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Craniofacial morphology in the nevoid basal cell carcinoma syndrome
Int. I. Oral Surg. 1976: 5 : 3 0 0 - 3 1 0 (KeY words: roentgencephalometry; basal cell carcinoma; ]aw Cysts; orthodontics)
Craniofacial morphology in the nevoid basal cell carcinoma syndrome A roentgencephalometric and clinical study ERIK DAHL, SVEN KREIBORG AND BIRGIT LETH JENSEN
Departments of Orthodontics and Oral Surgery, Royal Dental College, Copenhagen, Denmark
ABSTRACT-- A roentgencephalometric analysis of eight males and four females with nevoid basal cell carcinoma syndrome (NBS) is presented. The patients were 14-54 years of age. Fourteen angular and 26 linear variables were measured and compared with control data. The main roentgencephalometric features were: proportionate increase of the size of the calvarium, protrusion of the frontal and parietal region, low position of the occipital region, increased interorbital distance, increased length of the mandible, mandibular retrognathia due to changes in shape and position of the mandible. The suggestion of a characteristic craniofacial morphology as a part of the syndrome was substantiated. Together with other skeletal aberrations the roentgencephalometric findings seemed to indicate that the syndrome is a dysostosis of generalized type.
(Received [or publication 25 March, accepted 20 May 1976)
The stigmata originally attributed to the nevoid basal cell carcinoma syndrome (NBS) were multiple basal cell nevi, cysts of the jaws and skeletal anomalies t0. Since then a large number of associated anomalies have been recorded including anomalies of ribs and vertebrae, shortened metacarpals, and intracranial calcifications. Deviations in the craniofacial structures have been described in several case reports ~,6,0,11,14,~s. The most commonly reported symptoms in the r skeleton are
prominence of the frontal and parietal bones, a well-developed supraorbital ridge~ ocular hypertelorism and mild mandibular prognatbism. GORLIN, VICKERS, KELLN & WILLIAMSON ls and GORLIN & SEDaNOt~ considered a characteristic facial appearance as part of the syndrome. The previous case reports represent mainly subjective clinical descriptions of the craniofacial aberrations in the affected individnals. The purpose of the present report was to present a systematic roentgeneepha-
BASAL CELL CARCINOMA SYNDROME Table 1. Age distribution
Controls
NBS
Males FemaIes Males Females (n=8) (n=4) (n=102) (n=51) Mean age Range
27
27
24
24
15--54
14-50
19-25
22-27
lometric description and analysis of the craniofacial morphology in a group of adults with NBS.
301
ties of the mandible due to pathologic fractures. The male control group consisted of 102 adults. Cephalometrie radiographs of these subjects were collected and analyzed by SOLOWe~ The cephalometrie films were remeasured by DAHL 7 and his measurements served as control data in the present study. The female control group consisted of 51 adults. The roentgencephalometrie data for this group were reported by INGERSLEV• SOLOWin. The age distribution of the patients and the controls is shown in Table 1. Both the patients and the controls were Danes with the same ethnic background.
Method Material .Twelve patients with NBS were examined, eight males and four females. The patients have previously been reported from a clinical, histopathological, and surgicM point of view by DONATSKY,
HJ~RTINO-I"I.ANSI~N,
PHILIPSEN
&
FEJ'gRSKOVa. In the present report a 68-year-old male was excluded from the original sample because of total loss of the teeth and deformi-
For each subject roentgencephalometric films in the lateral and posteroanterior projection and a radiograph of the right hand and forearm were obtained by a technique described by BJORKZ,4. For the lateral projection the enlargement corresponding to the midsagittal plane was 5.6 %. For the posteroanterior projection the enlargement corresponding to a plane through the ear rods of the cephalostat was 8.6 %20 No correction was made for the enlargements.
f eU
i
~bo o RL pg
,' , ""
ML
A
B
Fig. 1. Reference points and lines on the cephalometric radiographs. A, Lateral projection. B, Posteroanterior projection.
302
DAHL, K R E I B O R O A N D J E N S E N
T a b l e 2. Statistical data for NBS-males and control group (for each variable the values for the patient group are listed above the control data) Range n
:~
s~
224.6 214.0 181.9 167.0 185.5 170.0 153.6 137.0 162,6 152.5 143.5 136.0 4B.3 46.5 144.1 142.5 96.6 94.0
212.75 198,39 167.61 152.62 177.68 157.83 140.87 122.82 144.68 131.98 137.17 126.40 43.37 38.77 137.76 126.86 89.88 85.78
48.58 39.48 71.80 31.95 33.38 30.99 79.41 26.84 107.78 38.73 13.3I 25.22 7.83 7.93 21.51 25.07 24.8i 12.36
73.2 67.5 53,1 50.0 38.6 43.0 122.4 118.0 118,2 119.0
83.6 81.5 64.6 60.5 53.5 56,0 139.0 144.0 150.5 150.0
78.88 73.76 58.97 55,38 46.87 49.77 130.93 130.31 134.34 134.55
16.01 9.42 16.20 6,23 23.15 8.81 33.53 26.26 139.29 36.14
8 101 8 101
26.8 21.0 97.5 -
34.2 34.5 112.3 -
31.16 26,24 107.25 96.07
7.65 5.23 26.47 9.61
8 101 8 102
22.7 103.0 104.5
30.8 118.2 133.5
27.28 25.02 110.99 118.25
7.61 9.61 30,11 33.87
min.
max.
8 100 8 102 8 102 8 102 8 84 8 84 8 102 8 102 8 102
205.2 184.0 157.1 140.0 168.5 144.0 127.8 205.5 133.3 119.0 130.5 111.0 40.0 31.0 130.4 116.5 81.7 75.0
8 1.02 8 102 8 102 8 102 8 102
t
F
Calvarium n-op ba-br eu-eu n-br br-1 bad ba-o s-ba-o s-n-f
6'17'44
1.23
4'92*4*
2.24*
9"60*44
1.08
5.65**"
2.95**
3.40***
2.78**
5.90***
1.89
4.45***
1.01
5.96***
1.17
3.07**
2.01
4.44 **4
1.70
2.48*
2.60*
1.68
2.63*
0.33
1..28
0,05
3.85***
5.77***
1.46
5'72**4
2.75**
1.84
1.26
3.41'*
1.12
Cranial base n-s s-ni s-ba n-s-ha n-s-cd Orbits mo-mo Io-Io" Nasal bones n-na s-n-na
Levels of significance: ::'5 %, " 4 1 % , ***0,1%. Control data f r o m KISLINGaT.
