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Factor analysis of craniofacial morphology in cleft lip and palate in man
Arch5 or~i B,ol. Vol 21. pp 465 to 472. Pergamon
FACTOR
Press 1976. Printed m Great
Britam
ANALYSIS OF CRANIOFACIAL MORPHOLOGY CLEFT LIP AND PALATE TN MAN
IN
S. L. HOROWITZ School of Dental and Oral Surgery.
Columbia
University,
New York,
10032, U.S.A
BRIGITTE GRAF-PINTHUS and M. BETTEX Children’s Hospital. University of Bern. Switzerland HELI VINKKA Institute of Dentistry, University of Turku, Finland and L. J. GERSTMAN City University of New York, New York. U.S.A. Summary-The lateral cephalometric X-radiographs of 39 children with repaired cleft lip and palate were compared with those of an equal number of non-cleft children matched for age (f0.75 yr) and sex. Of 28 spatial, angular and linear measurements used to evaluate skeletal morphology, 15 showed significant differences. Using factor analysis, covariation between variables was reduced to a set of six factors: I, nasopharyngeal-maxillary complex; II, cranial base; III, mandibular; IV, lower face; V, ramus; VI, palate, The six-factor solution accounts for 92 per cent of the variance, with Factors I and IV providing the best discrimination between cleft and non-cleft individuals.
INTRODUCTION Complete unilateral cleft lip and palate (CLP) is diagnosed readily by observation and is most often classified according to a system based on the position and extent of the visible cleft. While the cleft is the principal focus of attention from birth. an increasing body of cephalometric evidence indicates that deeper skeletal structures of the cranium and face show morphological abnormalities. Careful analysis of specific patterns of skeletal malformation may help establish a logical basis for further research into the embryogenetic mechanisms responsible for the CLP syndrome. The aim of our investigation was to extend this knowledge by analyzing patterns of co-variation among the variables measured in order to determine combinations of craniofacial skeletal features that best describe the CLP individual.
MATERIALS AND METHODS The lateral cephalometric X-radiographs of 39 caucasoid children born with complete unilateral clefts of the lip and palate were available. The group was almost evenly divided with respect to sex, having 19 males between the ages of 4 yr, three months and 13 yr six months (mean age 8.4 yr). and 20 females between the ages of 3 yr, one month and 12 yr, 0 months (mean age 8.04 yr). Only subjects were included on whom data regarding the original defect and previous therapy were available. Selection of the sample population was based on the following criteria: (a) all subjects had repaired complete unilateral 465
cleft lip and palate; (b) they were of Swiss background and resided in the Cantons of Bern, Aargau. Neuchatel and Friebourg, Switzerland; (c) all of the children had been followed from birth by the cleft palate team of the Children’s Hospital of the university of Bern and had therefore received very similar treatment. Surgical repair of the lip, following the technique of Le Mesurier (1962). was done at about 6 months of age. The palate was closed between IX months-2 yr of age, using a modification of the Veau (1931) procedure, as follows: (a) incision of the mucosa on both sides of the cleft and mobilization of the velar musculature; (b) relief incision of the mucosa on both sides of the velum and mobilization of the lateral walls of the pharynx; (c) suturing of the nasal mucosa; (d) suturing of the velar musculature. in both cases using chromic catgut. The fibro-mucosa was dissected free from bone and incised laterally 2~ 3 cm from the alveolar ridge. In order to lessen tension at the suture line, the major palatine arteries were pulled l-2 mm out of the foramina. The uvula, mucosa of the velum and fibro-mucosa of the hard palate then were sutured with nylon at the midline. All surgical procedures were done by one surgeon (M.B.) Early orthopaedic and subsequent orthodontic treatment was performed by one orthodontist (B.G.-P.) and included the fitting of a split maxillary prosthesis within the first two postnatal weeks in all but a few cases (Graf-Pinthus and Bettex, 1974). These plates extended to the posterior border of the hard palate and obturated the anterior palatal cleft. In each case, several plates were required in order to accommodate for the rapid growth changes that occurred while the maxilIar> segments were being re-aligned.
S. L. Horowitz
466
ct ul
RAM
Y
5
44
\ Fig. 1. Points and planes used. Points: sella (s): the midpoint of the outline of the hypophyseal fossa. s-e: a point midway between the outlines of the greater wings of the sphenoid bone on the spheno-ethmoidal plane. nasion (na): the most anterior point on the outline of the frontonasal suture. gnathion (gn): the most inferior-anterior point on the outline of the mental symphysis. gonion (go): a point on the outline of the angle of the mandible located by bisecting the angle formed by a line tangent to the posterior border of the ramus and another line tangent to the lower border of the body of the mandible. basion (ba): the most anterior and mferior point on the outline of the forament magnum. Planes: cranial base plane (CRB): formed by connecting points s and s-e. (Wei. 1968) palate plane (PAL): a tangent to the outline of the floor of the nose (i.e. the superior surface of the image of the palate) in the area of the maxillary first molar and premolar teeth; mandibular plane (MAN): formed by connecting points q,~ and qo: clivus plane (CLI): formed by connecting points s and ba; ramus plane (RAM): a tangent to the lower portion of the posterior outline of the mandibular ramus (Koski. 1973); anterior face plane (AF): formed by connecting points II and yn; posterior face plane (PF): formed by connecting points sand go; v: the point of intersection of planes CRB and AF: w: the point of intersection of planes AF and PAL; x: the point of intersection of planes PAL and PF; v: the point of intersection of the pharyngeal outline of the clivus and a line tangent to the posterior outline of the pterygo-maxillary fissure; (ventral surface of the pterygoid process) L: the point of intersection of a line tangent to the posterior outline of the pterygo-maxillary fissure and the PAL plane. Linear Dimensions: upper anterior face height (UAFH): the distance between point na and the intersection of the AF plane and PAL plane (point w); lower anterior face height (LAFH): the distance between the intersection of the AF and PAL planes (point w) and point gn; upper posterior face height (UPFH): the distance between point ,Y and the intersection of the PF plane and PAL plane (point x); lower posterior face height (LPFH): the distance between the intersection of the PF and PAL planes (point x) and point go.
Obturation was continued until the time of palate closure. A control sample comprised 39 non-cleft children of similar Swiss origin and places of residence
Fig. 2. Areds measured by polar planimeter. (a) NMCnaso-maxillary complex; (b) SUBN-subnasal area. Areas:+measured by polar planimeter (Tirk. 194X) (Figs. 2 and 3) nasomaxillary complex (NMC): an area bounded by lines connecting the points s~IIu-~.-~~-.~-\~I~L~. lower face (SUBN) (subnasal): includes mandible and dental area bounded by lines connecting the points l”‘-(Irluthio,l-gorlio,lx-w. nasopharynx (PHAR); an area bounded by lines connecting the points z-Ja_then following the pharqngeal outline of the clivus to point basion-- z.
matched subjects
for sex and age (& 0.75 yr) with the CLP and having either Class I or II dental occlu-
sion. Tracings of the head-films of each child were made on acetate paper, and radiographic points. planes, linear dimensions and areas defined; Figs. I-3. Angular measurements were made to the nearest 0.5 degrees, and linear measurements to the closest 0.5 mm. Planimeter measurements of areas were recorded to the closest 0.1 cm’. Reliability checks made using replicate tracings of the head-films of 10 subjects selected at random showed that the limits of measurement variabilitys s(i),
d
2n
(Solow, 1966) fell between 0.87~1.68 degrees for angular measures, 0.60 and 1.24 mm for linear dimensions, and 0.18 and 0.27 cm’ for planimeter readings. Twenty-one angular, linear and area measurements were obtained from each tracing. In addition, ratios were calculated to express certain dimensional relationships of the face: UAFH/LAFH, UPFH/LPFH, UAFH/UPFH, LAFH/LPFH, and NMC/SUBN. The age in months of each subject and sex were also included as variables. making a total of 2X in all. As sex differences proved to be insignificant when variables were considered singly. data for males and females in both the CLP and control groups were combined.
Factor analysis in cleft lip/palate
Fig.
3. Area
(PHAR) representing the nasopharynx, measured by polar planimeter.
