Expanding the clinical spectrum of SOX18-related Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome

Eur J Med Genet. 2022 Nov;65(11):104607. doi: 10.1016/j.ejmg.2022.104607. Epub 2022 Sep 10.


Pathogenic variants in SOX18 are associated with hypotrichosis-lymphedema-telangiectasia-renal defects syndrome (HLTRS) and hypotrichosis-lymphedema-telangiectasia syndrome (HLTS). Eleven patients with SOX18 related HLTRS/HLTS have been previously described. Cardinal features include varying degrees of hypotrichosis, lymphedema and telangiectasias. We report a 15-year-old female patient with a likely de novo SOX18 pathogenic variant identified on duo exome sequencing. In addition to the classic features, the currently reported patient presented with novel clinical features including musculoskeletal abnormalities and strikingly poor wound healing. Chronic skin ulcers have been a major cause of morbidity for the patient and have led to significant functional limitation. Further, our experience with wound management has been detailed. We hope to improve understanding of the clinical spectrum of this ultra-rare disorder by reviewing the phenotypic features in all reported patients including our patient.

Keywords: Brachydactyly; HLTRS; Polydactyly; SOX18; Syndactyly; Ulcer.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adolescent
  • Alopecia
  • Female
  • Glomerulonephritis, Membranoproliferative
  • Humans
  • Hypotrichosis* / genetics
  • Lymphedema* / genetics
  • SOXF Transcription Factors
  • Telangiectasis* / genetics


  • SOX18 protein, human
  • SOXF Transcription Factors

Supplementary concepts

  • Glomerulonephritis sparse hair telangiectases