Three Cases of Oculo-Facio-Cardio-Dental (OFCD) Syndrome

Three s of Oculo-Facio-Cardio-Dental (OFCD) Syndrome Objective: Oculo-facio-cardio-dental (OFCD) syndrome is a rare condition with ocular, facial, cardiac, and dental disorders. The purpose of this report is to describe three female patients by using facial measurements, tooth measurements, and cephalometric analysis. Design: Facial measurements, tooth measurements, and the results of cephalometric analyses were compared with standards using panoramic roentgenograms, dental casts, and lateral cephalograms. Results: A long face and thick upper and lower lips were noted for all cases from facial measurements, and a long crown length and long dental root were noted for all cases from tooth measurements. Relative mandibular protrusion and a large anterior lower facial height, accompanied by a steep mandible and large gonial angle, were seen from the cephalometric analyses. Conclusions: The results of a long face and long dental root were in accordance with previous reports. In addition, thick upper and lower lips, relative mandibular protrusion, large anterior lower facial height accompanied by a steep mandible, and a large gonial angle may be characterized as specific features of this syndrome. HIROYUKI TSUKAWAKI, D.D.S. MICHIKO TSUJI, D.D.S. TATSUO KAWAMOTO, D.D.S., PH.D. KIMIE OHYAMA, D.D.S., PH.D. KEY WORDS: craniofacial dysmorphology, dental anomalies, OFCD syndrome, thick lips Oculo-facio-cardio-dental (OFCD) syndrome [OMIM 300166] was first reported by Hayward (1980) and was summarized by Gorlin et al. (1996) as a syndrome mainly characterized by ocular, facial, cardiac, and dental disorders. Inheritance may be X-linked dominant and may be lethal in males (Gorlin et al., 1996; Hedera and Gorski, 2003). Thus far, only 17 cases of this syndrome have been documented (Hayward, 1980; Marashi and Gorlin, 1990; Wilkie and Chambers, 1990; Wilkie et al., 1993; Aalfs et al., 1996; Gorlin et al., 1996; Obwegeser and Gorlin, 1997; Schulze et al., 1999; Bartbelemy et al., 2001; Hedera and Gorski, 2003; Kawamoto et al., 2004). Although there are several reports on the ocular, facial, cardiac, and dental findings in these cases, few reports describe tooth measurements (Hayward, 1980; Marashi and Gorlin, 1990; Wilkie and Chambers, 1990; Kawamoto et al., Dr. Tsukawaki is Clinical Fellow; Drs. Tsuji and Kawamoto are Instructors; and Dr. Ohyama is Professor and Chair, Section of Maxillofacial Orthognathics, Department of Maxillofacial Reconstruction and Function, Division of Maxillofacial/Neck Reconstruction, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. ed at the 42nd Annual Meeting of the Teratology Society, Hamamatsu, Japan, July 2002. Submitted August 2004; Accepted September 2004. Address correspondence to: Tatsuo Kawamoto, D.D.S., Ph.D., Maxillofacial Orthognathics, Maxillofacial Reconstruction Division of Maxillofacial/Neck Reconstruction, Graduate School, Tokyo Medical and Dental University, 1 5 45, Yushima, Bunkyo-ku, Tokyo, Japan 113 8549. E-mail t-kawamoto.mort@ tmd.ac.jp. 2004), facial measurements (Wilkie et al., 1993; Aalfs et al., 1996; Schulze et al., 1999; Hedera and Gorski, 2003), or the results of cephalometric studies (Kawamoto et al., 2004). The purpose of this paper is to report on the detailed analysis of the dentofacial region and ocular, facial, cardiac, and dental findings in two patients recently diagnosed with OFCD syndrome and in a previously reported patient who received integrated orthodontic-prosthodontic treatment by Kawamoto et al. (2004). All of the studies complied with the Code of Ethics of the World Medical Association (Declaration of Helsinki). Written informed consent was obtained from all of the patients before the study, but after the nature of the study had been fully explained. 1 CASE REPORTS The case patient was a woman who first visited at the age of 16 years, 6 months, with a chief complaint of malocclusion. She had been uneventfully delivered at 41 weeks gestation. Her birth weight and height were 3810 g and 51 cm, respectively, and she was the first child of healthy parents (mother: 27 years, 4 months; father: 26 years, 6 months). There was no remarkable event during pregnancy (neither rubella nor rubeola), and congenital cataract and microphthalmia were noted bilaterally. Subsequent to secondary glaucoma and re- 467

468 Cleft Palate Craniofacial Journal, September 2005, Vol. 42 No. 5 FIGURE 3 Panoramic roentgenogram of 1. FIGURE 1 1: age is 16 years, 6 months at the first visit. tinodialysis, this patient lost her bilateral sight. She suffers from an atrial septal defect (ASD), for which surgery was performed at the age of 5. No circulatory disorders have been found since then. Hearing on her right side is also impaired slightly. The parents were not consanguineous, and no disorder was found in her 3-years-younger sister. Her height was 152.8 cm at age 18 years, which is nearly 1 SD (Suwa and Tachibana, 1993). Her nose had a high nasal bridge, broad nasal tip, and separated nasal cartilages (Fig. 1). The patient s forearm on the right side was slightly shorter than the left, with radioulnar synostosis on the same side. Her first toes were long and so wide that a gap between the first and second toes was noticeable, along with hammer-type flexion of toes 2 through 4. Lateral