Type of Genetic Variant in SCN1A Does Not Predict Response to the Ketogenic Diet in Children with Dravet Syndrome
Abstract number :
3.342
Submission category :
10. Dietary Therapies (Ketogenic, Atkins, etc.)
Year :
2021
Submission ID :
1826318
Source :
www.aesnet.org
Presentation date :
12/6/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:53 AM
Authors :
Lila Worden, MD - Connecticut Children's; Katherine Helbig - Children's Hospital of Philadelphia; Ingo Helbig - Children's Hospital of Philadelphia; Olivia Robinson - Children's Hospital of Philadelphia; AG Christina Bergqvist - Children's Hospital of Philadelphia
Rationale: Children with Dravet syndrome are frequently referred for ketogenic diet therapies for refractory epilepsy, however response to the diet based type of genetic variant has not been explored.
Methods: Retrospective chart review of all patients with Dravet syndrome seen at Children’s Hospital of Philadelphia between 1997 and 2020. Responders were defined as ≥ 50% reduction in seizure frequency of all seizure types. Non-responders were defined as < 50% seizure reduction, or those who stopped the diet for any reason even if seizures improved. Genetic testing was reviewed by a genetic counselor (K.H.). SCN1A variants were characterized as loss-of-function (frameshift, nonsense, splicing, and deletion variants), missense, or other. Fisher exact test was used for comparison of responder rate by genetic mutation type with alpha level of 0.05.
Results: Thirty-six patients were identified, all of whom had genetic testing. Three patients had pathogenic variants in PCDH19; 33 had pathogenic variants in SCN1A. Thirty of 33 patients with confirmed genetic variants in SCN1A were included in the analysis. Two were excluded as genetic test results were unavailable for primary review; one patient had a large deletion spanning 10 genes including SCN1A. Twenty patients had a loss-of-function variant, 8 patients had a missense variant, and 2 patients had other variants (in frame deletion, and combination of insertion/deletion).
There was no significant difference between ketogenic diet responder rate at 3 months, 6 months, 1 year, 2 years, or 3 years for loss-of-function or missense variant groups (p-value ranges, 0.16 to 1.0). There was a non-significant trend toward a more sustained long-term responder rate at 3 years in the missense variant group (4 of 8) compared to the loss-of-function group (3 of 17, excluding missing data).
Conclusions: In this cohort, there is no correlation between responder rate to ketogenic diet and type of SCN1A variant in Dravet syndrome. Ketogenic dietary therapies should be considered for all children with Dravet syndrome.
Funding: Please list any funding that was received in support of this abstract.: None.
Dietary Therapies (Ketogenic, Atkins, etc.)