Retinal Detachment and Encephalocele

Knobloch, William H.; Layer, James M.

doi:10.3928/0191-3913-19710801-11

Cited by 43 publications

(42 citation statements)

References 7 publications

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“…However, the combination of VRD and encephalocele justifies our diagnosis of KNO. Furthermore, other abnormal pulmonary conditions (such as scimitar syndrome) were reported in one of the original patients of Knobloch and Layer [1971].…”

Section: Discussionmentioning

confidence: 99%

Knobloch syndrome: Novel mutations inCOL18A1, evidence for genetic heterogeneity, and a functionally impaired polymorphism in endostatin

et al. 2004

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Knobloch syndrome (KNO) is an autosomal recessive disorder characterized by high myopia, vitreoretinal degeneration with retinal detachment, and congenital encephalocele. Pathogenic mutations in the COL18A1 gene on 21q22.3 were recently identified in KNO families. Analysis of two unrelated KNO families from Hungary and New Zealand allowed us to confirm the involvement of COL18A1 in the pathogenesis of KNO and to demonstrate the existence of genetic heterogeneity. Two COL18A1 mutations were identified in the Hungarian family: a 1-bp insertion causing a frameshift and a premature in-frame stop codon and an amino acid substitution. This missense variant is located in a conserved amino acid of endostatin, a cleavage product of the carboxy-terminal domain of collagen alpha 1 XVIII. D1437N (D104N in endostatin) likely represents a pathogenic mutation, as we show that the endostatin N104 mutant is impaired in its affinity towards laminin. Linkage to the COL18A1 locus was excluded in the New Zealand family, providing evidence for the existence of a second KNO locus. We named the second unmapped locus for Knobloch syndrome KNO2. Mutation analysis excluded COL15A1, a member of the multiplexin collagen subfamily similar to COL18A1, as being responsible for KNO2.

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Section: Discussionmentioning

confidence: 99%

Knobloch syndrome: Novel mutations inCOL18A1, evidence for genetic heterogeneity, and a functionally impaired polymorphism in endostatin

et al. 2004

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“…Characterization of patients with Knobloch syndrome revealed mutations affecting either the short form of type XVIII collagen or all its isoforms (9,10). Altogether 35 patients from 12 families have been described with this rare autosomal recessive disorder that is characterized by several eye findings in addition to occipital encephalocele (9,10,12,30). Although there is some clinical variability among the patients, an explanation based on structural changes in the inner limiting membrane and the BM of the VHP has been put forward for the observed high myopia, vitreoretinal degeneration, and retinal detachment (11).…”

Section: Discussionmentioning

confidence: 99%

“…Eyes from Col18a1 −/− (11) and control mice were examined on postnatal Days 1,4,8,10,12,14,16 and 24, and at the age of 11 months. Expression of the type XVIII collagen variants in the iris and ciliary body was studied in 16-day-old mouse eyes.…”

Section: Histological and Immunofluorescence Examination Of Mouse Eyesmentioning

confidence: 99%

Lack of type XVIII collagen results in anterior ocular defects

et al. 2003

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Mice lacking type XVIII collagen have defects in the posterior part of the eye, including delayed regression of the hyaloid vasculature and poor outgrowth of the retinal vessels. We report here that these mice also have a fragile iris and develop atrophy of the ciliary body. The irises of Col18a1-/- mice can be seen to adhere to the lens and cornea. After the pupils begin to function, the double layer of epithelial cells separates at the apical cell contacts, leading to defoliation of its posterior pigment epithelial cell layer, and extracellular material begins to accumulate in the basement membrane zones of the iris. In contrast to the iris epithelia, where no clear signs of cellular atrophy were detected, the lack of type XVIII collagen resulted in atrophy of the pigmented epithelial cells of the ciliary body, and there were also ultrastructural abnormalities in the basement membrane zones. These changes did not lead to chronically elevated intraocular pressures, however. Our results indicate that type XVIII collagen is needed for the integrity of the epithelial basement membranes of the iris and the ciliary body and that its gene should therefore be taken into account as a new potential cause of anterior segment disorders in the eye.

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“…The other condition combining a retinal detachment and central nervous system lesions is that described by Knobloch & Layer (1971), but the cerebral lesion is an encephalocele and intelligence is usually normal.…”

Section: Discussionmentioning

confidence: 99%