Long-term dental outcomes in patients with fibrodysplasia ossificans progressiva: a report of three cases of tooth extraction.

Fibrodysplasia ossificans progressiva (FOP) is an extremely rare autosomal dominant disorder characterized by congenital skeletal malformation and progressive heterotopic ossification. In the oral and maxillofacial region, deformity of the temporomandibular joint is a common feature of FOP, as well as restricted mouth opening derived from heterotopic ossification in the masticatory muscles. Since surgical procedures are generally not recommended because of the risk of flare-ups and increased heterotopic ossification, reports of tooth extractions and their outcomes in patients with FOP are limited. The present article reports the long-term oral outcomes of three Japanese patients with FOP, in whom the teeth were deliberately extracted to avoid the risk of oral inflammation causing further heterotopic ossification. The extractions were conducted under local or general anesthesia, and healing of sockets was nonproblematic with the formation of new bone. Undesirable events, including progression of heterotopic ossification in the oral and maxillofacial region and further restriction of mouth opening, were not apparent. The extractions also alleviated the existing inflammation, contributing to maintaining their oral hygiene. These cases suggest that deliberate planning and judicious surgery could induce favorable healing after tooth extractions in patients with FOP, leading to long-term stability of their oral health status.

Dental Arch Relationship Outcomes Following 2-Stage Palatoplasty for Japanese Patients With Complete Unilateral Cleft Lip and Palate: A 3-Center Study.

OBJECTIVE: To compare dental arch relationship outcomes following 3 different 2-stage palatal repair protocols. DESIGN: Retrospective, cross sectional. SETTING: Three cleft palate centers (A, B, C) in Japan. PATIENTS: Ninety (A: 39, B: 26, C: 25) consecutively treated Japanese patients with complete unilateral cleft lip and palate. INTERVENTIONS: In A, the soft palate and the posterior half of the hard palate were repaired at a mean age of 1 year 7 months. In B, the soft palate and hard palate were closed separately at a mean age of 1 year 6 months and 5 years 8 months, respectively. In C, the soft palate and hard palate were closed at a mean age of 1 year and 1 year 5 months, respectively. MAIN OUTCOME MEASURES: Dental arch relationships were assessed using the 5-Year-Olds' (5-Y) index by 5 raters and the Huddart/Bodenham (HB) index by 2 raters. RESULTS: Intra- and inter-rater reliabilities showed substantial or almost perfect agreement for the 5-Y and HB ratings. No significant differences in mean values and distributions of 5-Y scores were found among the 3 centers. The mean HB index scores of molars on the minor segment were significantly smaller in C than those in A and B (P < .05). CONCLUSIONS: There were no significant differences in dental arch relationships at 5 years among the times and techniques of hard palate closure. However, further analysis of the possible influence of infant cleft size as a covariable on a larger sample size is needed.

A Survey of Orthodontic Treatment in Team Care for Patients With Syndromic Craniosynostosis in Japan.

OBJECTIVE: To understand the actual condition of orthodontic treatment in team care for patients with syndromic craniosynostosis (SCS) in Japan. DESIGN: A nationwide collaborative survey. SETTING: Twenty-four orthodontic clinics in Japan. PATIENTS: A total of 246 patients with SCS. MAIN OUTCOME MEASURE: Treatment history was examined based on orthodontic records using common survey sheets. RESULTS: Most patients first visited the orthodontic clinic in the deciduous or mixed dentition phase. Midface advancement was performed without visiting the orthodontic clinic in about a quarter of the patients, and more than a half of the patients underwent "surgery-first" midface advancement. First-phase orthodontic treatment was carried out in about a half of the patients, and maxillary expansion and protraction were performed. Tooth extraction was required in about two-thirds of patients, and the extraction of maxillary teeth was required in most patients. Tooth abnormalities were found in 37.8% of patients, and abnormalities of maxillary molars were frequently (58.3%) found in patients who had undergone midface surgery below the age of 6 years. CONCLUSIONS: Many patients underwent "surgery-first" midface advancement, and visiting the orthodontic clinic at least before advancement was considered desirable. First-phase orthodontic treatment should be performed considering the burden of care. Midface advancement below the age of 6 years had a high risk of injury to the maxillary molars. This survey is considered useful for improving orthodontic treatment in team care of patients with SCS.

