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.
Clinic for Special Children, Strasburg, Pa 17579, USA. kstrauss@clinicforspecialchildren.org
Kevin A
KA
Strauss
Erik G
EG
Puffenberger
Matthew J
MJ
Huentelman
Steven
S
Gottlieb
Seth E
SE
Dobrin
Jennifer M
JM
Parod
Dietrich A
DA
Stephan
D Holmes
DH
Morton
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