BASAL CELL C A R C I N O M A S Y N D R O M E
303
Table 2. Statistical data for NBS-males and control group (for each variable the values for the patient group are listed above the control data) Range n
Y
s~
57.4 58.0 62.3 61.5 55.9 55.5 74.3 75.5 81.5 90.5 13.8 16.0 38.3 37.0 112.8 128.5
53,38 52.33 56.21 55.96 50.30 50.07 64.18 67.09 78.10 81.66 7.72 7.58 35.66 30.63 108.74 109.83
5,08 6.17 15.61 8.99 14.09 7.87 62.14 10.20 7.50 9.45 8.00 7.94 4.36 7.30 9.56 40.04
123.1 114.5 94.5 78.0 127.1 104.0 72.8 73.5 33.1 14.0 53.6 46.0 79.5 81.5 42,5 38.0
141.2 141.5 113.7 102.0 154.8 135.0 84.2 90.0 52.5 47.5 62.2 67.5 93.5 115.0 54.1 55.5
131.44 126.52 101.06 89.86 139.55 120.42 77.98 81.19 40.60 28.40 58.87 54.77 84.90 97.87 48.62 44.76
34.94 24.48 47.46 19.72 66.81 38.81 12.80 10.15 33.50 35.42 10.39 15.28 41.13 50,37 19.77 8.61
8 102
128.1 107.0
151.4 144.0
138.09 126.49
63,52 40.38
8 102 8 102 8 101 8 101
-6.3 -7.0 21.9 7.5 -2.0 -1.0 -2.0 -1.0
5.8 8.5 42.2 36.0 2.5 8.0 2.5 9.5
0.12 0.41 32.88 20,48 0.31 2.94 0.13 3.16
11.00 9.43 45.53 33.22 2.42 3.12 2.06 2.30
rain.
max.
8 102 8 102 8 102 8 102 8 102 8 102 8 102 8 102
50.5 46.5 49.8 49.0 45.3 44.0 50.0 60.5 73.2 75.5 4.8 0.0 32.4 23.5 105.0 92.5
8 102 8 102 8 102 8 102 8 102 8 102 8 102 8 102
t
F
1.16
1.21
0,22
1.74
0.22
1.79
1.06
6.09***
3.18"*
1,26
0.14
1.01
5,14"*
1.67 4.19., ,
Maxilla ss-pm n-sp s-pro em-em s-n-ss NSL/NL sp-is ILs/NL
0,87
Mandible pgn-cd ag-ag ML/RL s-n-pg NSL/ML NSL/MBL ILi/ML ii-gn Jaw relations n-gn ss-n-pg NL/ML max. overjet overbite
Levels of significance: *5 %, * ' 1 % , "**0.1%.
2.67**
1,43
4,53***
2,41"
8.17'**
1.72
2.72**
1.26
5.59***
1.06
2.88':'*
1,47
4.97***
1.23
2.41"
2.30*
4.88***
1.57
0,26
1,17
5.79***
1.37
4.08***
1,30
5.46***
1,11
DAHL, KREIBORG AND JENSEN
304
The reference points and lines are indicated in Fig. 1. F o r definitions see BJ6RK~, SOLOW ~0, and DM-IL7. Fotlrteen angular and 26 linear variables describing calvarium, cranial base, orbits, na~al bones, maxillae and mandible were measured. The estimates of the statistical parameters were calculated according to SOLOW-~~ The difference between the variances was tested by Snedecor's F-test and the difference between the means by Student's t-test. The statistical calculations were performed at NEUCC, The Northern Europe University Computing Center, Copenhagen.
Calvarium. The size of the calvarium was considerably increased both in length, height, and width (n-op, ba-br, eu-eu). The chords of the ealvarian bones were all significantly increased as was the anteroposterior diameter of the forarnen magnum. The shape in profile of the calvarium was characterized by a protrusion of the frontal bone (sn-f) and a low position of the occipital region (s-ba-o). Cranial base. The length of the anterior part of the cranial base (n-s) was significantly increased, whereas the distance from the sella-point to the internal surface of the frontal bone (s-hi) showed no significant difference between the groups. The shape of the cranial base was identical in the two groups. Orbits. Both the medial (mo-mo) and the lateral (lo-lo) interorbital distances were significantly larger in the patients than in the controls. Nasal bones. The inclination of the nasal bones in relation to the anterior cranial base (s-n-no) was smaller, whereas the length of
Results MALES The results of the roentgencephalometric analysis are presented in Table 2. "the 5 %, i %, and 0 . 1 % levels o f significance are indicated in the Table b y one, two, and three asterisks, respectively. In the following only differences significant at the 1% and 0.1% levels will be considered. Ten of the fourteen angular variables and 15 of the 26 linear variables were significantly different in the two groups.
,,, ,:1 ,
,, ;
,
,,..-, ~.-~.~"
A
,, ,.,
~,;'g"
, I
I
~
, ,) '
,,
i
B
i
i,
I
i
i
,
s :I !
I
!,14"" /_.',.
',.,E-~
C
Fig. 2. Metacarpal sign: the extended tangent to the fourth and fifth metacarpal will normally pass distal to the third metacarpal (A). If the tangent intersects the third metacarpal the sign is positive (B). Borderline case ((2).
