G.P.6: Oculopharyngeal Muscular Dystrophy with PABPN1 mutation in two Chinese Singaporean families

Abstract

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominant disorder presenting with progressive ptosis and dysphagia, due to GCN trinucleotide repeat in PABPN1 . OPMD is rarely seen in the Far East and genetically confirmed case has not been reported in Singapore. We describe two unrelated Chinese Singaporean families with autosomal dominant OPMD. The first patient, a 67-year-old Chinese, presented with progressive ptosis since age 30 and dysphagia for 5 years. He was initially thought to have a mitochondrial myopathy and muscle biopsy performed did show subtle mitochondrial abnormalities—few ragged red and COX negative fibres—but no rimmed vacuoles. However, in view of possible positive family history of similar condition in his father and paternal grandfather (both diseased), OPMD was suspected and genetic screening was performed, which showed heterozygous expansion of GCN in PABPN1 (13 repeats). The second patient, a 52-year-old Chinese man, had bilateral asymmetrical ptosis for about 10 years and progressive dysphagia for 6 years. He was initially diagnosed to have seronegative myasthenia gravis (MG) based on positive single fibre EMG study. His father, at the age of 75, had also similar presentation and was also diagnosed to have seronegative MG, based on single fibre EMG study. However, his condition did not improve with immunosuppressant and plasmapheresis. Genetic screening for OPMD performed on the proband showed 13 GCN repeats in PABPN1 . This is the first report of Singaporean families of Chinese descent with genetically confirmed OPMD, which may be under diagnosed in Singapore. OPMD can mimic other conditions such as mitochondrial myopathy or MG and hence often misdiagnosed, resulting in unnecessary treatment or procedure. It should be considered in any patient who present with late-onset progressive ptosis and dysphagia. Molecular genetic testing of PABPN1 is recommended for suspected case of OPMD.