Familial cleidocranial dysplasia misdiagnosed as rickets over three generations.
Cleidocranial dysplasia (CCD) is a rare autosomal dominant skeletal dysplasia characterized by hypoplastic clavicles, late closure of the fontanels, dental problems and other skeletal features. CCD is caused by mutations, deletions or duplications in runt-related transcription factor 2 (RUNX2), which encodes for a protein essential for osteoblast differentiation and chondrocyte maturation. We describe three familial cases of CCD, misdiagnosed as rickets over three generations. No mutations were detected on standard DNA sequencing of RUNX2, but a novel deletion was identified on quantitative polymerase chain reaction (qPCR) and multiple ligation-dependent probe amplification (MLPA). The present cases indicate that CCD could be misdiagnosed as rickets, leading to inappropriate treatment, and confirm that mutations in RUNX2 are not able to be identified on standard DNA sequencing in all CCD patients, but can be identified on qPCR and MLPA.
Pediatrics Unit, S. Chiara General Hospital, Trento, Italy.
Roberto
R
Franceschi
Pediatrics Unit, S. Chiara General Hospital, Trento, Italy.
Evelina
E
Maines
Pediatrics Unit, S. Chiara General Hospital, Trento, Italy.
Michela
M
Fedrizzi
Department of Evolutive Age, Medical Genetics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
Maria Rosaria
MR
Piemontese
Department of Evolutive Age, Medical Genetics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
Patrizia
P
De Bonis
Radiology Unit, S. Maria del Carmine, Rovereto, Italy.
Nivedita
N
Agarwal
Pediatrics Unit, S. Chiara General Hospital, Trento, Italy.
Maria
M
Bellizzi
Pediatrics Unit, S. Chiara General Hospital, Trento, Italy.
Annunziata
A
Di Palma
D000328:Adult; D000369:Aged, 80 and over; D002675:Child, Preschool; D002973:Cleidocranial Dysplasia / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D003951:Diagnostic Errors; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D012279:Rickets / Q000175:diagnosis*
D050659:Core Binding Factor Alpha 1 Subunit
RUNX2; cleidocranial dysplasia; hypoplastic clavicles; rickets