B A S A L CELL C A R C I N O M A S Y N D R O M E
305
T a b l e 3. OccmTence of radiographic a n d clinical features Males
Females
1
2
3
4
5
6
7
8
9
10
11
12
Calcification of falx cerebri
+
+
+
+
+
+
+
+
+
+
+
+
Calcifications in the sella region
+
+
-
+
+
+
+
+
+
+
--
+
Increased vascular markings in calvarium
--
+
+
+
+
Widened lambdoidal suture
+
-
+
+
+
-
+
--
+
+
Enlarged frontal sinus
+
+
+
+
+
+
+
•
P r o m i n e n t glabella region
+
--
+
+
+
+
+
+
BiNd ribs':'
+
+
+
+
+
+
+
+
--
+
+
+
Cervical spine abnormalities
+
--
+
--
+
+
--
+
+
-
Positive metacarpal sign
Heavy eyebrows
+
+
•
+
+
+
--
* f r o m DONATSKY et aI.s
the nasal bones (n-ha) did not differ from the controls. Maxilla. T h e m a x i l l a was r e t r o g n a t h i c r e l a t i v e t o the c r a n i a l b a s e (s-n-ss) a n d t h e a n t e r i o r d e n t o a l v e o l a r h e i g h t (sp-is) was increased. Otherwise the linear and angular m e a s u r e m e n t s e x h i b i t e d n o s i g n i f i c a n t differences. Mandible. T h e t o t a l l e n g t h ( p g n - c d ) a n d t h e p o s t e r i o r w i d t h (ag-ag) of t h e m a n d i b l e w e r e i n c r e a s e d . T h e g o n i o n a n g l e (ML/RL) was e x t r e m e l y large. R e l a t i v e to t h e c r a n i a l base, t h e m a n d i b l e w a s s o m e w h a t r e t r o g n a t h i c (s-n-pg). T h e m a n d i b u l a r line ( N S L / M L ) a n d t h e m a n d i b u l a r b a s e line ( N S L /
M B L ) w e r e b a c k w a r d inclined. T h e incisors h a d a lingual i n c l i n a t i o n in r e l a t i o n t o the m a n d i b u l a r line. Jaw relationships. I n t h e sagittal d i r e c t i o n t h e m a x i l l a r y o v e r j e t was reduced, b u t t h e r e w a s n o significant d i f f e r e n c e in the j a w rel a t i o n s h i p (ss-n-pg). Only one p a t i e n t exhibited a manifest mandibular overjet and t h r e e h a d a n e d g e - t o - e d g e incisor r e l a t i o n ship. T h e vertical j a w relationship ( N L / M L ) was i n c r e a s e d a n d t h e total facial h e i g h t (n-gn) w a s l a r g e r in t h e patients. T h e overb i t e was significantly smaller. T h e m o l a r o c c l u s i o n could n o t b e registered i n the N B S g r o u p due to extensive loss of teeth.
306
DAHL, KREIBORG AND JENSEN positive metacarpal sign and one was a borderline case (Fig. 2). In one individuaI the radiograph revealed muttiple lacunae in the radius, ulna, and phalanges. OTHER RADIOGRAPHIC AND CLINICAL FINDINGS The examination of the cephalometric radiographs revealed that a number of skeletal signs not registered in the roentgencephalometric analysis oceurred frequently in the NBS patients (Table 3). Calcification of falx cerebri was found in all 12 cases and calcifications in the sel[a turcica region occurred in almost all the individuals. Increased vascular markings in the calvarium were found in one-third of the cases, and the lambdoidal suture appeared strikingly open and serrated in about half of the cases. About two thirds of the patients revealed an enlarged frontal sinus. Seven of the 8 males showed a prominent glabella region whereas none of the females exhibited this characteristic. It was noted that 10 of the 12 cases revealed heavy eyebrows, frequently meeting in the midline (Fig. 3). Eight of the examined patients had bifid ribs 7. Cervical spine anomalies were present in three cases.
Fig. 3. Facial appearance of a patient with NBS.
FEMALES Due to the small n u m b e r of patients in the female group, the roentgencephalometric data are not tabulated for this group. Compared with the control group, t h e NBS remates revealed changes in the craniofacial m o r p h o l o g y similar to the deviations found in the male sample. RADIOGRAPHIC EXAMINATION OF THE RIGHT HAND One of the 12 examined patients showed a
Discussion F r o m the roentgencephalometric analysis it would appear that the craniofacial morphology in the NBS group differed from that of the control group. The findings support the opinion of GoRLnn et al.~,1a that a characteristic facial appearance is part of the syndrome (Figs. 3, 4, 5). T h e major deviations were found in the size and shape of the calvarium and of the mandible. The length, height, and width of the calvarium were proportionally increased in the NBS group. This m a y be explained only to a certain extent by the fact that the average
BASAL CELL CARCINOMA SYNDROME body height of the patients was 182 cm compared with an average height of 178 cm for the control group. The calvarian size increase as well as the prominence of the frontal region has been consistently reported in previous descriptions whereas the low position of the occipital region seems to be a new observation. The causal mechanism behind the calvarian size and shape characteristics in NBS is still obscure. Some authors~,14, 19 have reported congenital hydrocephalus in connection with the syndrome and this might be a factor in the calvarian aberrations in some cases. The increased distance from nasion to sella could be explained by the prominent glabella region and a corresponding forward position of nasion. This was supported by the finding that the distance from the sella point to the internal surface of the frontal bone (s-ni) exhibited no significant difference between the NBS and control groups. Increased interorbital distance is very common in these patients. In the present sample increased intercanthal and interpupillary distance were also found7 and the patients exhibited a marked bony hypertelorism. The data revealed that the angle between the nasal bones and the anterior cranial base was decreased in the NBS group. This finding is in agreement with the clinical observation of a depressed nasal bridge described by GORLIN e t a D z and BECKER, KOPF & LANDE2, The size and inclination of the maxilla were within normal limits and the reduction of the prognathic angle might be explained topographically by the forward position of the nasion. The increased anterior dentoalveolar height could be considered secondary to the altered mandibular morphology. M a n d i b l e . Although the length of the mandible was increased, the angle of prog-
307
nathism was smaller because of the backward inclination of the mandible and the forward position of the nasion. The position of the condyles in relation to the cranial base was unchanged. The large gonion angle in the NBS group indicated a change in mandibular shape. The smaller difference between the angles N S L / M B L and N S L / M L in the patients indicated that underdevelopment of the gonial region was hwolved in the mandibular deviations. It appeared from the lateral radiographs (Fig. 4) that a general charaeteristie of the examined NBS patients was the close relationship of the mandibular canal to the lower border of the mandible. Calcification of the falx cerebri in NBS patients has been described by some authors6,1a,:t~, t8 but the frequency of 1 0 0 % found in the present investigation was larger than in other reports. The calcifications in the sella turcica region have been reported in several case reports and might represent calcifications of the tentorium cerebelli and the petroclinoid ligaments. The prominence of the glabella and supraorbital regions might be related to the enlarged frontal sinus in most eases. T h e abnormal eyebrows found in almost aI1 the cases might be of diagnostic significance in NBS. The radiographic examination of the right hand revealed that about 8 % of the NBS patients showed a positive metacal~pal sign, which is similar to the frequency of about 10 % in the general population s. The present investigation could not confirm the suggestion of GORLIN & PINDBORG11 and nECKER e t aL e that a short fourth metacarpal is a frequent finding in NBS patients. Three of the patients revealed cervical spine anomalies but only the cervical vertebrae were examined in the present investigation. A thorough radiographic examination of the total spine would seem pertinent.