crossbite on both sides, overjet (5.0 mm), extreme deep overbite (13.0 mm), and isolated cleft palate were noted. Oligodontia (including a missing upper right second premolar, upper left lateral incisor, upper left canine, upper left second premolar, lower left lateral incisor, lower left second premolar, lower right central incisor, lower right lateral incisor, and lower right second premolar) were also observed. In addition, tubercle anomalies of the upper right central incisor, root dilacerations, enamel hypoplasia, delayed secondary dentition, persistent primary teeth, and root exposure were noted (Figs. 2 and 3). This girl, who first visited at the age of 10 years, 9 months, had a chief complaint of delayed eruption of permanent teeth and malocclusion. She had been uneventfully delivered at 39 weeks gestation. Her birth weight and height were 3060 g and 48.6 cm, respectively. She was the second child of healthy parents (mother: 27 years, 11 months; father: 28 years, 6 months) and there was no remarkable event during pregnancy. Congenital cataract, microphthalmia, and regressive vision impairment were noted bilaterally, and bilateral hearing loss was recognized slightly. The parents were not consanguineous, and no disorder was found in her 4-yearsolder sister. Her height was 155.6 cm at 11 years, 7 months, which is greater than 1 SD. She had a high nasal bridge, broad nasal tip, separated nasal cartilages, and thick curved eyebrows (Fig. 4). Radioulnar synostosis was recognized bilaterally and hammer-type flexion was present in toes 2 through 5. Anterior and lateral crossbite, overjet (2.0 mm), overbite (2.0 mm), and submucous cleft palate with bifid uvula were noted. Hypodontia (including a missing upper left central incisor, lower left lateral incisor), root dilacerations, delayed secondary dentition, persistent primary teeth, and rampant caries were also observed (Figs. 5 and 6). 3 3 was previously reported with regard to integrated orthodontic-prosthodontic treatment (Kawamoto et al., 2004). This woman underwent postintegrated orthodontic- 2 FIGURE 2 1: oral findings. FIGURE 4 2: age is 10 years, 9 months at the first visit.

Tsukawaki et al., THREE CASES OF OCULO-FACIO-CARDIO-DENTAL (OFCD) SYNDROME 469 FIGURE 5 2: oral findings. prosthodontic treatment at the age of 28 years, 4 months. She had been uneventfully delivered at 37 weeks gestation. Her birth weight and height were 2400 g and 46 cm, respectively, and she was the third child of healthy parents (mother: 28 years, 6 months; father: 27 years, 8 months). No remarkable event was noted during pregnancy. Congenital cataract, strabismus, nystagmus, and regressive vision impairment were noted bilaterally, and the patient suffered from a ventricular septal defect (VSD); she has been followed by a cardiologist since 6 years of age with no further cardiac symptoms. Her hearing was normal. Her parents were not consanguineous, and her 3-years-older brother had been diagnosed with polyostotic fibrous dysplasia. Her height was 158.4 cm at 28 years, 4 months, which is close to the mean value. Her nose had a high nasal bridge, broad nasal tip, and separated nasal cartilages (Fig. 7), and she had long second toes bilaterally. Overjet (2.0 mm), overbite (4.5 mm), and submucous cleft palate with bifid uvula were noted. Oligodontia (including a missing upper right lateral incisor, upper right second premolar, upper left lateral incisor, upper left first premolar, lower left central incisor, lower left lateral incisor, lower left second premolar, lower left first molar, and lower right central incisor) were also observed (Figs. 8 and 9). Facial Measurements The total head height, facial breadth, philtrum length, and thickness of the upper and lower lips were measured (Fig. 10), and the findings were compared in Table 1 with those of normal controls (Fujita, 1976; Igarashi and Kajii, 1988). FIGURE 7 3: post-orthodontic prosthodontic treatment at age 28 years, 4 months. 1 s total head height was greater than 6 SD, face breadth exceeded 2 SD, philtrum length exceeded 2 SD, thickness of her upper lip was nearly 2 SD, and thickness of her lower lip exceeded 2 SD. 2 s total head height was greater than 6 SD, thickness of her upper lip was nearly 4 SD, and thickness of her lower lip exceeded 4 SD. 3 s total head height was nearly 4 SD, thickness of her upper lip was nearly 5 SD, and thickness of her lower lip was nearly 6 SD. Tooth Measurements Tooth crown width and length, as well as tooth root length, were obtained from panoramic roentgenograms and dental casts. The ratios of the clinical crown to the radiographic crown were measured (Marashi and Gorlin, 1990; Kawamoto et al., 2004), as well as the approximate lengths of the tooth crowns and roots of their permanent teeth. The results were compared with those of normal controls (Shirasu et al., 1974). The crown width of 1 s upper left second molar exceeded 2 SD, whereas that of the upper left first molar was smaller than3 SD. In addition, the crown lengths of her upper right canine, upper right first premolar, upper right second molar, upper left second molar, and lower right first premolar exceeded 3 SD, and that of her lower left first premolar was larger than 2 SD. However, the crown lengths of the patient s FIGURE 6 Panoramic roentgenogram of 2. FIGURE 8 3: oral findings.

