CHST3-related skeletal dysplasia in 14 patients: Identification of 8 novel variants and further expansion of the phenotypic spectrum

Ghada A. Otaify, Rasha M. Elhossini, Sherif F. Abdel-Ghafar, Inas M. Sayed, Ghada M.H. Abdel-Salam, Mona S. Aglan*, Mohamed S. Abdel-Hamid*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


Biallelic variants in CHST3 gene result in congenital dislocation of large joints, club feet, short stature, rhizomelia, kypho-scoliosis, platyspondyly, epiphyseal dysplasia, flared metaphysis, in addition to minor cardiac lesions and hearing loss. Herein, we describe 14 new patients from 11 unrelated Egyptian families with CHST3-related skeletal dysplasia. All patients had spondyloepiphyseal changes that were progressive with age in addition to bifid distal ends of humeri which can be considered a diagnostic key in patients with CHST3 variants. They also shared peculiar facies with broad forehead, broad nasal tip, long philtrum and short neck. Rare unusual associated findings included microdontia, teeth spacing, delayed eruption, prominent angulation of the lumbar-sacral junction and atrial septal defect. Mutational analysis revealed 10 different homozygous CHST3 (NM_004273.5) variants including 7 missense, two frameshift and one nonsense variant. Of them, the c.384_391dup (p.Pro131Argfs*88) was recurrent in two families. Eight of these variants were not described before. Our study presents the largest series of patients with CHST3-related skeletal dysplasia from the same ethnic group. Furthermore, it reinforces that lethal cardiac involvement is a critical clinical finding of the disorder. Therefore, we believe that our study expands the phenotypic and mutational spectrum, and also highlights the importance of performing echocardiography in patients harboring CHST3 variants.

Original languageEnglish
Pages (from-to)2100-2112
Number of pages13
JournalAmerican Journal of Medical Genetics, Part A
Issue number8
Publication statusPublished - Aug 2023


  • CHST3 gene
  • joint dislocation
  • novel variants
  • osteoarthropathy
  • skeletal dysplasia
  • spondyloepiphyseal changes
  • Homozygote
  • Humans
  • Mutation
  • Dwarfism/diagnostic imaging
  • Osteochondrodysplasias/diagnostic imaging

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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