Type III Osteogenesis Imperfecta and COL1A1 Pathological Variants Are Associated With Higher Incidence and Progression of Hearing Loss.

PURPOSE: This study interrogates longitudinal natural history data to determine whether hearing loss (HL) incidence, onset, degree, and type in osteogenesis imperfecta (OI) caused by heterozygous collagen missense variants are associated with a specific gene or combinations of causal gene and OI type.

METHODS

Audiological evaluation was conducted in 73 children with Type III or IV OI carrying COL1A1 or COL1A2 missense, exon-skipping, or small deletion variants, with adult follow-up.

RESULTS

A total of 71% of Type III OI participants experienced HL, compared with 39% of those with Type IV OI. Conductive HL persisted (33%) or transitioned to mixed conductive/sensorineural (67%) with progression. While HL was predominantly mild in most participants, six Type III participants (25%) but only one Type IV OI participant (7%) progressed to more severe loss. Most Type III and IV OI participants had HL onset in the first decade of life, with 46% and 33% of onsets, respectively, occurring before school age. More than half of participants with COL1A1 or COL1A2 variants had HL. Interfamilial and intrafamilial variability in HL was noted. Statistical interaction between genotype and phenotype indicated the greatest HL progression among Type III OI with COL1A1 variants.

CONCLUSIONS

Our data reveal significant HL onset in the first decade, and an interaction of Type III OI and COL1A1 variants among those with HL progression. These findings will guide clinical management, facilitating early monitoring tailored to genotype and phenotype.