Axial involvement as a prominent feature in SMPX-related distal myopathy

A 78-year-old man with no family history of neuromuscular conditions presented with slowly progressive lower limb weakness with bilateral foot drop started in his late 40s. After age 70 he developed proximal upper limb weakness with difficulties in raising his arms. On examination, he had severe bilateral weakness of ankle dorsiflexion, impairment in arm abduction (possible up to 80 degrees), and mild bilateral scapular winging. Strength in distal upper limb muscles was preserved. Serum CK level was mildly elevated, and EMG was consistent with a myopathy. No information on a previously performed muscle biopsy was available. He had been extensively studied with targeted gene panels covering MYH7, CRYAB, MYOT, LDB3, DES, GNE, TTN, and VCP to exclude the most common myofibrillar and distal myopathies, as well as with genetic testing for Facioscapulohumeral muscular dystrophy types 1 and 2. In light of the patient's Maltese origin, additional testing of the SMPX gene was requested and identified a pathogenic missense mutation c.233G>A (p.S78N), previously reported in distal myopathy in patients native to Malta[[1]Johari M Sarparanta J Vihola A Jonson PH Savarese M Jokela M et al.Missense mutations in small muscle protein X-linked (SMPX) cause distal myopathy with protein inclusions.Acta Neuropathol. 2021; 142: 375-393https://doi.org/10.1007/s00401-021-02319-xCrossref PubMed Scopus (6) Google Scholar]. Interestingly, a muscle MRI of the upper body showed significant fatty replacement of cervical and thoracic erector spinae muscles, from the C2 to T9 levels. An involvement of the inferior part of serratus anterior, similarly to what is seen in GNE myopathy[[2]Torchia E Lucchini M Bortolani S Monforte M Garibaldi M Mirabella M et al.Upper body involvement in GNE myopathy assessed by muscle imaging.Neuromuscular Disorders. 2022 May 1; 32: 410-418Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar,[3]Tasca G Monforte M Iannaccone E Laschena F Ottaviani P Leoncini E et al.Upper girdle imaging in facioscapulohumeral muscular dystrophy.PloS one. 2014 Jun 16; 9e100292Crossref PubMed Scopus (66) Google Scholar] and likely contributing to scapular winging, was also detected(Figure 1). SMPX-related myopathy (MPD7, OMIM#301075) is a rare X-linked disorder described only in ten patients so far as an adult-onset distal myopathy. The description of our patient, showing significant although subclinical paravertebral muscle involvement also reported in one patient of the original cohort, adds to the phenotypic and imaging spectrum of the disease. SMPX gene testing should be considered in undiagnosed male patients with distal and axial weakness. In our case, geographic origin was also an important diagnostic clue. D. Salman: Writing – original draft, Visualization, Validation, Resources, Project administration, Methodology, Formal analysis, Data curation, Conceptualization. C. Bolano-Diaz: Writing – original draft, Investigation. R. Muni-Lofra: Supervision. K. Wong: Investigation, Formal analysis. M. Elseed: Supervision. E Harris: Writing – review & editing, Supervision. J. Diaz-Manera: Supervision. M. Guglieri: Supervision. C. Marini-Bettolo: Validation, Supervision. V. Straub: Writing – review & editing, Visualization, Validation, Supervision. G. Tasca: Writing – review & editing, Visualization, Validation, Supervision, Project administration, Methodology, Investigation, Conceptualization. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. We thank the patient for his willingness to share clinical information and images. This manuscript has not been previously published. The authors take full responsibility for the data and have full access to all the data. All authors report no disclosures relevant to the manuscript.