Size of Tooth Crowns and Position of Teeth Concerning the Extension of Facial Plexiform Neurofibroma in Patients with Neurofibromatosis Type 1

Size of Tooth Crowns and Position of Teeth Concerning the Extension of Facial Plexiform Neurofibroma in Patients with Neurofibromatosis Type 1 REINHARD E. FRIEDRICH 1, MANFRED GIESE 2, CLAUDIA STELLJES 1, CHRISTINE FROEDER 1 and HANNA A. SCHEUER 3 1 Oral and Maxillofacial Surgery, Eppendorf University Hospital, Hamburg, Germany; 2 Oral and Maxillofacial Surgery, Military Hospital, Hamburg, Germany; 3 Orthodontics, Eppendorf University Hospital, Hamburg, Germany Abstract. Neurofibromatosis type 1 (NF1) is an autosomal dominant inherited tumour syndrome. NF1 is also a disorder of bone in terms of altered bone metabolism and bone dysplasia. Facial plexiform neurofibroma (PNF) is frequently associated with osseous alterations and may cause severe disfigurement. These PNFs regularly affect the oral cavity and teeth. PNF pose many problems in reconstructive and oral surgery. This study was undertaken to describe oral findings related to PNFs and to investigate the size and position of teeth in these tumours. Materials and Methods: Forty-eight patients with NF1 were investigated. Tumour type was histologically proven in all patients with PNF following aesthetic/functional orofacial surgery. Twenty-four patients were affected with a PNF and 24 had disseminated cutaneous neurofibroma (DCNF). In the PNF group, the side of the PNF was registered; PNF was unilateral in all cases. DCNF patients were 15 females and 9 males (mean age: 23.92±10.48 years, minimum: 6, maximum 45 years). Patients with PNF were 17 males and 7 females (mean age: 23.92±13.76 years, minimum 6, maximum 61 years). The right side was affected in 16 and the left in 8 PNF patients. All patients were orally investigated and dental casts were obtained. Distances of the alveolar processes and of the teeth were measured in transverse and sagittal planes. In order to evaluate the possible impact of the tumour localisation inside the trigeminal nerve, the topography of the affected facial Correspondence to: Professor Dr. R.E. Friedrich, Oral and Maxillofacial Surgery, Eppendorf University Hospital, Martinistr. 52, 20246 Hamburg, Germany. Tel: +49 40741054885, e-mail: rfriedrich@uke.de Key Words: Neurofibromatosis type 1, teeth, jaw malformation, plexiform neurofibroma, anthropometry, tooth retention, asymmetry of jaws. areas was assigned to the trigeminal nerve branches. Radiographs were taken to asses the formation of dental roots, to reveal retained teeth and to estimate dysplastic areas of the jaws. Results: The size of tooth crowns did not differ from published standards on tooth parameters of Caucasian individuals. The dental arches were symmetrically arranged in all patients of the DCNF group. However, the position of teeth showed some relevant differences in the PNF group. We observed spacing between teeth, probably due to interdental invasion of plexiform neurofibroma or interference of tumour tissue with the mesial drift of teeth. Maxilla and mandible showed characteristic alterations in the PNF group that were confined to the side and extension of a PNF. Conclusion: Oral inspection should be carried out in all patients with NF1. Unilateral alterations of the position of teeth and asymmetries of the jaws should alert the investigator to search for an ipsilateral PNF of the second or third trigeminal branch. The size and dimensions of tooth crowns appear not to be affected by the disease. Neurofibromatosis type 1 (NF1) is an autosomal dominant inherited disease affecting about 1:2500 children living at birth (1). A plethora of signs and symptoms were reported in NF1-affected individuals (2, 3). Small peripheral nerve sheath tumors, predominantly arising in the skin are the hallmark of the disease (2). NF1 