Distal spinal muscular atrophy featured by predominant calf muscle involvement in VRK1 associated disease - Case series and review
Publication date
2022-06
Authors
Demaegd, Koen C.
Brilstra, Eva H
Hoogendijk, J E
de Bie, Charlotte I
De Pagter, Mirjam S.
Van Hecke, Wim
Mühlebner, Angelika
van Es, M.A.
Milone, Margherita
van Rheenen, Wouter
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Advisors
Supervisors
Document Type
Article
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cc_by_nc_nd
Abstract
We describe the shared clinical, biochemical, radiological and myopathological characteristics of four patients with distal spinal muscular atrophy (dSMA) caused by vaccinia-related kinase 1 (VRK1) variants and provide a review of the literature on phenotype-genotype correlations in VRK1-related disease. The clinical phenotype was characterized by adult-onset dSMA with predominant calf muscle involvement and mildly elevated serum creatinine kinase (CK) levels. Muscle imaging showed predominant atrophy and fatty replacement of calf muscles. We identified the novel compound heterozygous variants c.607C>T (p.Arg203Trp) and c.858G>T (p.Met286Ile) in two siblings with adult-onset dSMA. Additionally, two unrelated patients both carried the known c.583T>G (p.Leu195Val) VRK1 variant, with either c.197C>G (p.Ala66Gly) or c.701A>G (p.Asn234Ser) as a second variant. We conclude that compound heterozygous VRK1 variants cause distal spinal muscular atrophy with predominant posterior leg muscle involvement.
Keywords
Humans, Intracellular Signaling Peptides and Proteins, Leg, Muscle, Skeletal/diagnostic imaging, Muscular Atrophy, Muscular Atrophy, Spinal/genetics, Pedigree, Protein Serine-Threonine Kinases, Distal weakness calf weakness distal spinal muscular atrophy vaccinia-related kinase 1 (VRK1) gene, Clinical Neurology, Neurology, Genetics(clinical), Pediatrics, Perinatology, and Child Health, Case Reports, Review
Citation
Demaegd, K, Brilstra, E H, Hoogendijk, J E, de Bie, C I, de Pagter, M S, van Hecke, W, Mühlebner, A, van Es, M A, Milone, M & van Rheenen, W 2022, 'Distal spinal muscular atrophy featured by predominant calf muscle involvement in VRK1 associated disease - Case series and review', Neuromuscular Disorders, vol. 32, no. 6, pp. 527-532. https://doi.org/10.1016/j.nmd.2022.04.007