title: Central nervous system anomalies in two females with Borjeson-Forssman-Lehmann syndrome.
abstract: 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.
authors.affiliation: Epilepsy Center, Dept. Neurology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Germany. Electronic address: burkhard.kasper@uk-erlangen.de.
authors.forename: Burkhard S
authors.initials: BS
authors.lastname: Kasper
authors.affiliation: Dept. Neuroradiology, University Hospital Erlangen, Friedrich-Alexander University Erlangen, Germany.
authors.forename: Arnd
authors.initials: A
authors.lastname: Dörfler
authors.affiliation: Institute for Clinical Genetics, Faculty of Medicine Carl Gustav Carus, TU Dresden, 01307, Dresden, Germany.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Di Donato
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA.
authors.forename: Ekkehard M
authors.initials: EM
authors.lastname: Kasper
authors.affiliation: Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany; Institut für Humangenetik, Universitätsklinikum Düsseldorf, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Wieczorek
authors.affiliation: Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Hoyer
authors.affiliation: Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Zweier
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging*; D004827:Epilepsy / Q000150:complications* / Q000000981:diagnostic imaging* / Q000235:genetics; D005145:Face / Q000002:abnormalities* / Q000000981:diagnostic imaging; D005260:Female; D005385:Fingers / Q000002:abnormalities* / Q000000981:diagnostic imaging; D006130:Growth Disorders / Q000150:complications* / Q000000981:diagnostic imaging* / Q000235:genetics; D006801:Humans; D007006:Hypogonadism / Q000150:complications* / Q000000981:diagnostic imaging* / Q000235:genetics; D008607:Intellectual Disability / Q000000981:diagnostic imaging / Q000235:genetics; D038901:X-Linked Intellectual Disability / Q000150:complications* / Q000000981:diagnostic imaging* / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009421:Nervous System Malformations / Q000150:complications* / Q000000981:diagnostic imaging* / Q000235:genetics; D009765:Obesity / Q000150:complications* / Q000000981:diagnostic imaging* / Q000235:genetics; D055815:Young Adult
keywords: Band heterotopia; Borjeson-Forssman-Lehmann; PHF6, cerebral malformation