This observational cross-sectional study was conducted in a national facioscapulohumeral muscular dystrophy (FSHD) expertise center to estimate the penetrance of FSHD1 and to evaluate phenotype-genotype correlations in ten FSHD1 probands carrying 4-9 D4Z4 unit alleles and 140 relatives. The relationship between age-corrected clinical severity score and repeat size, sex, and D4Z4 methylation levels were evaluated. The maximum likelihood estimates of symptomatic and those of symptomatic plus asymptomatic FSHD showed that penetrance depends on repeat size and increases until late adulthood. Many asymptomatic carriers with subtle facial weakness with or without mild shoulder girdle weakness (25% [17/69]) were observed. Non-penetrance was observed less frequently than in recent population studies (17% [12/69]), and most asymptomatic patients reported some shoulder pain. D4Z4 methylation tended to be lower in moderately to severely affected mutation carriers with 7 or 9 repeats.
