Background Oculopharyngodistal myopathy (OPDM) has been reported as a rare, adult-onset hereditary muscle disease with putative autosomal dominant and autosomal recessive inheritance. Patients with OPDM present with progressive ocular, pharyngeal, and distal limb muscle involvement. The genetic defect causing OPDM has not been elucidated. Methods Clinical and genetic findings of 47 patients from 9 unrelated Turkish families diagnosed with OPDM at the Department of Neurology, Istanbul Faculty of Medicine, between 1982 and 2009 were evaluated. Results The mean age at onset was around 22 years. Both autosomal dominant and autosomal recessive traits were observed, without any clear difference in clinical phenotype or severity. The most common initial symptom was ptosis, followed by oropharyngeal symptoms and distal weakness, which started after the fifth disease year. Intrafamilial variability of disease phenotype and severity was notable in the largest autosomal dominant family. Atypical presentations, such as absence of limb weakness in long-term follow-up in 9, proximal predominant weakness in 4, and asymmetric ptosis in 3 patients, were observed. Swallowing difficulty was due to oropharyngeal dysphagia with myopathic origin. Serum creatine kinase levels were slightly increased and EMG revealed myopathic pattern with occasional myotonic discharges. Myopathologic findings included rimmed and autophagic vacuoles and chronic myopathic changes. Importantly, a considerable proportion of patients developed respiratory muscle weakness while still ambulant. Linkage to the genetic loci for all known muscular dystrophies, and for distal and myofibrillar myopathies, was excluded in the largest autosomal dominant and autosomal recessive OPDM families. Conclusions We suggest that OPDM is a clinically and genetically distinct myopathy.
