Combined achondroplasia and short stature homeobox-containing (SHOX) gene deletion in a Danish infant

Eur J Med Genet. 2024 Feb:67:104894. doi: 10.1016/j.ejmg.2023.104894. Epub 2023 Dec 7.

Abstract

Short stature or shortening of the limbs can be the result of a variety of genetic variants. Achondroplasia is the most common cause of disproportionate short stature and is caused by pathogenic variants in the fibroblast growth factor receptor 3 gene (FGFR3). Short stature homeobox (SHOX) deficiency is caused by loss or defects of the SHOX gene or its enhancer region. It is associated with a spectrum of phenotypes ranging from normal stature to Léri-Weill dyschondrosteosis characterized by mesomelia and short stature or the more severe Langer mesomelic dysplasia in case of biallelic SHOX deficiency. Little is known about the interactions and phenotypic consequences of achondroplasia in combination with SHOX deficiency, as the literature on this subject is scarce, and no genetically confirmed clinical reports exist. We present the clinical findings in an infant girl with concurrent achondroplasia and SHOX deficiency. We conclude that the clinical findings in infancy are phenotypically compatible with achondroplasia, with no features of the SHOX deficiency evident. This may change over time, as some features of SHOX deficiency only become evident later in life.

Keywords: Achondroplasia; FGFR3; Infant; SHOX; Short stature homeobox protein.

Publication types

  • Case Reports

MeSH terms

  • Achondroplasia* / genetics
  • Denmark
  • Female
  • Gene Deletion
  • Genes, Homeobox
  • Growth Disorders / genetics
  • Homeodomain Proteins / genetics
  • Humans
  • Infant
  • Osteochondrodysplasias* / genetics
  • Short Stature Homeobox Protein / genetics

Substances

  • Homeodomain Proteins
  • Short Stature Homeobox Protein
  • SHOX protein, human