Familial focal epilepsy with variable foci-1 (FFEVF1) is an autosomal dominant form of epilepsy characterized by focal seizures arising from different cortical regions in different family members. Many patients have an aura and show automatisms during the seizures, whereas others may have nocturnal seizures. There is often secondary generalization. Some patients show abnormal interictal EEG, and some patients have intellectual disability or autism spectrum disorders. Seizure onset usually occurs in the first or second decades, although later onset has been reported, and there is phenotypic variability within families. Penetrance of the disorder is incomplete at about 70%. The phenotypic spectrum of FFEVF1 is wide, and may include nocturnal epilepsy, febrile seizures, and focal epilepsy with febrile seizures-plus (FEFS+) (summary by Klein et al., 2012; Liu et al., 2020). Detailed electrophysiologic, brain imaging, and/or histologic studies have indicated that some patients have subtle or clear evidence of focal cortical dysplasia (FCD), which may be associated with additional somatic mosaic loss-of-function DEPDC5 mutations in affected brain tissue (Baulac et al., 2015).
Reviews
Samanta (2022) provided a review of DEPDC5-related epilepsy, noting that there is a phenotypic spectrum, including autosomal dominant sleep-related hypermotor epilepsy (ADSHE), familial mesial temporal lobe epilepsy (FMTLE), autosomal dominant epilepsy with auditory features (ADEAF), febrile seizures and febrile seizures-plus (FEFS+), rolandic epilepsy, infantile spasms, and sudden unexpected death in epilepsy (SUDEP). The disorder results from enhanced activation of the mTOR (601231) signaling pathway.
Genetic Heterogeneity of Familial Focal Epilepsy with Variable Foci
See also FFEVF2 (617116), caused by mutation in the NPRL2 gene (607072) on chromosome 3p21; FFEVF3 (617118), caused by mutation in the NPRL3 gene (600928) on chromosome 16p13; and FFEVF4 (617935), caused by mutation in the SCN3A gene (182391) on chromosome 2q24. [from
OMIM]