is a tumour predisposition syndrome and the most frequent inherited disease associated with cancer (4). NF1 is also a disease of bones (5, 6). In the craniomaxillofacial area, defects of the skull and alterations of the jaws, preferentially hypoplasia or even aplasia of bones, are well-known findings and leading diagnostic features of the disease (7, 8). Retention and displacement of teeth may cause problems in oral surgery of affected individuals (2, 8, 9). The dental health of NF1 patients appears not to be affected by the disease but by the quality of public health care systems (10). Osteoporosis is a frequent finding in patients with NF1 0250-7005/2012 $2.00+.40 2207

Figure 1. A: Schematic drawing of Vizor measuring plate according to Schmuth. B: Reference points used to determine distances on the dental casts. Sagittal directions of teeth are measured in the median plane (A- B, A-C, A-E, A-D, A-E, A-F). (6) and jaw malformation can be associated with retained or missing teeth (9). From earlier reports, we are aware that malformations in the craniofacial area are very often skeletal findings indicating an adjacent plexiform neurofibroma derived from a trigeminal nerve branch (9, 11). The development of teeth is closely interwoven with the development of the jaws. However, it is not clear whether the teeth of patients with NF1 differ from the normal population in terms of size and position in the jaws. The aim of this study was to measure the size of tooth crowns in individuals with NF1 and to determine the position of teeth, with special emphasis on the registration of adjacent tumour. Materials and Methods Forty-eight patients with NF1 were investigated. All patients fulfilled the current diagnostic criteria of NF1 (7). All patients gave informed consent to the investigation. In all patients with facial plexiform-diffuse neurofibromas affecting the trigeminal nerve, the histological diagnosis was based on adequate tissue specimen following aesthetic/functional orofacial surgery by one of the authors (REF). Twenty-four patients were affected with a facial plexiform neurofibroma (PNF) and 24 had no facial plexiform neurofibroma. Facial PNF was unilateral in all cases (PNF group). Patients with disseminated cutaneous neurofibroma (DCNF group) were 15 females and 9 males (mean age: 23.92±10.48 years, minimum: 6, maximum 45 years). Patients with PNF (PNF group) were 17 males and 7 females (mean age: 23.92±13.76 years, minimum 6, maximum 61 years). The right side was affected in 16 and the left in 8 patients with PNF. All patients were orally investigated and dental casts were obtained. Distances determined on the surface of the alveolar processes, between the teeth, and between anatomical landmarks and teeth were measured in transverse and sagittal planes. The palatine raphe was used as a landmark of the median plane and allowed calculation of distances of the tooth crowns in the transverse directions. Measurements of teeth sizes and distances between teeth were made after application of Schmuth s vizor measuring plate (12) to the dental casts. This surface plate is implemented with a millimetre calibration. The plate is oriented parallel to the palatine raphe of the maxilla or in the median plane Figure 2. Affection of the trigeminal nerve branches in 24 patients with plexiform neurofibroma (multiple entries per patient possible; Branch=branches of trigeminal nerve). More than 80% of patients with plexiform neurofibroma were affected in the first branch of the trigeminal nerve. of the mandible. In order to determine transverse differences of the dental arch of the maxilla, the transverse distances were measured as a line starting from the most buccal part of a tooth crown and ending at the palatine raphe. In the mandible, the distances were calculated in the same way related to the median plane. Sagittal