RESULTS
A. Univariate
analysis
The means and standard deviations of each of the variables are presented in Table 1. The variables are Table
1. The means, standard
deviations,
listed in an order that will prove of value in following the analysis presented in this report. Table 1 shows that certain portions of the face are particularly vulnerable to growth disturbances in CLP. The upper posterior face region, for example. shows differences in angles formed by the palate plane-CRB/PAL (lo), PAL/CL1 (22), and PAL/PF (23) (Fig. I). These angles are significantly larger in CLP and reflect a rotation of the palate plane in a clockwise direction. The apparent upward tipping posteriorly could result from increased upper anterior face height, but the data show that UAFH (4) actually is shorter in CLP than in the controls. A short upper posterior face height also would produce clockwise rotation of the palate plane and it is clear (Table 1) that UPFH (5) is the critical factor. Lower posterior face development was affected as well. The mandibular angles MAN/PF (I l), RAM/ PAL (18) and RAM/MAN (19) all are significantly larger in the CLP group. The obtuse gonial angle (19) is the key variable that affects the other two angles measured. The relative contributions that upper and lower face lengths made to total face height also differ between the groups. Proportions of the anterior portion of the face differed between CLP and non-cleft children. The UAFH (4) was shorter and the LAFH (16) longer in CLP subjects, producing a significant difference in the UAFH/LAFH ratio (25). The posterior face was similarly affected, as UPFH (5) is
t and P values for CLP subjects and noncleft controls Control II = 39
CLP n - 39 Variable 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28.
Sex age in mos. NMC (cm’) UAFH (mm.) UPFH (mm.) PHAR (cm’) CRB/AF angle CRB/CLI angle CRB/PF angle CRB/PAL angle MAN/PF angle MAN/AF angle MAN/CL1 angle MAN/PAL angle SUBN (cm*) LAFH (mm.) LPFH (mm.) RAM/PAL angle RAM/MAN angle RAM/CL1 angle RAM/CRB angle PAL/CL1 angle PAL/PF angle NMC/SUBN ratio UAFH/LAFH ratio UPFH/LPFH ratio UAFH/UPFH ratio LAFH/LPFH ratio
X 21 females: 99.1 23.4 43.2 30.7 4.3 70.2 137.3 105.9 12.9 114.3 69.3 83.0 27.3 26.5 59.8 31.2 81.9” 125.4 137.5 94.9 55.6 87.0 8.8 7.3 10.1 14.4 19.5
467
s.d. 19 males 31.7 4.1 4.2 5.4 0.7 5.3 5.3 5.4 6.1 4.9 4.2 5.2 5.4 3.5 5.4 4.2 6.2 6.2 6.2 6.9 4.3 4.8 1.1 0.7 2.5 2.4 3.0
X
s.d.
t
21 females: 29.0 2.9 3.3 3.8 0.7 5.5 5.4 5.7 5.4 4.6 3.7 5.9 5.7 3.4 5.0 4.6 5.9 5.9 7.7 7.9 4.1 3.8 1.0 0.8 2.8 1.0 4.0
19 males
97.1 26.4 45.4 36.3 5.4 72.3” 136.8 106.1 10.2 111.4 70.1 80.7 27.4 26.3 57.8 28.1 86.1” 121.3 139.3 96.1 53.4 83.9 10.1 7.9 13.3 12.6 21.1
3.691 2.514 5.264 7.053 1.697 0.489 0.186 2.045 2.641 0.876 1.862 0.078 0.253 1.689 3.092 3.032 2.934 1.117 0.705 2.292 3.108 5.530 3.376 5.234 4.164 1.957
P
0.05-0.02 0.02-0.0 I
0.01-0.001 0.01-0.001 0.01-0.001
0.0550.02 0.01-0.001 io.001 0.01lo.001 < 0.001
S. L. Horowitz
468
shorter and LPFH (17) longer in the CLP children (UPFH/LPFH ratio (26)). Further expression of differences in facial dimensions is found in significantly smaller planimeter measurements of the nasomaxillary complex (3) and nasopharynx (6). In the CLP subjects. both of these areas were significantly smaller, a finding related directly to the shorter upper posterior face height (5) dimension. The ratio computed for NMCSUBN (24) differs between the groups, and this is attributable to the smaller naso-maxillary complex area of the CLP subjects. The univariate analysis shows that CLP subjects differed from non-cleft individuals in many respects. Nevertheless. several of the measurements presented in Table I provide redundant information. As all of these measures have equal weight as variables when treated independently, the desired parsimony cannot be achieved without further data analysis.
Craniofacial morphology cannot be reduced satisfactorily to a collection of discrete, univariate measurements without offending the concept that ske-
et al.
letal growth is an integrated process (Bronowski and Long, 195 1; Dullemeijr, 1972). As a working hypothesis. it is assumed that cephalometric measurements of different parts of the craniofacial skeleton are not independent. but are correlated in some undefined way best expressed as a vector of measurements (Howells, 1969). It is feasible, if no assumptions of dependence or independence of the variables measured is made, to apply factor analysis to explore the patterns of co-variation among various skeletal areas. Details of the computational techniques used in factor analysis are beyond the scope of this report (Harman, 1967), but the general goal is to reduce the total number of variables to the smallest possible number of sets, This creates a new group of completely separate measures (factors). each of which is independent of the other computed factors. Thus, the correlation between any two factors in zero. Applications of factor analysis to problems of human craniofacial morphology are in the reports of Howells (1951. 1957) Landauer (1962). Brown, Barrett and Darroch (1965) Solow (1966). Brown (1967). Kanda and Kurisu (1967) and Rigal (1973).
Table 2. Rotated
factor matrix
Factors Variable 2. Age 3. 4. 5. 6.
(NM,) 518”
(&B)
(M:N)
- 069
032
(::) 681*
(R:M)
(Pc;IL)
016
074 -090 120 -448 -279
NMC UAFH UPFH PHAR
061 -013 058 038
301 331 092 - 048
107 017 168 070
7. 8. 9. IO.
CRBiAF CRBCLI CRB,‘PF CRB!PAL
-132 -114 - 046 -01 I
034 - 103 II6 039
-080 -277 326 -018
059 -077 -076 572*
1 I. 12. 13. 14.
MANjPF MAN,‘AF MAN/CL1 MAN/PAL
-111 -- 101
-276 -001 358 097
Ill -082 095 - 604*
- 133 -135 027 OH9
004 039 024 029
15. SUBN 16. LAFH
399 18X
-037 060
17. LPFH
- 250
106
IX. 19. 20. 21.
153 - 074 092 032
029 (x)4 015 670*
06 I 609* 146 059
0.45
0.62
RAM/PAL RAM/MAN RAMCLI RAMICRB
22. PAL/CL1 23. PAL/PF Per cent of variance accounted for
039 571*
060 047
- 429
-059
066 -235 500*
-077 -241
0.26
0.77
0.88
0.92
Decimals omitted from loadings for typographical convenience. Boxed loadings exceed 0.7 criterion. * Loadings that approach the criterion, With the exception of LPFH each of these variables participate in two factor systems.
(17).
Factor
analysis
Factor analysis provides a useful tool for determining which particular skeletal components interact on a common developmental basis. Factors are drawn from the total number of variables until no further significant residual relationships are found among the independent measurements. After the most parsimonious set of factors is found, each variable is scaled in respect of its degree of participation in each factor. specified as a coefficient of loading. These loadings, like correlation coefficients, vary between Gl and are positive or negative depending on whether the variable participates directly or inversely in the factors. The squares of loadings define the percentage of variance accounted for by a variable, whence a loading of 0.7 or greater implies a strong (> 50 per cent) contribution to a factor. In this study, 22 of the variables were subjected to a principal-components factor-analysis with varimax rotation by means of the BMD 03M computer program (Dixon, 1973). The excluded variables were sex, as it had proved to be insignificant, and the five ratios in Table 1, because they were redundant upon the variables which had produced them. The analysis yielded a six-dimensional solution. In Table 2, the factors are numbered in descending rank order of the variance each accounts for and factor loadings which exceed the 0.7 criterion of strong participation are boxed. The signs of the loadings indicate the relations of the original variables to the factors, negatives specifying an inverse relationship. The factors can be described as follows: I, a nasomaxillaryypharyngeal complex factor that has high loadings for the naso-maxillary complex area (3). pharynx area (6). upper anterior face height (4) and upper posterior face height (5). There is also a relatively high participation of age (2). II, a crania1 base factor having high loadings on angles formed by the cranial base plane, CRB/AF (7) CRB/CLI (8) CRB/PF (9) and CRB/PAL (10). The angle RAM/CRB (21) does not quite reach the 0.7 criterion. III, a mandibular factor with high loadings on angles formed by the gonion-gnathion plane, MAN/PF (1 I), MAN/AF (12) MAN/CL1 (13) and MAN/PAL (14). The RAM/MAN (19) angle and LAFH (16) also participate in this factor with lower loadings. IV, a lower face factor in which the subnasal area (15) and lower anterior face height (16) have high loadings. There is also relatively high participation of age (2) and lower posterior face height (17). V, a ramus factor having high loadings on angles Table 3. Means, standard
deviations,
formed by the ramus plane, RAM/PAL (18) RAM/ MAN (19) RAM/CL1 (20) and RAM/CRB (21). VI, a palate factor that has high loadings on two angles formed by the palate plane, PAL/CL1 (22) and PAL/PF (23). The angles CRB/PAL (lo), MAN/PAL (14) and RAM/PAL (18) as well as LPFH also cohtribute without reaching the 0.7 criterion. This six-factor solution accounts for 92 per cent of the variance. The discrete nature of the six factors is seen in Table 2. No variables participate significantly in more than one factor. Furthermore. the variables participating in each of the six different factors appear to form logical developmental groupings. Factors II. III, V and VI. for example, all express topographic facial relationships. On the other hand, Factors I and IV represent size components of the face and do not overlap with factors that express relationships. A similar type of clustering was found by Schweiger (1966) who studied a mixed cleft sample using multiple correlation procedures. As the dimensions included in Factors I and IV show positive increments in size as the result of growth, it is reasonable to assume that age would participate in these factors to some degree. The analysis confirms this assumption, as relatively high loadings on age (2) are found only in I and IV, and in none of the other factors, C.