308
DAHL, KREIBORG AND JENSEN
Fig. 4. Lateral cephalometric radiograph of a patient with NBS.
The present roentgencephalometric findings combined with the qualitative radiologic features of the intracranial calcifications, widened suture lines, increased v a s c u -
lar markings, and anomalies of the ribs and cervical spine suggest a characteristic pattern of malformations in this syndrome comparable with that found in other recog-
BASAL CELL CARCINOMA SYNDROME
Fig. 4. Posteroanterior cephalometric radiograph of patient with NBS.
309
310
DAHL, KREIBORG AND JENSEN
nized dysplasia syndromes involving the skeleton. Roentgencephalometric examination may thus aid in early diagnosis of the syndrome. Acknowledgments - The authors wish to express their gratitude to Dr. E. HJ6RTmo-HANSEN and Dr, O. DONATSKYwho made the patient group available for this study. Their assistance during the collection of the material is highly appreciated.
References 1. BANO, G.: Keratocysts, skeletal anomalies, ichthyosis, and defective response to parathyroid hormone in a patient without basalcell carcinoma. J. Oral Surg. 1970: 29: 242-248. 2. BECKER, M. H., KOVF, A. W. & LANDE, A.: Basal cell nevus syndrome: its roentgenologic significance. Am. J. Roentgenol. 1967: 99: 817-825. 3. BJ6RK, A.: The relationship of the jaws to the cranium. In: LUNDSTR6rd, A. (ed.): h~troduction to orthodontics. McGraw-Hill, New York 1960, p. 104-140. 4. BJORK, g . : The use of metallic implants in the study of facial growth in children: Method and application. Am. J. Phys. Anthropol. 1968: 29: 243-254. 5, BLOOM, R. A.: The metacarpal sign. Br. J. Radiol. 1970: 43: 133-135. 6. CAWSON, R. A. & KEgR, G. A.: The syndrome of jaw cysts, basal cell tumors and skeletal anomalies. Proc. R. Soc. Med. 1964: 57: 799-801. 7. DAHL, E.: Craniofacial morphology in congenital clefts of the lip and palate. Acta Odontol. Scand. 1970: 28: Suppl. 57. 8. DONATSKY, O,, HJLJRTING-t'IANsI3N,E., PHILlVSmW, H. P. & FBmRSKOV, O.: Clinical, Address: Erik Dahl Department of Orthodontics Royal Dental College Jagtve] 160 DK-2100 Copenhagen 0 Denmark
radiologic, and histopathologic aspects of 13 cases o.f nevoid basal cell carcinoma syndrome. Int. J. Oral Surg. 1.976: 5: 19-28. 9. FOR~S, I.: Naevobasaliom. Z. Haut-Geschleetkr. 1967: 42: 131-140. 10. GORLr~, R. J. & GOLTZ, R. W.: Multiple nevoid basal-cell epithelioma, jaw cysts and bLfid rib. IV. Engl. J. Med. 1960: 262: 908912. 11. G o ~ , R. L & PrNDBORG,J. L: Syndromes of the head and neck, McGraw-Hfl/, New York 1964, p. 400-409. 12. GORLn% R. J. & SEDANO,H, O.: The multiple nevoid basal cell carcinoma syndrome revisited. Birth Defects - Original Article Series 1971: 7: 140-148. 13. GOgL~, R. L, VICKERS,R. A., KI~LLN,E. & WmLIAMSON, J. I.: The multiple basal-cell nevi syndrome. Cancer 1965: 18: 89-104. 14. GORL1N, R. J., YUNIS, J. J. & TUNA, N.: Multiple nevoid basal cell carcinoma, odontogenic keratocysts and skeletal anomalies, Acta Derm.-Venereol. 1963: 43: 39-55. 15 It,IGERSLEV, C. H. & SOLOW, B.: Sex differences in craniofacial morphology. Acta Odontol. Scan& 1975: 33: 85-94. 16. JONES, J. E., DESPER, P. C., WELTON, W. A. & FLmK, E. B.: The nevoid basal-cell carcinoma syndrome. Arch. Intern. Med 1965: 115: 723-729. 17. IGSLrNG, E.: Cranial morphology in Down's syndrome. Munksgaard, Copenhagen 1966. 18. MILLS,J. & FotmKr~S, J.: Gorlin's syndrome. A radiological and cytogenetic study of nine cases. Brit. J. Radiol. 1967: 40: 366371. 19. RATER, C. I., SELmL A. C. & VAN EPVS, E. F.: Basal cell nevus syndrome. Am. J. Roentgenol. 1968: 103: 589-594. 20. SOLOW, B.: The pattern of craniofacial associations. Acta Odontol. Scan& 1966: 24: Suppl. 46. 21. TAMOt,reY,H. I.: Basal cell nevoid syndrome. Am. Surg. 1969: 35: 279-283.