distances were calculated from the point of intersection between the transverse line between the conspecific tooth and the palatine raphe. Figure 1 illustrates the measurements schematically. Maximum diameters of the tooth crowns were calculated with a sliding calliper applied perpendicular to the long axis of every tooth. Measurements were taken in millimetres. For all patients, each side was measured separately. Positional anomalies were determined relative to the dental arch. Deviations to the palatal/lingual and buccal/labial side were registered using Schmuth s plate. Severly destroyed, prosthetically restored or retained teeth and all third molars were excluded from evaluation. Rotations of the teeth were determined in units of 10. Positional anomalies >90 were classified as a single group. Teeth of upper and lower jaws were evaluated separately. In PNF-affected individuals, the positional anomalies were determined dependent on the tumourous and the non-affected side. In the PNF group, the side of the PNF was registered. In order to evaluate the possible impact of the tumour localisation inside the trigeminal nerve, different types of nerve affection by PNF were registered (group 1: first branch only affected; group 2: second branch only affected, group 3: third branch only affected; group 4: first and second branch affected, group 5: second and third branch affected, group 6: first, second and third branch affected (hemifacial PNF)). Results The most frequent phenotype of patients with PNF was hemifacial extension restricted to one body side (11 patients, 2208

Friedrich et al: Size and Position of Teeth in NF1 Associated with PNF Figure 3. Schematic drawings of the occlusal view of some dental casts of patients with plexiform neurofibroma. All these patients had evidence of extensive intraoral tumours that were histologically proven diffuse plexiform neurofibroma. 45.83%). Five patients (20.83%) had tumours in the orbitotemporal region extending to the first and/or second trigeminal branch (16.7%). PNFs of four patients were restricted to the first branch (16.7%), three PNFs (12.7%) to the cheek and mandibular region affecting the second and third branch, and one PNF (4.2%) to the nose and infraorbital region affecting the second branch (Figure 2). In 10 PNF cases (41.7%), tumours were seen adhering to the mandibular alveolar ridge, in two of them with slight transgression of the midline in the incisor region. A deformation restricted to the mandible was not noted in this study. A consistent finding of the dental arch in patients with PNF is a significant kinking of the affected side distal to the canines, with consequent medial shifting of the whole affected arch segment (Figure 3). This constellation of findings was noted in seven patients (29.2%) with simultaneous shortening of the mandibular corpus in six of these patients (25%). A widening with gapping between teeth ( spacing ) of the affected side was noted in four patients (16.7%). Partial retention of teeth was noted in five patients (20.8%). These findings were restricted to patients with PNF (Tables I and II). Maxilla. In all 24 DCNF group patients, no space-occupying lesions or obvious alterations of the jaws surface were detectable on the casts. However, in the PNF group, several space-occupying lesions or alterations of the maxillary surfaces were detected. These results are summarized in Table I. Mandible. In all 24 DCNF group patients, the mandible appeared to be symmetrically developed and the dental arch showed no anomalies. In the PNF group, malformations to the maxilla were noted. These findings are summarized in Table II. 2209

