Distinct Phenotype in Dravet Syndrome Helps Outline Treatment

Australian researchers were able to characterize a distinct phenotype of speech, language, and oral motor dysfunctions associated with Dravet syndrome, a genetic disorder caused by a mutation in gene sodium channel alpha 1 subunit (SCN1A), according to a study recently published in Neurology.¹

Symptoms of Dravet syndrome typically start at approximately 6 months — following normal development — with febrile status epilepticus producing multiple kinds of repeated seizures over the next 4 years.^2,3 Nearly all patients develop high levels of cognitive disability affecting language function.^4-6

In the current study, the investigators assembled a cohort of 20 patients (15 female, 5 male) with a median age of 11.5 (range 15 months to 28 years) diagnosed with Dravet syndrome and identified as having the SCN1A mutation at a clinic in Melbourne, Australia.  All patients were being treated with antiepileptic drugs (AEDs).

The cohort was separated by verbal ability into 2 groups: minimally verbal (MV) and verbal (V). Both groups were able to communicate intentionally; only 3 patients in the MV group were able to use non-symbolic communication in the form of gestures, eye contact, and vocalization. Patients in the V group were able to speak conversationally, but had impairments ranging from normal (1 patient), mild (4 patients), and moderate (5 patients) to severe (3 patients). Breathing mechanisms were impaired in all patients.

All participants in the MV group exhibited significant impairment of oral motor skills, although 1 patient was able to move the jaw and tongue independently. Impairments in movements of the lips and tongue were evident in 12 out of 15 participants in the V group. Many patients demonstrated slack control of neck and trunk muscles, which contributed to oral motor problems. Of the 3 patients who were unimpaired, 2 were under the age of 2.

Sounds involving lip retraction (“eee” sounds) were within normal limits, while lip rounding (“ooh” sounds) was weak and asymmetrical. Of the V group patients, 6 were unable to elevate the tongue and 3 others had involuntary tongue movements. Receptive and expressive language was also affected by Dravet syndrome, as both were severely impaired in 9 out of 13 patients tested.

In addition, in the MV group medications such as benzodiazepines given for therapy in 7 patients were associated with difficulty producing saliva, while 1 other patient had unsuccessful salivary duct surgery. Five patients had mild dysphagia and 3 had percutaneous endoscopic gastrostomy tubes placed for nutrition.

Overall, the investigators found language impairments in the study cohort to increase with age, as 3 out of 4 of the adults were mild to moderately unintelligible, while the 2 youngest patients (age 15 months) still showed developmentally normal oral motor and language abilities. The distinct phenotypic profile of Dravet syndrome suggests that targeted therapies aimed at improving oral motor function in patients would be beneficial.

References

1. Turner SJ, Brown A, Arpone M, et al.  Dysarthria and broader motor speech deficits in Dravet syndrome. Neurology. 2017;88:743-749.
2. Dravet C, Bureau M, Oguni H, et al. Dravet syndrome (severe myoclonic epilepsy in infancy). In: Bureau M, Genton P, Dravet C, et al, eds. Epileptic Syndromes in Infancy, Childhood and Adolescence, 5^th ed. Montrouge, France: John Libbey Eurotext Ltd.; 2012:125-156.
3. Ragona F. Cognitive development in children with Dravet syndrome. Epilepsia. 2011;52 Suppl 2:39-43.
4. Brunklaus A, Ellis R, Reavey E, et al. Prognostic, clinical and demographic features in SCN1A mutation-positive Dravet syndrome. Brain. 2012;135:2329-2336.
5. Battaglia D, Chieffo D, Siracusano R, et al. Cognitive decline in Dravet syndrome: is there a cerebellar role? Epilepsy Res. 2013;106:211-221.
6. Chieffo D, Battaglia D, Lettori D, et al. Neuropsychological development in children with Dravet syndrome. Epilepsy Res. 2011;95:86-93.