Variability of the recessive oculopharyngeal muscular dystrophy phenotype

Oculopharyngeal muscular dystrophy (OPMD) is usually transmitted as an autosomal‐dominant trait and characterized by an expansion from 6 to 8 or more GCG/GCA repeats in the poly‐(A) binding protein nuclear 1 (PABPN1) gene on chromosome 14q11. Autosomal‐recessive OPMD with a homozygous (GCG)7 expansion of PABPN1 has only been described in two Canadian patients, who showed a comparably mild phenotype, suggesting that it is less severe than the dominant form. We clinically and genetically characterized the first two reported cases of autosomal‐recessive OPMD in Europe. Remarkably, both patients revealed severe and diverse phenotypes, with an unusual onset and atypical clinical course in one patient. Former studies found a 1%–2% frequency of the (GCG)7 allele, which theoretically produces an incidence of 1:10,000 of autosomal‐recessive OPMD in the general population. We conclude that the apparent rarity of the autosomal‐recessive form of OPMD may be due to the fact that genetic testing is generally administered only to patients with typical clinical features or a positive family history. Muscle Nerve, 2007