470 Cleft Palate Craniofacial Journal, September 2005, Vol. 42 No. 5 FIGURE 9 Panoramic roentgenogram of 3. upper right lateral incisor and upper left central incisor were smaller than3 SD, and those of her upper right central incisor and lower central incisor were smaller than 2 SD. The root lengths of her upper right central incisor, upper right lateral incisor, upper right canine, upper right first molar, upper right second molar, upper left central incisor, upper left first premolar, upper left first molar, upper left second molar, lower left canine, lower left first premolar, lower left first molar, lower left second molar, lower right central incisor, lower right canine, lower right first premolar, lower right first molar, and lower right second molar exceeded 3 SD (Table 2). For 2, crown widths of the upper right lateral incisor and lower right central incisor exceeded 2 SD, whereas those of the lower left first molar and lower right first molar were smaller than3 SD. The patient s crown lengths of the upper right central incisor, upper right lateral incisor, and lower left first molar exceeded 3 SD, and that of her lower right first molar was larger than 2 SD. However, the crown lengths of her upper right first molar, upper left first molar, lower left central incisor, and lower right central incisor were smaller than3 SD. The root lengths of her upper right central incisor, upper right first molar, upper left first molar, lower left central incisor, lower left canine, lower left first molar, lower right central incisor, lower right lateral incisor, and lower right first molar exceeded 3 SD, and that of her upper right lateral incisor was larger than 2 SD (Table 3). 3 s upper right central incisor, upper right canine, upper left central incisor, upper left canine, lower left canine, lower left first premolar, lower right canine, and lower right first premolar crown widths exceeded 3 SD, and that of her upper right second premolar was larger than 2 SD. The crown width of her upper left lateral incisor was smaller than3 SD and that of her upper right second premolar was smaller than2 SD. The crown lengths of her upper right central incisor, upper right canine, upper left canine, upper left second premolar, upper left first molar, lower left canine, lower left first premolar, lower right canine, and lower right first premolar exceeded 3 SD, and that of her lower left lateral incisor was larger than 2 SD (Table 4). Cephalometric Analysis Angular measurements, linear measurements, and profilograms were obtained from lateral cephalograms, and angular FIGURE 10 Physical parameters of the head and face. (1) Total head height: vertical distance from the vertex to the menton; (2) face breadth: maximum distance between the zygomas measured by calipers; (3) philtrum length: distance from the base of the columella to the midline depression of the vermilion border; (4) upper lip thickness: distance at the midline from the vermilion border of the upper lip to the aperture; (5) lower lip thickness: distance at the midline from the vermilion border of the lower lip to the aperture. measurements included the anteroposterior position of the maxillary (SNA), anteroposterior position of the mandible (SNB), the SNA-SNB difference (ANB), gonial angle, ramus inclination, and mandibular plane angle (Fig. 11). The values obtained were then compared with standards (Downs, 1948; Graber, 1952; Iizuka and Ishikawa, 1957; Iizuka, 1958). Linear measurements included midface depth/total cranial base length (Ba-A/Ba-N; %), anterior lower facial height/total facial height (ANS-Me/N-Me; %), mandibular ramus height/total facial height (Ar-Go/N-Me; %), total cranial base length/total facial height (N-Me/Ba-N; %), and direct length of mandibular ramus height (Ar-Go). All linear measurements in Figure 12 TABLE 1 1 2 3 Facial Measurements* Total Head Height (cm) 26.50 26.60 24.50 Face Breadth (cm) ** 14.80 12.70 13.40 Philtrum Length (cm) ** 2.00 1.50 1.60 ** Upper Lip Thickness (cm) 0.95 1.20 1.40 ** Lower Lip Thickness (cm) 1.22 1.45 1.60 * Patients larger than controls; ** beyond 2 SD, but not more than 3 SD; beyond 3 SD; 1 18 years, 0 months old; 2 11 years, 7 months old; 3 28 years, 4 months old.

