G.P.107 OPMD or OPDM: How to differentiate?

Abstract Oculopharyngeal muscular dystrophy (OPMD) is a late onset muscular dystrophy (2nd–6th decades) with an expansion of GCG repeats in exon 1 of PABPN1. Oculopharyngodistal myopathy (OPDM) is also an adult-onset hereditary muscle disease with putative autosomal dominant and autosomal recessive inheritance. The genetic defect in OPDM remains unknown. OPDM and OPMD overlap clinically and histopathologically, since both disorders have a similar distribution of weakness, rimmed vacuoles and mitochondrial disarray. We studied 9 patients with oculopharyngeal weakness and rimmed vacuoles to find a practical approach to differentiate OPMD and OPDM. All patients (mean age 63 y, range 21–79 y) had ptosis, dysphagia and limb muscle weakness. Muscle biopsies showed rimmed vacuoles, dystrophic features and mitochondrial disarray. Five cases had HLA-1 immunostaining and electron microscopy (EM) performed. None of the patients had diffuse HLA-1 upregulation in the sarcolemma. On EM 8.5 nm intranuclear filaments (OPMD filaments) were found in three patients and 16–18 nm filaments (IBM filaments) in the other 2. Genetic testing confirmed PABPN1 mutations in the three patients with OPMD filaments. The other two patients were diagnosed as OPDM. In summary, HLA-1 staining is helpful in differentiating sporadic IBM from OPMD or OPDM since it is absent in the latter two conditions. Persistent EM examination looking for 8.5 nm intranuclear filaments can aid the diagnosis of OPMD. The diagnosis of OPDM requires clinical, histopathological and genetic analysis to exclude OPMD.