Excess paternal age in apparently sporadic osteogenesis imperfecta

The objective of this study was to examine whether parental age is associat ed with the occurrence of apparently sporadic osteogenesis imperfecta (OI). We compared parental age and the joint distribution of maternal and patern al age with expected distributions based on statutory birth records for eac h year and location of birth, The study included patients with OI based in the United Kingdom. The study was restricted to cases born in England, Wale s, and Scotland between 1961 and 1998. Subgroup analysis was by clinical ty pe [Sillence et al., 1979: J Med Genet 16:101-116] and apparent mode of inh eritance based on pedigree analysis. Of 730 eligible cases, 357 were appare ntly sporadic. The mean age of fathers at birth of children with apparently sporadic OI was 0.87 years greater than expected (P=0.010; 95% confidence interval=0.21 to 1.54 years). The relative risk was 1.62 for fathers in the highest quintile of paternal age compared with fathers in the lowest quint ile. The magnitude of the paternal age excess did not differ significantly between Sillence types (analysis of variance P=0.534). In sporadic cases, p aternal age was 0.51 years greater than expected, given maternal age, year, and location of birth (P=0.033). In contrast, in familial cases, there was no significant paternal age excess, and paternal age was not significantly different from that expected given maternal age. Increased paternal age is a significant risk factor for sporadic OI. This effect is not accounted fo r by increasing maternal age. The magnitude of the paternal age excess is s mall in comparison with that in some other autosomal dominant disorders. (C ) 2001 Wiley-Liss, Inc.