Recessive symptomatic focal epilepsy and mutant contactin-associated protein-like 2.
Contactin-associated protein-like 2 (CASPR2) is encoded by CNTNAP2 and clusters voltage-gated potassium channels (K(v)1.1) at the nodes of Ranvier. We report a homozygous mutation of CNTNAP2 in Old Order Amish children with cortical dysplasia, focal epilepsy, relative macrocephaly, and diminished deep-tendon reflexes. Intractable focal seizures began in early childhood, after which language regression, hyperactivity, impulsive and aggressive behavior, and mental retardation developed in all children. Resective surgery did not prevent the recurrence of seizures. Temporal-lobe specimens showed evidence of abnormalities of neuronal migration and structure, widespread astrogliosis, and reduced expression of CASPR2.
Strauss
Kevin A
KA
Clinic for Special Children, Strasburg, Pa 17579, USA. kstrauss@clinicforspecialchildren.org
Puffenberger
Erik G
EG
Huentelman
Matthew J
MJ
Gottlieb
Steven
S
Dobrin
Seth E
SE
Parod
Jennifer M
JM
Stephan
Dietrich A
DA
Morton
D Holmes
DH
D002648:Child; D002675:Child, Preschool; D004569:Electroencephalography; D004828:Epilepsies, Partial / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D015870:Gene Expression; D006720:Homozygote; D006801:Humans; D018810:Magnetic Resonance Angiography; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D012026:Reflex, Stretch; D055502:Secondary Prevention; D012640:Seizures / Q000209:etiology; D013702:Temporal Lobe / Q000378:metabolism / Q000473:pathology
C403049:CNTNAP2 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins