Clinical Guidance
DEPDC5-related epilepsy encompasses a range of epilepsy syndromes, almost all of which are characterized by focal seizures, with seizure onset in a discrete area of the brain. While about 60% of individuals with DEPDC5-related epilepsy have a normal brain MRI , some have epilepsy associated with a cortical malformation, usually focal cortical dysplasia type II or hemimegalencephaly. Most affected individuals have a family history of focal epilepsy. To date, nearly 200 symptomatic individuals have been identified with a pathogenic variant in DEPDC5 [, , , , , , , , , , , , , , , , , , , , , , , , , ]. The following description of the phenotypic features associated with this condition is based on these reports. Table 2. DEPDC5-Related Epilepsy: Frequency of Select Features in Symptomatic Individuals1
Feature | Feature Subtype (if applicable) | % of Persons w/Feature2 | Comment |
|---|
Epilepsy related complications | All types | 100%3 | Most commonly frontal lobe seizures/ sleep-related hypermotor epilepsy (30%) |
Infantile spasms | 6% | — | — |
SUDEP | 10% | — | — |
Brain malformations | All types | 20% | — |
Focal cortical dysplasia | 17% | Mostly type II | — |
Hemimegalencephaly | 2% | — | — |
Polymicrogyria | 1% | One person was reported w/bilateral polymicrogyria.4 | — |
Developmental/learning issues | Developmental delays (language, motor) | 8% | — |
Intellectual disability | 12% | Most reported persons w/ID have FCD/focal epilepsy or drug-resistant epilepsy. | — |
Developmental delay | 7% | — | — |
Autism spectrum disorder | 5% | FCD = focal cortical dysplasia; SUDEP = sudden unexpected death in epilepsy Asymptomatic heterozygotes are common in families with DEPDC5-related epilepsy. Penetrance is therefore reduced and may be as low as 60% . | — |
Source: GeneReviews — "DEPDC5-Related Epilepsy"