Table I. Tumours and alterations of the dental arch of the maxilla in both groups. Maxilla PNF DCNF N=24 N=24 (%) (%) Alveolar ridge widened 14 (58.3) 0 raised 7 (29.7) 0 flattened 3 (12.5) 0 shortened 1 (4.7) 0 Tuber widened 7 (29.7) 0 flattened 6 (25.0) 0 Swelling is extends into the median sagittal plane 7(29.7) 0 Displacement of palatine raphe 12 (50.0) 0 Dental arch of affected side widened 5 (20.3) 0 medially displaced 1(4.17) 0 Displacement of incisors 9(37.5) 0 Partial retention of teeth 5 (20.8) 0 PNF: Plexiform neurofibroma; DCNF: disseminated cutaneous neurofibromas. Table II. Tumours and alterations of the dental arch of the mandible in both groups. Mandible PNF DCNF N=24 N=24 (%) (%) Alveolar ridge widened 10 (41.7) 0 raised 5 (20.8) 0 flattened 1 (4.2) 0 shortened 6 (25.0) 0 Swelling is transgressing the median plane 2 (8.3) 0 Dental arch of affected side widened 4 (16.7) 0 medially displaced 7 (29.2) 0 Partial retention of tooth/teeth 5 (20.8) 0 PNF: Plexiform neurofibroma; DCNF: disseminated cutaneous neurofibromas. Localization of PNF. Assignment of the PNF to the trigeminal nerve branches showed a predominance of all branches of one side (hemifacial involvement, Figure 2). In this series the localization of PNF in the branches was lowest in the mandibular (58.3%), medium in the second (79.2%) and most frequent in the first (83.3%). There was no correlation between age and extension of PNF. The correlation between intraoral space-occupying lesions of the jaws and extraoral extension of PNF was statistically significant [chi-square, p<0.01 (maxilla), p<0.001 (mandible)). Table III. Comparison of distances in transversel and sagittal directions (in mm) of mandibular and maxillary halves in the plexiform neurofibroma group (all PNF patients). C, canine, PM1, first premolar, PM2, second premolar, M1, first molar, M2, second molar, A-C, A-D, A-E, A-F see Figure 1B; N, number of teeth, n.s., not significant. Affected side Non-affected side N MV±SD N MV±SD p-value Distance of maxillary teeth to palatine raphe C 15 12.73±1.83 17 10.94±1.68 <0.01 PM1 16 14.34±2.20 15 12.07±2.55 <0.01 PM2 14 16.00±1.52 14 14.14±2.82 <0.05 M1 11 16.59±1.71 14 14.64±2.34 <0.05 M2 7 20.29±2.14 12 18.83±1.53 n.s. Distance of maxillary teeth in sagittal direction C (A-B) 15 7.80±2.73 18 10.11±2.11 <0.01 PM1 (A-C) 17 13.29±2.95 16 15.19±2.66 <0.05 PM2 (A-D) 15 19.87±4.05 16 21.19±2.37 n.s. M1 (A-E) 11 26.18±3.19 14 28.40±3.04 n.s. M2 (A-F) 6 34.33±4.50 13 36.77±3.32 n.s. Distance of mandibular teeth to the median plane C 17 9.82±0.81 17 9.53±1.74 n.s. PM1 16 12.75±1.53 17 13.76±1.60 <0.05 PM2 15 14.67±1.99 17 15.76±2.19 n.s. M1 9 17.56±1.33 10 17.20±1.55 n.s. M2 8 19.13±2.59 12 20.83±2.95 n.s. Distances of mandibular teeth in sagittal direction C (A-B) 17 5.24±1.89 17 5.94±1.43 n.s. PM1 (A-C) 16 10.6±2.24 17 11.12±1.65 n.s. PM2 (A-D) 14 16.43±3.13 16 16.63±2.50 n.s. M1 (A-E) 9 21.56±3.50 10 23.00±3.77 n.s. M2 (A-F) 8 30.00±3.38 11 31.73±4.13 n.s. C, Canine, PM1, first premolar, PM2, second premolar, M1, first molar, M2, second molar, A-C, A-D, A-E, A-F see Figure 1B; N, number of teeth, n.s., not significant. Transversal symmetry assessment. PNF group: The halves of each jaw were compared to each other. Casts with insufficiently definable median plane were excluded. This decision was made for maxillary casts of five patients with PNF who showed no clearly visible palatine raphe as a consequence of excessive tumour growth overlapping the median [tumour growth strictly ending at the median plane (physical investigation)]. Based on 19 evaluable casts, the width of the maxillary arch was wider on the affected side than on the other, in particular in the canine and first premolar region (p<0.01) and the second premolar and first premolar region (p<005). The dental arch of the affected side of the maxilla was shortened compared to the non-affected side. These findings were also seen in the mandible, with less peculiarity (Table III). 2210

