Cognitive development in Dravet syndrome: a retrospective, multicenter study of 26 patients.
OBJECTIVE
To clarify the role of epilepsy and genetic background in determining the cognitive outcome of patients with Dravet syndrome.


METHODS
In this retrospective study, we reviewed the clinical history and cognitive development of 26 patients who had been followed with standardized evaluations since seizure onset. The cognitive outcome was quantified as differential general quotient (dGQ) between ages 12 and 60 months. Statistical analysis correlated the dGQ with genotype and epilepsy course.


RESULTS
Epilepsy started at the mean age of 5.6 months. All patients experienced prolonged convulsive seizures, whereas absences and myoclonus were reported in 17. Cognitive outcome was poor in almost all patients; the mean dGQ was 33 points, varying from 6-77 points. The analysis of individual cognitive profiles identified seven patients in whom the dGQ was <20 points; the main clinical characteristic in this subset of patients was lack of early absences and myoclonus. The statistical analysis of the whole series failed to reveal significant differences in cognitive outcome with regard to the presence of SCN1A mutations and their type. In particular, mutation-carrier patients with the best cognitive outcome harbored either missense or truncating mutations.


CONCLUSIONS
Dravet syndrome encompasses different epileptic and cognitive phenotypes that probably result from both genetic and epigenetic factors. In this series, early appearance of myoclonus and absences was associated with the worst cognitive outcome.
Department of Pediatric Neuroscience, IRCCS Foundation Neurological Institute C. Besta, Milano, Italy.
Francesca
F
Ragona
Tiziana
T
Granata
Bernardo
B
Dalla Bernardina
Francesca
F
Offredi
Francesca
F
Darra
Domenica
D
Battaglia
Monica
M
Morbi
Daniela
D
Brazzo
Simona
S
Cappelletti
Daniela
D
Chieffo
Ilaria
I
De Giorgi
Elena
E
Fontana
Elena
E
Freri
Carla
C
Marini
Alessio
A
Toraldo
Nicola
N
Specchio
Pierangelo
P
Veggiotti
Federico
F
Vigevano
Renzo
R
Guerrini
Francesco
F
Guzzetta
Charlotte
C
Dravet
D000293:Adolescent; D017668:Age of Onset; D002648:Child; D002657:Child Development / Q000502:physiology*; D002675:Child, Preschool; D003071:Cognition / Q000502:physiology*; D004569:Electroencephalography; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007558:Italy; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000502:physiology; D020190:Myoclonic Epilepsy, Juvenile / Q000235:genetics* / Q000523:psychology*; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics; D012189:Retrospective Studies; D012640:Seizures / Q000150:complications / Q000235:genetics; D015222:Sodium Channels / Q000235:genetics; D013226:Status Epilepticus / Q000150:complications / Q000235:genetics
D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels