Osteogenesis imperfecta: The audiological phenotype lacks correlation with the genotype

Freya K R Swinnen, Paul J. Coucke, Anne M. De Paepe, Sofie Symoens, Fransiska Malfait, Filomena V. Gentile, Luca Sangiorgi, Patrizia D'Eufemia, Mauro Celli, Ton J T M Garretsen, Cor Wrj Cremers, Ingeborg J M Dhooge, Els M R De Leenheer

Research output: Contribution to journalArticlepeer-review


Background: 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. Methods. 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. Results: 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. Conclusions: 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.

Original languageEnglish
Article number88
JournalOrphanet Journal of Rare Diseases
Issue number1
Publication statusPublished - 2011


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

ASJC Scopus subject areas

  • Medicine(all)
  • Genetics(clinical)
  • Pharmacology (medical)


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