Dental arch relationship outcomes in one- and two-stage palatoplasty for Japanese patients with complete unilateral cleft lip and palate.

OBJECTIVE: To compare dental arch relationship outcomes following one- and two-stage palatal repair. DESIGN: Nonrandomized, clinical trial with concurrent control. SETTING: Hokkaido University Hospital. PATIENTS: Sixty-eight consecutively treated Japanese patients with complete unilateral cleft lip and palate. INTERVENTIONS: Thirty-one of the 68 patients underwent two-stage palatoplasty with delayed hard palate closure, and 37 patients underwent one-stage pushback palatoplasty. MAIN OUTCOME MEASURES: Dental casts were taken at 4.9 to 6.3 (mean: 5.2) years of age in the two-stage group and at 4.0 to 6.3 (mean: 5.1) years of age in the one-stage group, and dental arch relationships were assessed using the 5-Year-Olds' Index (5-Y) by four raters and the Huddart/Bodenham Index (HB) by two raters. RESULTS: Intrarater and interrater reliabilities evaluated using weighted kappa statistics were good or better for the 5-Y and HB ratings. The mean 5-Y score was 2.94 in the two-stage group and 3.13 in the one-stage group (P value was not significant). However, there was a significant difference in distributions between the groups (P < .05). The HB scores of molars were significantly greater in the two-stage group than in the one-stage group (P < .05). The rank correlation coefficients between the 5-Y and total HB score (ρ = -0.840, P < .01) and between the 5-Y and the score of the incisors in the HB (ρ = -0.814, P < .01) were significantly increased. CONCLUSIONS: These results suggest that the anteroposterior relationship was not significantly different between the groups, but the transversal relationship was better in the two-stage group than in the one-stage group.

Radiographic characteristics of the hand and cervical spine in fibrodysplasia ossificans progressiva.

Fibrodysplasia ossificans progressiva (FOP) is a disabling heritable disorder of connective tissue characterized by progressive heterotopic ossification in various extraskeletal sites. Early correct diagnosis of FOP is important to prevent additional iatrogenic harm or trauma. Congenital malformation of the great toes is a well-known diagnostic clue, but some patients show normal-appearing great toes. The thumb shortening and cervical spine abnormalities are other skeletal features often observed in FOP. This study aimed to address the quantitative assessment of these features in a cohort of patients with FOP, which potentially helps early diagnosis of FOP. Radiographs of the hand and cervical spine were retrospectively analyzed from a total of 18 FOP patients (9 males and 9 females) with an average age of 13.9 years (range 0.7-39.3 years). The elevated ratio of the second metacarpal bone to the distal phalanx of the thumb (> +1SD) was a consistent finding irrespective of the patient's age and gender. Infant FOP patients, in addition, exhibited an extremely high ratio of the second metacarpal bone to the first metacarpal bone (> +3SD). The height/depth ratio of the C5 vertebra increased in patients over 4 years of age (> +2SD). Additionally, the ratio of (height+depth) of the C5 spinous process to the C5 vertebral depth was markedly elevated in young patients (> +2SD). We quantitatively demonstrated the hand and cervical spine characteristics of FOP. These findings, which can be seen from early infancy, could be useful for early diagnosis of FOP even in patients without great toe abnormalities.

Maxillary protraction in patients with cleft lip and palate in mixed dentition: cephalometric evaluation after completion of growth.

