Angular Analysis Based on Frankfort Horizontal Plane
The angle between FH and Occ had a slight increase by 2.73°(P = 0.019) on average with a significant difference at 6–18 years. The increase of the angle between Mx and FH developed between 6 months to 2 years by 7.14° (P = 0.007). The relative angle of MP to FH increased before 6 months by 5.26° (P = 0.006) with a plateau period from 2 years to 18 years by over 10° increase (P = 0.001). The angle between MRP and FH only increased 6.38° in the 2- to 6-year-old Crouzon’s patients [P = 0.03; see figure, Supplemental Digital Content 5, which displays angular analysis based on Frankfort horizontal plane show the relative angles of middle and lower face changing by age in Crouzon syndrome (16-year-old, female) compared with control (16-year-old, female), http://links.lww.com/PRSGO/A889].
Angular Analysis of Adjacent Planes
The angle between SN and MRP consists of 5 angles, the SN-FH, FH-Mx, Mx-Occ, Occ-MP, and MP-MRP angles (Fig. 2). Although the largest SN-MRP angle only slightly increased from 2 to 18 years of age, the 5 angles included in it, changed significantly throughout development. As above, the angle between SN and FH increased before 6 months of age, and the angle between FH and Mx increased from 6 to 2 years of age. The Mx-Occ remained stable or even decreased slightly with time when compared with controls. The Occ-MP angle increased 4.8° (P = 0.008) before 6 months with minor decrease between 6 months to 2 years, and then the angle increased again, by 10.21° at 2–6 years (P = 0.002), 5.86° at 6–18 years (P = 0.004), and 6.22° over 18 years (P = 0.045), respectively. The MP-MRP angle is stable except a decrease by 6.21° at 2–6 years (P = 0.002).
Cephalometric Angular Measurements
The SNA showed a persistent decrease from birth to 62 years old by 11.58°, yielding statistical significance (P < 0.001). The SNB decreased 10.87° (P = 0.002) before 6 months and at adulthood remained decreased at 5.56° (P < 0.001). The ANB decreased after 6 months by 5.97° on average (P < 0.001) with the peak change after 18 years old. The angle N-S-PP increased from 2 years old by 4.55° (P = 0.04) to 18 years old by 8.16° (P = 0.015) with an average increase of 3.64° (P = 0.011). The angle N-S-AR increased 8.36° (P < 0.001) before 6 months and got 3.01° (P = 0.002) increase in adulthood.
The facial convexity angle (N-A-Pog) is unchanged in the whole age range in Crouzon’s syndrome compared with controls. The N-S-GN angle increased before 6 months by 10.29° (P < 0.001) to 18 years old by 11.95° (P = 0.003). The S-N-Pog angle decreased early and developed before 6 months by 12.32° (P < 0.001), with the final decrease of 6.92° (P < 0.001; see figure, Supplemental Digital Content 6. Facial lateral curvature related cephalometric angles changing by age, http://links.lww.com/PRSGO/A890).
In the linear distances with sella as the anterior reference point, the distance S-A, S-Pog, and S-PNS decreased before 6 months by 6% (P = 0.039), 11% (P = 0.039), and 13% (P = 0.004), respectively. After 6 months, all the other linear measurements share the sella as the reference anchor point, also shortened (see figure, Supplemental Digital Content 7, which displays linear measurements represented with Sella or ANS as one end of the distance, http://links.lww.com/PRSGO/A891).
Specifically, with ANS as the reference point, ANS-BA shortened by approximately 20% after 6 months into adulthood (P < 0.001). The length of ANS-N approximated normal throughout growth. The length of ANS-Men only increased 14% (P = 0.037) before 6 months and 11% (P = 0.041) between 2 and 6 years old. The whole facial height N-Men is unchanged compared with controls.
It is helpful to divide growth influences and effects into 2 parts, the upper and the lower facial structure. The ratio of the upper anterior facial height to upper posterior facial height (N-ANS/S-PNS) increased by 26% (P < 0.001). The ratio of lower facial height to total facial height (ANS-Men/N-Men) remained stable. The ratio of posterior facial height to anterior facial height (S-Go/N-Men) decreased by 11% (P < 0.001). The change of the occlusal relation index, the modified 3-D Wit’s measurement (a projective linear measurement between the 3-D cephalometric hard tissue A point and B point landmarks that are projected perpendicular on the 3-D occlusal plane) is the most significant. It began before 6 months by 307% (P = 0.046), increased 366% (P = 0.012) at 6 months to 2 years, and achieved a 215% (P < 0.001) increase throughout development compared with controls.
