Bedside diagnosis of rippling muscle disease

Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant myopathy caused by an abnormal (GCG) 8–13-trinucleotide-repeat expansion in the polyadenylate-binding protein nuclear 1 (PABN1; PABP2) gene located on chromosome 14q11. Clinical and laboratory evidence of peripheral nervous system (PNS) involvement has been reported in a few genetically confirmed OPMD patients who carried long (11–13) CGC repeats, but these findings have recently been questioned. Herein we report a patient with genetically proven OPMD who presented in his eighties with rapidly progressive dysphagia and clinical and laboratory features of neuropathic rather than myopathic involvement. An 83-year-old man of Italian descent sought medical attention after 1 year of rapidly progressive dysphagia leading to repeated aspiration pneumonia and severe weight loss. His past medical history disclosed only asymptomatic post-streptococcal mitral valve insufficiency. He vaguely recalled that his mother, sister, and maternal aunt had swallowing difficulty in their old age, but only his mother had eyelid ptosis. His only daughter, 48 years old, is asymptomatic; she was offered genetic counseling, but this has not yet been performed. Neurological examination of the patient revealed slight bilateral fixed eyelid ptosis, incomplete upward and lateral pseudoconjugate eye movements without diplopia, and a stable nasal voice. He had neither selective wasting nor weakness of tongue, facial, trunk, or limb muscles. Clinical and percussion myotonia and involuntary muscle movements were absent. Deep tendon reflexes were hypoactive in all four limbs, and ankle jerks were absent. Sensation was not impaired except for a reduction of vibratory sense in the legs. An ice-pack test was negative. Velolaryngeal motility was reported as normal on direct visualization. Cine-barium swallow, on the contrary, showed epiglottic hypomobility with immediate contrast medium aspiration. He initially required a nasogastric tube and then percutaneous gastrostomy feeding. Neck and chest computed tomography did not reveal a mass lesion. Electrocardiography was normal. Broad laboratory screening, including creatine kinase (CK), immunoelectrophoresis, vitamins B12 and E, folate, copper, and serum thyroid hormones, was normal. Hepatitis C virus, human immunodeficiency virus, antinuclear antibody, extractable nuclear antigens, anti-neutrophil cytoplasmic antibody, acetylcholine receptor, anti-GQ1b, and paraneoplastic antibodies were absent. Cerebrospinal fluid was acellular with a normal protein level. Needle electromyographic (EMG) examination of proximal and distal limb muscles showed normal insertional activity and polyphasic motor unit action potentials of mainly normal amplitude and long duration. Fasciculation potentials were detected in some upper limb muscles. Cricopharyngeal and paraspinal thoracic muscles were spared. Nerve conduction studies showed low-amplitude sural sensory nerve action potentials (1.4 lV; ageadjusted normal values: 2 lV for those over 65 years of age) and low-amplitude peroneal compound muscle action potentials (0.9–1.5 mV; age-adjusted normal values: 2 mV for those over 65 years of age). Repetitive nerve stimulation studies were normal. Quadriceps muscle biopsy demonstrated groups of atrophic, angulated type II fibers and rare central nuclei. No ragged red fibers or rimmed cytoplasmic vacuoles were observed (Fig. 1). Although the results were not consistent with the diagnosis of a myopathy, keeping the patient’s family history in mind we suspected a diagnosis of OPMD. Genetic analysis disclosed that the patient was heterozygous with an expansion of 8 GCG repeats on one allele and 6 on the other allele. In our case, peripheral nervous system (PNS) involvement did not correlate with a high number of triplet repeats. Apart from oculopharyngeal involvement, our patient had a nearly subclinical sensorimotor axonal neuropathy and mainly neurogenic histopathological muscle abnormalities. This case suggests that the diagnosis of OPMD should be considered even if the family history is uncertain in patients with slight oculomotor impairment, very late onset of rapidly progressing dysphagia, and prominent features of PNS involvement. VC 2010 Wiley Periodicals, Inc.