Tsukawaki et al., THREE CASES OF OCULO-FACIO-CARDIO-DENTAL (OFCD) SYNDROME 471 TABLE 2 Summary of Tooth Crown Width, Crown Length, Root Length ( 1)* 1 Tooth (FDI Numbering System) Tooth Crown Width Crown Length Root Length Upper 11 12 13 14 15 16 17 21 22 23 24 25 26 27 8.30 6.50 10.40 10.50 8.60 10.10 10.30 8.1 0.55 7.0 0.46 7.6 0.26 7.2 0.42 7.0 0.28 9.9 0.23 9.4 0.72 8.1 0.55 7.0 0.46 ## ### ### 7.6 0.26 7.2 0.42 7.0 0.28 9.9 0.23 9.4 0.72 9.50 6.00 12.70 8.70 7.30 8.60 8.80 7.60 7.40 8.90 10.5 0.41 9.2 0.58 9.8 0.91 7.6 0.36 7.0 0.60 6.7 0.39 6.8 0.56 10.5 0.41 9.2 0.58 9.8 0.91 7.6 0.36 7.0 0.60 6.7 0.39 6.8 0.56 31.60 18.00 26.50 12.30 17.10 13.40 36.60 21.00 15.10 13.80 12.1 0.84 12.2 0.83 15.0 1.14 12.6 0.71 13.5 1.71 11.6 1.60 11.6 0.61 12.1 0.84 12.2 0.83 15.0 1.14 12.6 0.71 13.5 1.71 11.6 1.60 11.6 0.61 Lower 31 32 33 34 35 36 37 41 42 43 44 45 46 47 ### 5.80 10.10 12.50 11.30 11.48 5.3 0.32 6.0 0.57 6.4 0.32 7.1 0.10 7.1 0.19 11.0 0.17 11.0 0.71 5.3 0.32 6.0 0.57 6.4 0.32 7.1 0.10 7.1 0.19 11.0 0.17 11.0 0.71 ## 7.20 10.50 ** 8.90 6.70 5.40 11.10 9.80 6.60 7.20 8.8 0.80 9.1 0.87 9.8 1.09 7.9 0.49 7.3 0.76 6.5 0.68 6.3 1.01 8.8 0.80 9.1 0.87 9.8 1.09 7.9 0.49 7.3 0.76 6.5 0.68 6.3 1.01 30.30 29.80 19.70 21.30 17.00 32.50 26.00 16.60 18.70 11.0 1.00 12.3 1.23 14.5 1.13 13.5 0.67 13.2 1.23 12.6 0.59 12.5 0.38 11.0 1.00 12.3 1.23 14.5 1.13 13.5 0.67 13.2 1.23 12.6 0.59 12.5 0.38 * Based on FDI tooth numbering system (http://dentalfox.ca/faqs/fdinumbering.html; accessed June 30, 2005): not erupted; not measured; Patient larger than control: ** beyond 2 SD but not over 3 SD; beyond 3 SD; Patient smaller than control: ## beyond 2 SD, but not more than 3 SD; ### beyond 3 SD. are percentages, except Ar-Go (actual length). The values obtained were also compared with those of standards (Coben, 1955; Miura et al., 1960; Mitani, 1977). For the profilograms, nasion (N); orbitale (Or); anterior nasal spine (ANS); point A (A); upper incisor (U1); lower incisor (L1); point B (B); pogonion (Pog); menton (Me); gonion (Go); and articulare (Ar) were measured (Fig. 13), and the values obtained were compared with standards (Sakamoto, 1959). Regarding 1 s angular measurements, SNA and ANB were nearly 1 SD, whereas the gonial angle and mandibular plane angle exceeded 3 SD. Among the linear measurements, Ar-Go/N-Me (%) was smaller than 2 SD, and Ar-Go/ N-Me (actual length) was nearly 1 SD. In contrast, ANS- Me/N-Me (%) exceeded 3 SD, and N-Me/Ba-N (%) was nearly 4 SD (Table 5). The profilogram showed that point A was positioned posteriorly and the presence of a long face was accompanied by a steep mandible and large gonial angle (Fig. 14). For 2, SNA exceeded 1 SD, SNB exceeded 2 SD, the gonial angle exceeded 3 SD, and the mandibular plane angle exceeded 4 SD, whereas ANB was 1.9. N-Me/Ba-N (%) was nearly 3 SD, and ANS-Me/N-Me (%) exceeded 3 SD (Table 5). The profilogram showed that point A and point B were positioned anteriorly, although point B was more severe. Her long face was characterized by a steep mandible and large gonial angle (Fig. 14). For 3, SNA and ANB were nearly 2 SD, SNB was nearly 1 SD, the ramus inclination exceeded 1 SD, the mandibular plane angle exceeded 2 SD, and the gonial angle exceeded 3 SD. Ar-Go/N-Me (%) was smaller than 1 SD. In contrast, ANS-Me/N-Me (%) exceeded 1 SD, and N-Me/ Ba-N (%) was nearly 6 SD (Table 5). The profilogram showed that point A was positioned posteriorly. Her long face was characterized by a steep mandible and large