Discrirnirzation
I Nasomaxillary-pharyngeal complex II Cranial base III Mandibular IV Lower fdce V Ramus VI Palate
hetwem
su@ct
groups
Factor analysis establishes that six morphologic domains of the head and face exist in the collection of variables measured. As this biologically coherent substrate of factors was determined from the total study population (CLP plus controls, n = 78). it is possible to make practical use of the information to distinguish cleft from non-cleft individuals, To this end, the computer program employs the factor loadings in Table 2 as a set of weights, generating for each subject a set of factor scores, the values of which specify the degree of participation of each subject in each factor. Factor scores are equivalent to c-scores, as the mean and variance of a complete set of such scores are 0 and 1, respectively. When, however, factor scores are partitioned between two groups of equal size, their means symmetrically offset from zero, their standard deviations vary and the distance between them may serve as an index of group discrimination. When the factor scores for CLP and control subjects are partitioned, we obtain the results shown in Table 3 which shows that the two groups are well discriminated on Factors I and IV. partially discriminated on Factors III and VI. but undiscri-
f and P values of factor scores for CLP subjects and non-cleft controls CLP
Factor
469
in cleft lip/palate
Control
X
sd.
Z
s.d.
t
P
-0.557 0.07 1 0.212 0.337 -0.172 0.198
0.818 I.022 0.974 0.919 0.860 1.140
0.557 -0.071 -0.212 - 0.337 0.172 -0.198
0.571 0.996 0.956 0.873 1.106 0.803
5.898 0.623
1.902
3.146 1.536 1.771
S. L. Horowitz
470
-
170MO
I.0 I -
!(“=lS) I
I
I
-0,5 0 + 0.5 FACTOR I LOADINGS: NASOMAXILLARY-PHARYNGEAL
1
+ 1.0
1.0
COMPLEX
Fig. 4. Two-dimensional IV loadings. Solid line-
plot by age of Factor I vs. Factor CLP subjects; broken line-control subjects.
minated
II and
on Factors
V. Factors
I and
IV are,
course. the two domains of linear measurements, and also the only domains in which age substantially participated. The influence of age may thus be assessed by further partitioning the scores of both groups into a younger versus an older set, at the age midpoint of 97 months. Figure 4 presents the results of this analysis in a two-dimensional plot of Factor I vs Factor IV loadings. According to the conventions of analytic geometry. cleft subject loadings lie predominantly in the second quadrant. control subject loadings in the fourth quadrant. For both cleft and control groups. the larger data point represents the group average factor loadings. the smaller points the averages for younger and older subjects indicated by their mean ages in months. For both factors, older subjects have more positive loadings than younger subjects, the parallel lines demonstrating that younger cleft subjects and older cleft subjects are equally well-discriminated from their age-matched controls. If two lines are drawn from the control sample mean (large open data point) to the means for younger cleft and older cleft subjects (small solid data points), the line to the 74-month data point is approximately horizontal and the line to the 12%month data point is predominantly vertical. This difference permits the conclusion that younger cleft subjects are best discriminated from controls on the basis of Factor I (nasomaxillary -pharyngeal complex) loadings, older cleft subjects on the basis of Factor IV (lower face) loadings. of
DISCUSSION
Underdevelopment of the maxilla in repaired CLP (Graber. 1949; Levin, 1963; Hagerty and Hill, 1963; Ross, 1965) was confirmed. On the other hand, our data do not show the relative retrusion of the maxilla previously reported in repaired CLP (Subtelny, 1962; Hama. 1964), or in unoperated complete clefts (OrtizMonasterio et al.. 1959). Concurrent retrusion and
et ul
hypoplasia of the maxilla have been found by some workers (Ross, 1965; Dahl, 1970), while maxillary length and position in repaired CLP children did not differ from the controls in one study (Aduss. 1971). The maxillae are reported to be wider than normal in children with CLP (Nakamura. Savara and Thomas, 1972). It has been shown that the palate plane in CLP is located in a relatively superior position in the nasopharyngeal area (Levin, 1963; Hama, 1964; Brader. 1957: Blaine, 1969; Dahl, 1970). Our findings confirmed this and it appears to be a consequence of the short UPFH (5) dimension, which affects several posterior facial angles formed by the PAL plane, including CRB/PAL (10). Nearly all cephalometric studies of cleft individuals show an increase in the RAM/MAN (19) (i.e. gonial) angle size in CLP, but the findings regarding other mandibular characteristics are inconsistent. The length of the mandible is variously described as either short (Levin. 1963; Hama, 1964; Dahl. 1970) or unaffected (Ross and Coupe, 1965). Ramus height is reported to be shorter than normal in most investigations. and a higher position of the mandibular condyles has been described (Levin. 1963; Hama. 1964; Ross and Coupe, 1965). Increased mandibular retrognathism is a common finding (Harvold, 1961; Hama. 1964; Dahl, 1970; Aduss, 1971). Although the CRB/AF (7) angle, which is one measure of retrognathism, was not significantly smaller in the CLP subjects (Table 1). clearly the form of the mandible is different than in non-cleft individuals. The size of the gonial angle warrants attention as a key morphologic trait. When this angle is obtuse, a retrognathic appearance is produced because the chin is displaced in a downward and backward direction (Harnd. 1964; Dahl. 1970). In addition, the gonion point is often situated more superiorly than normal due to the underdevelopment of the posterior face. There is no consensus regarding cranial base features in repaired CLP. Angles of the cranial base in clefts have been described variously as smaller (Moss, 1956). no different than normal (Brader. 1957: Hama, 1964; Engman. 1965; Aduss, 1971) and larger than normal (Blaine. 1969; Dahl. 1970). Univariate comparisons in our material show that the only angle formed by the cranial base plane to differ in CLP and the controls is CRB/PAL (IO). (Table 1) Nevertheless, cranial base angles did participate significantly in factors II and V. The length of the cranial base is reported to be either decreased (Dahl, 1970) or no different than in non-cleft persons (Ross. 1965). Area measurements are basically hybrids that express the relationships of a number of linear and angular variables in a single value. In our study. two of the areas measured. NMC (3) and PHAR (6) were significantly smaller in the CLP group. Brader (1957) found a comparably smaller pharyngeal area in his mixed cleft sample. The obvious association between the smaller nasomaxillary~pharyngeal complex area and the reduced upper posterior face height dimension in CLP indicates the need for more intensive growth studies of these critical areas. Some comment regarding published cephalometric findings on CLP is necessary because of the many inconsistencies (Pinkerton. Olin and Meredith, 1966).