Friedrich et al: Size and Position of Teeth in NF1 Associated with PNF Table IV. Side-to-side comparison of distances between maxillary and mandibular teeth in sagittal and transversal directions (in mm) in patients with plexiform neurofibroma. This evaluation is restricted to patients with PNF affecting one side of the face completely (all three branches) and those with PNF of the second and/or third branch. Affected side Non-affected side N MV±SD N MV±SD p-value Distances of maxillary teeth to palatine raphe C 6 13.17±2.56 8 9.75±1.28 <0.01 PM1 8 14.31±2.87 8 10.38±1.60 <0.01 PM2 5 16.60±1.95 6 13.00±2.19 <0.01 M1 4 17.00±1.83 7 13.43±1.90 <0.01 M2 2 22.00±1.41 5 18.60±1.14 <0.05 Distances of maxillary teeth in sagittal direction C (A-B) 6 6.33±2.25 9 10.44±2.30 <0.01 PM1 (A-C) 9 12.78±3.31 9 15.78±2.95 <0.05 PM2 (A-D) 6 21.00±4.86 8 22.25±2.76 n.s. M1 (A-E) 4 25.00±3.56 8 29.50±3.55 <0.05 M2 (A-F) 2 29.00±1.41 6 36.17±4.62 <0.01 Distances of mandibular teeth to the median plane C 9 9.67±0.71 9 9.33±2.29 n.s. PM1 8 11.88±0.99 9 13.67±1.80 <0.05 PM2 8 14.00±1.60 8 15.88±2.03 <0.05 M1 2 16.50±0.71 3 17.67±2.52 n.s. M2 2 17.00±1.41 5 22.40±2.70 <0.01 Distances of mandibular teeth in sagittal direction C (A-B) 9 5.00±2.55 9 6.11±1.62 n.s. PM1 (A-C) 8 10.13±2.80 9 10.89±1.90 n.s. PM2 (A-D) 7 16.71±3.90 8 16.75±2.82 n.s. M1 (A-E) 2 20.00±2.83 3 24.33±3.06 n.s. M2 (A-F) 2 28.00±0.00 4 32.50±4.65 n.s. C, Canine, PM1, first premolar, PM2, second premolar, M1, first molar, M2, second molar, A-C, A-D, A-E, A-F see Figure 1B; N, number of teeth, n.s., not significant. The effect of the tumour extensions in the trigeminal nerve branches was determined. In one group where tumours affected the first and/or second branch, all values of transverse line segments of the casts were collected. The intra-individual analysis of the distances of the teeth to the palatine raphe of affected and non-affected sides showed no statistically significant differences (maxilla). However, these differences became evident in the second group that consisted of patients who were hemifacially affected by PNF (all three trigeminal nerve branches affected). These findings are summarized in Table IV. DCNF group: The comparison of tooth distances in the transverse plane of patients with DCNF showed no asymmetries. Table V. Patients with distinct anomalies of dental occlusion. PNF DCNF (N=24) (N=24) (%) (%) Occlusion not definable 12 (50) 0 Consecutive to reduced number of teeth 6 (25) 0 Consecutive to anomalies of teeth positions 6 (25) 0 Intercuspidation restricted to one side (not affected by PNF) 4 (16.7) 0 Supra-occlusion 1 (4.17) 0 Infra-occlusion 5 (20.8) 0 Recess in the occlusal plane 1 (4.17) 0 Open bite 4 (16.7) 0 PNF: Plexiform neurofibroma; DCNF: disseminated cutaneous neurofibromas. Occlusion of teeth. All patients of the DCNF group had regular dental occlusion and no severe alterations of the dental arches. In the PNF group, however, the occlusion could be defined on dental casts in about 50% of patients only. The findings concerning the interference with dental occlusion attributable to the subgroups are listed in Table V. The comparison of occlusal relations between the other 12 patients affected by PNF and DCNF-group patients revealed no differences concerning tooth alignment. Positional anomalies of teeth. Rotated teeth were predominantly found in the PNF group [121 (28.21%) vs. 107 (21.9%), p<0.05], excepting the upper canines and the lower second premolars. The first upper molars of PNF patients were significantly more frequently rotated than the teeth of the same position in patients with DCNF (p<0.01, chi-square). In the lower jaw, rotations of the first premolars and second molars of patients with PNF occurred significantly more frequent (p<0.05). Findings are summarized in Table VI and Figure 4. The side-specific analysis of positional anomalies in patients with PNF revealed predominant deviations from the expected