HNRNPA2B1 myopathy presenting in a family with an early onset oculopharyngeal muscular dystrophy-like phenotype

Neuromuscul Disord. 2024 Jan:34:27-31. doi: 10.1016/j.nmd.2023.11.002. Epub 2023 Nov 17.

Abstract

Genetic variation at HNRNPA2B1 is associated with inclusion body myopathy, Paget's disease and paediatric onset oculopharyngeal muscular dystrophy. We present a pedigree where a mother and two daughters presented with adolescent to early-adulthood onset of symptoms reminiscent of oculopharyngeal muscular dystrophy or chronic progressive external ophthalmoplegia, with a later limb-girdle pattern of weakness. Creatine Kinase was ∼1000 U/L. Myoimaging identified fatty replacement of sartorius, adductors longus and magnus, biceps femoris, semitendinosus and gastrocnemii. Muscle biopsies showed a variation of fibre size, occasional rimmed vacuoles and increased internalised myonuclei. Cases were heterozygous for a frameshift variant at HNRNPA2B1, consistent with a dominant and fully-penetrant mode of inheritance. Genetic variation at HNRNPA2B1 should be considered in adults with an oculopharyngeal muscular dystrophy-like or chronic progressive external ophthalmoplegia-like myopathy where initial testing fails to identify a cause.

Keywords: Myopathy; Oculpharyngeal muscular dystrophy, Chronic progressive external ophthalmoplegia, Limb girdle muscular dystrophy.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Humans
  • Muscle, Skeletal / pathology
  • Muscular Diseases* / genetics
  • Muscular Dystrophy, Oculopharyngeal* / diagnosis
  • Muscular Dystrophy, Oculopharyngeal* / genetics
  • Muscular Dystrophy, Oculopharyngeal* / pathology
  • Ophthalmoplegia, Chronic Progressive External* / pathology
  • Pedigree
  • Phenotype

Substances

  • hnRNP A2