This 60-year-old patient initially presented with facial weakness, and subsequently developed ptosis and dysphonia. More recently they noticed difficulty rising from a chair (proximal lower extremity weakness). Multiple family have had similar symptoms. Laboratory studies showed mild elevation of CPK. EMG demonstrated myopathic features predominantly in proximal lower extremity muscles. Mild non-inflammatory myopathic changes and occasional muscle fibers with rimmed vacuoles were present on muscle biopsy.
Based on Figures #1 and #2 which of the following tests should be recommended?
A. anti-IBM (cn-1A / NT5c1A)
B. Anti-synthetase autoantibodies
D. PABPN1 GCN repeat testing
Answer: PABPN1 GCN repeat testing
The ultrastructural images demonstrate the presence of finely fibrillary (~8.5nm thickness) material within the nucleus characteristic of Oculopharyngeal Muscular Dystrophy (OPMD) due to trinucleotide repeat expansion (poly-alanine) in the PABPN1 gene. The fibrillary inclusion material is finer than the amyloid-like intranuclear or intrasarcoplasmic material seen in sporadic Inclusion Body Myositis (sIBM).
Of note: sporadic Inclusion Body Myositis (sIBM) is not the only muscle disease to show rimmed-vacuoles.
Reference(s) / additional reading:
Trollet C, Boulinguiez A, Roth F, Stojkovic T, Butler-Browne G, Evangelista T, Lacau St Guily J, Richard P. Oculopharyngeal Muscular Dystrophy. 2001 Mar 8 [updated 2020 Oct 22]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews®[Internet]. Seattle (WA): University of Washington, Seattle; 1993–2022. PMID: 20301305.
Richard P, Trollet C, Gidaro T, Demay L, Brochier G, Malfatti E, Tom FM, Fardeau M, Lafor P, Romero N, Martin-N ML, Sol G, Ferrer-Monasterio X, Saint-Guily JL, Eymard B. PABPN1 (GCN)11 as a Dominant Allele in Oculopharyngeal Muscular Dystrophy -Consequences in Clinical Diagnosis and Genetic Counselling. J Neuromuscul Dis. 2015 Jun 4;2(2):175-180. doi: 10.3233/JND-140060. PMID: 27858728; PMCID: PMC5271460.
Richard P, Trollet C, Stojkovic T, de Becdelievre A, Perie S, Pouget J, Eymard B; Neurologists of French Neuromuscular Reference Centers CORNEMUS and FILNEMUS. Correlation between PABPN1 genotype and disease severity in oculopharyngeal muscular dystrophy. Neurology. 2017 Jan 24;88(4):359-365. doi: 10.1212/WNL.0000000000003554. Epub 2016 Dec 23. PMID: 28011929; PMCID: PMC5272966.
Yamashita S. Recent Progress in Oculopharyngeal Muscular Dystrophy. J Clin Med. 2021 Mar 29;10(7):1375. doi: 10.3390/jcm10071375. PMID: 33805441; PMCID: PMC8036457.
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