Epileptic Encephalopathies of Infancy and Autism

Genetic testing of epileptic encephalopathies of infancy: an approach.



The epileptic encephalopathies of infancy are a group of disorders characterized by intractable seizures, persistent abnormality of cortical function documented on EEG, and consequently impaired neuro-developmental outcomes.

The etiologies vary and include; structural brain malformations, acquired brain insults, and inborn errors of metabolism in the majority of the affected patients. In a proportion of these cases no obvious etiology is identifiable on investigation.

Recent advances in molecular diagnostics have led to the discovery of a number of gene defects that may be causal in many epileptic encephalopathies.

Identification of the causative mutation is important for prognostic and genetic counseling, and may also carry treatment implications.

The recently described genes include;

Cyclin-Dependent Kinase-Like 5 gene (CDKL5),

Protocadherin 19 (PCDH19),

Sodium channel neuronal type 1a subunit gene (SCN1A),

Aristaless-Related Homeobox Gene (ARX),

and Syntaxin binding protein 1 gene (STXBP1),amongst others.

Distinct electro-clinical syndromes are increasingly being identified amongst patients carrying the various mutations. In this review, we outline the approach to clinical evaluation and genetic testing of epileptic encephalopathies in infancy.


Further Readings of Interest

SCN1a and Autism


CDKL5 and Autism


PCDH19 and Autism


ARX and Autism




Epilepsy and Autism



Routine developmental and autism screening in an epilepsy care setting.


Epilepsy Center, Ann & Robert H. Lurie Children’s Hospital of Chicago

We assessed the yield of routine screening for delay and autism in a hospital-based program. Developmental delay (delay) and co-morbidities like autism are common in children with epilepsy.

Parents completed developmental and autism screeners for 65 children (average age=2.5y; 38(58%) boys).

Forty-nine (75%) were established epilepsy patients, and 16 (25%) were new patients.

For development, 47 (72%) children screened positive and 8 (12%) had borderline results.

Twenty-four (37%) scored positive for autism, all of whom also screened positive for developmental delay.

Delays and neurologic deficits accounted for the positive autism results in 20 of the 24. Developmental findings were confirmatory (already receiving services) in 32/55 (58%) children and actionable in 17 (31%) (requiring further evaluation). Referrals for further evaluations were made for most with actionable findings.

The yield of routine screening of children in a tertiary center is sufficiently high to support its use and to consider screening of all children seen with epilepsy.


A national profile of childhood epilepsy and seizure disorder.

Paediatrics journal. http://www.ncbi.nlm.nih.gov/pubmed/22271699

* Estimated lifetime prevalence of epilepsy/seizure disorder was 10.2/1000 (95% confidence interval [CI]: 8.7-11.8) or 1%

* Current reported epilepsy/seizure disorder was 6.3/1000 (95% CI: 4.9-7.8).

* Epilepsy/seizure disorder prevalence was higher in lower-income families and in older, male children.

* Children with current reported epilepsy/seizure disorder were significantly more likely than those never diagnosed to

experience depression (8% vs 2%),

anxiety (17% vs 3%),

attention-deficit/hyperactivity disorder (23% vs 6%),

conduct problems (16% vs 3%),

developmental delay (51% vs 3%), (Fisher at al posted above 84% to borderline)

autism/autism spectrum disorder (16% vs 1%), (Fisher at al posted above 37%)

and headaches (14% vs 5%) (all P < .05).

*They had greater risk of limitation in ability to do things (relative risk: 9.22; 95% CI: 7.56-11.24), repeating a school grade (relative risk: 2.59; CI: 1.52-4.40), poorer social competence and greater parent aggravation, and were at increased risk of having unmet medical and mental health needs. Children with prior but not current seizures largely had intermediate risk.

This entry was posted in Autism, co-morbid, Depression, Environment, Epigenetics, epilepsy, Immune System, Inflammation, Mice, Neurology, Physiology, Treatment. Bookmark the permalink.

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