Reducing body myopathy - A new pathogenic FHL1 variant and literature review

Neuromuscul Disord. 2021 Sep;31(9):847-853. doi: 10.1016/j.nmd.2021.03.013. Epub 2021 Apr 15.

Abstract

Reducing body myopathy (RBM) is a rare disease marked by progressive muscle weakness caused by a mutation in FHL1 gene. We describe a new pathogenic variant and contrasted it with 44 other cases identified in the literature. A male child presented at age 3 suffering frequent falls and progressive muscular weakness. At age 8, he was wheelchair-bound and required ventilatory support. His mother and sister died due to the same problem. Creatine kinase was 428 IU/L (<190). Muscle biopsy showed typical reducing bodies, and genetic analysis identified a novel pathogenic hemizygous variant, c.370_375del. We identified 44 previous reported cases separated in two groups: 28 cases with mean age onset 7.6 ± 5 years and 16 with 26.7 ± 4.2 years. The time for the diagnosis was shorter to younger group. The initial symptoms, rigid spine, contractures, scoliosis and axial and neck weaknesses, dysphagia, cardiac involvement, were predominant in younger group. The variant c.369C > G predominated in younger group and c.448T > C in older one. Pathogenic variants positions seemed related to severe phenotype. Most wheelchair patients belonged to younger group. The data from this compilation and our case provided a general characterization spectrum and prognosis between two groups of age onset with RBM.

Keywords: Age onset; Muscle biopsy; Pathogenic variant; Prognosis; Reduction body myopathy.

Publication types

  • Review

MeSH terms

  • Adolescent
  • Adult
  • Biopsy
  • Child
  • Child, Preschool
  • Female
  • Genetic Diseases, X-Linked / pathology
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • LIM Domain Proteins* / genetics
  • Male
  • Middle Aged
  • Muscle Proteins* / genetics
  • Muscle, Skeletal / pathology
  • Muscular Diseases / genetics
  • Muscular Diseases / pathology*
  • Mutation
  • Mutation, Missense
  • Pedigree
  • Phenotype
  • Young Adult

Substances

  • FHL1 protein, human
  • Intracellular Signaling Peptides and Proteins
  • LIM Domain Proteins
  • Muscle Proteins