Severe retinal complications in Knobloch Syndrome-Three siblings without clinically apparent occipital defects and a review of the literature

Background Knobloch syndrome results from recessive mutations in COL18A1 and is characterized by retinopathy and occipital scalp, brain and skull defects. Methods and Materials We report three siblings, born to consanguineous parents, two of whom with genetically confirmed Knobloch syndrome due to a homozygous pathogenic variant c.4054_4055del; p.Leu1352Valfs*72 in COL18A1. Results With the lack of classic occipital findings, an initial diagnosis of familial exudative vitreoretinopathy was entertained in these siblings because of the history of retinal detachments, retinal pigmentary changes and abnormal vitreous. The diagnosis of Knobloch syndrome was eventually made through molecular genetic testing using an extensive panel. In one patient presenting with acute retinal detachment and posteriorly dislocated intraocular lens implant, reattachment surgery was successful in stabilizing vision. Conclusion The clinical diagnosis of Knobloch syndrome can be difficult to reach in the absence of the typical occipital scalp defects. A careful medical history, detailed clinical examination and molecular genetic testing will reveal the correct diagnosis of Knobloch syndrome in atypical cases.

Automated summary

This study reports three siblings with Knobloch syndrome. One patient was initially misdiagnosed as having a different retinal disease due to the absence of typical occipital scalp defects. The correct diagnosis was eventually made through molecular genetic testing.