Orbital dysmorphology, midface hypoplasia, and mandibular, relative prognathism, of Crouzon’s syndromes have been previously reported.2 , 4 , 6 , 11–13 As integral parts of a whole facial skeletal structure, changes in the above structures with growth, support the concept of a correlation between facial structure and skull base anatomy.7 , 8 , 14 The present study was designed mainly on 3-D angular analysis of dominant craniofacial planes in Crouzon’s syndrome, which is the first time this technique has been used in morphospace analysis, to our knowledge. Specifically, the midpoint of bilateral landmarks was used if a plane was produced by bilateral landmarks, to set all the planes as perpendicular to the sagittal plane and without lateral tilt. The angular and linear measurements developed from defined landmarks, to clarify the primary role that the cranial base plays on facial development, and the sequence of change in the skeleton, defined by age.
Plane angular analysis is based on SN and reflects the reference plane to document the changing position of facial structures relative to the cranial base. The markedly increased angle between SN and FH was the main recorded anatomical relationship anomaly that existed before 6 months; further changes are postulated to occur directly or indirectly thereafter related to this early developing abnormal relationship. This is consistent with Carr et al.,4 who have shown that the orbit deformity of Crouzon’s syndrome, developed in infancy. The widened and shortened anterior cranial fossa happens in the early development of the Crouzon’s syndrome infant.15 This increased SN-FH angular measurement is consistent, in time and space, with the anterior cranial fossa and its abnormal increased orbit height.11
In our previous study, related to cranial base development in Crouzon’s patients, the deformity of anterior cranial fossa was influential in the development of posterior fossa deformity. Multiple studies show the relationship of midface deformity with middle cranial fossa, and the relation between the posterior cranial fossa dimensions, and that of the mandible.8–10 Our previous study shows Crouzon’s syndrome developed widened and shortened cranial base. The shortened cranial base length mainly began at anterior skull base and transmitted to posterior, resulting in kyphotic cranial base. As the deformity is passed posteriorly in the cranial base, the facial deformities do not change appreciably. This cranial base distortion is synchronous and positional related to facial malformation development, but the degree of severity is not inconsistent between cranial base and facial structures. Specifically, the mandible did not develop the most severe malformation, although its anatomical counterpart in the cranial base, the posterior cranial base, developed the most severe malformation.
In the current study, the position of the maxillary plane, occlusal plane and mandibular plane are inferiorly and posteriorly rotated compared with anterior cranial base over time. The significantly increased angle of the MRP develops 2 years later than other planes. All the angles between above planes and Sella-Nasion plane statistically increase over time. This results in a longer face shape in Crouzon’s syndrome as reported in previous work.1 , 6 , 16
As orbital dysmorphology is one of the main characteristics of Crouzon’s syndrome,11 , 17 analysis of the relative position between lower planes and Frankfort horizontal plane may clarify the influence of the orbit development on face shape. The most significantly increased angle regionally is between FH and the maxillary plane. This is consistent with the severe midface retrusion of Crouzon’s syndrome previously reported.12 Conjointly analyzing this with the shorten anteroposterior length of midface (shown in our linear measurements), and unchanged midface volume in Crouzon’s syndrome,2 reflect this hallmark facial deformity this occurs is without midface height reduction.