Objective : To clarify the short- and long-term effects of maxillary protraction (MP) in mixed dentition in patients with unilateral cleft lip and palate (UCLP). Design : Retrospective study. Setting : University of Tokyo Hospital. Patients and Intervention : Eleven Japanese patients with UCLP in mixed dentition were treated with MP and followed up until the completion of growth. Multibracket treatment had been performed after MP treatment in all patients. Main Outcome Measure : Lateral cephalograms taken before and after MP and after completion of growth were used. Posterior and anterior vertical reference lines (PV, AV) were used to measure the horizontal movements of point A, pogonion, and maxillary first molar (U6). SNA, SNB, ANB, maxillary and mandibular length, mandibular plane angle, Wits value, upper incisor inclination, overjet, and overbite were also measured. Results : Large variation was found in the effects of MP, and five patients eventually required orthognathic surgery. In average change with MP, the maxilla showed favorable forward growth. Point A had moved forward from PV but not AV. The mandible rotated backward. However, ANB and the Wits value did not improve. U6 moved forward, and the overjet improved. After MP, the skeletal Class III relationship became severe. Conclusions : MP was effective as an early treatment for UCLP patients. However, its effects showed large variation and were in conflict with facial growth. Conscientious explanation of the expected effects and associated problems should be given to the patients/parents before its application.

Evaluation of mandibular hypoplasia in patients with hemifacial microsomia: a comparison between panoramic radiography and three-dimensional computed tomography.

OBJECTIVE: To compare the accuracy of three-dimensional computed tomography (3D-CT) and panoramic radiography in the evaluation of mandibular hypoplasia in patients with hemifacial microsomia (HFM). DESIGN: Retrospective study of imaging data. Setting : Images selected from the archives of the University of Tokyo Hospital. SUBJECTS: Twenty patients with unilateral HFM who had undergone both panoramic radiography and 3D-CT in the same period. METHOD: Mandibular deformities were classified according to the Pruzansky classification; eight patients had Grade I deformity and 12 patients had Grade II deformity. Ramus heights were measured on both panoramic radiographs and 3D-CT. MAIN OUTCOME MEASURES: Magnification in panoramic radiographs and extent of mandibular asymmetry as estimated by the affected/unaffected side ratio based on two methods were examined. The Pearson product-moment correlation coefficient was used to estimate correlations between parameters. RESULTS: The magnification of ramus heights on panoramic radiographs showed large variations in Grade II patients. The affected/unaffected side ratio estimated by the two methods showed a strong correlation in Grade I patients (correlation coefficient 0.99; p < .0001). Conversely, a weak correlation was seen in Grade II patients (correlation coefficient 0.77; p  =  .0036), and affected/unaffected side ratios from panoramic radiographs were both over- and underestimated. CONCLUSIONS: The accuracy of evaluation using panoramic radiography was fairly reliable in Grade I patients. Conversely, accuracy was poor in Grade II patients, and evaluation using 3D-CT seems preferable. The combination of two methods with careful consideration is recommended for clinical applications.

Facial morphology and occlusion of a patient with fibrodysplasia ossificans progressiva (FOP): a case report.

Fibrodysplasia ossificans progressiva (FOP) is a rare disease characterized by postnatal heterotopic ossification (HO). When HO affects the masticatory muscles, mouth opening becomes restricted. This paper presents the changes in facial morphology and occlusion of a patient with FOP who was followed from the age of 8 to age 21. At the initial examination, he had a severely protruded maxilla and Angle Class II Division 1 malocclusion. His mouth opening was restricted (5.0 mm). He had a large overjet and this enabled him to clean his teeth and to eat. Orthodontic correction was not planned, and his facial growth was closely followed with attention to his oral hygiene. The maxillary protrusion and a low mandibular plane angle became more prominent as the patient aged. His mandible rotated in a counterclockwise direction. His molars had delayed eruption or were impacted and seven were extracted. His mouth opening increased slightly and his oral hygiene improved to excellent.

Primary treatment for cleft lip and/or cleft palate in children in Japan.

