Abstract
Severe myoclonic epilepsy in infancy (SMEI) is an age-dependent epileptic encephalopathy
occurring in the first year of life and is one of the intractable epilepsies. Heterozygous
mutations in the voltage-gated sodium channel α subunit type1 gene (SCN1A) are frequently
identified in patients with SMEI; two-thirds of these mutations are truncation mutations
(non-sense and frameshift), and one-third are missense mutations. Although most reported
SMEI cases arise as sporadic mutations, close relatives of SMEI patients have also
been shown to manifest other types of epilepsies at a higher rate than that in the
general population. Here, we report a familial case of SMEI, in which two brothers
were affected with SMEI while their father had previously experienced simple febrile
seizures. A gene-based analysis identified a novel missense mutation in the SCN1A
gene (c.5138G>A, S1713N) in both brothers and in their father. Clinically, both siblings
showed failure in locomotion, an impairment of the sleep–wake cycle after late infancy,
and the subsequent appearance of frontal foci. The similarity in clinical manifestations
in both brothers suggests that the impairment of elements of the brainstem, particularly
aminergic neurons, develops after late infancy in SMEI. However, the siblings differed
in age at onset of SMEI and of myoclonic seizures, as well as in the severity of speech
delay. Our molecular and clinical findings suggest that different genetic backgrounds
and/or environmental factors may critically affect the clinical features of patients
with SCN1A mutations, consistent with the heterogeneity prevalent in this disorder.
Keywords
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Article info
Publication history
Accepted:
November 17,
2004
Received in revised form:
October 27,
2004
Received:
November 5,
2003
Identification
Copyright
© 2004 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
