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

• Authors: 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
• Journal: Neuromuscular disorders : NMD (Neuromuscul Disord) Vol. 32 Issue 6 Pg. 527-532 (06 2022) ISSN: 1873-2364 [Electronic] England
• PMID: 35641352 (Publication Type: Case Reports, Review)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Intracellular Signaling Peptides and Proteins
• Protein Serine-Threonine Kinases
• VRK1 protein, human

Topics

• Humans
• Intracellular Signaling Peptides and Proteins
• Leg
• Muscle, Skeletal (diagnostic imaging)
• Muscular Atrophy
• Muscular Atrophy, Spinal (genetics)
• Pedigree
• Protein Serine-Threonine Kinases