Craniofacial morphology in the nevoid basal cell carcinoma syndrome A roentgencephalometric and clinical study ERIK DAHL, SVEN KREIBORG AND BIRGIT LETH JENSEN
Departments of Orthodontics and Oral Surgery, Royal Dental College, Copenhagen, Denmark
ABSTRACT-- A roentgencephalometric analysis of eight males and four females with nevoid basal cell carcinoma syndrome (NBS) is presented. The patients were 14-54 years of age. Fourteen angular and 26 linear variables were measured and compared with control data. The main roentgencephalometric features were: proportionate increase of the size of the calvarium, protrusion of the frontal and parietal region, low position of the occipital region, increased interorbital distance, increased length of the mandible, mandibular retrognathia due to changes in shape and position of the mandible. The suggestion of a characteristic craniofacial morphology as a part of the syndrome was substantiated. Together with other skeletal aberrations the roentgencephalometric findings seemed to indicate that the syndrome is a dysostosis of generalized type.
(Received [or publication 25 March, accepted 20 May 1976)
The stigmata originally attributed to the nevoid basal cell carcinoma syndrome (NBS) were multiple basal cell nevi, cysts of the jaws and skeletal anomalies t0. Since then a large number of associated anomalies have been recorded including anomalies of ribs and vertebrae, shortened metacarpals, and intracranial calcifications. Deviations in the craniofacial structures have been described in several case reports ~,6,0,11,14,~s. The most commonly reported symptoms in the r skeleton are
prominence of the frontal and parietal bones, a well-developed supraorbital ridge~ ocular hypertelorism and mild mandibular prognatbism. GORLIN, VICKERS, KELLN & WILLIAMSON ls and GORLIN & SEDaNOt~ considered a characteristic facial appearance as part of the syndrome. The previous case reports represent mainly subjective clinical descriptions of the craniofacial aberrations in the affected individnals. The purpose of the present report was to present a systematic roentgeneepha-
BASAL CELL CARCINOMA SYNDROME Table 1. Age distribution
Controls
NBS
Males FemaIes Males Females (n=8) (n=4) (n=102) (n=51) Mean age Range
27
27
24
24
15--54
14-50
19-25
22-27
lometric description and analysis of the craniofacial morphology in a group of adults with NBS.
301
ties of the mandible due to pathologic fractures. The male control group consisted of 102 adults. Cephalometrie radiographs of these subjects were collected and analyzed by SOLOWe~ The cephalometrie films were remeasured by DAHL 7 and his measurements served as control data in the present study. The female control group consisted of 51 adults. The roentgencephalometrie data for this group were reported by INGERSLEV• SOLOWin. The age distribution of the patients and the controls is shown in Table 1. Both the patients and the controls were Danes with the same ethnic background.
Method Material .Twelve patients with NBS were examined, eight males and four females. The patients have previously been reported from a clinical, histopathological, and surgicM point of view by DONATSKY,
HJ~RTINO-I"I.ANSI~N,
PHILIPSEN
&
FEJ'gRSKOVa. In the present report a 68-year-old male was excluded from the original sample because of total loss of the teeth and deformi-
For each subject roentgencephalometric films in the lateral and posteroanterior projection and a radiograph of the right hand and forearm were obtained by a technique described by BJORKZ,4. For the lateral projection the enlargement corresponding to the midsagittal plane was 5.6 %. For the posteroanterior projection the enlargement corresponding to a plane through the ear rods of the cephalostat was 8.6 %20 No correction was made for the enlargements.
f eU
i
~bo o RL pg
,' , ""
ML
A
B
Fig. 1. Reference points and lines on the cephalometric radiographs. A, Lateral projection. B, Posteroanterior projection.
302
DAHL, K R E I B O R O A N D J E N S E N
T a b l e 2. Statistical data for NBS-males and control group (for each variable the values for the patient group are listed above the control data) Range n
:~
s~
224.6 214.0 181.9 167.0 185.5 170.0 153.6 137.0 162,6 152.5 143.5 136.0 4B.3 46.5 144.1 142.5 96.6 94.0
212.75 198,39 167.61 152.62 177.68 157.83 140.87 122.82 144.68 131.98 137.17 126.40 43.37 38.77 137.76 126.86 89.88 85.78
48.58 39.48 71.80 31.95 33.38 30.99 79.41 26.84 107.78 38.73 13.3I 25.22 7.83 7.93 21.51 25.07 24.8i 12.36
73.2 67.5 53,1 50.0 38.6 43.0 122.4 118.0 118,2 119.0
83.6 81.5 64.6 60.5 53.5 56,0 139.0 144.0 150.5 150.0
78.88 73.76 58.97 55,38 46.87 49.77 130.93 130.31 134.34 134.55
16.01 9.42 16.20 6,23 23.15 8.81 33.53 26.26 139.29 36.14
8 101 8 101
26.8 21.0 97.5 -
34.2 34.5 112.3 -
31.16 26,24 107.25 96.07
7.65 5.23 26.47 9.61
8 101 8 102
22.7 103.0 104.5
30.8 118.2 133.5
27.28 25.02 110.99 118.25
7.61 9.61 30,11 33.87
min.
max.
8 100 8 102 8 102 8 102 8 84 8 84 8 102 8 102 8 102
205.2 184.0 157.1 140.0 168.5 144.0 127.8 205.5 133.3 119.0 130.5 111.0 40.0 31.0 130.4 116.5 81.7 75.0
8 1.02 8 102 8 102 8 102 8 102
t
F
Calvarium n-op ba-br eu-eu n-br br-1 bad ba-o s-ba-o s-n-f
6'17'44
1.23
4'92*4*
2.24*
9"60*44
1.08
5.65**"
2.95**
3.40***
2.78**
5.90***
1.89
4.45***
1.01
5.96***
1.17
3.07**
2.01
4.44 **4
1.70
2.48*
2.60*
1.68
2.63*
0.33
1..28
0,05
3.85***
5.77***
1.46
5'72**4
2.75**
1.84
1.26
3.41'*
1.12
Cranial base n-s s-ni s-ba n-s-ha n-s-cd Orbits mo-mo Io-Io" Nasal bones n-na s-n-na
Levels of significance: ::'5 %, " 4 1 % , ***0,1%. Control data f r o m KISLINGaT.