Factor analysis Poor sample selection may account for many of these discrepancies (Nakamura, Savara and Thomas, 1972). Some studies report data on groups of subjects who vary widely in age (Brader. 1957; Haggerty and Hill, 1963; Moss. 1956) or in groups mixed as to type of cleft (Brader, 1957; Engman et al., 1965; Schweiger, 1966). The majority of reports give no history of treatment, and lack of an adequate control population is a frequent shortcoming. What emerges clearly from our study of a relatively homogeneous population of individuals with repaired unilateral cleft lip and palate and a carefully matched control sample is the important role of posterior craniofacial development in the CLP syndrome. The factor analysis particularly provides new information concerning the interrelationships involved in the posterior growth deficiencies. which is of special interest because of the large number of CLP children who have problems with deglutition in infancy and in attaining adequate speech skills later. The nasomaxillary-pharyngeal complex factor (I), which demonstrates affinity of upper face height and the dimensions of the pharynx and nasomaxillary areas, is the most powerful single factor and accounts for 25 per cent of the variance. It is thus apparent that abnormal skeletal development at sites distant from the clinically obvious clefts of the lip and palate also contribute significantly to the pathogenesis of th: CLP syndrome. Although there is a considerable amount of knowledge regarding causal mechanisms that lead to disturbed embryogenesis of the primary and secondary palates (Poswillo, 1975), information concerning abnormal development of the nasopharynx is scanty. In non-cleft children, longitudinal studies have shown that the antero-posterior dimension of the nasopharynx is established in early childhood and changes little through adolescence, while growth in nasopharynx height increases continuously during this period (King, 1952; Castelli, Ramirez and Nasjleti, 1974). On the basis of cephalometric findings, Bergland (1963) proposed that the increase in nasopharynx height with age is attributable to a vertical growth component of the spheno-occipital synchondrosis. Increase in choanal width atso plays a part in increasing nasopharynx size, while increase in depth has the least influence. The histologic studies of Melsen (I 974) show that there is continued growth of the clivus through apposition of bone on the nasopharyngeal surfaces of sphenoid and occipital bones and at the anterior border of the foramen magnum, even after closure of the spheno-occipital synchondrosis. This would also increase nasopharynx height to a variable extent. depending on the clivus inclination. Normally. the nasopharynx area increases in size by another growth mechanism. As remodelling of the palate occurs through resorption on the nasal surface and apposition on the inferior surface. there is a generally downward and forward movement of the palate plane relative to the clivus which enlarges the nasopharyngeal space (Enlow, 1968). Limited data relating to nasopharynx development in CLP show that height increases with age, but that both vertical and depth dimensions are smaller than normal until 7 yr of age (Coccaro, Pruzansky, and Subtelny. 1967). Nasopharynx width is larger in cleft
in cleft lip/palate
471
than unaffected individuals (Subtelny. 1955) while the area of the oropharynx, measured planimetrically, is smaller. (Brader, 1957). If the causal mechanisms of deficient nasomaxillary pharyngeal growth in CLP have yet to be demonstrated conclusively, the role of some postnatal influences may be inferred. The adverse effects of a muscle ring that is incomplete because of a cleft in the soft palate have been pointed out by Subtelny (1955). Surgical repair of the cleft restores much of the physiological capacity of this muscle ring but morphological evidence showing diminished posterior craniofacial growth in CLP presented in this and earlier studies strongly suggests that the functional level attained remains below that of non-cleft individuals and that there is little catching-up of growth in this area. Surgical repair may well contribute to this growth lag. Furthermore, as the musculature of the pharynx and related structures. including the mandible, helps to determine the position of the cervical vertebrae and head (Huntington. 1968). it is likely that impaired function of this complex muscle system in CLP subjects has an adverse effect on skeletal growth in the pharyngeal area. Disturbed oro-nasal airflow is part of the CLP syndrome and may have an influence on skeletal development. The hypothesis that growth at the sphenooccipital synchondrosis and subsequent increase in the pharyngeal space are associated with respiratory function was proposed years ago by Keith and Campion (1922). In a contemporary version of this concept (Moss and Salentijn. 1969). respiratory function is considered to be a primary influence on the growth of the nasal, oral and pharyngeal functional spaces. If respiratory function and nasopharynx growth are so closely correlated it may be hypothesized that impairment of respiratory flow would result in diminished growth of this area. Narrowing of the nasal airway occurs in a significant number of individuals with CLP due to hyperplasia of the conchae, deviation of the septum, or nasal aperture stenosis (Drettner. 1961). This is presumed to be the cause of the higher nasal pathway resistance found in these patients (Warren, Duany and Fischer, 1969). The increase in adenoid tissue that is a concomitant of the CLP syndrome also causes narrowing of the nasopharyngeal airway (Brader. 1957). To the extent that inferences can be drawn from radiographic evaluation of subjects studied at various ages, it appears from our data that the nasopharyngeal-maxillary complex (Factor I), as well as the lower face area (Factor IV), is positively correlated with the age of the subjects, although in different ways (Fig. 4). In the lower face, the initial divergence between the groups is maintained throughout the growth period studied, so that CLP subjects at the upper end of the age range diverge more and more from the control subjects as they grow older. Conversely, while nasomaxillary~pharyngeal complex (Factor I) loadings are divergent in the two groups in the youngest subjects studied, they converge with age. As a result, the oldest of the CLP subjects achieve loadings that approach those of the youngest non-cleft controls. Indeed, an older cleft subject is not discriminated from a young normal on Factor I.
S. L. Horowitz
472
REFERENCES
Aduss H. 1971. Craniofacial growth in complete unilateral cleft lip and palate. Angle Orthod. 3. 202-213. Bergland 0. 1963. The bony nasopharynx. Actu odont. scmd. 21. supplement 35. 53-97. Blaine A. 1969. Differential analysis of cleft palate anomalies. J. dent. Rrs. 48. 1042248. Bradcr A. C. 1957. A cephalometric x-ray appraisal of morphological variations in cranial base and associated pharyngeal structures: implications in cleft palate therapy. Angle Orthod. 21. 179-195. Bronowski J. and Long W. M. 1951. Statistical methods rn anthropology. h’c~ttrrc 168. 794. Brown T. 1967. Skull of the Australian aboriginal. A multivariate analysis of craniofacial association. D.D.Sc. Thesis-University of Adelaide. pp. 42261. Brown T., Barrett M. J. and Darroch J. N. 1965. Cramofacial factors in two ethnic groups. Growth 29. 109 -123. Castelli W. A.. Ramirez P. C. and Nasjlcti C. E. 1973. Linear growth study of the pharyngeal cavity. J. drnt. Res. 52. I245- 124X. Coccaro P. J., Pruzansky S. and Suhtelny J. D. 1967. Nasopharyngeal growth. Clef Palarc, J. 4. 214-226. Dahl E. 1970. Craniofacial morphology in congenital clefts of the lip and palate. Actu odmt. sand. 28. supplement 57, 899105. Dixon W. 1973. BMD:Biornedicul Comptc~r Programs. University of California Press. Berkeley. Drettner B. 1960. The nasal airway and hearing in patients with cleft palate. Actu oto-iar. 52. 131-142. Dullemeijer P. 1972. Methodology in craniofacial biology Acta morph. nrerl.-stand. 10. 9923. Engmann L. T.. Spriestershach D. C. and Moll K. L. 1965. Crania1 base angle and nasopharyngeal depth. Clefi Pularc, J. 2. 32 39. Enlow D. H. 1968. The Hurnun Facr. p, 163. Harper and Row. New York. Graber T. M. 1949. Craniofacial morphology in cleft palate and cleft lip deformities. Surq. qyec. ohstet. 88. 3599367. Graf-Pinthus B. and Bettex M. 1974. Long-term ohservation following presurgical orthopedic treatment in complete clefts of the lip and palate. Cleft Palate J. 11. 253-260. Hagerty R. F. and Hill M. J. 1963. Facial growth and dentition in the unoperated cleft palate. J. drrlt. Rrs. 42. 412421. Hama K. 1964. Morphological study of the craniofacial skeleton within a profile in cleft lip and palate. J. Osuka Unit. dent. Sch. 4. 41-67. Harman H. A. 1967. hiloden? Fuctor Analysis. University of Chicago Press, Chicago. Harvold E. 1961. Cephalometric roentgenography in the study of cleft palate. In: Conyettficii Awmulirs of‘ the Fucr und Associuted Structures. (Edited by Pruzansky S.) pp 327--336. Thomas. Springfield, Ill. Howells W. W. 1951. Factors of human physique. Am. J. phys. Anthrop. 9. 159-192. Howells W. W. 1957. The cranial vault: factors of size and shape. Am. J. phys. Anthrop. 15. 1948. Howells W. W. 1969. The use of multivariate techniques in the study of skeletal populations. Ain. J. phys. Al& rap. n.s. 31. 31 I-314. Huntington D. A. 196X. Anatomical and physiological basis for speech. In: Clrfr Pulurr und Cor,~,,ru,~i~utio,~.
et al. (Edited by Spriestershach D. C. and Sherman D.) Chap. I. pp I-25. Academic Press. New York. Kanda S. and Kurisu K. 1967. Factor analytic studies on the Japanese skulls. Med. J. Osuku b’nir. 18. t-9. Keith A. and Campion G. G. 1922. A contribution to the mechanism of growth of the human face. Itrr. J. Orrhod. Oral
Swg.