position of teeth retained in a jaw of a tumourous side. Positional anomalies of second premolars were significantly more frequent in patients with PNF (p<0.01). Displaced teeth. Displacements of teeth were rarely seen. Substantial deviation of a tooth from the dental arch was more frequently diagnosed in patients with PNF (maxilla p<0.01; mandible p<0.05). In the maxilla of patients with PNF the teeth were preferentially moved to the palatal side, in particular the lateral incisors. Tumour side-specific differences of tooth translocations revealed statistically significant differences for the comparison of maxillary teeth only (p<0.01). 2211

Table VI. Comparison of rotated teeth in both patient groups. PNF DCNF N No. of rotated teeth % N No. of rotated teeth % p-value Maxilla I1 31 8 25.80 38 9 23.68 n.s. I2 32 9 28.13 40 9 22.50 n.s. C 32 8 25.00 41 12 29.27 n.s. PM1 32 3 9.38 35 3 8.57 n.s. PM2 31 7 22.58 27 4 14.18 n.s. M1 24 8 33.33 35 3 8.57 <0.01 M2 17 3 17.65 30 4 13.33 n.s. Total 199 46 23.12 246 44 17.89 n.s. Mandible I1 41 18 43.90 48 16 33.33 n.s. I2 40 12 30.00 45 13 28.89 n.s. C 41 14 34.15 42 13 30.95 n.s. PM1 37 16 43.24 39 9 23.08 <0.05 PM2 35 12 34.29 31 12 38.71 n.s. M1 19 1 5.26 26 0 0.00 n.s. M2 17 2 11.76 28 0 0.00 <0.05 Total 230 75 32.61 259 63 24.32 <0.05 Maxilla/ 429 121 28.21 505 107 21.18 <0.05 Mandible (total) C, Canine, PM1, first premolar, PM2, second premolar, M1, first molar, M2, second molar, A-C, A-D, A-E, A-F see Figure 1B; N, number of teeth, n.s., not significant. Missing teeth. This item was determined on patients with completed second dentition (excluding third molars). This analysis does not discriminate between missing teeth following extraction and aplasia of teeth. In order to compare patients of the same age groups this analysis was restricted to 15 patients with PNF (mean age: 27 years, min.: 10 years, max.: 38 years) and 17 patients with DCNF (mean age: 27.1 years, min.: 19 years, max.: 40 years). A statistically significant higher number of missing teeth in patients with PNF compared to patients with DCNF was calculated comparing the teeth of all patients (missing teeth: 50 vs. 38, p<0.05). Analysis of single tooth groups revealed no statistically significant difference. In patients with PNF significantly more second molars were missing in both jaws of the tumourous side (maxilla: p<0.01, mandible: p<0.05, Table VII). Sizes of tooth crowns. The mesiodistal diameters of tooth crowns showed no differences between both NF1 groups. In the PNF group, side-specific differences were excluded: PNF does not interfere with the size of tooth crowns. Comparison of the measured data with anthropometric standard values (13) excluded the hypothesis of anomalous sizes of tooth crowns in NF1. Figure 4. Distribution of rotated teeth in patients with plexiform neurofibroma (PNF) according to the side (tumour-affected vs. nonaffected by PNF). 2212

Friedrich et al: Size and Position of Teeth in NF1 Associated with PNF Table VII. Comparison of the number of missing teeth in patients with plexiform neurofibroma related to the affected or non-affected side. Affected side Not affected side N No. of missing teeth % N No. of missing teeth % p-value Maxilla I1 15 0 0 15 0 0 n.s. I2 15 0 0 15 0 0 n.s. C 15 0 0 15 0 0 n.s. PM1 15 2 13.33 15 4 26.67 n.s. PM2 15 4 26.67 15 2 13.33 n.s. M1 15 4 26.67 15 2 13.33 n.s. M2 15 7 46.67 15 0 0 <0.01 Total 105 17 16.19 105 8 7.62 n.s. Mandible I1 15 0 0 15 0 0 n.s. I2 15 1 6.67 15 0 0 n.s. C 15 0 0 15 0 0 n.s. PM1 15 3 20 15 1 6.67 n.s. PM2 15 3 20 15 1 6.67 n.s. M1 15 7 46.67 15 4 26.67 n.s. M2 15 5 33.33 15 0 0 <0.05 Total 105 19 18.1 105 6 5.71 <0.01 Maxilla/ 210 26 12.38 210 14 6.67 <0.05 mandible (total) C, Canine, PM1, first premolar, PM2, second premolar, M1, first molar, M2, second molar, A-C, A-D, A-E, A-F see Figure 1B; N, number of