We determined, by using a multidisciplinary strategy involving the use of advanced genomic procedures and in vivo functional analysis, that mutations in the ADAMTS18 gene, recently proposed to cause Knobloch syndrome, can also be responsible, although with a relatively low frequency, for early-onset severe retinal dystrophy possibly accompanied by other CNS features, such as autism and neurodevelopmental delay. This evidence concerns the gene ADAMTS18 and Knobloch syndrome 1.