Rudiog.
8. 607-633.
study of pharyngeal K ing E. W. 1952. A roentgenographic growth. Arlglt, Orthod. 22. 23-37. Koski K. 1973. Variability of the craniofacial skeleton. ilrn. J. Orthod. 64. 188 196. Landauer C. A. 1962. A factor analysis of the facial skeleton. Ha/n. Biol. 34. 2399253. Le Mesurier A. B. 1962. Hrwrlrps md Their 7ivurmwt. Williams and Wilkens. Baltimore. Levin H. S. 1963. A cephalometric analysis of cleft palate deficiencies in the middle third of the face. Any/r Orthod. 33. 186~194. Melsen B. 1974. The cranial base. ilcru odorIt. scund. 32. 877101. Moss M. L. 1956. Malformations of the skull base associated with cleft palate deformity. Plastic reconstr. Swg.. 17. 226234. Moss M. L. and Salentijn L. 1969. The primary role of functional matrices in facial growth. Am. J. Orfhod. 55. 566-577. Nakamura S.. Savara B. and Thomas D. R. 1972. Facial growth of children with cleft lip and/or palate. Cje$ Pularc J. 9. 119~131. Ortir-Monasterio F., Rebeil A. S., Valderrama M. and Cruz R. 1959. Cephalometric measurements on adult patients with nonoperated cleft palates. Plastic recottstr. Sury. 24. 53-61. Pinkerton C. J., Olin W. H. and Meredith H. V. 1966. Cephalometric studies of the mandible in individuals with clefts: Part 1: A review. Cleff Palute J. 3. 258-267. Poswillo D. 1975. Causal mechanisms of craniofacial deformity. Br. wed. Bull. 31, 101-106. Rigal R. 1973. Etude cephalometriquc de I’inclinaison du plan palatin annort de l’analvse factorielle en comn.santes . principales.I. Thesis. University of Toulouse. Ross R. B. 1965. Cranial base in children with lip and palate clefts. Clefi Palate J. 2. 157- 166. Ross R. B. and Coupe T. B. 1965. Craniofacial morphology in six pairs of monozygotic twins disconcordant for cleft lip and palate. Can. dew. Ass. J. 31. 149-157. Schweiger -J. W. 1966. Cranial base angle. amount of palatal tissue. and nasopharyngeal depth in individuals with clefts. Cl@ Palutr J.. 4. I 15-l 19. Solow B. 1966. The pattern of craniofacial associations. Actu odont. scmd. 24. suppl. 46, 36. Suhtelny J. D. 1955. Width of the nasopharynx and related anatomic structures in normal and unoperated cleft palate children. Atn. J. Orthod. 41. 889-909. Suhtelny J. D. 1962. A review of cleft palate growth studies reported in the past 10 years. Plastic wcomtr. Surg. 30. 56-67.
Tirk T. M. 1948. A study of the growth of the head by planimeter method. Angle Orthod. 18. 7694. Veau V. 1931. Dioision Pulatirw, Masson et Cie. Paris. Warren D. W., Duany L. F. and Fischer N. D. 1969. Nasal pathway resistance in normal and cleft lip and palate subjects. CI& Palate J. 6. 134-140. Wei S. 1968. The variability of roentgenographic cephalometric lines of reference. Angle Orthod. 38. 74-78.
FACTOR
Press 1976. Printed m Great
Britam
ANALYSIS OF CRANIOFACIAL MORPHOLOGY CLEFT LIP AND PALATE TN MAN
IN
S. L. HOROWITZ School of Dental and Oral Surgery.
Columbia
University,
New York,
10032, U.S.A
BRIGITTE GRAF-PINTHUS and M. BETTEX Children’s Hospital. University of Bern. Switzerland HELI VINKKA Institute of Dentistry, University of Turku, Finland and L. J. GERSTMAN City University of New York, New York. U.S.A. Summary-The lateral cephalometric X-radiographs of 39 children with repaired cleft lip and palate were compared with those of an equal number of non-cleft children matched for age (f0.75 yr) and sex. Of 28 spatial, angular and linear measurements used to evaluate skeletal morphology, 15 showed significant differences. Using factor analysis, covariation between variables was reduced to a set of six factors: I, nasopharyngeal-maxillary complex; II, cranial base; III, mandibular; IV, lower face; V, ramus; VI, palate, The six-factor solution accounts for 92 per cent of the variance, with Factors I and IV providing the best discrimination between cleft and non-cleft individuals.
INTRODUCTION Complete unilateral cleft lip and palate (CLP) is diagnosed readily by observation and is most often classified according to a system based on the position and extent of the visible cleft. While the cleft is the principal focus of attention from birth. an increasing body of cephalometric evidence indicates that deeper skeletal structures of the cranium and face show morphological abnormalities. Careful analysis of specific patterns of skeletal malformation may help establish a logical basis for further research into the embryogenetic mechanisms responsible for the CLP syndrome. The aim of our investigation was to extend this knowledge by analyzing patterns of co-variation among the variables measured in order to determine combinations of craniofacial skeletal features that best describe the CLP individual.
MATERIALS AND METHODS The lateral cephalometric X-radiographs of 39 caucasoid children born with complete unilateral clefts of the lip and palate were available. The group was almost evenly divided with respect to sex, having 19 males between the ages of 4 yr, three months and 13 yr six months (mean age 8.4 yr). and 20 females between the ages of 3 yr, one month and 12 yr, 0 months (mean age 8.04 yr). Only subjects were included on whom data regarding the original defect and previous therapy were available. Selection of the sample population was based on the following criteria: (a) all subjects had repaired complete unilateral 465
cleft lip and palate; (b) they were of Swiss background and resided in the Cantons of Bern, Aargau. Neuchatel and Friebourg, Switzerland; (c) all of the children had been followed from birth by the cleft palate team of the Children’s Hospital of the university of Bern and had therefore received very similar treatment. Surgical repair of the lip, following the technique of Le Mesurier (1962). was done at about 6 months of age. The palate was closed between IX months-2 yr of age, using a modification of the Veau (1931) procedure, as follows: (a) incision of the mucosa on both sides of the cleft and mobilization of the velar musculature; (b) relief incision of the mucosa on both sides of the velum and mobilization of the lateral walls of the pharynx; (c) suturing of the nasal mucosa; (d) suturing of the velar musculature. in both cases using chromic catgut. The fibro-mucosa was dissected free from bone and incised laterally 2~ 3 cm from the alveolar ridge. In order to lessen tension at the suture line, the major palatine arteries were pulled l-2 mm out of the foramina. The uvula, mucosa of the velum and fibro-mucosa of the hard palate then were sutured with nylon at the midline. All surgical procedures were done by one surgeon (M.B.) Early orthopaedic and subsequent orthodontic treatment was performed by one orthodontist (B.G.-P.) and included the fitting of a split maxillary prosthesis within the first two postnatal weeks in all but a few cases (Graf-Pinthus and Bettex, 1974). These plates extended to the posterior border of the hard palate and obturated the anterior palatal cleft. In each case, several plates were required in order to accommodate for the rapid growth changes that occurred while the maxilIar> segments were being re-aligned.