gonial angle (Fig. 14). Differential Diagnosis DISCUSSION OFCD syndrome has been misdiagnosed as rubella embryopathy (Wilkie et al., 1993; Aalfs et al., 1996; Bartbelemy et al., 2001; Kawamoto et al., 2004). However, differential diagnosis is made possible by the presence of dental anomalies in permanent dentition and by the absence of maternal rubella infection during pregnancy. Similar to the previous 17 reports on OFCD syndrome, the four main symptoms (including ocular, facial, cardiac, and dental findings) were recognized in the present patients (Table 6). According to these findings, two

472 Cleft Palate Craniofacial Journal, September 2005, Vol. 42 No. 5 TABLE 3 Summary of Tooth Crown Width, Crown Length, Root Length ( 2) 2 Tooth (FDI Numbering System) Tooth Crown Width Crown Length Root Length Upper 11 12 13 14 15 16 17 21 22 23 24 25 26 27 ** 9.20 7.50 10.30 10.40 8.1 0.55 7.0 0.46 7.6 0.26 7.2 0.42 7.0 0.28 9.9 0.23 9.4 0.72 8.1 0.55 7.0 0.46 7.6 0.26 7.7 0.42 7.0 0.28 9.9 0.23 9.4 0.72 12.70 10.70 ### 5.50 ### 5.40 10.5 0.41 9.7 0.58 9.8 0.91 7.6 0.36 7.0 0.60 6.7 0.39 6.8 0.56 10.5 0.41 9.7 0.58 9.8 0.91 7.6 0.36 7.0 0.60 6.7 0.39 6.8 0.56 ** 21.10 14.30 14.50 17.60 12.1 0.84 12.2 0.83 15.0 1.14 12.6 0.71 13.5 1.71 11.6 1.60 11.6 0.61 12.1 0.84 12.2 0.83 15.0 1.14 12.6 0.71 13.5 1.71 11.6 1.60 11.6 0.61 Lower 31 32 33 34 35 36 37 41 42 43 44 45 46 47 5.90 ### 10.30 ** 6.10 ### 10.40 5.3 0.32 6.0 0.57 6.4 0.32 7.1 0.10 7.1 0.19 11.0 0.17 11.0 0.71 5.3 0.32 6.0 0.57 6.4 0.32 7.1 0.10 7.1 0.19 11.0 0.17 11.0 0.71 ### 6.80 9.40 8.70 ### 7.20 9.40 ** 7.40 8.8 0.80 9.1 0.87 9.8 1.09 7.9 0.49 7.3 0.76 6.5 0.68 6.3 1.01 8.8 0.80 9.1 0.87 9.8 1.09 7.9 0.49 7.3 0.76 6.5 0.68 6.3 1.01 21.20 19.80 15.80 19.40 18.40 20.40 11.0 1.00 12.3 1.23 14.5 1.13 13.5 0.67 13.2 1.23 12.6 0.59 12.5 0.38 11.0 1.00 12.3 1.23 14.5 1.13 13.5 0.67 13.2 1.23 12.6 0.59 12.5 0.38 * Based on FDI tooth numbering system (http://dentalfox.ca/faqs/fdinumbering.html; accessed June 30, 2005): not erupted; not measured; Patient larger than control: ** beyond 2 SD but not over 3 SD; beyond 3 SD; Patient smaller than control: ## beyond 2 SD, but not more than 3 SD; ### beyond 3 SD. new cases were diagnosed as having OFCD syndrome; 3 had been shown previously to have OFCD syndrome (Kawamoto et al., 2004). Facial Measurements The facial findings reported were a long face and a long philtrum. Measurements of head circumference (Wilkie et al., 1993; Aalfs et al., 1996; Schulze et al., 1999; Hedera and Gorski, 2003), inner canthal distance (Wilkie et al., 1993), and corneal diameters (Wilkie et al., 1993; Aalfs et al., 1996) also have been reported. Furthermore, only Wilkie et al. (1993) compared the measured values with standard values. All of our cases had a long face and thick upper and lower lips. Because thick lips have not been previously reported for OFCD syndrome, this finding could be useful in future studies. Tooth Measurements Regarding tooth size, macrodontia (Hayward, 1980; Wilkie et al., 1990; Kawamoto et al., 2004), microdontia (Aalfs et al., 1996; Schulze et al., 1999; Bartbelemy et al., 2001; Kawamoto et al., 2004), and long dental root (Hayward, 1980; Marashi and Gorlin, 1990; Wilkie and Chambers, 1990; Wilkie et al., 1993; Aalfs et al., 1996; Obwegeser and Gorlin, 1997; Schulze et al., 1999; Bartbelemy et al., 2001; Hedera and Gorski, 2003; Kawamoto et al., 2004) have been reported. However, actual length has been measured only for extracted incisors and canine teeth (Hayward, 