Broad Phenotypic Spectrum of FLNA-associated Disorders Resulting in Brain Malformation, Epilepsy, Mental Retardation and Stroke

Aims: Mutations of the X-linked Filamin A gene (FLNA) on Xq28 are detected in patients with periventricular nodular heterotopia (PVNH). Due to its X-linked character the most common form of PVNH affects mostly females, while mutations of the FLNA gene in hemizygous males are mostly lethal. Clinically, PVNH is characterized by focal and/or generalized seizures, mild to profound mental retardation and in some cases also with ischemic cerebral lesions due to a profound vasculo-/coagulopathy. Furthermore, gain of function mutations of FLNA result in distinct skeletal phenotypes without any obvious neurological deficits. Recently, we could identify a distinct FLNA mutation in a male patient causing PVNH associated with dysmorphic features and severe constipation.