Autism spectrum disorder and epilepsy often co-occur; however, the extent to which the association between autism symptoms and epilepsy is due to shared aetiology or to the direct effects of seizures is a topic of ongoing debate. Angelman syndrome (AS) is presented as a suitable disease model to explore this association.
Data from medical records and questionnaires were used to examine the association between age of epilepsy onset, autism symptoms, genetic aberration and communication level. Forty-eight participants had genetically verified AS (median age 14.5 years; range 1–57 years). A measure of autism symptoms (the Social Communication Questionnaire; SCQ) was completed for 38 individuals aged ≥ 4 years. Genetic cause was subgrouped into deletion and other genetic aberrations of the 15q11-q13 area. The number of signs used to communicate (< 20 sign and ≥ 20 signs) was used as a measure of nonverbal communication.
Mean age of epilepsy onset was 3.0 years (range 3 months–7.8 years). Mean SCQ score for individuals without epilepsy was 13.6 (SD = 6.7) and with epilepsy 17.0 (SD = 5.6; p = 0.17); 58% used fewer than 20 signs to communicate. There were no age differences between groups according to presence of epilepsy, level of nonverbal communication or type of genetic aberration. SCQ scores were higher in individuals with the deletion than in those with other genetic aberrations (18.7 vs 10.8 p = 0.008) and higher in the group who used < 20 signs to communicate (19.4 vs 14.1 p = 0.007). Age of epilepsy onset was correlated with SCQ (r = − 0.61, p < 0.001). Multiple regression showed that age of seizure onset was significantly related to SCQ score (β = − 0.90; p = 0.006), even when the type of genetic abnormality was controlled (R2 = 0.53; F = 10.7; p = 0.001).
The study provides support for the notion that seizures themselves contribute more to autism symptoms than expected from the underlying genetic pathology alone. The study demonstrates how a rare genetic syndrome such as Angelman syndrome may be used to study the relation between epilepsy and autism symptomatology.
Dagli AI, Mueller J, Williams CA. Angelman syndrome. In.: GeneReviews[Internet]; 2015.
Peters SU, Goddard-Finegold J, Beaudet AL, Madduri N, Turcich M, Bacino CA. Cognitive and adaptive behavior profiles of children with Angelman syndrome. Am J Med Genet A. 2004;128:110–3. CrossRef
Moss J, Howlin P, Oliver C. The assessment and presentation of autism spectrum disorder and associated characteristics in individuals with severe intellectual disability and genetic syndromes. In: Burack J, Hodapp R, Iarocci G, Zigler E, (Eds). The Oxford Handbook of Intellectual Disability and Development. New York: Oxford University Press; 2011. pp. 275–302.
Tanaka M, DeLorey TM, Delgado-Escueta A, Olsen RW. GABRB3, epilepsy, and neurodevelopment. In: Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV, editors. Jasper’s basic mechanisms of the epilepsies. [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2012.
Curatolo P, Aronica E, Jansen A, Jansen F, Kotulska K, Lagae L, et al. Early onset epileptic encephalopathy or genetically determined encephalopathy with early onset epilepsy? Lessons learned from TSC. Eur Journal Paediatr Neurol. 2016;20:203–11. CrossRef
Scott RC, Tuchman R. Epilepsy and autism spectrum disorders. Relatively related Neurology. 2016;87:130–1. PubMed
Sethi NK. Letter re: autism and epilepsy. A population-based nationwide cohort study. Neurology. 2017;88:110. PubMed
Rutter M, Bailey A, Lord C. The Social Communcation Questionnaire. 1st ed. Western Psychological Services: Los Angeles, CA; 2003.
Richards C, Powis L, Moss J, Stinton C, Nelson L, Oliver C. Prospective study of autism phenomenology and the behavioural phenotype of Phelan-McDermid syndrome: comparison to fragile X syndrome, Down syndrome and idiopathic autism spectrum disorder. J Neurodev Disord. 2017;9:37. CrossRefPubMedPubMedCentral
Curatolo P, Moavero R, de Vries PJ. Neurological and neuropsychiatric aspects of tuberous sclerosis complex. Lancet Neurol. 2015;4:733–45. CrossRef
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