Polymicrogyria and Intractable Epilepsy in Siblings With Knobloch Syndrome and Homozygous Mutation of COL18A1

Knobloch and Layer described a triad of symptoms – vitreoretinal degeneration, high myopia, and congenital encephalocele – in 5 affected siblings in a large consanguineous family.1 The cause of what is now Knobloch syndrome (KS) was identified as mutation of COL18A1, the gene encoding collagen XVIII.2 We present an unusual case of two brothers with severe global developmental delay, medically intractable epilepsy, diffuse polymicrogyria, and high myopia, born to non-consanguineous parents of Palestinian ethnicity. Although the brothers lack typically-associated skull defects, they were found to harbor a novel homozygous pathogenic mutation in COL18A1, leading to a diagnosis of KS on the severe end of the phenotypic spectrum. Epilepsy and brain malformations are uncommon in cases of KS; hence, this report expands the current clinical spectrum and reinforces the diagnostic utility of trio whole exome sequencing analysis in appropriately selected cases of polymicrogyria.