Abstracts

Rationale: Dravet syndrome is a severe epilepsy syndrome usually caused by a mutation in the neuronal sodium channel gene SCN1A. Based on personal observations of many children at a large Dravet parents meeting, we had the impression that there may be a specific facial phenotype associated with Dravet syndrome characterized by a small, upturned nose; thin upper lip; smooth, long philtrum; wide-set eyes; and long forehead. Methods: Families of children with SCN1A-confirmed Dravet syndrome who were members of the International Dravet Syndrome Epilepsy Action League (IDEA League) supplied standard digital photographs of the face of their affected children and unaffected siblings. The photographs were studied in two ways. First, the photographs were compiled into a booklet with cases and siblings randomly mixed. The booklet was sent to a sample of Canadian Pediatric Neurologists who were asked anonymously to identify which children in the booklet were affected by the syndrome and which were siblings. Secondly, the photographs were studied to provide 17 standard measurements that were accurate to <1mm (photogrammetry). To correct for photographic technique and varying magnification, the measurements were analyzed by 16 ratios such as philtrum/face width. Intra-observer reliability was almost perfect. Results: The booklet included 12 children with Dravet syndrome: 5 males, 7 females, mean age 8.8 years (2.6-16.6 years). There were 12 unaffected siblings: 6 males, 6 females, mean age 9.3 years (4-18 years). The review was by 16 pediatric neurologists. Consensus was defined for each photograph as 10 of 16 pediatric neurologists agreeing if the child was affected or was a sibling. Consensus was achieved in 20 out of 24 cases/siblings (83%). However, when consensus was achieved, only 12 of 20 (60%) were correctly identified as affected or sibling. For the photographic measurements we chose subjects based on the quality of the images - 13 affected children: 6 males, 7 females, mean age 8.6 years (4-16.7 years) and 10 unaffected siblings included 4 males and 6 females, mean age 11.4 years (6.3-21.8 years). Comparison of the 16 measured ratios of facial features yielded no significant differences between Dravet patients and siblings (p>0.05, 2-tailed t-tests). Conclusions: This study does not demonstrate a specific facial phenotype in Dravet syndrome that can be observed in photographs by pediatric neurologists or identified by standard measurements. The face of children with Dravet syndrome is apparently indistinguishable from their siblings indicating that SCN1A mutations have no dysmorphic effects.