Diagnosis, Workup and Treatment

While the patient was under anesthesia, an optical coherence tomography test and electroretinography were performed. The OCT revealed retinal thinning, photoreceptor loss, poor retinal lamination and macular hypoplasia. The ERG was mildly abnormal in both eyes, with both rod and cone dysfunction. The patient was noted to have an axial length of 26.25 mm by ultrasound.


Knobloch syndrome is known to be caused by a mutation in the gene encoding for collagen 18A1 (COL18A1), which is a nonfibril-forming collagen expressed in human epithelial and endothelial basement membranes throughout the body, but particularly in ocular tissues. Our patient was found to be a compound heterozygote with a previously reported truncating mutation on one allele and a novel truncating mutation on the other allele.

The distinct ophthalmic phenotype of this disorder was characterized by Arif Khan, MD, and coworkers in 2012 in a case series of eight patients with a genetically confirmed diagnosis of Knobloch syndrome. All eight children had smooth cryptless irides, high myopia and a distinctive vitreo-retinal degeneration, which consisted of RPE atrophy, prominent choroidal vessels, macular atrophy and fibrillar vitreous condensations. Six of the children had ectopia lentis, and four of the children had posterior perinuclear opacity. Systemic associations include developmental delay, renal anomalies and pulmonary hypoplasia. Although occipital defects may be absent, abnormalities include a patch of alopecia (as seen in our patient), cutis aplasia or encephalocele.

The prognosis of children with Knobloch syndrome is greatly affected by the extent of CNS malformation, systemic involvement and increased risk of retinal detachment. The prognosis is also dependent upon whether or not there is any functional isoform of collagen 18 present.

Our patient underwent a systemic evaluation, including renal ultrasound, which was normal and did not have evidence of developmental delay. Spectacle correction improved his visual acuity and nystagmus. Goals of treatment include close monitoring for retinal tears or detachment and ectopia lentis.

Identification of additional mutations that result in Knobloch Syndrome has the potential to reveal novel molecular mechanisms that control eye development. The discovery of new mutations continues to be an important contribution to the small fund of knowledge we currently have on this rare genetic entity.  REVIEW

The author would like to thank Alex Levin, MD and Wadakarn Wuthisiri, MD of the Wills Eye Institute Department of Pediatric Ophthalmology and Ocular Genetics for their assistance with the preparation of this case.

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