BASAL CELL C A R C I N O M A S Y N D R O M E
303
Table 2. Statistical data for NBS-males and control group (for each variable the values for the patient group are listed above the control data) Range n
Y
s~
57.4 58.0 62.3 61.5 55.9 55.5 74.3 75.5 81.5 90.5 13.8 16.0 38.3 37.0 112.8 128.5
53,38 52.33 56.21 55.96 50.30 50.07 64.18 67.09 78.10 81.66 7.72 7.58 35.66 30.63 108.74 109.83
5,08 6.17 15.61 8.99 14.09 7.87 62.14 10.20 7.50 9.45 8.00 7.94 4.36 7.30 9.56 40.04
123.1 114.5 94.5 78.0 127.1 104.0 72.8 73.5 33.1 14.0 53.6 46.0 79.5 81.5 42,5 38.0
141.2 141.5 113.7 102.0 154.8 135.0 84.2 90.0 52.5 47.5 62.2 67.5 93.5 115.0 54.1 55.5
131.44 126.52 101.06 89.86 139.55 120.42 77.98 81.19 40.60 28.40 58.87 54.77 84.90 97.87 48.62 44.76
34.94 24.48 47.46 19.72 66.81 38.81 12.80 10.15 33.50 35.42 10.39 15.28 41.13 50,37 19.77 8.61
8 102
128.1 107.0
151.4 144.0
138.09 126.49
63,52 40.38
8 102 8 102 8 101 8 101
-6.3 -7.0 21.9 7.5 -2.0 -1.0 -2.0 -1.0
5.8 8.5 42.2 36.0 2.5 8.0 2.5 9.5
0.12 0.41 32.88 20,48 0.31 2.94 0.13 3.16
11.00 9.43 45.53 33.22 2.42 3.12 2.06 2.30
rain.
max.
8 102 8 102 8 102 8 102 8 102 8 102 8 102 8 102
50.5 46.5 49.8 49.0 45.3 44.0 50.0 60.5 73.2 75.5 4.8 0.0 32.4 23.5 105.0 92.5
8 102 8 102 8 102 8 102 8 102 8 102 8 102 8 102
t
F
1.16
1.21
0,22
1.74
0.22
1.79
1.06
6.09***
3.18"*
1,26
0.14
1.01
5,14"*
1.67 4.19., ,
Maxilla ss-pm n-sp s-pro em-em s-n-ss NSL/NL sp-is ILs/NL
0,87
Mandible pgn-cd ag-ag ML/RL s-n-pg NSL/ML NSL/MBL ILi/ML ii-gn Jaw relations n-gn ss-n-pg NL/ML max. overjet overbite
Levels of significance: *5 %, * ' 1 % , "**0.1%.
2.67**
1,43
4,53***
2,41"
8.17'**
1.72
2.72**
1.26
5.59***
1.06
2.88':'*
1,47
4.97***
1.23
2.41"
2.30*
4.88***
1.57
0,26
1,17
5.79***
1.37
4.08***
1,30
5.46***
1,11
DAHL, KREIBORG AND JENSEN
304
The reference points and lines are indicated in Fig. 1. F o r definitions see BJ6RK~, SOLOW ~0, and DM-IL7. Fotlrteen angular and 26 linear variables describing calvarium, cranial base, orbits, na~al bones, maxillae and mandible were measured. The estimates of the statistical parameters were calculated according to SOLOW-~~ The difference between the variances was tested by Snedecor's F-test and the difference between the means by Student's t-test. The statistical calculations were performed at NEUCC, The Northern Europe University Computing Center, Copenhagen.
Calvarium. The size of the calvarium was considerably increased both in length, height, and width (n-op, ba-br, eu-eu). The chords of the ealvarian bones were all significantly increased as was the anteroposterior diameter of the forarnen magnum. The shape in profile of the calvarium was characterized by a protrusion of the frontal bone (sn-f) and a low position of the occipital region (s-ba-o). Cranial base. The length of the anterior part of the cranial base (n-s) was significantly increased, whereas the distance from the sella-point to the internal surface of the frontal bone (s-hi) showed no significant difference between the groups. The shape of the cranial base was identical in the two groups. Orbits. Both the medial (mo-mo) and the lateral (lo-lo) interorbital distances were significantly larger in the patients than in the controls. Nasal bones. The inclination of the nasal bones in relation to the anterior cranial base (s-n-no) was smaller, whereas the length of
Results MALES The results of the roentgencephalometric analysis are presented in Table 2. "the 5 %, i %, and 0 . 1 % levels o f significance are indicated in the Table b y one, two, and three asterisks, respectively. In the following only differences significant at the 1% and 0.1% levels will be considered. Ten of the fourteen angular variables and 15 of the 26 linear variables were significantly different in the two groups.
,,, ,:1 ,
,, ;
,
,,..-, ~.-~.~"
A
,, ,.,
~,;'g"
, I
I
~
, ,) '
,,
i
B
i
i,
I
i
i
,
s :I !
I
!,14"" /_.',.
',.,E-~
C
Fig. 2. Metacarpal sign: the extended tangent to the fourth and fifth metacarpal will normally pass distal to the third metacarpal (A). If the tangent intersects the third metacarpal the sign is positive (B). Borderline case ((2).