1980; Wilkie et al., 1990) and only by radiographs of the upper canine teeth (Marashi and Gorlin, 1990). For the present cases, macrodontia and long dental root were significantly greater than normal (Fujita, 1995), where the crown width and crown and root length exceeded 2 SD. For cases 1, 2, and 3, the crown width exceeded 2 SDfor teeth 1, 2, and 9, respectively; for s 1 and 3, the crown length exceeded 2 SD for teeth 1 and 8, respectively. In addition, teeth 18, 10, and 9 were classified as long dental root for s 1, 2, and 3, respectively. Such tooth size abnormalities are generally assumed to arise during the morphological differentiation period of tooth germ cells (Schour and Massler, 1940). With respect to tooth size, anomalies in tooth root length are also assumed to be prevalent in the upper incisors and canine teeth, as well as in the lower premolars and molars, whereas anomalies of crown width are prevalent in the upper central incisors (Akagi and Takeuchi, 1985; Ishikawa and Akiyoshi, 1989). Macrodontia and long dental root throughout the entire dentition rarely have been reported, except for this syndrome. Most reports on this syndrome have noted a long dental root in the incisor, canine, and first premolar (Hayward, 1980; Marashi and Gorlin, 1990; Wilkie and Chambers, 1990; Wilkie et al., 1993; Aalfs et al., 1996; Obwegeser and Gorlin, 1997; Schulze et al., 1999; Bartbelemy et al., 2001; Kawamoto et

Tsukawaki et al., THREE CASES OF OCULO-FACIO-CARDIO-DENTAL (OFCD) SYNDROME 473 TABLE 4 Summary of Tooth Crown Width, Crown Length, Root Length ( 3) 3 Tooth (FDI Numbering System) Tooth Crown Width Crown Length Root Length Upper 11 12 13 14 15 16 17 21 22 23 24 25 26 27 ### ## 10.00 8.90 7.45 10.10 8.50 9.40 4.90 8.90 6.30 9.70 9.50 8.1 0.55 7.0 0.46 7.6 0.26 7.2 0.42 7.0 0.28 9.9 0.23 9.4 0.72 8.1 0.55 7.0 0.46 7.6 0.26 7.2 0.42 7.0 0.28 9.9 0.23 9.4 0.72 11.90 13.98 7.87 6.94 7.46 10.66 14.95 9.22 8.90 7.31 10.5 0.41 9.2 0.58 9.8 0.91 7.6 0.36 7.0 0.60 6.7 0.39 6.8 0.56 10.5 0.41 9.2 0.58 9.8 0.91 7.6 0.36 7.0 0.60 6.7 0.39 6.8 0.56 22.0 30.24 13.16 13.59 12.15 23.23 30.30 12.83 11.13 10.54 12.1 0.84 12.2 0.83 15.0 1.14 12.6 0.71 13.5 1.71 11.6 1.60 11.6 0.61 12.1 0.84 12.2 0.83 15.0 1.14 12.6 0.71 13.5 1.71 11.6 1.60 11.6 0.61 Lower 31 32 33 34 35 36 37 41 42 43 44 45 46 47 7.55 8.35 10.70 11.35 6.45 7.80 8.00 7.65 11.35 5.3 0.32 6.0 0.57 6.4 0.32 7.1 0.10 7.1 0.19 11.0 0.17 11.0 0.71 5.3 0.32 6.0 0.57 6.4 0.32 7.1 0.10 7.1 0.19 11.0 0.17 11.0 0.71 14.95 11.92 7.63 6.67 8.90 12.92 12.09 8.01 7.17 8.8 0.80 9.1 0.87 9.8 1.09 7.9 0.49 7.3 0.76 6.5 0.68 6.3 1.01 8.8 0.80 9.1 0.87 9.8 1.09 7.9 0.49 7.3 0.76 6.5 0.68 6.3 1.01 28.87 19.54 11.61 11.87 15.58 23.08 15.81 11.83 12.61 11.0 1.00 12.3 1.23 14.5 1.13 13.5 0.67 13.2 1.23 12.6 0.59 12.5 0.38 11.0 1.00 12.3 1.23 14.5 1.13 13.5 0.67 13.2 1.23 12.6 0.59 12.5 0.38 * Based on FDI tooth numbering system (http://dentalfox.ca/faqs/fdinumbering.html; accessed June 30, 2005): not erupted; not measured; Patient larger than control: ** beyond 2 SD but not over 3 SD; beyond 3 SD; Patient smaller than control: ## beyond 2 SD, but not more than 3 SD; ### beyond 3 SD. TABLE 5 Cephalometric Measurements Measurement 1 Mean SD 2 Mean SD 3 Mean SD Angular () SNA () SNB () ANB () Gonial angle () Ramus inclination () Mandibular plane angle () # 79.60 78.10 1.50 139.50 2.10 47.40 82.32 78.90 3.39 122.23 2.93 28.81 3.45 3.45 1.77 4.61 4.40 5.23 * ** Horizontal (depth) Ba-A/Ba-N (%) 96.10 97.50 4.00 103.40 100.30 3.40 