Dental Anomalies Associated with Craniometaphyseal Dysplasia

J Dent Res. 2014 Jun;93(6):553-8. doi: 10.1177/0022034514529304. Epub 2014 Mar 24.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acid Phosphatase / analysis
  • Animals
  • Bone Density / physiology
  • Bone Diseases, Developmental / diagnostic imaging
  • Bone Diseases, Developmental / genetics*
  • Cephalometry / methods
  • Cone-Beam Computed Tomography / methods
  • Craniofacial Abnormalities / diagnostic imaging
  • Craniofacial Abnormalities / genetics*
  • Disease Models, Animal
  • Gene Knock-In Techniques
  • Humans
  • Hyperostosis / diagnostic imaging
  • Hyperostosis / genetics*
  • Hypertelorism / diagnostic imaging
  • Hypertelorism / genetics*
  • Isoenzymes / analysis
  • Mandible / diagnostic imaging
  • Maxilla / diagnostic imaging
  • Mice
  • Mutation / genetics
  • Osteoclasts / pathology
  • Phenylalanine / genetics
  • Phosphate Transport Proteins / genetics
  • Sequence Deletion
  • Skull Base / diagnostic imaging
  • Tartrate-Resistant Acid Phosphatase
  • Tooth Abnormalities / diagnostic imaging
  • Tooth Abnormalities / genetics*
  • Tooth Movement Techniques / methods
  • Vertical Dimension
  • X-Ray Microtomography / methods


  • Isoenzymes
  • Phosphate Transport Proteins
  • ank protein, mouse
  • Phenylalanine
  • Acid Phosphatase
  • Acp5 protein, mouse
  • Tartrate-Resistant Acid Phosphatase

Supplementary concepts

  • Schwartz-Lelek syndrome