Central nervous system anomalies in two females with Borjeson-Forssman-Lehmann syndrome

Borjeson-Forssman-Lehmann syndrome (BFLS) is a rare disorder caused by mutations in the PHF6 gene. It manifests as syndromic X-linked recessive intellectual disability (ID) in males and as sporadic ID due to de novo mutations in females. Clinical features include variable ID and a range of somatic manifestations constituting a distinct phenotype in both males and females, respectively, including seizures in a few. Central nervous system (CNS) imaging data are largely unavailable for BFLS. Here we report on CNS MRI findings from two female individuals with BFLS due to a de novo duplication in PHF6 who presented with typical BFLS and epilepsy. Brain findings encompass an intriguing combination of structural abnormalities including a simplified gyral pattern and aspects resembling subcortical band heterotopia as signs of malformation of cortical development (MCD). This finding is of note, since PHF6 has been suggested to play pivotal roles in CNS development including neuronal migration.