OBJECTIVE: To investigate current trends in primary treatment for children with cleft lip and/or cleft palate in Japan. DESIGN: Nationwide, retrospective study under the direction of the Academic Survey Committee of the Japanese Cleft Palate Association based on analysis of data obtained via a booklet-style questionnaire completed by institutions providing primary treatment for cleft lip and/or palate patients. PARTICIPANTS, PATIENTS: Patients were 4349 children undergoing primary repair for cleft lip and/or palate at 107 participating institutions between 1996 and 2000. MAIN OUTCOME MEASURE(S): Cleft type, laterality; use of infant palatal plate; and timing and technique of primary repair for cleft lip and/or palate were evaluated by cleft surgeons at 107 participating institutions. RESULTS: Of a total of 2874 patients with cleft lip and palate or cleft palate only, infant palatal plates were used with 1087 (37.8%) and were not used with 1787 (62.2%). Primary unilateral lip repair was performed at the age of 2 to 6 months in more than 90% of patients. Bilateral cleft lip was treated by one-stage repair in 285 patients (44.5%) and by two-stage repair in 258 (40.2%). Primary one-stage palatal repair was performed in 2212 (76.9%) and two-stage palatal repair in 262 (9.1%) cleft palate patients. Information on treatment of the remaining 400 (14%) patients was unavailable. CONCLUSION: This investigation clarified current trends in primary treatment for cleft lip and/or palate in Japan. The results suggest the need for an increase in regional core hospitals and greater variation in treatment options.

A novel mutation of ALK2, L196P, found in the most benign case of fibrodysplasia ossificans progressiva activates BMP-specific intracellular signaling equivalent to a typical mutation, R206H.

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant congenital disorder characterized by progressive heterotopic ossification in muscle tissues. Constitutively activated mutants of a bone morphogenetic protein (BMP) receptor, ALK2, have been identified in patients with FOP. Recently, a novel ALK2 mutation, L196P, was found in the most benign case of FOP reported thus far. In the present study, we examined the biological activities of ALK2(L196P) in vitro. Over-expression of ALK2(L196P) induced BMP-specific activities, including the suppression of myogenesis, the induction of alkaline phosphatase activity, increased BMP-specific luciferase reporter activity, and increased phosphorylation of Smad1/5 but not Erk1/2 or p38. The activities of ALK2(L196P) were higher than those of ALK2(G356D), another mutant ALK2 allele found in patients with FOP and were equivalent to those of ALK2(R206H), a typical mutation found in patients with FOP. ALK2(L196P) was equally or more resistant to inhibitors in comparison to ALK2(R206H). These findings suggest that ALK2(L196P) is an activated BMP receptor equivalent to ALK2(R206H) and that ALK2(L196P) activity may be suppressed in vivo by a novel molecular mechanism in patients with this mutation.

Treatment of ankylosed maxillary central incisors by single-tooth dento-osseous osteotomy and alveolar bone distraction.

When tooth ankylosis occurs in growing children, the ankylosed tooth fails to erupt and gradually positions itself below the occlusal plane. This causes functional and esthetic problems, and orthodontic treatment is often impossible. To clarify this problem, we developed a new treatment protocol for the movement of ankylosed teeth. This consists of single-tooth dento-osseous osteotomy and alveolar bone distraction using orthodontic multibracket appliances. A special distraction device is not required, thus reducing the burden to patients. Two cases in which an ankylosed maxillary central incisor was successfully treated with this protocol are presented.

Deformity of the great toe in fibrodysplasia ossificans progressiva.

BACKGROUND: As invasive medical procedures can induce permanent heterotopic ossification in fibrodysplasia ossificans progressiva (FOP), caution should be exercised in clinical practice. The present study was conducted to examine the characteristics of the great toe deformity in patients with FOP, which may lead to an early diagnosis of this condition. METHODS: The subjects consisted of 31 feet from 16 FOP patients (8 males, 8 females) with an average age of 17.3 years (range 1-47 years) at the time of this study. Gross and radiographic findings, including the hallux valgus angles (HVA), intermetatarsal angles (IMA), and the deformity of the proximal phalanx and metatarsal bone, were examined. RESULTS: Of the 31 feet, 29 (93.5%) showed several degrees of great toe deformity. A shortened great toe was the typical gross finding and was observed in 20 feet (64.5%). The mean HVA and IMA were 19.7° and 8.5°, respectively; and 22 (71.0%) feet satisfied the radiographic definition of hallux valgus (HVA ≥ 20° or IMA ≥ 10°). The proximal phalanx was consistently shortened but morphologically dissimilar from case to case. The metatarsal bone was also shortened and sharpened to the medial side, deviating the proximal phalanx laterally from the metatarsal axis. Fusion between the distal and proximal phalanx occurred with advancing age. Only two feet in one patient showed no obvious deformity of the great toe. CONCLUSIONS: A shortened great toe and hallux valgus were frequently found in patients with FOP. Shortening and sharpening of the proximal phalanx and metatarsal bone consistently existed and contributed to the great toe deformity. These findings were thought to exist from birth and may be a key to an early diagnosis.