S. L. Horowitz
466
ct ul
RAM
Y
5
44
\ Fig. 1. Points and planes used. Points: sella (s): the midpoint of the outline of the hypophyseal fossa. s-e: a point midway between the outlines of the greater wings of the sphenoid bone on the spheno-ethmoidal plane. nasion (na): the most anterior point on the outline of the frontonasal suture. gnathion (gn): the most inferior-anterior point on the outline of the mental symphysis. gonion (go): a point on the outline of the angle of the mandible located by bisecting the angle formed by a line tangent to the posterior border of the ramus and another line tangent to the lower border of the body of the mandible. basion (ba): the most anterior and mferior point on the outline of the forament magnum. Planes: cranial base plane (CRB): formed by connecting points s and s-e. (Wei. 1968) palate plane (PAL): a tangent to the outline of the floor of the nose (i.e. the superior surface of the image of the palate) in the area of the maxillary first molar and premolar teeth; mandibular plane (MAN): formed by connecting points q,~ and qo: clivus plane (CLI): formed by connecting points s and ba; ramus plane (RAM): a tangent to the lower portion of the posterior outline of the mandibular ramus (Koski. 1973); anterior face plane (AF): formed by connecting points II and yn; posterior face plane (PF): formed by connecting points sand go; v: the point of intersection of planes CRB and AF: w: the point of intersection of planes AF and PAL; x: the point of intersection of planes PAL and PF; v: the point of intersection of the pharyngeal outline of the clivus and a line tangent to the posterior outline of the pterygo-maxillary fissure; (ventral surface of the pterygoid process) L: the point of intersection of a line tangent to the posterior outline of the pterygo-maxillary fissure and the PAL plane. Linear Dimensions: upper anterior face height (UAFH): the distance between point na and the intersection of the AF plane and PAL plane (point w); lower anterior face height (LAFH): the distance between the intersection of the AF and PAL planes (point w) and point gn; upper posterior face height (UPFH): the distance between point ,Y and the intersection of the PF plane and PAL plane (point x); lower posterior face height (LPFH): the distance between the intersection of the PF and PAL planes (point x) and point go.
Obturation was continued until the time of palate closure. A control sample comprised 39 non-cleft children of similar Swiss origin and places of residence
Fig. 2. Areds measured by polar planimeter. (a) NMCnaso-maxillary complex; (b) SUBN-subnasal area. Areas:+measured by polar planimeter (Tirk. 194X) (Figs. 2 and 3) nasomaxillary complex (NMC): an area bounded by lines connecting the points s~IIu-~.-~~-.~-\~I~L~. lower face (SUBN) (subnasal): includes mandible and dental area bounded by lines connecting the points l”‘-(Irluthio,l-gorlio,lx-w. nasopharynx (PHAR); an area bounded by lines connecting the points z-Ja_then following the pharqngeal outline of the clivus to point basion-- z.
matched subjects
for sex and age (& 0.75 yr) with the CLP and having either Class I or II dental occlu-
sion. Tracings of the head-films of each child were made on acetate paper, and radiographic points. planes, linear dimensions and areas defined; Figs. I-3. Angular measurements were made to the nearest 0.5 degrees, and linear measurements to the closest 0.5 mm. Planimeter measurements of areas were recorded to the closest 0.1 cm’. Reliability checks made using replicate tracings of the head-films of 10 subjects selected at random showed that the limits of measurement variabilitys s(i),
d
2n
(Solow, 1966) fell between 0.87~1.68 degrees for angular measures, 0.60 and 1.24 mm for linear dimensions, and 0.18 and 0.27 cm’ for planimeter readings. Twenty-one angular, linear and area measurements were obtained from each tracing. In addition, ratios were calculated to express certain dimensional relationships of the face: UAFH/LAFH, UPFH/LPFH, UAFH/UPFH, LAFH/LPFH, and NMC/SUBN. The age in months of each subject and sex were also included as variables. making a total of 2X in all. As sex differences proved to be insignificant when variables were considered singly. data for males and females in both the CLP and control groups were combined.
Factor analysis in cleft lip/palate
Fig.
3. Area
(PHAR) representing the nasopharynx, measured by polar planimeter.
RESULTS
A. Univariate
analysis
The means and standard deviations of each of the variables are presented in Table 1. The variables are Table
1. The means, standard
deviations,
listed in an order that will prove of value in following the analysis presented in this report. Table 1 shows that certain portions of the face are particularly vulnerable to growth disturbances in CLP. The upper posterior face region, for example. shows differences in angles formed by the palate plane-CRB/PAL (lo), PAL/CL1 (22), and PAL/PF (23) (Fig. I). These angles are significantly larger in CLP and reflect a rotation of the palate plane in a clockwise direction. The apparent upward tipping posteriorly could result from increased upper anterior face height, but the data show that UAFH (4) actually is shorter in CLP than in the controls. A short upper posterior face height also would produce clockwise rotation of the palate plane and it is clear (Table 1) that UPFH (5) is the critical factor. Lower posterior face development was affected as well. The mandibular angles MAN/PF (I l), RAM/ PAL (18) and RAM/MAN (19) all are significantly larger in the CLP group. The obtuse gonial angle (19) is the key variable that affects the other two angles measured. The relative contributions that upper and lower face lengths made to total face height also differ between the groups. Proportions of the anterior portion of the face differed between CLP and non-cleft children. The UAFH (4) was shorter and the LAFH (16) longer in CLP subjects, producing a significant difference in the UAFH/LAFH ratio (25). The posterior face was similarly affected, as UPFH (5) is
t and P values for CLP subjects and noncleft controls Control II = 39
CLP n - 39 Variable 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28.
Sex age in mos. NMC (cm’) UAFH (mm.) UPFH (mm.) PHAR (cm’) CRB/AF angle CRB/CLI angle CRB/PF angle CRB/PAL angle MAN/PF angle MAN/AF angle MAN/CL1 angle MAN/PAL angle SUBN (cm*) LAFH (mm.) LPFH (mm.) RAM/PAL angle RAM/MAN angle RAM/CL1 angle RAM/CRB angle PAL/CL1 angle PAL/PF angle NMC/SUBN ratio UAFH/LAFH ratio UPFH/LPFH ratio UAFH/UPFH ratio LAFH/LPFH ratio
X 21 females: 99.1 23.4 43.2 30.7 4.3 70.2 137.3 105.9 12.9 114.3 69.3 83.0 27.3 26.5 59.8 31.2 81.9” 125.4 137.5 94.9 55.6 87.0 8.8 7.3 10.1 14.4 19.5
467
s.d. 19 males 31.7 4.1 4.2 5.4 0.7 5.3 5.3 5.4 6.1 4.9 4.2 5.2 5.4 3.5 5.4 4.2 6.2 6.2 6.2 6.9 4.3 4.8 1.1 0.7 2.5 2.4 3.0
X
s.d.
t
21 females: 29.0 2.9 3.3 3.8 0.7 5.5 5.4 5.7 5.4 4.6 3.7 5.9 5.7 3.4 5.0 4.6 5.9 5.9 7.7 7.9 4.1 3.8 1.0 0.8 2.8 1.0 4.0
19 males
97.1 26.4 45.4 36.3 5.4 72.3” 136.8 106.1 10.2 111.4 70.1 80.7 27.4 26.3 57.8 28.1 86.1” 121.3 139.3 96.1 53.4 83.9 10.1 7.9 13.3 12.6 21.1
3.691 2.514 5.264 7.053 1.697 0.489 0.186 2.045 2.641 0.876 1.862 0.078 0.253 1.689 3.092 3.032 2.934 1.117 0.705 2.292 3.108 5.530 3.376 5.234 4.164 1.957
P
0.05-0.02 0.02-0.0 I
0.01-0.001 0.01-0.001 0.01-0.001
0.0550.02 0.01-0.001 io.001 0.01lo.001 < 0.001
S. L. Horowitz
468
shorter and LPFH (17) longer in the CLP children (UPFH/LPFH ratio (26)). Further expression of differences in facial dimensions is found in significantly smaller planimeter measurements of the nasomaxillary complex (3) and nasopharynx (6). In the CLP subjects. both of these areas were significantly smaller, a finding related directly to the shorter upper posterior face height (5) dimension. The ratio computed for NMCSUBN (24) differs between the groups, and this is attributable to the smaller naso-maxillary complex area of the CLP subjects. The univariate analysis shows that CLP subjects differed from non-cleft individuals in many respects. Nevertheless. several of the measurements presented in Table I provide redundant information. As all of these measures have equal weight as variables when treated independently, the desired parsimony cannot be achieved without further data analysis.
Craniofacial morphology cannot be reduced satisfactorily to a collection of discrete, univariate measurements without offending the concept that ske-
et al.
letal growth is an integrated process (Bronowski and Long, 195 1; Dullemeijr, 1972). As a working hypothesis. it is assumed that cephalometric measurements of different parts of the craniofacial skeleton are not independent. but are correlated in some undefined way best expressed as a vector of measurements (Howells, 1969). It is feasible, if no assumptions of dependence or independence of the variables measured is made, to apply factor analysis to explore the patterns of co-variation among various skeletal areas. Details of the computational techniques used in factor analysis are beyond the scope of this report (Harman, 1967), but the general goal is to reduce the total number of variables to the smallest possible number of sets, This creates a new group of completely separate measures (factors). each of which is independent of the other computed factors. Thus, the correlation between any two factors in zero. Applications of factor analysis to problems of human craniofacial morphology are in the reports of Howells (1951. 1957) Landauer (1962). Brown, Barrett and Darroch (1965) Solow (1966). Brown (1967). Kanda and Kurisu (1967) and Rigal (1973).
