麻豆传媒

BALTIMORE -- Children with infantile spasms were not likely to have a sibling who also had infantile spasms, other forms of epilepsy, or autism spectrum disorder (ASD), a showed.

Of 475 patients with video-confirmed infantile spasms in a large clinical database, 294 had at least one sibling; of those, one patient had a sibling with infantile spasms, five had a sibling with another form of epilepsy, and six had a sibling with ASD, reported Shaun Hussain, MD, of the UCLA Mattel Children's Hospital in Los Angeles, and colleagues, at the American Epilepsy Society annual meeting.

Autism affects approximately and the link between the two disorders is unclear. They may share genetic susceptibility or it's possible that infantile spasms cause ASD, Hussain suggested.

"The big issue out there is that in most cases of autism, there is no obvious cause," Hussain said. "Although we believe genetics play a big role -- and countless genes have been linked to autism -- we can't identify a gene mutation in the vast majority of cases." Most children with autism also have a normal MRI and a normal, or nearly normal, EEG, he noted.

"If autism risk is mostly genetic, including autism in the setting of prior infantile spasms, we should have found far more patient-siblings with autism in our cohort," Hussain told 麻豆传媒.

"In our cohort, we believe autism among patients is largely a function of the infantile spasms, not just background genetic risk," he continued. "If we can figure out why autism is occurring among children with infantile spasms, we may be able to shed light on the pathogenesis of autism in general."

Autism was not rigorously determined in their analysis, but if its approximate prevalence was 35%, then 103 patients would have met criteria for autism or would be likely to develop autism, Hussain and colleagues calculated. "Given sibling and non-identical twin concordance rates for autism of approximately 30%, we would have expected to encounter 31 patient-siblings with autism, if autism risk is simply genetic and not a result of infantile spasms. We encountered just six (2%) siblings with an autism diagnosis," the researchers wrote.

"Similarly, with concordance rates for infantile spasms as high as 1.5%, we expected to encounter four to five siblings with infantile spasms, but only encountered a single (0.3%) sibling recurrence, with unknown etiology despite exome sequencing," they continued.

These findings suggest a limited degree of shared genetic predisposition, that "the relatively high risk of ASD among children with history of infantile spasm may be mediated by the infantile spasm itself, and that ASD risk may be potentially modifiable by treatment," Hussain and co-authors added.

"We're optimistic," Hussain said in a statement. "We've seen several kids with longstanding infantile spasms who seemed severely autistic, but after they were diagnosed and treated, their autistic symptoms -- especially impaired social awareness and engagement -- dissipated."

A major strength of this analysis was that the researchers studied 475 children with infantile spasms, noted Gregory Holmes, MD, of the University of Vermont College of Medicine in Burlington, who was not involved with the study. "This is a rare disorder and this number is remarkable," he said.

"There is considerable data that epilepsy and ASD are co-morbid conditions and one does not cause the other," Holmes pointed out. "I think these results have to be interpreted cautiously and not extrapolated to other epilepsies, where there is good evidence that seizures are not causative of spasms," he told 麻豆传媒.

"Infantile spasms are severe epileptic encephalopathies and, unless they respond to treatment, the children usually go on to have significant cognitive issues and may have ASD," Holmes continued. "Trying to determine if effectively treating spasms results in reduced ASD is very difficult since children with refractory infantile spasms likely have a greater disease burden at onset," he added.

Despite its limitations, the data may offer some guidance to parents of children with infantile spasms "who seek to estimate the risk of infantile spasms, epilepsy, and ASD in a subsequent child," Hussain and co-authors noted. The findings warrant replication and further investigation, they added.

"This was an exploratory study, and it may be that children with infantile spasms may just have a special type of autism," Hussain said. "On the other hand, we may have stumbled upon a means to treat or even prevent ASD in general."

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