{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:16:01Z","timestamp":1788430561235,"version":"build-2803163510"},"reference-count":19,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Intramural Research Grant","award":["8-13"],"award-info":[{"award-number":["8-13"]}]},{"name":"Intramural Research Grant","award":["5-6"],"award-info":[{"award-number":["5-6"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>A 56-year-old man with a family history of myopathy developed generalized muscle weakness at age 45. At age 52, he was diagnosed with inclusion-body myopathy with Paget disease of bone and frontotemporal dementia (IBMPFD), confirmed by muscle pathology and a pathogenic VCP mutation (c.464G&gt;A, p.R155H). Concurrent testing identified a heterozygous SCN4A variant (c.215C&gt;T, p.P72L), a known modifier in myotonic dystrophy type 2 (DM2). At age 56, neurological examination showed proximal muscle weakness (MMT grade 3), distal lower extremity weakness (grade 4\u20135), and areflexia. He ambulated independently with knee locking, though squatting was impossible. No myotonia or periodic paralysis was observed. Multimodal imaging captured classic IBMPFD hallmarks: skeletal muscle computed tomography (CT) showed advanced fatty degeneration of paraspinal and limb muscles; brain magnetic resonance imaging (MRI) revealed mild frontal lobe atrophy; and bone scintigraphy showed increased uptake in the lumbar spine and iliums. Although the SCN4A p.P72L variant exacerbates DM2, the patient\u2019s three-year progression from independent walking to cane use remained consistent with the natural history of IBMPFD. This case suggests that in the presence of a robustly penetrant VCP phenotype, the SCN4A variant does not necessarily exert a clinical modifying effect.<\/jats:p>","DOI":"10.3390\/diagnostics16172833","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T09:20:43Z","timestamp":1788427243000},"page":"2833","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inclusion-Body Myopathy with Paget Disease of the Bone and Frontotemporal Dementia (IBMPFD) with SCN4A Mutation: Modifying Factor or Not?"],"prefix":"10.3390","volume":"16","author":[{"given":"Sekai","family":"Tsujimoto","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Medicine, Fukui General Hospital, Fukui 910-8561, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3446-0913","authenticated-orcid":false,"given":"Koji","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Fukui General Hospital, Fukui 910-8561, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2947-9743","authenticated-orcid":false,"given":"Mamiko","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Fukui General Hospital, Fukui 910-8561, Japan"},{"name":"Graduate School of Health Science, Fukui Health Science University, Fukui 910-3190, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshio","family":"Hamada","sequence":"additional","affiliation":[{"name":"Department of Neurology, Fukui Prefectural Hospital, Fukui 910-8526, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asuka","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Fukui General Hospital, Fukui 910-8561, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Nakaya","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Fukui General Hospital, Fukui 910-8561, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toyoaki","family":"Miura","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Fukui General Hospital, Fukui 910-8561, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9452-112X","authenticated-orcid":false,"given":"Ichizo","family":"Nishino","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Research, National Institute of Neuroscience (NIN), National Center of Neurology and Psychiatry (NCNP), Tokyo 187-8502, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0724-0018","authenticated-orcid":false,"given":"Wakako","family":"Yoshioka","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Research, National Institute of Neuroscience (NIN), National Center of Neurology and Psychiatry (NCNP), Tokyo 187-8502, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6305-2444","authenticated-orcid":false,"given":"Yasutaka","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Graduate School of Health Science, Fukui Health Science University, Fukui 910-3190, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e200265","DOI":"10.1212\/NXG.0000000000200265","article-title":"Muscle biopsy findings in valosin-containing protein multisystem proteinopathy","volume":"11","author":"Schiava","year":"2025","journal-title":"Neurol. 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