Sibship stability of genotype and phenotype in myotonic dystrophy

Myotonic dystrophy (DM1) is caused by an unstable CTG repeat expansion. Despite the evidence of birth order effect in congenital DM1, the expansion's dynamics among sibships is still unknown. The objective of this study was to determine phenotype and CTG repeat size variability in DM1 sibships, and to investigate their predictive values. We compared 86 sib pairs for CTG repeat, 61 for age at onset and 89 for DM1 phenotype. CTG repeats remained stable for 66 of the 86 sib pairs, including 25 of 27 maternal transmissions and 30 of 42 paternal transmissions. Variations of less than 10 years in the age at onset were observed in 44 of 61 sib pairs, including 16 of 18 maternal transmissions and 19 of 28 paternal transmissions. The same phenotypic severity or a variation of only one class was observed among 86 of the 89 sib pairs, including all of the 35 maternal transmissions and 30 of the 33 paternal transmissions. Birth order, intergenesic interval, oldest sib's CTG repeat or parental age and CTG repeat did not exert any significant influence. These results suggest that genotype and phenotype remained stable among sibs, although the paternal origin of the mutation seemed to reduce the predictability of the severity.