal reports serious postsurgical complications and mortalities due to respiratory failure, as well as reports in the literature of neonatal death and anesthesia risk, we think that those who plan treatments of patients with TCS must be sensitive to airway problems. For example, pharyngoplasties should not be planned if they would compromise the ever,
since
we
airway to the point of inducing apneic episodes. In planning anesthesia for any surgical procedure, great care must be exercised in determining airway size and potential edema, which might compromise the pharynx. Tracheostomy must be considered as a
viable alternative to endotracheal intubation for the administration of general anesthesia. It is interesting to note that the mean pharyngeal width was greatest for the subjects with cleft palate who were used in this study for comparison with the normal subjects and patients with TCS. This finding is consistent with reports by Maue-Dickson et al34 of increased pharyngeal width in cleft palate fetal heads. It should be noted that nine of the sample population of patients with TCS had cleft palate with pharyngeal narrowing. This may suggest a different mechanism for clefting in TCS than in the isolated cleft palate. This study was supported in part by grants from the Max and Victoria Dreyfus Foundation and the Rosenhirsch Foundation.
1. Axellson
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