Purpose: To report in detail the electroclinical features of a large family in which we recently identified a missense mutation (M145T) of a well-conserved amino acid in the first transmembrane segment of domain I of the human SCN1A. We showed that the mutation is associated with a loss of SCN1A function. Methods: The family originates from southern Italy and contains 35 members spread over four generations. Of the 14 affected individuals, the 13 still living members (7 males, mean age 36.6 +/- 20.4) underwent a complete electroclinical evaluation. Results: All 13 affected family members had febrile seizures (FS) up to the age of 6 years. Age at onset of FS ranged from 5 to 45 months with a mean age of 12.8 +/- 12.9 months. One of the 13 was affected by post-traumatic epilepsy. Three of the 13 later developed temporal lobe epilepsy (TLE) with both simple focal seizures, and also very rare focal complex or nocturnal secondary generalized tonic-clonic seizures. In two of the three patients who later developed TLE, the MRI studies revealed mesial temporal sclerosis. Conclusions: Our findings illustrate that SCN1A mutations can cause simple FS associated with TLE, which differ from the characteristic clinical spectrum of GEFS+. It is open to conjecture if this unusual phenotype might at least in part be related to the fact that M145T is the first missense mutation found in DIS1 of SCN1A.

Electroclinical Features of a Family with Simple Febrile Seizures and Temporal Lobe Epilepsy Associated with SCN1A Loss-of-Function Mutation / Eleonora Colosimo, Antonio Gambardella, Massimo Mantegazza, Angelo Labate, Raffaela Rusconi, Emanuele Schiavon, Ferdinanda Annesi, R.R. Cassulini, Sara Carrideo, Rosanna Chifari, M.P. Canevini, Raffaele Canger, Silvana Franceschetti, Grazia Annesi, Enzo Wanke, Aldo Quattrone. - In: EPILEPSIA. - ISSN 0013-9580. - 48:9(2007), pp. 1691-1696.

Electroclinical Features of a Family with Simple Febrile Seizures and Temporal Lobe Epilepsy Associated with SCN1A Loss-of-Function Mutation

M.P. Canevini;Raffaele Canger;
2007

Abstract

Purpose: To report in detail the electroclinical features of a large family in which we recently identified a missense mutation (M145T) of a well-conserved amino acid in the first transmembrane segment of domain I of the human SCN1A. We showed that the mutation is associated with a loss of SCN1A function. Methods: The family originates from southern Italy and contains 35 members spread over four generations. Of the 14 affected individuals, the 13 still living members (7 males, mean age 36.6 +/- 20.4) underwent a complete electroclinical evaluation. Results: All 13 affected family members had febrile seizures (FS) up to the age of 6 years. Age at onset of FS ranged from 5 to 45 months with a mean age of 12.8 +/- 12.9 months. One of the 13 was affected by post-traumatic epilepsy. Three of the 13 later developed temporal lobe epilepsy (TLE) with both simple focal seizures, and also very rare focal complex or nocturnal secondary generalized tonic-clonic seizures. In two of the three patients who later developed TLE, the MRI studies revealed mesial temporal sclerosis. Conclusions: Our findings illustrate that SCN1A mutations can cause simple FS associated with TLE, which differ from the characteristic clinical spectrum of GEFS+. It is open to conjecture if this unusual phenotype might at least in part be related to the fact that M145T is the first missense mutation found in DIS1 of SCN1A.
Febrile seizures; Genetics; SCN1A; Temporal lobe epilepsy
Settore MED/26 - Neurologia
Settore MED/39 - Neuropsichiatria Infantile
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/31991
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