ABSTRACT
There is a broad phenotypic spectrum of patients with 17p13.3 deletions. One of the most prominent feature is lissencephaly caused by haploinsufficiency of the gene PAFAH1B1. The deletion of this gene and those distal to it, results in Miller-Dieker syndrome, however there have been many reports of patients with haploinsufficiency of the distal genes alone. The deletions of these genes including YWHAE CRK and TUSC5 have been studied extensively and YWHAE has been postulated to be the cause of neurological abnormalities. The patients with deletions of the Miller-Dieker syndrome distal region present with variable clinical features including brain abnormalities, growth retardation, developmental delay, facial dysmorphisms and seizures. While there have been many patients reported to have deletions involving the YWHAE gene along with other genes, here we present the first detailed clinical description of a patient with deletion of YWHAE alone, allowing a more accurate characterization of the pathogenicity of YWHAE haploinsufficiency. The patient reported here demonstrated brain abnormalities, learning disabilities, and seizures supporting the role of YWHAE in these features. We review the literature and use this case report to better characterize and further confirm the genotype-phenotype relationship of the genes within the critical region of Miller-Dieker Syndrome.