Table 2. Rotated
factor matrix
Factors Variable 2. Age 3. 4. 5. 6.
(NM,) 518”
(&B)
(M:N)
- 069
032
(::) 681*
(R:M)
(Pc;IL)
016
074 -090 120 -448 -279
NMC UAFH UPFH PHAR
061 -013 058 038
301 331 092 - 048
107 017 168 070
7. 8. 9. IO.
CRBiAF CRBCLI CRB,‘PF CRB!PAL
-132 -114 - 046 -01 I
034 - 103 II6 039
-080 -277 326 -018
059 -077 -076 572*
1 I. 12. 13. 14.
MANjPF MAN,‘AF MAN/CL1 MAN/PAL
-111 -- 101
-276 -001 358 097
Ill -082 095 - 604*
- 133 -135 027 OH9
004 039 024 029
15. SUBN 16. LAFH
399 18X
-037 060
17. LPFH
- 250
106
IX. 19. 20. 21.
153 - 074 092 032
029 (x)4 015 670*
06 I 609* 146 059
0.45
0.62
RAM/PAL RAM/MAN RAMCLI RAMICRB
22. PAL/CL1 23. PAL/PF Per cent of variance accounted for
039 571*
060 047
- 429
-059
066 -235 500*
-077 -241
0.26
0.77
0.88
0.92
Decimals omitted from loadings for typographical convenience. Boxed loadings exceed 0.7 criterion. * Loadings that approach the criterion, With the exception of LPFH each of these variables participate in two factor systems.
(17).
Factor
analysis
Factor analysis provides a useful tool for determining which particular skeletal components interact on a common developmental basis. Factors are drawn from the total number of variables until no further significant residual relationships are found among the independent measurements. After the most parsimonious set of factors is found, each variable is scaled in respect of its degree of participation in each factor. specified as a coefficient of loading. These loadings, like correlation coefficients, vary between Gl and are positive or negative depending on whether the variable participates directly or inversely in the factors. The squares of loadings define the percentage of variance accounted for by a variable, whence a loading of 0.7 or greater implies a strong (> 50 per cent) contribution to a factor. In this study, 22 of the variables were subjected to a principal-components factor-analysis with varimax rotation by means of the BMD 03M computer program (Dixon, 1973). The excluded variables were sex, as it had proved to be insignificant, and the five ratios in Table 1, because they were redundant upon the variables which had produced them. The analysis yielded a six-dimensional solution. In Table 2, the factors are numbered in descending rank order of the variance each accounts for and factor loadings which exceed the 0.7 criterion of strong participation are boxed. The signs of the loadings indicate the relations of the original variables to the factors, negatives specifying an inverse relationship. The factors can be described as follows: I, a nasomaxillaryypharyngeal complex factor that has high loadings for the naso-maxillary complex area (3). pharynx area (6). upper anterior face height (4) and upper posterior face height (5). There is also a relatively high participation of age (2). II, a crania1 base factor having high loadings on angles formed by the cranial base plane, CRB/AF (7) CRB/CLI (8) CRB/PF (9) and CRB/PAL (10). The angle RAM/CRB (21) does not quite reach the 0.7 criterion. III, a mandibular factor with high loadings on angles formed by the gonion-gnathion plane, MAN/PF (1 I), MAN/AF (12) MAN/CL1 (13) and MAN/PAL (14). The RAM/MAN (19) angle and LAFH (16) also participate in this factor with lower loadings. IV, a lower face factor in which the subnasal area (15) and lower anterior face height (16) have high loadings. There is also relatively high participation of age (2) and lower posterior face height (17). V, a ramus factor having high loadings on angles Table 3. Means, standard
deviations,
formed by the ramus plane, RAM/PAL (18) RAM/ MAN (19) RAM/CL1 (20) and RAM/CRB (21). VI, a palate factor that has high loadings on two angles formed by the palate plane, PAL/CL1 (22) and PAL/PF (23). The angles CRB/PAL (lo), MAN/PAL (14) and RAM/PAL (18) as well as LPFH also cohtribute without reaching the 0.7 criterion. This six-factor solution accounts for 92 per cent of the variance. The discrete nature of the six factors is seen in Table 2. No variables participate significantly in more than one factor. Furthermore. the variables participating in each of the six different factors appear to form logical developmental groupings. Factors II. III, V and VI. for example, all express topographic facial relationships. On the other hand, Factors I and IV represent size components of the face and do not overlap with factors that express relationships. A similar type of clustering was found by Schweiger (1966) who studied a mixed cleft sample using multiple correlation procedures. As the dimensions included in Factors I and IV show positive increments in size as the result of growth, it is reasonable to assume that age would participate in these factors to some degree. The analysis confirms this assumption, as relatively high loadings on age (2) are found only in I and IV, and in none of the other factors, C.
Discrirnirzation
I Nasomaxillary-pharyngeal complex II Cranial base III Mandibular IV Lower fdce V Ramus VI Palate
hetwem
su@ct
groups
Factor analysis establishes that six morphologic domains of the head and face exist in the collection of variables measured. As this biologically coherent substrate of factors was determined from the total study population (CLP plus controls, n = 78). it is possible to make practical use of the information to distinguish cleft from non-cleft individuals, To this end, the computer program employs the factor loadings in Table 2 as a set of weights, generating for each subject a set of factor scores, the values of which specify the degree of participation of each subject in each factor. Factor scores are equivalent to c-scores, as the mean and variance of a complete set of such scores are 0 and 1, respectively. When, however, factor scores are partitioned between two groups of equal size, their means symmetrically offset from zero, their standard deviations vary and the distance between them may serve as an index of group discrimination. When the factor scores for CLP and control subjects are partitioned, we obtain the results shown in Table 3 which shows that the two groups are well discriminated on Factors I and IV. partially discriminated on Factors III and VI. but undiscri-
f and P values of factor scores for CLP subjects and non-cleft controls CLP
Factor
469
in cleft lip/palate
Control
X
sd.
Z
s.d.
t
P
-0.557 0.07 1 0.212 0.337 -0.172 0.198
0.818 I.022 0.974 0.919 0.860 1.140
0.557 -0.071 -0.212 - 0.337 0.172 -0.198
0.571 0.996 0.956 0.873 1.106 0.803
5.898 0.623
1.902
3.146 1.536 1.771
S. L. Horowitz
470
-
170MO
I.0 I -
!(“=lS) I
I
I
-0,5 0 + 0.5 FACTOR I LOADINGS: NASOMAXILLARY-PHARYNGEAL
1
+ 1.0
1.0
COMPLEX
Fig. 4. Two-dimensional IV loadings. Solid line-
plot by age of Factor I vs. Factor CLP subjects; broken line-control subjects.
