TY - JOUR
T1 - Distal spinal muscular atrophy featured by predominant calf muscle involvement in VRK1 associated disease – Case series and review
AU - Demaegd, Koen
AU - Brilstra, Eva H.
AU - Hoogendijk, Jessica E.
AU - de Bie, Charlotte I.
AU - de Pagter, Mirjam S.
AU - van Hecke, Wim
AU - Mühlebner, Angelika
AU - van Es, Michael A.
AU - Milone, Margherita
AU - van Rheenen, Wouter
N1 - Funding Information: Margherita Milone reports Research funding from the Neurology Department and CCaTS-CBD Pilot Awards for Team Science, Mayo Clinic; a Muscular Dystrophy Association Care center grant (MDA 497263), and honorarium to serve as associate editor for Neurology Genetics. Publisher Copyright: © 2022 The Authors
PY - 2022/6
Y1 - 2022/6
N2 - 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.
AB - 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.
KW - Distal weakness calf weakness distal spinal muscular atrophy vaccinia-related kinase 1 (VRK1) gene
UR - http://www.scopus.com/inward/record.url?scp=85130909351&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.nmd.2022.04.007
DO - https://doi.org/10.1016/j.nmd.2022.04.007
M3 - Article
C2 - 35641352
SN - 0960-8966
VL - 32
SP - 527
EP - 532
JO - Neuromuscular disorders
JF - Neuromuscular disorders
IS - 6
ER -