B A S A L CELL C A R C I N O M A S Y N D R O M E
305
T a b l e 3. OccmTence of radiographic a n d clinical features Males
Females
1
2
3
4
5
6
7
8
9
10
11
12
Calcification of falx cerebri
+
+
+
+
+
+
+
+
+
+
+
+
Calcifications in the sella region
+
+
-
+
+
+
+
+
+
+
--
+
Increased vascular markings in calvarium
--
+
+
+
+
Widened lambdoidal suture
+
-
+
+
+
-
+
--
+
+
Enlarged frontal sinus
+
+
+
+
+
+
+
•
P r o m i n e n t glabella region
+
--
+
+
+
+
+
+
BiNd ribs':'
+
+
+
+
+
+
+
+
--
+
+
+
Cervical spine abnormalities
+
--
+
--
+
+
--
+
+
-
Positive metacarpal sign
Heavy eyebrows
+
+
•
+
+
+
--
* f r o m DONATSKY et aI.s
the nasal bones (n-ha) did not differ from the controls. Maxilla. T h e m a x i l l a was r e t r o g n a t h i c r e l a t i v e t o the c r a n i a l b a s e (s-n-ss) a n d t h e a n t e r i o r d e n t o a l v e o l a r h e i g h t (sp-is) was increased. Otherwise the linear and angular m e a s u r e m e n t s e x h i b i t e d n o s i g n i f i c a n t differences. Mandible. T h e t o t a l l e n g t h ( p g n - c d ) a n d t h e p o s t e r i o r w i d t h (ag-ag) of t h e m a n d i b l e w e r e i n c r e a s e d . T h e g o n i o n a n g l e (ML/RL) was e x t r e m e l y large. R e l a t i v e to t h e c r a n i a l base, t h e m a n d i b l e w a s s o m e w h a t r e t r o g n a t h i c (s-n-pg). T h e m a n d i b u l a r line ( N S L / M L ) a n d t h e m a n d i b u l a r b a s e line ( N S L /
M B L ) w e r e b a c k w a r d inclined. T h e incisors h a d a lingual i n c l i n a t i o n in r e l a t i o n t o the m a n d i b u l a r line. Jaw relationships. I n t h e sagittal d i r e c t i o n t h e m a x i l l a r y o v e r j e t was reduced, b u t t h e r e w a s n o significant d i f f e r e n c e in the j a w rel a t i o n s h i p (ss-n-pg). Only one p a t i e n t exhibited a manifest mandibular overjet and t h r e e h a d a n e d g e - t o - e d g e incisor r e l a t i o n ship. T h e vertical j a w relationship ( N L / M L ) was i n c r e a s e d a n d t h e total facial h e i g h t (n-gn) w a s l a r g e r in t h e patients. T h e overb i t e was significantly smaller. T h e m o l a r o c c l u s i o n could n o t b e registered i n the N B S g r o u p due to extensive loss of teeth.
306
DAHL, KREIBORG AND JENSEN positive metacarpal sign and one was a borderline case (Fig. 2). In one individuaI the radiograph revealed muttiple lacunae in the radius, ulna, and phalanges. OTHER RADIOGRAPHIC AND CLINICAL FINDINGS The examination of the cephalometric radiographs revealed that a number of skeletal signs not registered in the roentgencephalometric analysis oceurred frequently in the NBS patients (Table 3). Calcification of falx cerebri was found in all 12 cases and calcifications in the sel[a turcica region occurred in almost all the individuals. Increased vascular markings in the calvarium were found in one-third of the cases, and the lambdoidal suture appeared strikingly open and serrated in about half of the cases. About two thirds of the patients revealed an enlarged frontal sinus. Seven of the 8 males showed a prominent glabella region whereas none of the females exhibited this characteristic. It was noted that 10 of the 12 cases revealed heavy eyebrows, frequently meeting in the midline (Fig. 3). Eight of the examined patients had bifid ribs 7. Cervical spine anomalies were present in three cases.
Fig. 3. Facial appearance of a patient with NBS.
FEMALES Due to the small n u m b e r of patients in the female group, the roentgencephalometric data are not tabulated for this group. Compared with the control group, t h e NBS remates revealed changes in the craniofacial m o r p h o l o g y similar to the deviations found in the male sample. RADIOGRAPHIC EXAMINATION OF THE RIGHT HAND One of the 12 examined patients showed a
Discussion F r o m the roentgencephalometric analysis it would appear that the craniofacial morphology in the NBS group differed from that of the control group. The findings support the opinion of GoRLnn et al.~,1a that a characteristic facial appearance is part of the syndrome (Figs. 3, 4, 5). T h e major deviations were found in the size and shape of the calvarium and of the mandible. The length, height, and width of the calvarium were proportionally increased in the NBS group. This m a y be explained only to a certain extent by the fact that the average
BASAL CELL CARCINOMA SYNDROME body height of the patients was 182 cm compared with an average height of 178 cm for the control group. The calvarian size increase as well as the prominence of the frontal region has been consistently reported in previous descriptions whereas the low position of the occipital region seems to be a new observation. The causal mechanism behind the calvarian size and shape characteristics in NBS is still obscure. Some authors~,14, 19 have reported congenital hydrocephalus in connection with the syndrome and this might be a factor in the calvarian aberrations in some cases. The increased distance from nasion to sella could be explained by the prominent glabella region and a corresponding forward position of nasion. This was supported by the finding that the distance from the sella point to the internal surface of the frontal bone (s-ni) exhibited no significant difference between the NBS and control groups. Increased interorbital distance is very common in these patients. In the present sample increased intercanthal and interpupillary distance were also found7 and the patients exhibited a marked bony hypertelorism. The data revealed that the angle between the nasal bones and the anterior cranial base was decreased in the NBS group. This finding is in agreement with the clinical observation of a depressed nasal bridge described by GORLIN e t a D z and BECKER, KOPF & LANDE2, The size and inclination of the maxilla were within normal limits and the reduction of the prognathic angle might be explained topographically by the forward position of the nasion. The increased anterior dentoalveolar height could be considered secondary to the altered mandibular morphology. M a n d i b l e . Although the length of the mandible was increased, the angle of prog-
307
nathism was smaller because of the backward inclination of the mandible and the forward position of the nasion. The position of the condyles in relation to the cranial base was unchanged. The large gonion angle in the NBS group indicated a change in mandibular shape. The smaller difference between the angles N S L / M B L and N S L / M L in the patients indicated that underdevelopment of the gonial region was hwolved in the mandibular deviations. It appeared from the lateral radiographs (Fig. 4) that a general charaeteristie of the examined NBS patients was the close relationship of the mandibular canal to the lower border of the mandible. Calcification of the falx cerebri in NBS patients has been described by some authors6,1a,:t~, t8 but the frequency of 1 0 0 % found in the present investigation was larger than in other reports. The calcifications in the sella turcica region have been reported in several case reports and might represent calcifications of the tentorium cerebelli and the petroclinoid ligaments. The prominence of the glabella and supraorbital regions might be related to the enlarged frontal sinus in most eases. T h e abnormal eyebrows found in almost aI1 the cases might be of diagnostic significance in NBS. The radiographic examination of the right hand revealed that about 8 % of the NBS patients showed a positive metacal~pal sign, which is similar to the frequency of about 10 % in the general population s. The present investigation could not confirm the suggestion of GORLIN & PINDBORG11 and nECKER e t aL e that a short fourth metacarpal is a frequent finding in NBS patients. Three of the patients revealed cervical spine anomalies but only the cervical vertebrae were examined in the present investigation. A thorough radiographic examination of the total spine would seem pertinent.
