Variable Definition

(1)

Variable Definition

Splitting plane A plane perpendicular to sagittal plane and connected the point one centimeter higher than the middle point of bilateral uppermost orbital rim points and the internal occipital protuberance

Anterior cranial fossa depth The farrest distance from the base of anterior cranial fossa to splitting plane Middle cranial fossa depth The farrest distance from the base of middle cranial fossa to splitting plane Posterior cranial fossa depth The farrest distance from the base of posterior cranial fossa to splitting plane

Anterior cranial fossa width The distance between bilateral junctions of the posterior borders of the small wings of the sphenoid and temporal bone, measured on the splitting plane

Middle cranial fossa width The farrest distance between bilateral middle cranial fossae wall, measured on the splitting plane

Posterior cranial fossa width The distance between bilateral junctions of the arcuate eminence and petrous temporal bone, measured on the splitting plane Anterior cranial fossa length The distance from the point one centimeter higher than the middle point of bilateral uppermost orbital rim points to the center

of sella

Middle cranial fossa length The distance between the junction point of the posterior borders of the small wings of the sphenoid meets temporal bone, and ipsilateral junction point of the arcuate eminence meets petrous temporal bone, measured on the splitting plane

Posterior cranial fossa length The distance between the center of sella and the internal occipital protuberance

Entire cranial length The distance from the point one centimeter higher than the middle point of bilateral uppermost orbital rim points to the internal occipital protuberance

Anterior cranial fossa center angle The angle between 2 planes follow bilateral posterior borders of the small wings

Middle cranial fossa center angle The angle between a plane follow posterior borders of the small wing, and ipsilateral arcuate eminence and superior border of the petrous temporal bone

Posterior cranial fossa center angle The angle between 2 planes follow bilateral arcuate eminence and superior border of the petrous temporal bone Upper cranial height The farrest distance between cranium to the splitting plane

Table S1. Definition of landmarks, cephalometric distances, angles and planes

(2)

Classification Crouzon control

Age (Y) mean±SD Sex (M/F) Number Age (Y) mean±SD Sex (M/F) Number

I. Bilateral coronal synostosis 0.56±0.41 1/4 5 0.57±0.45 5/11 16

II. Sagittal synostosis 0.22±0.25 2/1 3 0.24±0.14 4/5 9

III. Pansynostosis 20.48±16.41 6/18 24 19.87±15.18 11/25 36

IV. Perpendicular combination

synostosis 0.64±0.46 3/1 4 0.67±0.34 6/6 12

Table S2 Demographic information of Crouzon syndrome and controls

(3)

Index Crouzon control T.test

Ave STD AVE STD p

Type I

Anterior cranial fossa volume 13696.94 1519.90 11518.11 2722.14 0.063 Middle cranial fossa volume 22199.35 9994.50 25406.41 3807.90 0.570 Posterior cranial fossa volume 35057.67 6621.79 45201.46 13055.91 0.055

Upper cranial volume

768712.66 288309.41 680765.25 207678.80 0.598 Overall intracranial volume 1044237.63 381934.78 845017.20 238070.25 0.321 Type II

Upper cranial volume

546309.54 254687.87 545686.31 149522.63 0.997 Overall intracranial volume 673801.75 224886.98 686781.46 165755.61 0.933 Type III

Anterior cranial fossa volume 21108.55 7647.95 16169.06 4008.78 0.007**

Middle cranial fossa volume 39351.31 11778.74 40816.16 10631.61 0.626 Posterior cranial fossa volume 67821.67 12396.61 83907.33 14500.47 <0.001**

Upper cranial volume

996111.15 133610.02 1051421.29 140330.33 0.142 Overall intracranial volume 1244734.57 161246.69 1332883.17 152609.71 0.046*

Type IV

Upper cranial volume

715377.67 196065.17 748767.96 140070.19 0.768 Overall intracranial volume 871159.77 175876.65 926601.78 169435.90 0.605

*: p<0.05

**: p<0.01

Table S3 Intracranial volume and segmented cranial fossa volume results of Crouzon syndrome and controls

(4)

Index Type I Type II

Ave STD AVE STD p Ave STD AVE STD p

Anterior cranial fossa depth 16.52 2.70 15.87 1.80 0.675 16.27 3.57 15.96 1.67 0.898 Anterior cranial fossa width 93.33 6.92 86.56 9.46 0.156 80.20 4.84 82.20 9.87 0.656 Anterior cranial fossa length 60.26 10.27 56.06 7.45 0.487 51.42 6.85 50.76 5.02 0.889 Anterior cranial fossa center angle 110.65 3.61 110.77 5.56 0.958 111.76 8.15 110.65 6.49 0.844 Middle cranial fossa depth 26.58 6.53 25.71 2.00 0.809 24.50 8.28 25.71 2.08 0.824 Middle cranial fossa width 96.99 6.05 109.83 11.49 0.013* 96.48 2.52 103.87 10.40 0.078 Middle cranial fossa length 65.39 5.79 66.65 6.34 0.718 62.83 6.80 63.11 5.40 0.952 Middle cranial fossa center angle 72.54 2.74 70.89 3.36 0.347 73.11 5.69 71.50 4.01 0.685 Posterior cranial fossa depth 28.06 3.00 28.07 3.11 0.995 26.00 7.09 26.82 3.31 0.864 Posterior cranial fossa width 86.21 4.60 101.24 11.85 0.001** 88.62 7.25 93.69 8.91 0.377 Posterior cranial fossa length 70.90 6.69 77.47 9.41 0.156 72.90 10.99 70.85 6.00 0.783 Posterior cranial fossa center angle 104.21 8.41 107.46 3.97 0.502 102.03 5.42 106.35 4.26 0.301 Circumference 441.82 50.49 430.18 46.21 0.662 397.50 50.70 399.55 35.21 0.953 Upper cranial height 83.16 12.21 77.23 8.01 0.412 73.40 11.68 72.71 6.83 0.930 Overall cranial length 131.37 16.83 133.66 16.50 0.818 124.40 17.36 121.66 10.35 0.816