94.58 97.50 4.00 Vertical (height) ANS-Me/N-Me (%) Ar-Go/N-Me (%) ## 63.20 32.70 55.70 40.80 2.80 3.60 85.00 83.10 1.90 145.90 85.70 43.50 60.90 32.50 Vertical/Horizontal (ratio) N-Me/Ba-N (%) 143.30 124.30 4.80 146.80 126.80 6.60 153.61 124.30 4.80 Perimeter (mm) Ar-Go # 46.90 52.00 5.10 48.90 44.90 5.30 52.49 52.00 5.10 Patient larger than control * beyond 1 SD, but not more than 2 SD; ** beyond 2 SD, but not more than 3 SD; beyond 3 SD; Patient smaller than control: # beyond 1 SD, but not more than 2 SD; ## beyond 2 SD, but not more than 3 SD; ### beyond 3 SD. For explanation of abbreviations, see captions for Figures 11 and 12. 80.91 76.15 129.20 82.62 31.98 54.30 34.90 3.07 2.84 4.65 5.55 2.40 1.90 3.10 ## # # * ** * # 75.10 75.00 0.10 140.00 10.30 39.70 59.90 33.62 82.32 78.90 3.39 122.23 2.93 28.81 55.70 40.80 3.45 3.45 1.77 4.61 4.40 5.23 2.80 3.60

474 Cleft Palate Craniofacial Journal, September 2005, Vol. 42 No. 5 FIGURE 11 Cephalometric landmarks and angular measurements. S sella turcica; N nasion; Or orbitale; A point A; B point B; Me menton; Go gonion; Ar articulare; Po porion. Angular measurements: (1) anteroposterior position of the maxillary ( SNA); (2) anteroposterior position of the mandible ( SNB); (3) SNA-SNB difference ( ANB); (4) gonial angle ( Ar-Go-Me); (5) ramus inclination ( FH-ramus plane); and (6) mandibular plane angle ( FH-mandibular plane). FIGURE 13 Profilogram according to Sakamoto (1959). S sella turcica; N nasion; Or orbitale; ANS anterior nasal spine; A point A; U1 upper incisor; L1 lower incisor; B point B; Pog pogonion; Me menton; Go gonion; Ar articulare. Abscissa: FH-parallel line through S; Ordinate: FH-perpendicular line through S. al., 2004), and only a few reports have noted long dental roots for all teeth from the incisors to the molars (Aalfs et al., 1996; Schulze et al., 1999). In the present study, long dental roots were found from the incisors to the molars for s 1 and 2, but a long dental root for the incisor, canine, and first premolar were noted for 3. In our cases, the abnormalities were found not only in the size of the teeth, but also in their number, shape, structure, time of eruption, and position. Accordingly, these abnormalities may be due to aberrations during morphological differentiation of tooth germ cells and over the process of tooth development. Cephalometric Analysis FIGURE 12 Cephalometric landmarks and linear measurements. N nasion; Or orbitale; A point A; Me menton; Go gonion; Ar articulare; Po porion; Ba basion. Linear measurements: midface depth (1)/total cranial base length (2) [Ba-A/Ba-N (%)]; anterior lower facial height (3)/total facial height (4) [ANS-Me/N-Me (%)]; mandibular ramus height (5)/total facial height (4) [Ar-Go/N-Me (%)]; total cranial base length (2)/total facial height (4) [N-Me/Ba-N (%)]; and direct length of mandibular ramus height (6) [Ar-Go (actual length)]. Although various phenotypes such as micrognathia (Wilkie et al., 1993), mandibular protrusion (Aalfs et al., 1996; Bartbelemy et al., 2001), long lower face (Bartbelemy et al., 2001), and other conditions have been reported for cephalometric studies on this syndrome, there are few reports based on cephalometric analysis with angular measurements, linear measurements, and profilograms. This study revealed a small ANB, relative mandibular protrusion, large gonial angle, steep mandible, large N-Me/Ba-N (%), and ANS-Me/N-Me (%), which reflect a long face for all three cases. In addition to the above characteristic skeletal pattern, our cases have severe deep bite