308
DAHL, KREIBORG AND JENSEN
Fig. 4. Lateral cephalometric radiograph of a patient with NBS.
The present roentgencephalometric findings combined with the qualitative radiologic features of the intracranial calcifications, widened suture lines, increased v a s c u -
lar markings, and anomalies of the ribs and cervical spine suggest a characteristic pattern of malformations in this syndrome comparable with that found in other recog-
BASAL CELL CARCINOMA SYNDROME
Fig. 4. Posteroanterior cephalometric radiograph of patient with NBS.
309
310
DAHL, KREIBORG AND JENSEN
nized dysplasia syndromes involving the skeleton. Roentgencephalometric examination may thus aid in early diagnosis of the syndrome. Acknowledgments - The authors wish to express their gratitude to Dr. E. HJ6RTmo-HANSEN and Dr, O. DONATSKYwho made the patient group available for this study. Their assistance during the collection of the material is highly appreciated.
References 1. BANO, G.: Keratocysts, skeletal anomalies, ichthyosis, and defective response to parathyroid hormone in a patient without basalcell carcinoma. J. Oral Surg. 1970: 29: 242-248. 2. BECKER, M. H., KOVF, A. W. & LANDE, A.: Basal cell nevus syndrome: its roentgenologic significance. Am. J. Roentgenol. 1967: 99: 817-825. 3. BJ6RK, A.: The relationship of the jaws to the cranium. In: LUNDSTR6rd, A. (ed.): h~troduction to orthodontics. McGraw-Hill, New York 1960, p. 104-140. 4. BJORK, g . : The use of metallic implants in the study of facial growth in children: Method and application. Am. J. Phys. Anthropol. 1968: 29: 243-254. 5, BLOOM, R. A.: The metacarpal sign. Br. J. Radiol. 1970: 43: 133-135. 6. CAWSON, R. A. & KEgR, G. A.: The syndrome of jaw cysts, basal cell tumors and skeletal anomalies. Proc. R. Soc. Med. 1964: 57: 799-801. 7. DAHL, E.: Craniofacial morphology in congenital clefts of the lip and palate. Acta Odontol. Scand. 1970: 28: Suppl. 57. 8. DONATSKY, O,, HJLJRTING-t'IANsI3N,E., PHILlVSmW, H. P. & FBmRSKOV, O.: Clinical, Address: Erik Dahl Department of Orthodontics Royal Dental College Jagtve] 160 DK-2100 Copenhagen 0 Denmark
radiologic, and histopathologic aspects of 13 cases o.f nevoid basal cell carcinoma syndrome. Int. J. Oral Surg. 1.976: 5: 19-28. 9. FOR~S, I.: Naevobasaliom. Z. Haut-Geschleetkr. 1967: 42: 131-140. 10. GORLr~, R. J. & GOLTZ, R. W.: Multiple nevoid basal-cell epithelioma, jaw cysts and bLfid rib. IV. Engl. J. Med. 1960: 262: 908912. 11. G o ~ , R. L & PrNDBORG,J. L: Syndromes of the head and neck, McGraw-Hfl/, New York 1964, p. 400-409. 12. GORLn% R. J. & SEDANO,H, O.: The multiple nevoid basal cell carcinoma syndrome revisited. Birth Defects - Original Article Series 1971: 7: 140-148. 13. GOgL~, R. L, VICKERS,R. A., KI~LLN,E. & WmLIAMSON, J. I.: The multiple basal-cell nevi syndrome. Cancer 1965: 18: 89-104. 14. GORL1N, R. J., YUNIS, J. J. & TUNA, N.: Multiple nevoid basal cell carcinoma, odontogenic keratocysts and skeletal anomalies, Acta Derm.-Venereol. 1963: 43: 39-55. 15 It,IGERSLEV, C. H. & SOLOW, B.: Sex differences in craniofacial morphology. Acta Odontol. Scan& 1975: 33: 85-94. 16. JONES, J. E., DESPER, P. C., WELTON, W. A. & FLmK, E. B.: The nevoid basal-cell carcinoma syndrome. Arch. Intern. Med 1965: 115: 723-729. 17. IGSLrNG, E.: Cranial morphology in Down's syndrome. Munksgaard, Copenhagen 1966. 18. MILLS,J. & FotmKr~S, J.: Gorlin's syndrome. A radiological and cytogenetic study of nine cases. Brit. J. Radiol. 1967: 40: 366371. 19. RATER, C. I., SELmL A. C. & VAN EPVS, E. F.: Basal cell nevus syndrome. Am. J. Roentgenol. 1968: 103: 589-594. 20. SOLOW, B.: The pattern of craniofacial associations. Acta Odontol. Scan& 1966: 24: Suppl. 46. 21. TAMOt,reY,H. I.: Basal cell nevoid syndrome. Am. Surg. 1969: 35: 279-283.