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Journal of the Anatomical Society of India

The Mandible In A Treacher Collins – Franceschetti Syndrome Family: A Radiocephalometric Study

Author(s): Mahdi Hasan, Gyan P. Singh, Vijay P. Sharma

Vol. 55, No. 2 (2006-07 - 2006-12)

Mahdi Hasan, Gyan P. Singh, Vijay P. Sharma
King George’s Medical University, Lucknow

Abstract:

Persons of two generations of a family with Treacher Collins-Franceschetti syndrome were examined for signs traditionally associated with this disorder. The father (43 years) and a son (14 years) exhibited 8 out of 9 features of this syndrome whereas the mother and two siblings revealed no visible anomalies. A cephalometric technique of evaluation by means of medial axis analysis and inflectional tangents was designed to capture the mandibular deformity. The mandibular cephalometric findings of the trait bearers were compared with non-trait bearing members of the family and normal data from the Department of Orthodontics, U.P. K.G. University of Dental Sciences, Lucknow. It has been demonstrated that the peculiarly concave curvature of the lower border of the mandible is a syndrome-specific characteristic. The curve of the lower border of the mandible may be described geometrically by the angular relationship between the line tangents drawn at points of inflection along its surface. The medial axis is a line that passes through the “middle” of a non-symmetric form. It is constructed as a set of line segments connecting the centres of circles of maximum size that fit within the form. Superimposition of the Treacher Collins-Franceschetti syndrome and normal mandible tracings showed downward and backward deformity of the symphyseal region. The use of conventional landmarks (Go-Me) leads one to interpret it as extreme concavity rather than a downward and backward warping of the anterior segment of the mandibular body found in the present study.

Key Words: Mandibular Morphology, TCOF, Inflectional tangents, Medial axis, Superimposition.

Introduction:

The original description of two important characteristics of this syndrome was provided in 1900 by Treacher Collins, a London ophthalmologist, on the basis of a review of two patients (Grayson et al., 1986). Both subjects presented with notching of the lower lids combined with an underdevelopment of the malar bones. However, it was Franceschetti and Klein who further defined the syndrome and proposed, a detailed classification system for the disorder and coined the term “mandibulo-facial dysostosis in 1949. Curiously, the syndrome, as it is at present understood, was never fully described by Treacher Collins, yet the syndrome is frequently credited to his name. We have followed the recent trend set by geneticist Dixon (1996) to add the name of Franceschetti to this syndrome which also falls in line with the nomenclature of the gene for this syndrome TCOF1 (Jabs et al., 1991; Edery et al., 1994; Splendore et al., 2000). The complete manifestation of the syndrome involves structures derived from the first and second pharyngeal arches and consists of all or most of the following features:

  1. downward and outward slant (antimongoloid) of the palpebral fissures
  2. notching or colobomas of the lateral part of the lower eyelids
  3. hypoplasia of the facial bones, especially the zygomatic bones, maxilla and mandible
  4. malformations of the external ear and occasionally of the middle and internal ears
  5. macrostomia
  6. high arched palate
  7. blind fistulae between the angle of the mouth and the ear
  8. atypical hair growth in the form of a tongue-shaped process of the hairline extending towardsmouth
  9. and occasionally, facial clefts

Treacher Collins-Franceschetti (TCOF) syndrome is an autosomal dominant deformation of craniofacial development (Dixon, 1996). The gene for the syndrome has been mapped to 5q32-33.1 (Dixon et al., 1991; Jabs et al., 1991; Edery et al., 1994; Splendore et al., 2000). Non-penetrance is rare (Marres et al., 1995) and roughly 60% represent new mutations (Jones et al., 1976). The frequency is approximately 1 per 50,000 live births (Gorlin et al., 2001).

Analysis of the skeletal deformity that accompany TCOF syndrome has been reported on the dry skull (Dahl and Bjork, 1981) and the lateral cephalogram (Garner et al., 1967; Roberts et al., Behrents et al., 1977; Grayson et al., 1986). The scope of the present study is limited to the analysis of the characteristic deformities of the mandible. Studies cited above indicate that the inferior border of the mandible exhibits a consistent form. It has been suggested that the peculiarly broad concave downward curvature of the inferior border is a syndrome-specific characteristic, distinguishing it from the other syndromes that involve the mandible. Roberts et al. (1975) attempted mathematically to characterize the concavity by drawing a line tangent near the menton and gonion. They measured height of nine perpendicular lines constructed along this line and expressed as a percentage of the length of the mandibular body. Becker et al. (1976) reported that the ascending ramus is at a more obtuse angle to the body of mandible in subjects with TCOF syndrome. Interestingly, Behrents (1982) concluded that this basic mandibular form is established ‘in utero’ and is maintained throughout the period of postnatal growth and development.

