Dravet syndrome: early clinical manifestations and cognitive outcome in 37 Italian patients.
Aims of our study were to describe the early clinical features of Dravet syndrome (SMEI) and the neurological, cognitive and behavioral outcome. The clinical history of 37 patients with clinical diagnosis of SMEI, associated with a point mutation of SCN1A gene in 84% of cases, were reviewed with particular attention to the symptoms of onset. All the patients received at least one formal cognitive and behavior evaluation. Epilepsy started at a mean age of 5.7 months; the onset was marked by isolated seizure in 25 infants, and by status epilepticus in 12; the first seizure had been triggered by fever, mostly of low degree in 22 infants; the first EEG was normal in all cases. During the second year of life difficult-to-treat seizures recurred, mostly triggered by fever, hot bath, and intermittent lights and delay in psychomotor development became evident. At the last evaluation, performed at a mean age of 16+/-6.9 years, mental retardation was present in 33 patients, associated with behavior disorders in 21. Our data indicate that the most striking features of SMEI are: the early onset of seizures in a previously healthy child, the long duration of the first seizure, the presence of focal ictal symptoms, and sensitivity to low-grade fever. Diagnosis of SMEI may be proposed by the end of the first year of life, and a definite diagnosis can be established during the second year based on the peculiar seizure-favoring factors, EEG photosensitivity and psychomotor slowing. The temporal correlation between high seizure frequency and cognitive impairment support the role of epilepsy in the clinical outcome, even if a role of channelopathy cannot be ruled out.
Ragona
Francesca
F
Department of Pediatric Neuroscience, Fondazione IRCCS, Istituto Nazionale Neurologico C Besta, Milano, Italy.
Brazzo
Daniela
D
De Giorgi
Ilaria
I
Morbi
Monica
M
Freri
Elena
E
Teutonico
Federica
F
Gennaro
Elena
E
Zara
Federico
F
Binelli
Simona
S
Veggiotti
Pierangelo
P
Granata
Tiziana
T
D000293:Adolescent; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002648:Child; D002653:Child Behavior Disorders / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D002675:Child, Preschool; D003072:Cognition Disorders / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D003937:Diagnosis, Differential; D018450:Disease Progression; D004831:Epilepsies, Myoclonic / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D007558:Italy; D008297:Male; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics; D012640:Seizures / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D015222:Sodium Channels / Q000235:genetics; D013577:Syndrome; D055815:Young Adult
D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels