Expanding the clinical spectrum and management of Traboulsi syndrome: report on two siblings homozygous for a novel pathogenic variant in ASPH

Ophthalmic Genet. 2021 Aug;42(4):493-499. doi: 10.1080/13816810.2021.1923039. Epub 2021 May 21.


Background: Traboulsi syndrome is a very rare, syndromic form of ectopia lentis that is potentially sight-threatening at a young age. It is characterized by typical facial, skeletal and ocular signs.

Materials and methods: Two siblings, born to consanguineous parents, with a clinical phenotype consistent with Traboulsi syndrome, underwent extensive ophthalmic imaging and exome-based genetic testing. Both were treated with unilateral clear lens extraction via a limbal approach.

Results: Two siblings, one male and one female, presented with systemic and ocular features consistent with Traboulsi syndrome. Lens subluxation was present in all 4fouraffected eyes, and spontaneous subconjunctival bleb formation was detected in one eye. This eye also showed evidence of keratoconus-related corneal thinning. The clinical diagnosis of Traboulsi syndrome was confirmed molecularly. A homozygous, novel, pathogenic nonsense variant was identified in exon 25 of the ASPH gene: c.2181_2183dup, p.(Val727_Trp728insTer). Excellent visual outcomes following clear lens extraction and postoperative rigid gas-permeable contact lens fitting were obtained.

Conclusions: We expanded the genetic spectrum of Traboulsi syndrome with a novel frameshift variant in the ASPH gene. We showed that lensectomy followed by gas-permeable contact lenses is an efficient therapeutic approach to treat lens subluxation in Traboulsi syndrome. However, lifelong follow-up is crucial to avoid (late) postoperative complications.

Keywords: ASPH; Traboulsi syndrome; clear lens extraction; consanguinity; exon 25; homozygous; novel pathogenic variant; rigid gas-permeable contact lenses; spontaneous filtering blebs.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Calcium-Binding Proteins / genetics*
  • Cataract Extraction
  • Codon, Nonsense / genetics*
  • Consanguinity
  • Craniofacial Abnormalities / diagnosis
  • Craniofacial Abnormalities / genetics*
  • Craniofacial Abnormalities / physiopathology
  • Craniofacial Abnormalities / surgery
  • Ectopia Lentis / diagnosis
  • Ectopia Lentis / genetics*
  • Ectopia Lentis / physiopathology
  • Ectopia Lentis / surgery
  • Exome Sequencing
  • Exons / genetics*
  • Female
  • Humans
  • Iris / abnormalities*
  • Iris / physiopathology
  • Iris / surgery
  • Male
  • Membrane Proteins / genetics*
  • Mixed Function Oxygenases / genetics*
  • Muscle Proteins / genetics*
  • Siblings
  • Slit Lamp Microscopy
  • Visual Acuity / physiology
  • Young Adult


  • Calcium-Binding Proteins
  • Codon, Nonsense
  • Membrane Proteins
  • Muscle Proteins
  • Mixed Function Oxygenases
  • ASPH protein, human

Supplementary concepts

  • Ectopia Lentis, Spontaneous Filtering Blebs, and Craniofacial Dysmorphism