The main objective of this article is to present an analysis of the mandibular morphology in a family where the father and a son (Fig. 1) suffered from Treacher Collins-Franceschetti syndrome, using the techniques of medial axis and inflectional tangents described by Grayson et al (1986).

Fig. 1: Showing ‘father’ and ‘son’ suffering from Treacher Collins-Franceschetti syndrome.

Materials And Methods: Control and Study Groups

Persons of two generations of a family with TCOF syndrome were examined for signs traditionally associated with this syndrome. The father (43 years) and a son (14 years of age) exhibited 8 out of 9 signs of TCOF (except the facial cleft) detailed above, whereas the mother, and two siblings (1 male, 18 y., 1 female 10 y.) revealed no visible anomalies. The father and son formed the study group, whereas the cephalometric measurements of the non-trait bearing family members and the normal cephalometric data available in the records of the Department of Orthodontics, U.P. K.G. University of Dental Sciences, Lucknow, served the control group. Samples were identified by code numbers for initial blind analysis and latter identified as affected and non-affected.

Methods:

A cephalometric technique of evaluation by means of the medial axis analysis (Bookstein, 1979) and inflectional tangents were designed to capture the mandibular deformity characteristic of TCOF syndrome. Frontal and lateral cephalograms were taken on the same cephalostat with a standardized radiographic technique with teeth in habitual occlusion. Each was traced, digitized, and measures of the craniofacial complex were calculated by a computer.

Inflectional Tangent:

The curve of the lower border of the mandible may be described geometrically by the angular relationship between line segments drawn at points of inflection along its surface. The technique is predicated on the fact that a simple, S-shaped curve has only one point of inflection (Fig. 2A). Only at this point will the arc curve away on opposite sides of a straight line that is tangent to the curve. This particular line, defined as the ‘inflectional tangent’, is illustrated for the curve in (Fig. 2B). The curved lower border of the mandible, like any concavity in a curve, must have two or more of these inflectional tangents (Fig. 3A and B). The angular relationship between the anterior and posterior inflectional tangents were measured and compared to that of the normal sample. The angles A (Fig. 4), B

Fig. 2 a: A single S-shaped curve has one point of inflection, b. A straight line tangent to the curve at the point of inflection showing the arc curving away on opposite sides of the line (arrows).

Fig. 3 A: The posterior inflectional tangent on the inferior border of the mandible. B. The anterior inflectional tangent on the inferior border of the mandible.

(Fig. 5) and C (Fig. 6) formed by the straight line segment with the anterior and posterior inflectional tangents were measured and compared with data derived the normal sample. Notice that these angles are, like all other cephalometric angles, measures of shape alone.

Fig. 4a: The ramus/posterior tangent angle in control group.

Fig. 4b: The ramus/Posterior tangent angle in study group

The Medial Axis Analysis

The medial axis, the other analytic technique employed, is a line that passes through the “middle” of a non-symmetric form. It may be constructed as a set of line segments connecting the centres of circles of maximum size that fit within the form (Fig. 7A). These line segments branch at a point where the form displays a bifurcation (Fig. 7B). The mandible may also be geometrically described by its medial axis. For the mandibular outlines from the “study” as well as the “control” groups, medial axes were computed.

Reliability of Method

To assess the magnitude of measurement error involved in this study, the lateral cephalograms were remeasured by VPS. The overall difference between the first and second determination was not statistically significant for any of the values. To minimize bias, all tracings and digitalizations were performed by GPS, who was unaware of patients’ clinical findings and whether they were trait bearers.

Results:

The ramus/posterior tangent angle (A) in the control group ranged from 121° to 137° whereas the study group ranged from 102° to 123° (Table 1). In case of father it was significantly reduced but the diminution was insignificant in the son. However, the notch angle (B) showed distinctly different distribution in comparing the study and control population (Table 1). The TCOF syndrome cases displayed angles ranging from 78° to 122° the controls ranged from 168° to 178°. The maximum difference was, however, detected in the value of the ramus/anterior tangle angle©. The value in the study group ranged from –3° to –25°, whereas the control group was comparatively much higher, in the range of 40° to 46°. The medial axis computed for the normal mandible is depicted in Fig. 8. Compared to this depiction, the medial axis of TCOF syndrome cases exhibits remarkable difference (Fig. 9A). The medial axis branches anteriorly where the form bifurcates.

