EVIDENCE FOR ANTICIPATION AND ASSOCIATION OF DELETION SIZE WITH SEVERITY IN FACIOSCAPULOHUMERAL MUSCULAR-DYSTROPHY

Facioscapulohumeral muscular dystrophy (FSHD) is characterized by mark ed inter- and intrafamilial heterogeneity in its clinical expression. The contribution of genetic factors to this variability is not well ch aracterized, We examined the relationship of phenotype to genotype in a clinically and genetically well-defined FSHD population. Quantitativ e isometric myometry (QMT) scores, normalized for age, gender, and hei ght, were used to quantify disease severity, We found a significant (r = 0.92 p < 0.004) correlation between disease severity and the size o f she 4q35-associated deletion. In addition; when relative disease sev erity of parent-offspring pairs Nas compared, the offspring were found to be significantly more severely affected (p = 0.011). This generati onal effect suggests the presence of anticipation in FSHD and raises t he possibility of an underlying dynamic mutation.