[Cytokines in bone diseases. BMP signaling and fibrodysplasia ossificans progressiva].

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder characterized by progressive heterotopic bone formation in skeletal muscle tissue. In 2007, FOP was authorized as one of the Intractable Disorders by the Ministry of Health, Labour and Welfare of Japan. The Research Committee on FOP is working on the molecular mechanisms underlying heterotopic bone formation and the development of new treatments for FOP.

Novel mutations of the HOXD13 gene in hand and foot malformations.

Homeobox genes encode a set of transcription factors of fundamental importance for body patterning during embryogenesis. Hoxa9-a13 and Hoxd9-d13 play an especially important part in vertebrate limb development. Synpolydactyly (SPD) is characterized by various malformations of the limbs. The expansion of the polyalanine tract in 1OXD13 is one of its major causes. Recently, there have been many analysis studies of HOXD13 in patients with SPD and limb malformations. We analyzed HOXD13 in 100 patients with limb malformations, which affects the limbs in the distal parts of the metacarpal and/or metatarsal bones. Seven mutations in the coding region and two mutations in the 5'-untranslated region were identified. All were novel mutations. In this study, the mutations were located upstream in the homeobox. Thus, translation of the homeobox was affected by upstream mutations. Consequently, this suggested the possibility that abnormalities in the hands and feet could be caused by novel HOXD13 gene mutations.

Segmental alveolar distraction for the correction of unilateral open-bite caused by multiple ankylosed teeth: a case report.

Ankylosed teeth fail to erupt to meet their counterparts in the opposite jaw. In cases where ankylosis occurs in multiple teeth, the occlusion shows an open bite. This article describes a case of unilateral open bite caused by multiple ankylosed teeth, where treatment involved segmental alveolar bone distraction. A 25-year-old female patient presented with a left-sided unilateral open bite. On the left-hand side, only the lower incisors were not ankylosed. On the right, the maxillary first molar was ankylosed. All these ankylosed teeth were positioned below the occlusal plane. Her mother and brother also had multiple ankylosed teeth, and a familial cause was considered. Orthodontic tooth movement was considered impossible and segmental osteotomy on the left maxillary alveolar bone and downward bone distraction were performed as an alternative. A distractor consisting of orthodontic bands, wires and screws was devised and worn in the left mandibular dentition. Multi-bracket orthodontic appliances were also used for distraction. The amount of vertical movement was 7 mm at the premolar region. Five months after distraction, the multibracket appliance was removed, and fixed and removable retainers were placed. Eight months after distraction, prosthodontic restorations on the occlusal surfaces of the ankylosed teeth were made to obtain the final occlusion. The unilateral open bite was successfully treated and a good occlusion was obtained. The occlusion has shown good long-term stability for more than 3 years.

Assessment of dental arch relationships in Japanese patients with unilateral cleft lip and palate.

OBJECTIVE: Evaluation of the dental arch relationships of Japanese patients with unilateral cleft lip and palate (UCLP) from the orthodontic clinic of the University of Tokyo Hospital (UTH) compared with patients treated by the Oslo Cleft Team, Norway. DESIGN: Retrospective study and comparison with previous reports. MATERIALS: Dental models of 24 patients with UCLP in UTH taken before orthodontic treatment and before alveolar bone grafting were included. Surgeons in many hospitals performed primary surgeries. These models were matched for age and gender with 24 models from a consecutive series of patients treated by the Oslo Cleft Team as part of the Eurocran Good Practice Archive. A total of 48 models were evaluated. MAIN OUTCOME MEASURE: Dental arch relationship was rated with the Goslon Yardstick. The strength of agreement of rating was assessed with weighted kappa statistics. RESULTS: Intra- and interexaminer agreements evaluated by weighted kappa statistics were high, indicating good reproducibility. Almost 60% of the patients in UTH were classified into poor or very poor categories, and the mean Goslon score was 3.50. These results show a contrast to those in Oslo and were the poorest in comparison with previous reports. CONCLUSION: Dental arch relationships in patients with UCLP in UTH were poor. This seemed to be attributable to surgical procedures, but a factor of racial difference in the craniofacial morphology was also considered. Further intercenter research is required to clarify this point.

