A genotype–phenotype description in two Indian patients: Broadening the spectrum in VRK1‐related complex motor disorders

Abstract

AbstractVRK1 (vaccinia‐related kinase 1) was initially reported to be associated with spinal muscular atrophy–pontocerebellar hypoplasia (SMA‐PCH). Congenital or infantile‐onset progressive sensory‐motor neuropathy with microcephaly, adult‐onset distal SMA, and adult‐onset motor neuron disease are the other phenotypes described recently with VRK1. Since VRK1‐related complex motor disorders other than PCH is rare, we aim to depict the diverse clinical phenotypes and the genotypes of two patients with VRK1 variants from India. Proband‐1 is a 7‐year‐old girl who presented with distal muscle weakness and wasting of upper and lower limbs with brisk deep tendon reflexes (DTR), mild intellectual disability, and behavioral problems. She had a homozygous c.1159 + 1G > A pathogenic variant in VRK1, inherited from parents. Proband‐2 is a 25‐year‐old adopted male with sensory‐motor neuropathy and brisk DTR. He had a homozygous c.7C > T (p.R3C) missense variant of uncertain significance in VRK1 predicted to be damaging by multiple computational tools.