June 2013
Volume 54, Issue 15
ARVO Annual Meeting Abstract  |   June 2013
Comparison of human and murine ocular findings in the Knobloch syndrome caused by mutations in COL18A1
Author Affiliations & Notes
  • Behrad Milani
    Ophthalmology, Univ of Illinois at Chicago, Chicago, IL
  • Stephen Tsang
    Columbia Univ-Harkness Eye Inst, Columbia Coll phys Surg, newyork, NY
  • Irene Maumenee
    Ophthalmology, Univ of Illinois at Chicago, Chicago, IL
  • Footnotes
    Commercial Relationships Behrad Milani, None; Stephen Tsang, None; Irene Maumenee, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 1341. doi:
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      Behrad Milani, Stephen Tsang, Irene Maumenee; Comparison of human and murine ocular findings in the Knobloch syndrome caused by mutations in COL18A1. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1341.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: To compare the ocular findings of men and mice with the Knobloch syndrome to advance understanding of the pathogenesis of low vision and retinal detachments.

Methods: A 17 year old patient was diagnosed with the Knobloch syndrome at age 5 months because of congenital nystagmus, poor fix and following, high myopia of -24D and aplasia of the macular area as well as a congenital scalp defect. His VA remained stable at 20/200 OU until he developed cataracts requiring surgery at age 15y. He developed a peripheral retinal hole for which he was successfully treated with laser therapy. He underwent a complete eye evaluation including biometry and OCT. Three animals homozygous for a col18a1 knock-out model mouse model underwent OCT and fluorescein angiography.

Results: Corneal biometry gave K readings of 39.9 + 3.3D axis 160 and 32.8+11.2D axis 109; pachymetry of the right eye was 578μm and of the left eye 529μm; OCT scans of the patient showed tessellated fundus and marked thinning of the retina of the posterior pole with absence of the foveal depression, apparent lack of photoreceptors, and an eccentric staphyloma. DNA analysis showed a two base pair deletion leading to a homozygous frameshift mutation in exon 6 of COL18A1. OCT and FA findings in a knock-out mouse model of col18a1 (Olsen and col.) showed apparent absence of photoreceptors, attenuated retinal and irregular choroidal vasculature.

Conclusions: The Knobloch syndrome is classified as heritable disorders of connective tissue and combines ocular, CNS and skeletal findings. It is a complex autosomal recessive syndrome, involving intrauterine developmental anomalies of the brain (meningoencephaloceles) and the macula (ateliotic macula) as well as acquired anomalies of the eye and the skeleton. Ocular complications consist of irregular astigmatism, juvenile cataracts and retinal detachments. The patients have a Stickler like facial appearance. OCT of a patient with a homozygous frameshift mutation showed a thinned retina with apparent absence of photoreceptors. OCT in the knock-out mouse showed comparable findings, making this a valid animal model.

Keywords: 539 genetics • 688 retina • 696 retinal degenerations: hereditary  

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