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Oculopharyngeal muscular dystrophy
11 November 2003
Authors
Clinical features
OPMD usually manifests after the age of 40 as slowly progressive ptosis of the upper eyelids, dysphagia, and dysphonia (Victor et al, 1962; Brais et al, 1999). Symptoms such as external ophthalmoplegia, and facial and proximal limb weakness develop subsequently, affecting extraocular and other voluntary muscles (Tome et al, 1994; Creel et al, 1998). Cardiac muscle is not affected. Although ptosis is usually the first symptom, patients sometimes report dysphagia or limb-girdle weakness as first symptoms (Victor et al, 1962; Brais et al, 1999; van der Sluijs et al, in press). The ptosis is nearly always bilateral, but asymmetric ptosis has been reported. The upper eyelids droop slowly and ultimately may limit vision. Read more
Natural course and prognosis
OPMD is a slowly progressive muscle disorder. The order in which symptoms appear and their severity differ from patient to patient. The progression of ptosis causes visual limitations, with restriction of the visual fields. Dysphagia may cause aspiration pneumonia and weight loss. Limb-girdle weakness causes patients the most problems and limits their ability to perform activities of daily life.
Epidemiology
OPMD is a rare muscle disorder manifesting after the age of 40 and has been described in various ethnic groups (Blumen et al, 1993; Bouchard et al, 1997; Fardeau et al, 1997; Medici et al, 1997; Meola et al, 1997; Becher et al, 2001; Muller et al, 2001). However, most reported patients are white – only one black family and a few Asian families with OPMD have been described. The prevalence of OPMD is highly variable. In France, the prevalence is estimated to be 1/200,000. In the Bukhara population in Israel it is 1/600, and in Quebec it is 1/7500.
Differential diagnosis
The differential diagnosis of OPMD depends on the presenting symptom(s) and is extensive. Possible differential diagnoses include chronic progressive external ophthalmoplegia, myasthenia gravis, limb-girdle dystrophies, and oculopharyngodistal myopathy. Oculopharyngodistal myopathy shares some clinical and histological characteristics with OPMD, being clinically characterised by ptosis, dysphagia, external ophthalmoplegia early in the course of the disease, and weakness of the distal leg muscles. However, the tubulofilaments characteristic of OPMD are not present in the skeletal muscle of patients with oculopharyngodistal myopathy and these patients do not bear the mutation in the PAPN1 gene (van der Sluijs et al, JNNP 2004).
Ancillary investigations
The diagnosis of OPMD is based on the clinical criteria of Brais and colleagues (1993) and is genetically confirmed by detection of a mutation in the PABPN1 gene. The major diagnostic criteria of Brais are 1) positive family history, 2) ptosis or previous surgical correction, and 3) dysphagia. Minor criteria are onset after 40 years; limitation of eye movements; and facial, tongue, and limb weakness. Exclusion criteria are severe external ophthalmoplegia before the age of 60, and the presence of myotonia.
Genetics
Genetically, OPMD is characterised by a mutation in exon 1 of the polyadenylate binding protein nuclear 1 ( PABPN 1) gene (previously called poly (A) binding-protein 2, PABP 2, gene)(Brais et al, 1998). Read more
Therapy
References
Becher MW, Morrison L, Davis LE, Maki WC, King MK, Bicknell JM, Reinert BL, Bartolo C, Bear DG. Oculopharyngeal muscular dystrophy in Hispanic New Mexicans. JAMA 2001;286:2437-40. Read more
OPMD is a rare, late-onset, autosomal dominant muscle disorder. The syndrome is characterised clinically by slowly progressive ptosis, dysphagia, and dysphonia. Limb-girdle weakness is usually a relatively late symptom. The disease is characterised histologically by nuclear filamentous inclusions in skeletal muscle fibres. The clinical and histological diagnosis can be confirmed by mutation analysis, which shows a mutation in exon 1 of the polyadenylate binding protein nuclear 1 (PABPN 1) gene.
Authors
B.M. van der Sluijs, M.D.
B.G.M. van Engelen, M.D., Ph.D.
Clinical features
OPMD usually manifests after the age of 40 as slowly progressive ptosis of the upper eyelids, dysphagia, and dysphonia (Victor et al, 1962; Brais et al, 1999). Symptoms such as external ophthalmoplegia, and facial and proximal limb weakness develop subsequently, affecting extraocular and other voluntary muscles (Tome et al, 1994; Creel et al, 1998). Cardiac muscle is not affected. Although ptosis is usually the first symptom, patients sometimes report dysphagia or limb-girdle weakness as first symptoms (Victor et al, 1962; Brais et al, 1999; van der Sluijs et al, in press). The ptosis is nearly always bilateral, but asymmetric ptosis has been reported. The upper eyelids droop slowly and ultimately may limit vision. Read more
Natural course and prognosis
OPMD is a slowly progressive muscle disorder. The order in which symptoms appear and their severity differ from patient to patient. The progression of ptosis causes visual limitations, with restriction of the visual fields. Dysphagia may cause aspiration pneumonia and weight loss. Limb-girdle weakness causes patients the most problems and limits their ability to perform activities of daily life.
Epidemiology
OPMD is a rare muscle disorder manifesting after the age of 40 and has been described in various ethnic groups (Blumen et al, 1993; Bouchard et al, 1997; Fardeau et al, 1997; Medici et al, 1997; Meola et al, 1997; Becher et al, 2001; Muller et al, 2001). However, most reported patients are white – only one black family and a few Asian families with OPMD have been described. The prevalence of OPMD is highly variable. In France, the prevalence is estimated to be 1/200,000. In the Bukhara population in Israel it is 1/600, and in Quebec it is 1/7500.
Differential diagnosis
The differential diagnosis of OPMD depends on the presenting symptom(s) and is extensive. Possible differential diagnoses include chronic progressive external ophthalmoplegia, myasthenia gravis, limb-girdle dystrophies, and oculopharyngodistal myopathy. Oculopharyngodistal myopathy shares some clinical and histological characteristics with OPMD, being clinically characterised by ptosis, dysphagia, external ophthalmoplegia early in the course of the disease, and weakness of the distal leg muscles. However, the tubulofilaments characteristic of OPMD are not present in the skeletal muscle of patients with oculopharyngodistal myopathy and these patients do not bear the mutation in the PAPN1 gene (van der Sluijs et al, JNNP 2004).
Ancillary investigations
The diagnosis of OPMD is based on the clinical criteria of Brais and colleagues (1993) and is genetically confirmed by detection of a mutation in the PABPN1 gene. The major diagnostic criteria of Brais are 1) positive family history, 2) ptosis or previous surgical correction, and 3) dysphagia. Minor criteria are onset after 40 years; limitation of eye movements; and facial, tongue, and limb weakness. Exclusion criteria are severe external ophthalmoplegia before the age of 60, and the presence of myotonia.
Genetics
Genetically, OPMD is characterised by a mutation in exon 1 of the polyadenylate binding protein nuclear 1 ( PABPN 1) gene (previously called poly (A) binding-protein 2, PABP 2, gene)(Brais et al, 1998). Read more
Therapy
Only symptomatic therapy exists. Neither medications nor other therapies have been found to slow down or stop the progression of muscle weakness in patients with OPMD.
Symptomatic therapy consists of advice, speech therapy, and physiotherapy. Surgical correction of ptosis and crycopharyngeal myotomy is possible.
References
Becher MW, Morrison L, Davis LE, Maki WC, King MK, Bicknell JM, Reinert BL, Bartolo C, Bear DG. Oculopharyngeal muscular dystrophy in Hispanic New Mexicans. JAMA 2001;286:2437-40. Read more