minated
II and
on Factors
V. Factors
I and
IV are,
course. the two domains of linear measurements, and also the only domains in which age substantially participated. The influence of age may thus be assessed by further partitioning the scores of both groups into a younger versus an older set, at the age midpoint of 97 months. Figure 4 presents the results of this analysis in a two-dimensional plot of Factor I vs Factor IV loadings. According to the conventions of analytic geometry. cleft subject loadings lie predominantly in the second quadrant. control subject loadings in the fourth quadrant. For both cleft and control groups. the larger data point represents the group average factor loadings. the smaller points the averages for younger and older subjects indicated by their mean ages in months. For both factors, older subjects have more positive loadings than younger subjects, the parallel lines demonstrating that younger cleft subjects and older cleft subjects are equally well-discriminated from their age-matched controls. If two lines are drawn from the control sample mean (large open data point) to the means for younger cleft and older cleft subjects (small solid data points), the line to the 74-month data point is approximately horizontal and the line to the 12%month data point is predominantly vertical. This difference permits the conclusion that younger cleft subjects are best discriminated from controls on the basis of Factor I (nasomaxillary -pharyngeal complex) loadings, older cleft subjects on the basis of Factor IV (lower face) loadings. of
DISCUSSION
Underdevelopment of the maxilla in repaired CLP (Graber. 1949; Levin, 1963; Hagerty and Hill, 1963; Ross, 1965) was confirmed. On the other hand, our data do not show the relative retrusion of the maxilla previously reported in repaired CLP (Subtelny, 1962; Hama. 1964), or in unoperated complete clefts (OrtizMonasterio et al.. 1959). Concurrent retrusion and
et ul
hypoplasia of the maxilla have been found by some workers (Ross, 1965; Dahl, 1970), while maxillary length and position in repaired CLP children did not differ from the controls in one study (Aduss. 1971). The maxillae are reported to be wider than normal in children with CLP (Nakamura. Savara and Thomas, 1972). It has been shown that the palate plane in CLP is located in a relatively superior position in the nasopharyngeal area (Levin, 1963; Hama, 1964; Brader. 1957: Blaine, 1969; Dahl, 1970). Our findings confirmed this and it appears to be a consequence of the short UPFH (5) dimension, which affects several posterior facial angles formed by the PAL plane, including CRB/PAL (10). Nearly all cephalometric studies of cleft individuals show an increase in the RAM/MAN (19) (i.e. gonial) angle size in CLP, but the findings regarding other mandibular characteristics are inconsistent. The length of the mandible is variously described as either short (Levin. 1963; Hama, 1964; Dahl. 1970) or unaffected (Ross and Coupe, 1965). Ramus height is reported to be shorter than normal in most investigations. and a higher position of the mandibular condyles has been described (Levin. 1963; Hama. 1964; Ross and Coupe, 1965). Increased mandibular retrognathism is a common finding (Harvold, 1961; Hama. 1964; Dahl, 1970; Aduss, 1971). Although the CRB/AF (7) angle, which is one measure of retrognathism, was not significantly smaller in the CLP subjects (Table 1). clearly the form of the mandible is different than in non-cleft individuals. The size of the gonial angle warrants attention as a key morphologic trait. When this angle is obtuse, a retrognathic appearance is produced because the chin is displaced in a downward and backward direction (Harnd. 1964; Dahl. 1970). In addition, the gonion point is often situated more superiorly than normal due to the underdevelopment of the posterior face. There is no consensus regarding cranial base features in repaired CLP. Angles of the cranial base in clefts have been described variously as smaller (Moss, 1956). no different than normal (Brader. 1957: Hama, 1964; Engman. 1965; Aduss, 1971) and larger than normal (Blaine. 1969; Dahl. 1970). Univariate comparisons in our material show that the only angle formed by the cranial base plane to differ in CLP and the controls is CRB/PAL (IO). (Table 1) Nevertheless, cranial base angles did participate significantly in factors II and V. The length of the cranial base is reported to be either decreased (Dahl, 1970) or no different than in non-cleft persons (Ross. 1965). Area measurements are basically hybrids that express the relationships of a number of linear and angular variables in a single value. In our study. two of the areas measured. NMC (3) and PHAR (6) were significantly smaller in the CLP group. Brader (1957) found a comparably smaller pharyngeal area in his mixed cleft sample. The obvious association between the smaller nasomaxillary~pharyngeal complex area and the reduced upper posterior face height dimension in CLP indicates the need for more intensive growth studies of these critical areas. Some comment regarding published cephalometric findings on CLP is necessary because of the many inconsistencies (Pinkerton. Olin and Meredith, 1966).
Factor analysis Poor sample selection may account for many of these discrepancies (Nakamura, Savara and Thomas, 1972). Some studies report data on groups of subjects who vary widely in age (Brader. 1957; Haggerty and Hill, 1963; Moss. 1956) or in groups mixed as to type of cleft (Brader, 1957; Engman et al., 1965; Schweiger, 1966). The majority of reports give no history of treatment, and lack of an adequate control population is a frequent shortcoming. What emerges clearly from our study of a relatively homogeneous population of individuals with repaired unilateral cleft lip and palate and a carefully matched control sample is the important role of posterior craniofacial development in the CLP syndrome. The factor analysis particularly provides new information concerning the interrelationships involved in the posterior growth deficiencies. which is of special interest because of the large number of CLP children who have problems with deglutition in infancy and in attaining adequate speech skills later. The nasomaxillary-pharyngeal complex factor (I), which demonstrates affinity of upper face height and the dimensions of the pharynx and nasomaxillary areas, is the most powerful single factor and accounts for 25 per cent of the variance. It is thus apparent that abnormal skeletal development at sites distant from the clinically obvious clefts of the lip and palate also contribute significantly to the pathogenesis of th: CLP syndrome. Although there is a considerable amount of knowledge regarding causal mechanisms that lead to disturbed embryogenesis of the primary and secondary palates (Poswillo, 1975), information concerning abnormal development of the nasopharynx is scanty. In non-cleft children, longitudinal studies have shown that the antero-posterior dimension of the nasopharynx is established in early childhood and changes little through adolescence, while growth in nasopharynx height increases continuously during this period (King, 1952; Castelli, Ramirez and Nasjleti, 1974). On the basis of cephalometric findings, Bergland (1963) proposed that the increase in nasopharynx height with age is attributable to a vertical growth component of the spheno-occipital synchondrosis. Increase in choanal width atso plays a part in increasing nasopharynx size, while increase in depth has the least influence. The histologic studies of Melsen (I 974) show that there is continued growth of the clivus through apposition of bone on the nasopharyngeal surfaces of sphenoid and occipital bones and at the anterior border of the foramen magnum, even after closure of the spheno-occipital synchondrosis. This would also increase nasopharynx height to a variable extent. depending on the clivus inclination. Normally. the nasopharynx area increases in size by another growth mechanism. As remodelling of the palate occurs through resorption on the nasal surface and apposition on the inferior surface. there is a generally downward and forward movement of the palate plane relative to the clivus which enlarges the nasopharyngeal space (Enlow, 1968). Limited data relating to nasopharynx development in CLP show that height increases with age, but that both vertical and depth dimensions are smaller than normal until 7 yr of age (Coccaro, Pruzansky, and Subtelny. 1967). Nasopharynx width is larger in cleft
in cleft lip/palate
471
than unaffected individuals (Subtelny. 1955) while the area of the oropharynx, measured planimetrically, is smaller. (Brader, 1957). If the causal mechanisms of deficient nasomaxillary pharyngeal growth in CLP have yet to be demonstrated conclusively, the role of some postnatal influences may be inferred. The adverse effects of a muscle ring that is incomplete because of a cleft in the soft palate have been pointed out by Subtelny (1955). Surgical repair of the cleft restores much of the physiological capacity of this muscle ring but morphological evidence showing diminished posterior craniofacial growth in CLP presented in this and earlier studies strongly suggests that the functional level attained remains below that of non-cleft individuals and that there is little catching-up of growth in this area. Surgical repair may well contribute to this growth lag. Furthermore, as the musculature of the pharynx and related structures. including the mandible, helps to determine the position of the cervical vertebrae and head (Huntington. 1968). it is likely that impaired function of this complex muscle system in CLP subjects has an adverse effect on skeletal growth in the pharyngeal area. Disturbed oro-nasal airflow is part of the CLP syndrome and may have an influence on skeletal development. The hypothesis that growth at the sphenooccipital synchondrosis and subsequent increase in the pharyngeal space are associated with respiratory function was proposed years ago by Keith and Campion (1922). In a contemporary version of this concept (Moss and Salentijn. 1969). respiratory function is considered to be a primary influence on the growth of the nasal, oral and pharyngeal functional spaces. If respiratory function and nasopharynx growth are so closely correlated it may be hypothesized that impairment of respiratory flow would result in diminished growth of this area. Narrowing of the nasal airway occurs in a significant number of individuals with CLP due to hyperplasia of the conchae, deviation of the septum, or nasal aperture stenosis (Drettner. 1961). This is presumed to be the cause of the higher nasal pathway resistance found in these patients (Warren, Duany and Fischer, 1969). The increase in adenoid tissue that is a concomitant of the CLP syndrome also causes narrowing of the nasopharyngeal airway (Brader. 1957). To the extent that inferences can be drawn from radiographic evaluation of subjects studied at various ages, it appears from our data that the nasopharyngeal-maxillary complex (Factor I), as well as the lower face area (Factor IV), is positively correlated with the age of the subjects, although in different ways (Fig. 4). In the lower face, the initial divergence between the groups is maintained throughout the growth period studied, so that CLP subjects at the upper end of the age range diverge more and more from the control subjects as they grow older. Conversely, while nasomaxillary~pharyngeal complex (Factor I) loadings are divergent in the two groups in the youngest subjects studied, they converge with age. As a result, the oldest of the CLP subjects achieve loadings that approach those of the youngest non-cleft controls. Indeed, an older cleft subject is not discriminated from a young normal on Factor I.
S. L. Horowitz
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