Recessive Symptomatic Focal Epilepsy and Mutant Contactin-Associated Protein-like 2
Kevin A. Strauss, M.D., Erik G. Puffenberger, Ph.D., Matthew J. Huentelman, Ph.D., Steven Gottlieb, M.D., Seth E. Dobrin, Ph.D., Jennifer M. Parod, B.S., Dietrich A. Stephan, Ph.D., and D. Holmes Morton, M.D.
Contactin-associated protein-like 2 (CASPR2) is encoded by CNTNAP2and clusters voltage-gated potassium channels (Kv1.1) at thenodes of Ranvier. We report a homozygous mutation of CNTNAP2in Old Order Amish children with cortical dysplasia, focal epilepsy,relative macrocephaly, and diminished deep-tendon reflexes.Intractable focal seizures began in early childhood, after whichlanguage regression, hyperactivity, impulsive and aggressivebehavior, and mental retardation developed in all children.Resective surgery did not prevent the recurrence of seizures.Temporal-lobe specimens showed evidence of abnormalities ofneuronal migration and structure, widespread astrogliosis, andreduced expression of CASPR2.
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From the Clinic for Special Children, Strasburg, Pa. (K.A.S., E.G.P., D.H.M.); the Translational Genomics Research Institute, Phoenix, Ariz. (M.J.H., J.M.P., D.A.S.); Lancaster General Hospital, Lancaster, Pa. (S.G.); and the Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, Wis. (S.E.D.). Drs. Strauss and Puffenberger contributed equally to this article.
Address reprint requests to Dr. Strauss at the Clinic for Special Children, 535 Bunker Hill Rd., Strasburg, PA 17579, or at kstrauss{at}clinicforspecialchildren.org or to Dr. Stephan at the Translational Genomics Research Institute, 445 N. 5th St., Phoenix, AZ 85004, or at dstephan{at}tgen.org.
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