teeth, n.s., not significant. Discussion This study shows the association of displacement of teeth and form of the jaws with the extension of facial PNF. It is likely that the development of the tumours in early childhood is crucial in this complex dental and osseous malformation (14). However, it has become clear that NF1 affects the primary dentition in general (15). The sizes of the crowns of permanent teeth in patients with NF1 do not differ from standards of Caucasian ethnicity. Oral manifestations of NF1 appear to occur frequently but are usually not associated with oral pathologies (10). Oral findings apparently associated with NF1 in patients with facial cutaneous neurofibromas range between 33% (16) and about 70% (10, 17, 18). The frequency of PNFs is unknown. According to recent magnetic resonance image-based studies it is highly probable that PNFs occur in about 50% of NF1- affected children (19). Earlier epidemiological studies on NF1 revealed PNF of the head and neck region in fewer than 5% (20-23). The frequency of patients with facial PNF in this study (50%) is biased due to the fact that patients with severely affected faces are preferentially admitted to clinics specialized in the treatment of facial deformities in the context of NF1 (16). NF1 is a primary disorder of bone. Neurofibromas are frequently associated with skeletal malformations, e.g. the vertebral column, but are not necessarily found in every case (2). This facultative association is also proven for the skull. Sphenoid wing dysplasia is an independent skeletal finding in NF1 not regularly associated with a PNF (8). Indeed, certain gross anomalies, such as shortening of mandible, appear to be a constitutive finding in NF1 (24). However, the characteristic unilateral oral findings, such as widening of the interdental spaces, widening of the dental arch, unilateral diffuse swelling of the alveolar ridges and palate, and a straightened but shortened appearance of the dental arch of the mandible are all associated with oral PNF (16). These findings are easily seen in severely affected patients. However, patients who are affected by a diffuse PNF in only small peripheral segments of the second or third branch of the trigeminal nerve show similar findings compared to those of our study but these are strictly related to the extension of the tumour (25-27). Based on our macroscopic evaluation, permanent teeth developing in the region of a trigeminal PNF may be affected in their position in relation to an adjacent 2213

PNF. The physical development of a tooth inside a PNF is not affected as far as the dimensions of the tooth crowns are concerned. Malformations of tooth roots in dysplastic parts of the jaws appear to be epiphenomena as a consequence of volume and feature of bone (9, 11). However, second mandibular molar aplasia is related to the extension of facial PNF (9). References 1 Lammert M, Friedman JM, Kluwe L and Mautner VF: Prevalence of neurofibromatosis 1 in German children at elementary school enrolment. Arch Dermatol 141: 71-74, 2005. 2 Riccardi VM: Neurofibromatosis. Phenotype, Natural History, and Pathogenesis. 2nd Edition. The Johns Hopkins University Press, Baltimore, pp. 30-31, 66, 108-118, 224-250, 1992. 3 Recklinghausen FD: Über die multiplen Fibrome der Haut und ihre Beziehung zu den multiplen Neuromen. Hirschwald, Berlin, 1882. 4 Rasmussen SA, Yang Q and Friedman JM: Mortality in neurofibromatosis type 1: an analysis using U.S. death certificates. A J Hum Genet 68: 1110-1118, 2001. 5 Tucker T, Schnabel C, Hartmann M, Friedrich RE, Frieling I, Kruse HP, Mautner VF and Friedman JM: Bone health and fracture rate in individuals with neurofibromatosis 1 (NF1). J Med Genet 46: 259-265, 2009. 6 Seitz S, Schnabel C, Busse B, Schmidt HU, Beil FT, Friedrich RE, Schinke T, Mautner VF and Amling M: High bone turnover and accumulation of osteoid in patients with neurofibromatosis 1. Osteoporosis Int 21: 119-127, 2010. 