Index Type III Type IV

Ave STD AVE STD p Ave STD AVE STD p

Anterior cranial fossa depth 21.17 5.00 17.75 2.29 0.004** 17.68 4.90 16.35 1.52 0.629 Anterior cranial fossa width 104.83 8.69 101.76 5.62 0.134 85.57 6.01 90.84 6.27 0.189 Anterior cranial fossa length 65.84 4.34 72.47 4.35 <0.001** 58.45 2.17 59.15 5.43 0.718 Anterior cranial fossa center angle 117.65 7.14 115.84 8.18 0.369 109.42 13.35 113.06 4.80 0.628 Middle cranial fossa depth 28.05 3.75 29.63 3.88 0.120 26.15 7.84 25.34 1.99 0.851 Middle cranial fossa width 131.43 8.93 133.24 7.33 0.414 104.33 6.86 114.64 9.04 0.049*

Middle cranial fossa length 77.61 7.07 84.54 7.54 <0.001** 67.45 1.62 68.91 4.27 0.339 Middle cranial fossa center angle 67.10 4.04 70.96 4.24 <0.001** 72.59 1.94 69.46 3.00 0.042*

Posterior cranial fossa depth 32.37 3.84 34.72 3.47 0.020* 26.20 2.91 28.45 3.14 0.242 Posterior cranial fossa width 126.00 13.88 126.01 6.72 0.995 96.31 5.38 106.27 9.67 0.028*

Posterior cranial fossa length 93.91 11.75 101.00 7.72 0.013* 77.41 10.22 79.60 7.90 0.715 Posterior cranial fossa center angle 108.74 7.04 101.95 5.89 <0.001** 105.40 12.21 108.03 4.67 0.700 Circumference 522.42 41.72 555.13 32.52 0.003** 439.07 29.41 447.16 31.36 0.657 Upper cranial height 89.76 4.14 87.74 5.47 0.120 81.42 12.98 80.11 5.01 0.855

(5)

Overall cranial length 159.48 11.51 173.67 10.54 <0.001** 135.77 8.86 139.07 12.97 0.585

*: p<0.05

**: p<0.01

Table S4 Cranial linear and angular measurements of Crouzon syndrome and controls

(6)

Index/Pearson correlation Depth Width Length Angle

r p r p r p r p

Type I

Anterior cranial fossa volume -0.126 0.874 0.911 0.090 0.764 0.236 0.755 0.244 Middle cranial fossa volume 0.981 0.019* 0.923 0.078 -0.713 0.287 -0.918 0.082 Posterior cranial fossa volume 0.979 0.021* 0.990 0.009** -0.237 0.763 0.341 0.659 Type II

Anterior cranial fossa volume 0.876 0.320 -0.395 0.742 -0.479 0.682 -0.673 0.530 Middle cranial fossa volume 0.991 0.085 -0.060 0.962 -0.794 0.416 -0.092 0.941 Posterior cranial fossa volume 0.879 0.316 -0.478 0.683 -0.535 0.641 0.908 0.275 Type III

Anterior cranial fossa volume 0.915 <0.001** 0.797 <0.001** 0.283 0.181 0.052 0.810 Middle cranial fossa volume 0.888 <0.001** 0.879 <0.001** 0.558 0.005** -0.221 0.299 Posterior cranial fossa volume 0.471 0.020* 0.295 0.162 0.219 0.303 -0.084 0.709 Type IV

Anterior cranial fossa volume -0.461 0.539 0.546 0.454 -0.362 0.638 0.790 0.211 Middle cranial fossa volume 0.956 0.044* 0.791 0.209 -0.712 0.289 0.084 0.916 Posterior cranial fossa volume 0.991 0.009** 0.634 0.366 0.531 0.469 -0.180 0.820 control

Anterior cranial fossa volume 0.726 <0.001** 0.677 <0.001** 0.608 <0.001** 0.327 0.014 Middle cranial fossa volume 0.835 <0.001** 0.762 <0.001** 0.852 <0.001** 0.361 0.006**

Posterior cranial fossa volume 0.894 <0.001** 0.879 <0.001** 0.921 <0.001** -0.524 <0.001**

*: p<0.05

**: p<0.01

Variable Definition