Reconstruction necessitated by severe hypoplasia or a columella defect.

In reconstruction necessitated by severe hypoplasia or a columella defect, the surgeon must consider various factors in each case, such as the characteristic columellar shape, color match, texture, patient age, original disease, and surrounding scars. In these cases, reconstruction of both the cartilaginous strut and the overlying skin is necessary and important to obtain good results. The authors report three cases of reconstruction of the columella with satisfactory results. Case 1 involved a 6-year-old girl with complete bilateral cleft lip and severe hypoplasia of the premaxilla and prolabium. Columellar reconstruction was performed with small triangular flaps at the columella base, together with a rib chondral graft for cartilaginous support. Case 2 involved a 12-year-old girl with a complete bilateral cleft lip and cleft palate. Columellar reconstruction was performed with small triangular flaps at the columella base, together with bilateral conchal cartilage grafts. Case 3 involved a 17-year-old boy with a right complete cleft lip and columellar defect caused by previous infection after secondary cheiloplasty. Columellar reconstruction was performed using a left nasal vestibular flap and septal cartilage grafting, together with a bilateral conchal cartilage graft beneath the flap. The authors consider the unilateral nasal vestibular flap to be very useful in carefully selected unilateral cleft cases.

Targeting of iNOS with antisense DNA plasmid reduces cytokine-induced inhibition of osteoblastic activity.

Proinflammatry cytokines, tumor necrosis factor-alpha combined with interleukin-1beta, induce excessive production of nitric oxide (NO) and its cytotoxic metabolite peroxynitrite (ONOO-) via inducible nitric oxide synthase (iNOS) in murine osteoblasts. In this study, to properly estimate the effects of antisense DNA of iNOS on osteoblastic activity, we produced transformed cell lines with antisense plasmid that specifically targets the iNOS gene for potential long-lasting inhibition. Transformed antisense cell lines were identified by 1) the detection of antisense transcripts, 2) the attenuated expression of iNOS protein, 3) the reduction of NO synthase activity, and 4) the level of NO production. These cell lines targeting iNOS, which showed decreased production of both NO and ONOO-, prevented the inhibition of osteoblastic differentiation as was assayed by the mRNA expression of type I collagen, alkaline phosphatase, osteocalcin, and Core binding factor in the presence of proinflammatory cytokines. Present results indicate that the antisense DNA plasmid of iNOS is potent to reduce the cytokine-induced inhibition of osteoblastic activity.

The treatment of hemimandibular hyperplasia preserving enlarged condylar head.

OBJECTIVE: To present a case of hemimandibular hyperplasia (HH) treated with orthognathic surgery that preserves the condyle without disturbing mandibular function. METHODS: A 27-year-old woman with HH was treated with orthognathic surgery preserving the enlarged condylar head. Radiographic examination showed typical enlargement of the right condyle, elongation of the right ascending ramus and mandibular body, and tilted occlusal plane. A mandibular sagittal split osteotomy on the unaffected side and subcondylar ramus osteotomy on the affected side, Le Fort I wedge osteotomy to relevel the tilted occlusal plane, and contouring of the lower mandibular margin were performed. RESULTS: Excellent results in the full-face appearance and occlusion were obtained. There was no change in the size of the reserved condylar head 4 years postoperatively. In a series of examinations of jaw function with electromyography, mandibular kinesiography, and computer-aided diagnostic axiography, more favorable findings were obtained postoperatively. CONCLUSIONS: In a case of HH without abnormally high growth activity, orthognathic surgery preserving hypertrophic condyle produced functional improvement in addition to good occlusal and aesthetic outcomes.