Genotype-phenotype relationships in FSHD

FSHD Facioscapulohumeral Muscular Dystrophy: Clinical Medidne and Molecular Cell Biology, edited by Meena Upadhyaya and David N.Cooper. © 2004 Garland/BIOS Scientific Publishers Limited, Abingdon.11.1 IntroductionFacioscapulohumeral muscular dystrophy (FSHD) is characterized by wide variation in clinical expression, both between and within families (Lunt and Harper, 1991). At its most severe there is proximal lower limb as well as upper limb and facial weakness from early childhood giving rise to a requirement for a wheelchair while still in teenage years (Lunt et al., 1995a). By contrast, there are affected subjects in their 70s who may have only minimal facial and shoulder girdle weakness, while a significant proportion of gene carriers, particularly women, may remain asymptomatic (Zatz et al., 1998). Within individual families the extremes of presentation rarely occur together. The one exception to this is where the origin of a new mutation may have been in postzygotic mitosis of the parent of a severely affected child, such that the parent manifests the same DNA mutation in only a proportion of their cells (somatic mosaicism). Thus, it is suggested that there is a likelihood of a link between phenotype and genotype.