Dravet syndrome is a clinical disorder caused by a genetic alteration, usually in the SCN1A gene. However, its diagnosis is mainly based on clinical criteria and may be made even when genetic analysis does not reveal any alteration, as is observed in around 20% of cases.
Dravet Syndrome was first described in 1978 as « Severe Myoclonic Epilepsy in Infancy » (SMEI) by Dr Charlotte DRAVET and has been recognized throughout the world since then; and much published on.
Dravet syndrome seems to equally affect boys and girls and no geographic region has a particularly high or low number of cases.
Clinical signs will vary as the syndrome evolves. A close examination during the three main evolution phases will allow you to notice some of the characteristic signs of Dravet syndrome.
Examination of a Dravet syndrome patient during the onset phase will reveal no pathological signs. However analysis of the semiology and of the seizure course may bring Dravet syndrome to mind.
Japanese authors tested and proposed a predictive Dravet syndrome risk factor test, to be used in children under one year of age, to help early diagnosis.
It is a two-phase test (described here below):
First phase calculation
If the calculated clinical risk score is ≥6 then genetic testing should be considered.
Second Phase: Calculation of genetic score
If the total calculated risk score is ≥7 then a diagnosis of Dravet syndrome should be strongly suspected.
This test was also used in Italy, confirming its utility.
Examination of Dravet syndrome patient during the worsening phase shows hypotonia, ataxia, segmental interictal myoclonic jerks, and coordination impairment.
Examination of Dravet syndrome patient during the stabilisation phase shows that motor problems may worsen, even leading to crouch gait.
When to perform an EEG?
Recording in a 9-months-old patient :
Recording in an awake 3-year-old patient :
Generalised, focal and multifocal abnormalities, spikes, spike-waves, multiple spike-waves, symmetrical or not, will be more frequent on central areas as well as in temporal and occipital ones.
Recording in an awake 4-year-old patient :
Recording in an awake 5-year-old patient :
Interictal EEG during the sleep period shows normal age-linked sleep patterns or the same pathological findings as in the wakefulness period. Therefore both generalised and focal spikes, and spike-waves are enhanced or appear if the seizures are more frequent.
Recording in an asleep 4-year-old patient :
Regarding ictal EEG, they depend on the type of seizure.
Recording in a 4-year-old patient :
Recording in a 6-year-old patient during a myoclonic status :
A special feature during sleep is sometimes observed with focal abnormalities.
Recording in an asleep 10-year-old patient
Recording in a 12-year-old patient during a focal seizure
In order to detect the first signs of abnormality, these tests should be assessed from the onset and even when development is apparently normal. These tests must be standardised and adapted to the age and cognitive level of the patient.
For example: Griffiths scale, Brunet-Lézine, Bailey, Wechsler Preschool and Primary Scale of Intelligence (WPPSI), Wechsler Intelligence Scale for Children Revised (WISC-R).
Some questionnaires may also be used, this time for parents, such as the Vineland Adaptive Behaviour Scales (VABS) and the Child Behaviour Check List (CBCL).
Testing should be repeated in order to adapt to education, pedagogic and rehabilitative methods as well as pharmacological treatments. But the frequency of the tests must be adjusted according to the patient’s age and the course of the disease.
At onset it is difficult to diagnose Dravet Syndrome. Not all clinical signs are present and therefore other types of epilepsies may be considered.
Recording in a 2-year-old patient suffering from a symptomatic focal epilepsy
The presence of alternating, usually clonic, seizures is a strong argument in favour of the diagnosis of Dravet Syndrome.
SCN1A mutation was found only in some very rare cases of patients suffering from focal epilepsy.
Carbamazepine is recommended in the treatment of focal epilepsy whereas it has been demonstrated that it worsens Dravet syndrome patients’ condition. Should you have doubts, avoid its use.
In comparison with the onset age, it is easier to establish a firm diagnosis during the evolution.
Recording in an asleep 4-year-old patient
Recording in an awake 5-year-old patient experiencing a myoclonic-atonic seizure
Patients with Doose syndrome do not carry an SCN1A mutation. No causative mutation is known for this syndrome.
After a period of severe and pharmacoresistant seizures, many patients may become seizure-free but their cognitive outcome often remains unfavourable.
Recording in an asleep 15-year-old patient
Recording in an awake 20-year-old patient
Adult Dravet syndrome and adult Lennox-Gastaut syndrome should be differentiated by a careful medical history so as to recognize the early typical history. Careful semiological analysis of the seizures and a prolonged video-EEG during wakefulness and sleep periods allowing interictal analysis and seizure capture may help.
Finally, genetic analysis is also necessary, knowing that the absence of the SCN1A mutation or deletion does not preclude the diagnosis of Dravet syndrome.