Pediatricians: Why – and How - Genetics Matter for Advice on Vaccine Choice

Pediatricians: Why – and How - Genetics Matter for Advice on Vaccine Choice

When vaccine product inserts and the CDC’s Vaccine Information Statements list fever as a potential side effect, most pediatricians shrug it off with advice to take acetaminophen.  When they see children with seizure disorders, they are mostly commonly concerned with what anti-seizure medication might help.  Consideration of root causes to prevent seizures are not present in pediatric practice – and concern over taking steps to reduce the likelihood of preventing progression from seizure susceptibility to full-blown seizure disorders are not even imagined.

It is universally known that some infections, like the common cold, or the influenza virus, can induce fever.  One fact that is not as well known that fevers can induce seizures – and that repeated fever can lead to seizure disorders including epilepsy.  GABAA receptors are a responsible for fast synaptic inhibition in the cerebral cortex.  This occurs via reduction of cellular excitability via GABAA receptor activation.  These receptors can be impaired due to mutations, and it has long been known that heritable variation in GABAA receptors is associated with familial forms of epilepsy (see, e.g., Fedi et al., 2007). It is known that children with genetic variants in the GABAA receptor γ2 subunit are at increased risk of febrile seizures (e.g., Hancii et al. (2014).  Moreover, the specific mechanisms by which the mutations confer greater risk has been elucidated by Kang et al., (2006): febrile seizures are likely produced by a temperature-induced dynamic reduction of susceptible mutant surface GABAA receptors in response to fever.

From a mechanistic viewpoint, it is clear that fevers are dangerous for individuals with GABAA receptor genetic variation.  So it’s puzzling to some why there is no genetic screen at birth for GABAA receptors, when clearly, every vaccination is a potential fever, and every fever a potential trigger for the mechanism that leads to epilepsy.

The answer to that question that is sometimes given is “it’s not cost-effective”, to which a parent of a child with vaccine-induce seizures and seizure disorders have various colorful and perfunctory responses, which often include four-letter words, but are also invariably focused on the correct statement that those assessing the cost of vaccine injury do not bear the cost themselves, but instead are more than happy to impose that cost on others in the name of the herd.

Perhaps we’ve been asking the wrong question. Rather than asking the question “Why is there no universal screen for GABAA receptor variation at birth?” perhaps another question worth posing is “Why are children who experience seizures not genotyped for GABAA receptor variation after their first seizure and before receiving any more vaccines?”  Clearly, the cost of genotyping for variants that place a subset of children at risk who have already presented with seizure following a vaccine is far lower than the cost of a population screen – and the benefit in that identifiable subpopulation is massive because it can save the massive cost of treatments and prevent the loss of life from fatal seizures.

According to CDC, up to 5% of young children will have a febrile seizure at some time in their life, and  febrile seizures happen in children between the ages of 6 months and 5 years, with most occurring between 14–18 months of age.  Therefore, the majority of genetic testing would be conducted before those with genetic risk of vaccine induced seizure are two years of age – making it clear to parents, doctors, and to society that the individual with the genetic risk has a demonstrated increased specific risk (as opposed to the lower general risk).  Once the genetic test is done, the general risk becomes irrelevant for the individual: their risk is present, or absent.

Let’s take California as an example.  California started genetic testing of all newborns in 1966 with PKU, and now routinely screens for 80 conditions at birth.  No one is arguing that knowledge of these 80 results is not cost-effective.  A new study looking at infant genomes found increased risks of disorders in newborns that standard screens miss – and therefore pediatric genetics is giving serious consideration to newborn genome sequencing (nGS) to help inform parents and doctors of the possible conditions that each child might face.  Those study authors concluded:

“As these newborn cohorts age, future analyses of economic and healthcare utilization patterns in our nGS and control cohorts will allow for the eventual assessment and quantification of both costs and benefits of GS in the newborn setting. The results from our study, as well as future efforts to prospectively analyze the long-term implications of nGS in larger cohorts, will help inform the effective and responsible application of nGS in wider medical practice.”

Pediatricians should offer genetic testing for febrile seizure risk to arm parents with critical information and to inform themselves on the advice they give parents about further risks of vaccination. The accountants who determine our healthcare options who claim that genetic testing is not cost-effective should ask any parent who has seen their child undergo seizures following vaccination if they would pay for a test out-of-pocket to determine if their child is at increased risk of seizure or epilepsy due to vaccination.  As increasing number of parents stand up for more responsibility in the healthcare of their children, and as the state tries to wrest rights of choice away, the side requesting more information has the best interest of a specific child – and all children – in the center of their minds.  The side wanting less information, or that dismisses information that might lead to a reduction of human pain and suffering clearly has something else in mind.

© 2019 James Lyons-Weiler and The Institute for Pure and Applied Knowledge

References:

  • Ceyhan-Birsoy et al., Interpretation of genomic sequencing results in healthy and ill newborns: results from the BabySeq Project. The American Journal of Human Genetics,doi:10.1016/j.ajhg.2018.11.016, 2019.
  • Hancili S. 2004. The GABAA receptor γ2 subunit (R43Q) mutation in febrile seizures. Pediatr Neurol. 2014 Apr;50(4):353-6. doi: 10.1016/j.pediatrneurol.2014.01.002. Epub 2014 Jan 4.