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Osteogenesis imperfecta: the audiological phenotype lacks correlation with the genotype

Freya KR Swinnen1*, Paul J Coucke2, Anne M De Paepe2, Sofie Symoens2, Fransiska Malfait2, Filomena V Gentile3, Luca Sangiorgi3, Patrizia D'Eufemia4, Mauro Celli4, Ton JTM Garretsen5, Cor WRJ Cremers6, Ingeborg JM Dhooge1 and Els MR De Leenheer1

Author Affiliations

1 Department of Otorhinolaryngology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium

2 Center for Medical Genetics, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium

3 Department of Medical Genetics and Rare Orthopaedic Diseases, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, I-40136 Bologna, Italy

4 Department of Pediatrics, La Sapienza University of Rome, Via Regina Elena 324, I-00161Rome, Italy

5 Department of Otorhinolaryngology, Medical Centre Alkmaar, Wilhelminalaan 12, NL-1815 JD Alkmaar, The Netherlands

6 FC Donders Institute for Neurosciences, Radboud University Nijmegen Medical Centre, Department of Otorhinolaryngology, PO Box 9101, NL-6500 HB Nijmegen, The Netherlands

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Orphanet Journal of Rare Diseases 2011, 6:88  doi:10.1186/1750-1172-6-88

Published: 29 December 2011



Osteogenesis Imperfecta (OI) is a heritable connective tissue disorder mainly caused by mutations in the genes COL1A1 and COL1A2 and is associated with hearing loss in approximately half of the cases. The hearing impairment usually starts between the second and fourth decade of life as a conductive hearing loss, frequently evolving to mixed hearing loss thereafter. A minority of patients develop pure sensorineural hearing loss. The interindividual variability in the audiological characteristics of the hearing loss is unexplained.


With the purpose of evaluating inter- and intrafamilial variability, hearing was thorougly examined in 184 OI patients (type I: 154; type III: 4; type IV: 26), aged 3-89 years, with a mutation in either COL1A1 or COL1A2 and originating from 89 different families. Due to the adult onset of hearing loss in OI, correlations between the presence and/or characteristics of the hearing loss and the underlying mutation were investigated in a subsample of 114 OI patients from 64 different families who were older than 40 years of age or had developed hearing loss before the age of 40.


Hearing loss was diagnosed in 48.4% of the total sample of OI ears with increasing prevalence in the older age groups. The predominant type was a mixed hearing loss (27.5%). A minority presented a pure conductive (8.4%) or pure sensorineural (12.5%) loss. In the subsample of 114 OI subjects, no association was found between the nature of the mutation in COL1A1 or COL1A2 genes and the occurrence, type or severity of hearing loss. Relatives originating from the same family differed in audiological features, which may partially be attributed to their dissimilar age.


Our study confirms that hearing loss in OI shows a strong intrafamilial variability. Additional modifications in other genes are assumed to be responsible for the expression of hearing loss in OI.

Osteogenesis Imperfecta; COL1A1; COL1A2; hearing loss; genotype-phenotype correlation