Developmental and Epileptic Encephalopathy 65 (CYFIP2)

Developmental and Epileptic Encephalopathy 65 (CYFIP2) is a severe early-onset encephalopathy with drug-resistant seizures, profound developmental impairment, hypotonia, feeding difficulty, movement abnormalities and often acquired microcephaly. Disease associated with non-hotspot variants may be milder.

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Genetics

Usually caused by a de novo heterozygous pathogenic variant in CYFIP2. Substitutions at the Arg87 hotspot are strongly associated with the severe DEE65 phenotype, whereas other loss-of-function variants can produce a broader neurodevelopmental spectrum.

Molecular Mechanism

CYFIP2 links the WAVE regulatory complex controlling actin polymerization with FMRP-dependent translational regulation. Arg87 variants destabilize the inhibited WAVE complex and produce excessive actin-remodeling activity, disturbing neuronal morphogenesis and network function.

Therapy

Treatment is symptomatic with individualized antiseizure medication, nutrition, rehabilitation and respiratory support when required. No targeted therapy is established; cannabidiol has only isolated case-level evidence.

CCP Activity

CCP is developing an inducible CYFIP2 Arg87Cys model.

Mouse Models Mouse Models & Gene Cards

Mouse Models	Gene Cards
TBD	TBD