Cleidocranial dysplasia: oral features and genetic analysis of 11 patients.
BACKGROUND
Cleidocranial dysplasia (CCD) is a dominantly inherited autosomal disease characterized by typical bone defects including short stature, persistently open or delayed closure of the cranial sutures, and hypoplastic or aplastic clavicles. Oral features are frequent and include supernumerary teeth, delayed eruption or impaction of the permanent teeth, and malocclusion. Heterozygous mutations in RUNX2 gene, which encodes a transcription factor essential for osteoblast differentiation, were identified as the etiological cause of CCD.


OBJECTIVE
Herein, we performed physical and radiographic examination and screening for RUNX2 mutations in 11 patients from five families with CCD.


RESULTS
All patients demonstrated the classical phenotypes related to CCD. Families whose affected members had several dental alterations such as multiple impacted and supernumerary teeth demonstrated heterozygous missense mutations (R190Q and R225Q) that impair the runt domain of RUNX2. On the other hand, CCD patients from families with low frequency of dental abnormalities showed no mutation in RUNX2 or mutation outside of the runt domain (Q292fs→X299).


CONCLUSIONS
The current findings suggest a correlation between dental alterations and mutations in the runt domain of RUNX2 in CCD patients. Further clinical and genetic studies are needed to clarify the relationship between phenotypes and genotypes in CCD and to identify other factors that might influence the clinical features of this uncommon disease.
Department of Oral Diagnosis, School of Dentistry, State University of Campinas, Piracicaba, São Paulo, Brazil.
A
A
Bufalino
L M R
LM
Paranaíba
A F
AF
Gouvêa
L A
LA
Gueiros
H
H
Martelli-Júnior
J J
JJ
Junior
M A
MA
Lopes
E
E
Graner
O P
OP
De Almeida
P A
PA
Vargas
R D
RD
Coletta
D000293:Adolescent; D000328:Adult; D002648:Child; D002973:Cleidocranial Dysplasia / Q000150:complications / Q000235:genetics*; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D005799:Genes, Dominant; D006579:Heterozygote; D006801:Humans; D008297:Male; D008310:Malocclusion / Q000209:etiology / Q000235:genetics; D020125:Mutation, Missense; D010375:Pedigree; D017434:Protein Structure, Tertiary / Q000235:genetics; D014095:Tooth, Impacted / Q000209:etiology / Q000235:genetics*; D014096:Tooth, Supernumerary / Q000209:etiology / Q000235:genetics*; D055815:Young Adult
D050659:Core Binding Factor Alpha 1 Subunit; C493709:RUNX2 protein, human