7 Gutmann DH, Aylsworth A, Carey JC, Korf B, Marks J, Pyeritz RE, Rubenstein A and Viskochil D: The diagnostic evaluation and multidisciplinary management of neurofibromatosis type 1 and neurofibromatosis type 2. JAMA 278: 51-57, 1997. 8 Friedrich RE: Reconstruction of the sphenoid wing in a case of neurofibromatosis type 1 and complex unilateral orbital dysplasia with pulsating exophthalmos. In Vivo 25: 287-290, 2011. 9 Friedrich RE, Giese M, Schmelzle R, Mautner VF and Scheuer HA: Jaw malformation plus displacement and numerical aberrations of teeth in neurofibromatosis type 1: a descriptive analysis of 48 patients based on panoramic radiographs and oral findings. J Craniomaxillofac Surg 31: 1-9, 2003. 10 Visnapuu V, Pienihäkkinen K, Peltonen S, Happonen RP and Peltonen J: Neurofibromatosis 1 and dental caries. Clin Oral Investig 15: 119-121, 2011. 11 Friedrich RE: Maxillofaziale und Orale Neurofibromatose Typ 1. Shaker, Aachen, 2010. 12 Utz KH, Müller F, Kettner N, Reppert G and Koeck B: Functional impression and jaw registration: a single session procedure for the construction of complete dentures. J Oral Rehab 31: 554-561, 2004. 13 Moyers RE, van der Linden FPGM and McNamara JA Jr.: Standards of Human Occlusal Development. Monograph No. 5, Craniofacial Growth Series for Human Growth and Development. University of Michigan, Ann Arbor, p. 45, 1976. 14 Waggoner DJ, Towbin J, Gottesman G and Gutmann DH: Clinicbased study of plexiform neurofibromas in neurofibromatosis 1. Am J Med Genet 92: 132-135, 2000. 15 Lammert M, Friedrich RE, Friedman JM, Mautner VF and Tucker T: Early primary tooth eruption in neurofibromatosis type 1 individuals. Eur J Oral Sci 115: 425-426, 2007. 16 Friedrich RE, Giese M and Schmelzle R: Zur Häufigkeit intraoraler weichgeweblicher Raumforderungen bei Neurofibromatose Typ 1. Dtsch Z Mund Kiefer Gesichts Chir 19: 273-276, 1995. 17 Shapiro SD, Abramovitch K, van Dis ML, Skoczylas LJ, Langlais RP, Jorgenson RJ, Young RS and Riccardi VM: Neurofibromatosis: oral and radiographic manifestations. Oral Surg Oral Med Oral Pathol 58: 493-498, 1984. 18 D Ambrosio JA, Langlais RP and Young RS: Jaw and skull changes in neurofibromatosis. Oral Surg Oral Med Oral Pathol 66: 391-394, 1988. 19 Nguyen R, Kluwe L, Fuensterer C, Kentsch M, Friedrich RE and Mautner VF: Plexiform neurofibromas in children with neurofibromatosis type 1: frequency and associated clinical deficits. J Pediatr 159: 652-655.e2, 2011. 20 Crowe FW, Schull WJ and Neel JV: A Clinical, Pathological, and Genetic Study of Multiple Neurofibromatosis. CC Thomas, Springfield, IL, 1956. 21 White AK, Smith RJH, Bigler CR, Brooke WF and Schauer PR: Head and neck manifestations of neurofibromatosis. Laryngoscope 96: 732-737, 1986. 22 Gardeur D, Palmieri A and Mashaly R: Cranial computed tomography in the phakomatoses. Neuroradiol 25: 293-304, 1983. 23 Huson SM, Compston DA, Clark P and Harper PS: A genetic study of von Recklinghausen neurofibromatosis in South East Wales. I. Prevalence, fitness, mutation rate, and effect of parental transmission on severity. J Med Genet 26: 704-711, 1989. 24 Heervä E, Peltonen S, Pirttiniemi P, Happonen RP, Visnapuu V and Peltonen J: Short mandible, maxilla and cranial base are common in patients with neurofibromatosis 1. Eur J Oral Sci 119: 121-127, 2011. 25 Badger GR: Solitary neurofibromatosis in the maxilla: report of oral findings. JADA 100: 213-214, 1980. 26 Gilbert JC, Hersham DS and Schow CE: Neurofibromatosis with mandibular deformities. Tex Dent J 90: 24-29, 1972. 27 Bekisz O, Darimont F and Rompen EH: Diffuse but unilateral enlargement associated with von Recklinghausen neurofibromatosis. J Clin Periodontol 27: 361-365, 2000. Received February 13, 2012 Revised April 27, 2012 Accepted April 27, 2012 2214