title: The distinct ophthalmic phenotype of Knobloch syndrome in children.
abstract: BACKGROUND
  Knobloch syndrome is defined as a triad of occipital defect, high myopia and vitreo-retinal degeneration (often with later retinal detachment); however, the ocular phenotype is not well defined. This report characterises eye findings of the syndrome in children with genetically confirmed disease.
  
  
  METHODS
  Case series of Saudi children with previously documented homozygous mutations in COL18A1 or ADAMTS18.
  
  
  RESULTS
  All eight children (4-15 years old; five families) had smooth (cryptless) irides, high myopia (-10 to -20 dioptres) and distinctive vitreo-retinal degeneration consisting of diffuse very severe retinal pigment epithelium atrophic changes with prominent choroidal vessel show, macular atrophic lesions with or without a 'punched out' appearance and white fibrillar vitreous condensations. In two probands and a sibling, this distinctive retinal appearance was the basis for initial clinical diagnosis. Six children had temporal ectopia lentis and four had posterior perinuclear lens opacity. Additional features included developmental delay (two), epilepsy (one) and heterotopic grey matter in the lateral ventricles (one). Four children had no clinically discernible occipital defect.
  
  
  CONCLUSIONS
  Taken together, smooth iridies, ectopia lentis and characteristic vitreo-retinal degeneration seem pathognomonic. Although it is a defining feature of the syndrome, clinically discernible occipital defect is not a sine qua non for the diagnosis. Ophthalmologists are uniquely able to diagnose Knobloch syndrome.
authors.affiliation: Division of Pediatric Ophthalmology, King Khaled Eye Specialist Hospital, Riyadh 11462, Saudi Arabia. arif.khan@mssm.edu
authors.forename: Arif O
authors.initials: AO
authors.lastname: Khan
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Aldahmesh
authors.forename: Jawahir Y
authors.initials: JY
authors.lastname: Mohamed
authors.forename: Saleh
authors.initials: S
authors.lastname: Al-Mesfer
authors.forename: Fowzan S
authors.initials: FS
authors.lastname: Alkuraya
mesh_terms: D051722:ADAM Proteins / Q000235:genetics; D000071096:ADAMTS Proteins; D000293:Adolescent; D001284:Atrophy; D002648:Child; D002675:Child, Preschool; D024102:Collagen Type VIII / Q000235:genetics; D003241:Consanguinity; D004479:Ectopia Lentis / Q000175:diagnosis / Q000235:genetics; D004596:Electroretinography; D004677:Encephalocele / Q000235:genetics / Q000473:pathology*; D005260:Female; D006801:Humans; D007498:Iris / Q000002:abnormalities*; D008297:Male; D047728:Myopia, Degenerative / Q000175:diagnosis* / Q000235:genetics; D010641:Phenotype; D012162:Retinal Degeneration / Q000175:diagnosis* / Q000235:genetics; D012163:Retinal Detachment / Q000151:congenital* / Q000235:genetics / Q000473:pathology; D055213:Retinal Pigment Epithelium / Q000473:pathology
chemical_list: D024102:Collagen Type VIII; D051722:ADAM Proteins; D000071096:ADAMTS Proteins; C510099:ADAMTS18 protein, human