Dental Anomalies Associated with Craniometaphyseal Dysplasia

Abstract

Craniometaphyseal dysplasia (CMD) is a rare genetic disorder encompassing hyperostosis of craniofacial bones and metaphyseal widening of tubular bones. Dental abnormalities are features of CMD that have been little discussed in the literature. We performed dentofacial examination of patients with CMD and evaluated consequences of orthodontic movement in a mouse model carrying a CMD knock-in (KI) mutation (Phe377del) in the Ank gene. All patients have a history of delayed eruption of permanent teeth. Analysis of data obtained by cone-beam computed tomography showed significant bucco-lingual expansion of jawbones, more pronounced in mandibles than in maxillae. There was no measurable increase in bone density compared with that in unaffected individuals. Orthodontic cephalometric analysis showed that patients with CMD tend to have a short anterior cranial base, short upper facial height, and short maxillary length. Microcomputed tomography (micro-CT) analysis in homozygous Ank (KI/KI) mice, a model for CMD, showed that molars can be moved by orthodontic force without ankylosis, however, at a slower rate compared with those in wild-type Ank (+/+) mice (p < .05). Histological analysis of molars in Ank (KI/KI) mice revealed decreased numbers of TRAP(+) osteoclasts on the bone surface of pressure sides. Based on these findings, recommendations for the dental treatment of patients with CMD are provided.

Keywords: ANKH; cone-beam computed tomography; craniofacial abnormalities; mouse model; orthodontics; tooth eruption.

Conflict of interest statement

The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article.

© International & American Associations for Dental Research.

Figures

Figure 1.

Dentofacial examination of patients with craniometaphyseal dysplasia (CMD). (A) Summary of patient ages, genders, and ANKH mutations. (B) Facial features of a patient with CMD with hypertelorism and a flat nasal bridge. (C) Intra-oral photographs of upper and lower arches. Arrows indicate palatal and lingual tori of a 14-year-old patient with CMD. (D) Representative axial and coronal views of cone-beam computed tomography (CBCT) images from a patient with CMD. Expansion of maxillae and thickening of cranial bones are indicated by black arrows and white arrows, respectively. (E) Representative sagittal and axial views (left panel) and coronal view (right panel) showed hypoplastic/partial obliteration of paranasal sinuses. 1, sphenoid sinus; 2, ethmoid sinus; 3, maxillary sinus; 4, frontal sinus. (F) CBCT image showing an expanded mandible, indicated by black arrows, in a patient with CMD.

Figure 2.

Orthodontic tooth movement in a craniometaphyseal dysplasia (CMD) mouse model. (A) microcomputed tomography (micro-CT) images (left panel) of maxillae from male 12-week-old Ank+/+ and AnkKI/KI mice with or without orthodontic force for 14 days. Distances between first and second molars are indicated by red arrows. The histogram (right panel) shows that distances are significantly smaller in AnkKI/KI mice (*p < .05; Student’s t test). (B) Histogram shows that the periodontal ligament area is significantly narrower on pressure sides compared with tension sides after 7 and 14 days of orthodontic tooth movement in Ank+/+ and AnkKI/KI mice (*p < .05; two-way analysis of variance [ANOVA]). Sections measured for each group: Ank+/+ day 7 (n = 11), AnkKI/KI day 7 (n = 8), Ank+/+ day 14 (n = 12), and AnkKI/KI day 14 (n = 8). (C) Histogram showing percentage increase or decrease of PDL area on pressure sides after 7 and 14 days of orthodontic tooth movement compared with that on mesial sides of contralateral control teeth without orthodontic force in Ank+/+ and AnkKI/KI mice (*p < .05; one-way ANOVA). Sections measured for each group: Ank+/+ day 7 (n = 11), and AnkKI/KI day 7 (n = 8). (D) Tartrate-resistant acid phosphatase (TRAP) staining of paraffin sections show alveolar bone (B) and root (R) on the pressure sides of Ank+/+ and AnkKI/KI mice after 7 and 14 days of orthodontic tooth movement. Yellow arrows indicate TRAP+ cells. Asterisk (*) shows root resorption. Double-ended white arrows indicate excessive cementum formation in AnkKI/KI mice. Scale bar = 100 μm. (E) Histogram showing decreased numbers of TRAP+ osteoclasts in AnkKI/KI mice after 7 and 14 days of orthodontic tooth movement (N.Oc/μm = number of osteoclasts/length of bones and roots on the pressure sides, *p < .05; one-way ANOVA).