Tsukawaki et al., THREE CASES OF OCULO-FACIO-CARDIO-DENTAL (OFCD) SYNDROME 475 TABLE 6 Summary of Clinical Findings in 16 Patients With OFCD Syndrome* Ocular Findings Congenital cataract Microphthalmia microcornea Regressive vision impairment Secondary glaucoma Facial Findings High nasal bridge Broad nasal tip separated nasal cartilages Long face (long narrow face, narrow face) Long philtrum Eyebrows laterally curved and thick Previously Reported s 1 2 3 14/16, 2 s 11/16, 4 s 10/16, 6 s 8/16, 7 s 10/16, 6 s 12/16, 4 s 9/16, 6 s 5/16, 9 s 7/16, 7 s Cardiac Findings ASD, VSD, mitral valve prolapse, cardiomegaly 10/16, 4 s Dental findings 1. Tooth number anomalies Oligodontia, hypodontia 8/16, 6 s 2. Tooth size anomalies Macrodontia Microdontia Long dental root (radiculomegaly) 3. Tooth shape anomalies Tubercle anomalies Root dilaceration (open apex) 2/16, 13 s 5/16, 10 s 14/16, 2 s 3/16, 11 s 13/16, 3 s 4. Tooth structural anomalies Amylogenesis imperfecta (enamel hypoplasia) 2/16, 14 s 5. Tooth eruption anomalies Delayed primary dentition Delayed secondary dentition Persistent primary teeth 3/16, 13 s 11/16, 3 s 10/16, 5 s 6. Malposition, malocclusion 12/16, 4 s Oral findings Extreme overjet, overbite Cleft palate, submucous cleft palate 5/16, 11 s 8/16, 4 s Limb findings 1. Hand findings Radioulnar synostosis 1/16, 15 s 2. Foot findings Leg/foot/toe length (asymmetry) Syndactyly of toe 6/16, 10 s 11/16, 3 s Camptodactyly (hammer-type flexion of toes, clinodactyly) 4/16, 11 s * OFCD oculo-facio-cardio-dental syndrome; not mentioned; present; absent; ASD atrial septal defect; VSD ventricular septal defect. occlusion, which may be due to the long crown length of the upper and lower incisors without clockwise rotation of the mandible. CONCLUSIONS As reflected in the clinical findings, this syndrome is a rare condition characterized by ocular, facial, cardiac, dental, and other anomalies. In this study, the diagnosis of OFCD syndrome was established for two new cases on the basis of clinical findings. For three cases, including one case of OFCD syndrome reported by Kawamoto et al. (2004), facial measurements, tooth measurements, and cephalometric analysis were made, and the following results were obtained: 1. A long face and thick upper and lower lips were noted from facial measurements for all cases. 2. A long crown length and long dental root were noted from tooth measurements for all cases. For s 1 and 2, long dental roots were noted for teeth from the incisors to the molars. For 3, long dental roots were found in the incisors, canine teeth, and first premolars; macrodontia was noted for many teeth, including the upper central incisors. 3. Cephalometric analysis revealed relative mandibular protrusion and a large anterior lower facial height accompanied by a steep mandible and large gonial angle. Acknowledgments. We are grateful to Dr. Hiromichi Komori, Assistant Professor, Section of Orthopedic Spinal Surgery, Department of Frontier Surgical Therapeutics, Division of Advanced Therapeutical Sciences, Graduate School of Tokyo Medical and Dental University, Tokyo, Japan, for his useful comments. We also thank Dr. Shoichi Suzuki, Lecturer, Section of Maxillofacial Orthognathics, Department of Maxillofacial Reconstruction and Function, Division of Maxillofacial/Neck Reconstruction, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan, for his advice.

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