The angle analysis between adjacent planes show the absolute change of each facial structure between its adjacent, superior, and inferior planes. The angles MP-MRP and SN-MRP remain stable, while the angle of Occ-MP is increased. This indicates a counterclockwise occlusal plane, which is consistent with class III malocclusion and relative mandibular prognathism characteristic of Crouzon’s syndrome.9 , 18
Facial lateral curvature related measurements indicate the whole face was inclined in a posterior direction in relation to the anterior cranial base. Decreased S-N-Pog, increased N-S-GN, and stable N-A-Pog manifest the holistic description of the posterior rotation of middle and lower face.19
In summary, the malformation development of Crouzon’s skull base and facial structures are synchronous in spatial relation, but inconsistent in the degree of severity. Before 6 months of age, the increase of angles based on SN in Crouzon’s syndrome patients is gradually noted from the top to the bottom of the facial skeleton. This strongly suggests, the earliest pathologic deformities begin at the top of the cranial skeleton at the anterior cranial base. Related to these deformities, there may be regional increased intracranial pressure, which influences structural development from anterior to the posterior cranial base. This would be augmented by brain growth anteriorly causing posterior translation of the bulk of brain tissue. The results of this study showed that the peak significant changes in cranial base to face angles were consistent with the downward movement of the maxilla. The severity of the deformation is also gradually reduced from top to bottom, shown as striking deformity in orbit and midface development, which then combines with relatively mild mandibular prognathism. The eventual maxillary and mandibular shapes are attributed to superimposition of influences of functional matrices and compensatory mechanisms and result in more evident deformity, with more visible morphologic changes of the face.19 , 20 In addition, the angle most directly influencing midface projection is the middle cranial fossa point, as the center of the skull base, potentially, the strongest influence for change with skull and face deformity.
Furthermore, dental maturation has a significant growth influence on midface development. Reitsma et al.21 , 22 reported severe early dental maturation delay in Crouzon’s syndrome, until puberty. This could be caused by the hypogenetic maxillary and mandibular bone, and the supporting structure of dental arch. The diminished growth dental arch, in turn, may cause compensatory growth of mandible, with resulting class III malocclusion. However, the mandible is not the most obvious structural abnormality in Crouzons syndrome, suggesting functional forces (eg, eating, chewing) may override compensatory grown influences intracranially. Coquerelle et al.23 also reported the reorientation of both deciduous and permanent teeth are highly correlated with the mandibular morphology. This supports Moss’s concept of functional matrices, being responsible for the primary morphogenetic and spatial influencing factors in mandibular growth.21
Implications for surgical treatment: our unpublished data9 show the posterior vault expansion and whole cranial vault cranioplasty, at an early age can stop, or at least decelerate the progressively kyphotic cranial base angulation, while the anterior expansion (Monobloc) has less benefit in limiting abnormal cranial base angulation. There is consistent and progressive anatomic distortion of the skull base, which is inconsistent in the degree of severity of Crouzon’s skull base and facial structures malformation, with differing types of skull surgeries. This also suggests the importance of the surgeries time sequence, that is, early posterior vault expansion reduces more overall skull deformity than later surgery. The different degree of correction with age, at surgery in both cranial base, and cranial vault surgical intervention (and possibly facial surgeries) provided to Crouzon’s patients, could achieve a more normal growth pattern in the mature craniofacial appearance. A detailed intervention timing and sequence surgery plan for Crouzon’s syndrome patients is in process. Facial surgeries may need to occur later in life than cranioplasty due to concerns related to hindering tooth and midface development. The vector correction is needed to be taken into consideration for the facial surgeries. To recover the counterclockwise rotated maxillary plane, may be a desired goal to rebuild the facial structures for Crouzon’s syndrome patients. Therefore, accompanying the monobloc or Lefort osteotomy and advancement, a clockwise rotation controlled by distraction, may be influential. In addition, to fully utilize the functional accommodation, concept orthodontic treatment may be additive/augmentative to correct deformity in childhood or early adolescence.25–29
Crouzon’s skull base distortion and facial structure malformation development are synchronous in spatial relation, but inconsistent in the degree of severity in influencing individual bone/region structures. The time sequence for the development of facial deformity in Crouzon’s syndrome is from the top to down (ie, cranial base to midface). The severity of deformity is also patterned in the same direction. The earliest facial structural change in the region of the orbit, yet the most obvious deformity is the midface, with anteroposterior shortening and mediolateral widening of the maxilla. Although the posterior cranial fossa growth resulted in local deformities (which are severe in Crouzon’s syndrome), its facial position counterpart, the mandible, did not produce the same obvious changes. The surgeries time sequence and the different degree of correction with age, of both cranial base or cranial vault surgical intervention and facial surgeries, are needed to be explored further. Functional factors of eating and breathing may likely override structural restrictions of bone growth in the cranial base.
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Supplemental Digital Content
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