Persistence of fetal vasculature in a patient with Knobloch syndrome: potential role for endostatin in fetal vascular remodeling of the eye.
OBJECTIVE
To report a child with Knobloch syndrome (KS) with features of persistent fetal vasculature (PFV) and to discuss the possible role of endostatin in vascular remodeling of the fetal eye.


METHODS
Case report with enzyme-linked immunosorbent assay (ELISA) analysis of serum endostatin.


METHODS
Ocular examination, fluorescein angiography, echography, ELISA analysis of serum endostatin, and typing for pathogenic mutations in COL18A1.


RESULTS
Slit-lamp examination in the left eye disclosed numerous findings of PFV, including an extensive persistent pupillary membrane, scarcity of iris crypts, and pigmented epicapsular stellate remnants on the anterior lens surface. Dilated fundus examination revealed a total posterior vitreous detachment, despite the young age of the patient, with numerous white intragel opacities that were compatible with remnants of the vasa hyaloidea propria. The fundus had a tesselated appearance with angiographically visible large choroidal vessels. There was a retinochoroidal staphyloma inferotemporal to the optic disc. There were no retinal vessels visible temporally, and there was no macular differentiation or foveal pit. Competitive ELISA analysis disclosed no detectable serum endostatin. None of the 8 reported pathogenic mutations in the COL18A1 gene was found in the patient.


CONCLUSIONS
Persistent fetal vasculature may be a clinical and important manifestation in some patients with KS and can be explained by a deficiency in endostatin. Endostatin deficiency may result in reduced or delayed regression of fetal blood vessels in the eye (including the intravitreal compartment), thereby resulting in incomplete development of the normal vasculature in the retina. Our typing results for the reported COL18A1 mutations confirm the genetic heterogeneity of KS.
The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Elia J
EJ
Duh
Yong-Gang
YG
Yao
Manesh
M
Dagli
Morton F
MF
Goldberg
D002531:Cerebellum / Q000002:abnormalities*; D002648:Child; D015862:Choroid Diseases / Q000235:genetics*; D043170:Collagen Type XVIII / Q000235:genetics; D004252:DNA Mutational Analysis; D004677:Encephalocele / Q000235:genetics*; D043169:Endostatins / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D015785:Eye Diseases, Hereditary / Q000235:genetics*; D005451:Fluorescein Angiography; D006801:Humans; D006965:Hyperplasia; D008297:Male; D009154:Mutation; D009216:Myopia / Q000235:genetics; D012164:Retinal Diseases / Q000235:genetics*; D013577:Syndrome; D014822:Vitreous Body / Q000002:abnormalities* / Q000098:blood supply* / Q000473:pathology
D043170:Collagen Type XVIII; D043169:Endostatins