Furthermore, the superimposition of the outline of the TCOF syndrome and normal mandible tracings (Fig. 9B) showed a remarkable downward and backward deformity of the symphyseal region of the father and son (TCOF syndrome cases) which was not discernible in the lateral view of the affected mandible (Fig. 10).

Fig. 5: The angular relationship between the anterior and posterior inflectional tangents (notch angle or angle B) for the normal sample (A), for the study population (B).

Fig. 6: The ramus/anterior tangent angle (C) is the angle between anterior inflectional tangent and an inferior extension of the ramus portion of the medial axis. Normal sample A (left) study sample B (right).

Fig. 7 A: The medial axis is seen as the line that connects centres of circles that fit within the walls of a nonsymmetric form (after Bookstein, 1979). B. The medial axis branches where the form bifurcates.

Fig. 8: Medial axis computed for the outline of the normal mandible.

Fig. 9 A: Medial axis of the TCOF syndrome mandible.
B. Superimposition of the TCOF syndrome tracing (blue) and normal mandibular tracing (green), orienting on the ramus medial axis and registering on the lower border of the mandible. Note the backwards and downwards warping of the symphyseal region.

Table 1

Analysis of angular relationship Affected Mandibles Normal Siblings Norms of
Deptt. of
Orthodontics,
UP KGDU
Father (43 Y) Son (14 Y) Male (18 Y) Female (10 Y)
Ramus/ posterior tangent
angle (A)
102° 123° 121° 137° 128°
Angular relationship
anterior and posterior
inflectional tangents notch
angle (B)
78° 122° 168° 178° 170°
Ramus/ anterior
inflectional tangent angle
(C)
–25° –3° 45° 40° 46°

Table 2

Analysis of angular relationship Data of Mandibulofacial dysostosis (Grayson et al., 1986) Our data of TCOF syndrome Father (43 y)
Ramus/posterior tangent angle (A) 95° to 130° 102°
Angular relationship anterior and posterior inflectional tangents “notch angle” (B) 115° to 150° 78°
Ramus/anterior inflectional tangent angle© –20° –25°

Discussion:

In the present study, inflectional tangents and medial axis analytical techniques, as recommended by Grayson et al. (1986) were employed to study the curve of the inferior border of the mandible. It yielded a description of form that conflicts with the traditional perception of the deformity, as reported earlier by Roberts et al. (1975). Thus, it is apparent that the extent of gross anatomic deformity can vary significantly according to the method used to describe it.

The use of conventional (Go-Me) landmarks to measure the mandibular deformity leads one to interpret it as extreme concavity rather than a downward and backward warping of the anterior segment of the mandibular body. The antegoneal notch, previously seen as a concavity on the inferior border of the mandible, is presented here as a function of downward deformation in the region of the symphysis menti. Angle C, being closer to the symphyseal region, shows obvious severity of the defect and it is negative in both the cases. Interestingly, the father shows the more severe form of deformity. No comparison of the present data with any previous study using inflectional tangents and medial axis analysis could be undertaken as TOCF syndrome cases are for the first time being subjected to these analyses in the present study. However, Table II depicts a comparison between TCOF syndrome cases and mandibulo-facial dysostosis data communicated by Grayson et al. (1986).

It should be emphasized that the methods employed in this study do not employ the traditional cephalometric landmarks. Analysis by conventional landmarks leads the investigator to draw conclusions that are biased by the selected landmarks. Measurement of the curve from gonion to menton (Jacobson, 1995) force one to measure the mandibular border as an extreme concavity missing important features of the deformity demonstrated in the present study. The cephalometric study by means of linear distance and angles among standard sets of landmarks has not changed significantly since its introduction in the early 20th century (Grayson et al., 1986). Newer methods, as describe din this article, are necessary for the state-of-the-art description of craniofacial form. Other methods for description of space curves and intersecting planes, such as three-dimensional modeling of craniofacial CT scans, will be required to capture the critical information available in these sophisticated graphic displays.

To our knowledge, on the strength of a survey of all available internet sites (google.com, yahoo.com, rediffmail.com, pubmed.com), this is the first report of 2 cases of Treacher Collins-Franceschetti syndrome from India, although around 450 cases from other countries have so far been published (Gorlin et al., 2001).

Acknowledgements:

Financial assistance from the Indian National Science Academy, New Delhi to MH is gratefully acknowledged. Thanks are also due to Dr Ashok Sahai, HOD, Anatomy, K.G. Medical University, Lucknow for providing research facilities and Prof. K.K. Mehrotra, Principal, Career Institute of Dental Sciences, Lucknow for some useful discussions

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