Distal spinal muscular atrophy featured by predominant calf muscle involvement in VRK1 associated disease – Case series and review

Koen Demaegd; Eva H. Brilstra; Jessica E. Hoogendijk; Charlotte I. de Bie; Mirjam S. de Pagter; Wim van Hecke; Angelika Mühlebner; Michael A. van Es; Margherita Milone; Wouter van Rheenen

doi:10.1016/j.nmd.2022.04.007

Distal spinal muscular atrophy featured by predominant calf muscle involvement in VRK1 associated disease – Case series and review

Koen Demaegd, Eva H. Brilstra, Jessica E. Hoogendijk, Charlotte I. de Bie, Mirjam S. de Pagter, Wim van Hecke, Angelika Mühlebner, Michael A. van Es, Margherita Milone, Wouter van Rheenen

Neurology

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Pages (from-to)	527-532
Number of pages	6
Journal	Neuromuscular Disorders
Volume	32
Issue number	6
DOIs	https://doi.org/10.1016/j.nmd.2022.04.007
State	Published - Jun 2022

Keywords

Distal weakness calf weakness distal spinal muscular atrophy vaccinia-related kinase 1 (VRK1) gene

ASJC Scopus subject areas

Pediatrics, Perinatology, and Child Health
Neurology
Clinical Neurology
Genetics(clinical)

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10.1016/j.nmd.2022.04.007

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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, 32(6), 527-532. https://doi.org/10.1016/j.nmd.2022.04.007

Demaegd, K, Brilstra, EH, Hoogendijk, JE, de Bie, CI, de Pagter, MS, van Hecke, W, Mühlebner, A, van Es, MA, 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

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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.",

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author = "Koen Demaegd and Brilstra, {Eva H.} and Hoogendijk, {Jessica E.} and {de Bie}, {Charlotte I.} and {de Pagter}, {Mirjam S.} and {van Hecke}, Wim and Angelika M{\"u}hlebner and {van Es}, {Michael A.} and Margherita Milone and {van Rheenen}, Wouter",

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year = "2022",

month = jun,

doi = "10.1016/j.nmd.2022.04.007",

language = "English (US)",

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AU - Mühlebner, Angelika

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AU - van Rheenen, Wouter

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Distal spinal muscular atrophy featured by predominant calf muscle involvement in VRK1 associated disease – Case series and review

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